Lore Decoster

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†

BACKGROUND Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.

Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu

Human epidermal growth factor receptor (HER)2/neu kinase domain mutations are found in approximately 1-4% of lung adenocarcinomas with a similar phenotype to tumors with epidermal growth factor receptor (EGFR) mutations. Afatinib is a potent irreversible ErbB family blocker. We determined the tumor genomic status of the EGFR and HER2 genes in non- or light smokers with lung adenocarcinoma in patients who were entered into an exploratory Phase II study with afatinib. Five patients with a non-smoking history and metastatic lung adenocarcinomas bearing mutations in the kinase domain of HER2 gene were identified, three of which were evaluable for response. Objective response was observed in all three patients, even after failure of other EGFR- and/or HER2-targeted treatments; the case histories of these patients are described in this report. These findings suggest that afatinib is a potential novel treatment option for this subgroup of patients, even when other EGFR and HER2 targeting treatments have failed.

RELEVANCE OF A SYSTEMATIC GERIATRIC SCREENING AND ASSESSMENT IN OLDER PATIENTS WITH CANCER RESULTS OF A PROSPECTIVE MULTICENTRIC STUDY

BACKGROUND To evaluate the large-scale feasibility and usefulness of geriatric screening and assessment in clinical oncology practice by assessing the impact on the detection of unknown geriatric problems, geriatric interventions and treatment decisions. PATIENTS AND METHODS Eligible patients who had a malignant tumour were ≥70 years old and treatment decision had to be made. Patients were screened using G8; if abnormal (score ≤14/17) followed by Comprehensive Geriatric Assessment (CGA). The assessment results were communicated to the treating physician using a predefined questionnaire to assess the topics mentioned above. RESULTS One thousand nine hundred and sixty-seven patients were included in 10 hospitals. Of these patients, 70.7% had an abnormal G8 score warranting a CGA. Physicians were aware of the assessment results at the time of treatment decision in two-thirds of the patients (n = 1115; 61.3%). The assessment detected unknown geriatric problems in 51.2% of patients. When the physician was aware of the assessment results at the time of decision making, geriatric interventions were planned in 286 patients (25.7%) and the treatment decision was influenced in 282 patients (25.3%). CONCLUSION Geriatric screening and assessment in older patients with cancer is feasible at large scale and has a significant impact on the detection of unknown geriatric problems, leading to geriatric interventions and adapted treatment.

Performance of Two Geriatric Screening Tools in Older Patients With Cancer

PURPOSE To compare the diagnostic characteristics of two geriatric screening tools (G8 and Flemish version of the Triage Risk Screening Tool [fTRST]) to identify patients with a geriatric risk profile and to evaluate their prognostic value for functional decline and overall survival (OS). PATIENTS AND METHODS Patients ≥ 70 years old with a malignant tumor were included if a new cancer event occurred requiring treatment decision. Geriatric screening with G8 and fTRST (cutoff ≥ 1 [fTRST (1)] and ≥ 2 [fTRST (2)] evaluated) was performed in all patients, as well as a geriatric assessment (GA) evaluating social situation, functionality (activities of daily living [ADL] + instrumental activities of daily living [IADL]), cognition, depression, and nutrition. Functionality was re-evaluated 2 to 3 months after cancer treatment decision, and death rate was followed. Functional decline and OS were evaluated in relation to normal versus abnormal score on both screening tools. RESULTS Nine hundred thirty-seven patients were included (October 2009 to July 2011). G8 and fTRST (1) showed high sensitivity (86.5% to 91.3%) and moderate negative predictive value (61.3% to 63.4%) to detect patients with a geriatric risk profile. G8 and fTRST (1) were strongly prognostic for functional decline on ADL and IADL, and G8, fTRST (1), and fTRST (2) were prognostic for OS (all P < .001). G8 had the strongest prognostic value for OS (hazard ratio for G8 normal v abnormal, 0.38; 95% CI, 0.27 to 0.52). CONCLUSION Both geriatric screening tools, G8 and fTRST, are simple and useful instruments in older patients with cancer for identifying patients with a geriatric risk profile and have a strong prognostic value for functional decline and OS.

Complete metabolic tumour response, assessed by 18-fluorodeoxyglucose positron emission tomography (18FDG-PET), after induction chemotherapy predicts a favourable outcome in patients with locally advanced non-small cell lung cancer (NSCLC)

BACKGROUND 18FDG-PET and multislice computerized axial tomography (CT) scan are used for diagnosis, staging and response evaluation in NSCLC patients. The correlation between the response assessment by both imaging techniques and survival was assessed in patients with unresectable stage III NSCLC treated with induction chemotherapy followed by consolidation radiotherapy. METHODS Thirty-one patients, enrolled in a phase II study evaluating the efficacy and toxicity of a novel triplet induction chemotherapy (paclitaxel, carboplatin and gemcitabine) (PACCAGE) before consolidation radiotherapy, were evaluated by CT and 18FDG-PET at baseline and after three cycles of chemotherapy. The correlation between CT and 18FDG-PET response and time to progression and overall survival was analyzed using the Kaplan-Meier estimates of survival and the log rank test. RESULTS Ten patients with a complete response (CR) on 18FDG-PET had a significantly longer time to progression and overall survival than patients with a non-CR (median 19.9 months versus 9.8 months, p=0.026, and median >49 months versus 14.4 months, p=0.004, respectively). Twenty patients with a partial CT response (PR) had a significantly longer time to progression (median 15 months versus 9.4 months, p=0.001) than patients with a non-PR but the difference in overall survival only showed a trend (23.3 months versus 14.4 months, p=0.093). CONCLUSIONS A CR on 18FDG-PET following induction chemotherapy for locally advanced, unresectable NSCLC seems to be a more powerful prognostic marker for survival compared to PR on CT.

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

OBJECTIVES The aim of this prospective study in older patients with cancer was to evaluate how clinical assessment (including age) determines the physicians treatment decisions, and how geriatric assessment (GA) further influences these decisions. PATIENTS AND METHODS Patients aged ≥70years 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. RESULTS In total, 937 patients with median age of 76years 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. CONCLUSIONS Physicians 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.

Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma

OBJECTIVES Afatinib, an oral irreversible ErbB family blocker, has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. Other potential biomarkers predicting response to afatinib, such as human epidermal growth factor receptor-2 (HER2) mutations and EGFR gene amplification, have not been validated yet. This phase II study investigated whether afatinib conferred clinical benefit in cohorts of adenocarcinoma patients with: (1) EGFR mutation and failing on erlotinib/gefitinib; or (2) increased copy number of EGFR by fluorescence in situ hybridization (FISH); or (3) HER2 mutation. MATERIALS AND METHODS Patients started daily afatinib 50mg monotherapy. Upon disease progression, patients could continue, at the investigators discretion, afatinib (40mg) with the addition of paclitaxel (80mg/m(2) weekly for 3 weeks/4-week cycle). Endpoints included confirmed objective response (OR), progression-free survival (PFS), disease control, and safety. RESULTS Of 41 patients treated (cohort 1: n=32; cohort 2: n=2; cohort 3: n=7), 33 received afatinib monotherapy; eight subsequently received afatinib plus paclitaxel. With afatinib monotherapy, one patient achieved a confirmed OR (partial response [PR]; cohort 2). Two further patients achieved unconfirmed PRs (one each in cohort 1 and cohort 3). Disease control was achieved by 17/32 (53%), 2/2 (100%) and 5/7 (71%) patients in cohorts 1, 2 and 3, respectively. In patients receiving combination therapy (median PFS: 6.7 weeks), one (cohort 3) had confirmed PR of 41.9 weeks. The most common afatinib-related adverse events were diarrhea (95%) and rash/acne (80%). CONCLUSION Afatinib demonstrated signs of clinical activity in heavily pretreated patients with activating HER2 or EGFR mutations or EGFR FISH-positive tumors.

Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib

Approximately half of BRAF-mutated Non-small cell lung cancers (NSCLCs) harbor a non-V600 BRAF mutation, accounting for ∼40,000 annual deaths worldwide. Recent studies have revealed the benefits of combined targeted therapy with a RAF-inhibitor (Dabrafenib) and a MEK-inhibitor (Trametinib) in treating V600 BRAF mutant cancers, including NSCLC. In contrast, sensitivity of non-V600 BRAF mutations to these inhibitors is not documented. Non-V600 mutations can either increase or impair BRAF kinase activity. However, impaired BRAF kinases can still activate the ERK pathway in a CRAF-dependent manner. Herein, beyond describing a cohort of BRAF mutant NSCLC patients and functionally analyzing 13 tumor-derived BRAF mutations, we demonstrate that both types of non-V600 BRAF mutations can be sensitive to clinically relevant doses of Dabrafenib and Trametinib in HEK293T cells, in lung epithelial cellular model (BEAS-2B) and in human cancer cell lines harboring non-V600 BRAF mutations. ERK activity induced by both types of these mutations is further reduced by combinatorial drug treatment. Moreover, the combination leads to more prolonged ERK inhibition and has anti-proliferative and pro-apoptotic effects in cells harboring both types of non-V600 BRAF mutations. This study provides a basis for the clinical exploration of non-V600 BRAF mutant lung cancers upon treatment with Trametinib and Dabrafenib.

Implementation of geriatric assessment-based recommendations in older patients with cancer: A multicentre prospective study.

PURPOSE The main objective of this study was to describe geriatric recommendations based on a geriatric assessment (GA) and to evaluate the implementation of these recommendations. PATIENTS AND METHODS A two-step approach of screening followed by a GA was implemented in nine hospitals in Belgium. Patients ≥ 70 years were included at diagnosis or at disease progression/relapse. Concrete geriatric recommendations were systematically documented and reported to the treating physicians and consisted of referrals to professional health care workers. Patient charts were reviewed after one month to verify which geriatric recommendations have been performed. RESULTS From August 2011 to July 2012, 1550 patients were included for analysis. The median age was 77 (range: 70-97) and 57.0% were female. A solid tumour was diagnosed in 91.4% and a haematological malignancy in 8.6%. Geriatric screening with the G8 identified 63.6% of the patients for GA (n=986). A median of two geriatric recommendations (range: 1-6) were given for 76.2% (95%CI: 73.4-78.8) of the evaluable patients (n=710). A median of one geriatric recommendation (range: 1-5) was performed in 52.1% (95%CI: 48.4-55.8) of the evaluable patients (n=689). In general, 460 or 35.3% (95%CI: 32.8-38.0) of all the geriatric recommendations were performed. Geriatric recommendations most frequently consisted of referrals to the dietician (60.4%), social worker (40.3%), and psychologist (28.9%). CONCLUSION This implementation study provides insight into GA-based recommendations/interventions in daily oncology practice. Geriatric recommendations were given in about three-fourths of patients. About one-third of all geriatric recommendations were performed in approximately half of these patients.

Evaluation of a Comprehensive Rehabilitation Program for Post-Treatment Patients With Cancer

PURPOSE/OBJECTIVES To evaluate the effects of a rehabilitation program on quality of life, fatigue, fear of movement (kinesiophobia), distress, anxiety, depression, and physical condition. DESIGN Pretest/post-test. SETTING An outpatient rehabilitation setting in the Oncology Centre at the University Hospital Brussels in Belgium. SAMPLE 36 patients who had completed cancer treatment with a curative potential. METHODS Participants completed a questionnaire and underwent a physical test at baseline and at the end of the program. The measurement instruments used included the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30, Functional Assessment of Cancer Therapy-Fatigue, Hospital Anxiety and Depression Scale, RAND-36, Tampa Scale for Kinesiophobia, Distress Barometer, and Tecumseh Step Test. MAIN RESEARCH VARIABLES Quality of life, fatigue, kinesiophobia, distress, anxiety, depression, and physical condition. FINDINGS Significant improvement was observed in quality of life (p < 0.001), physical condition (p = 0.007), fatigue (p = 0.01), and depression (p = 0.012). In contrast, kinesiophobia (p = 0.229), distress (p = 0.344), and anxiety (p = 0.101) did not change significantly. CONCLUSIONS A general and significant improvement in all aspects affecting quality of life and rehabilitation was observed, but less so for aspects that might be influenced by prognostic concerns. The relative contribution of the program versus spontaneous recovery and long-term impact need to be determined further in a prospective randomized study. IMPLICATIONS FOR NURSING Multidisciplinary rehabilitation should become part of the total care plan for patients with cancer.