Athanasios G. Pallis

EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts’ opinion for the treatment of non-small-cell lung cancer in an elderly population

Non-small-cell lung cancer (NSCLC) represents a common health issue in the elderly population. Nevertheless, the paucity of large, well-conducted prospective trials makes it difficult to provide evidence-based clinical recommendations for these patients. The present paper reviews the currently available evidence regarding treatment of all stages of NSCLC in elderly patients. Surgery remains the standard for early-stage disease, though pneumonectomy is associated with higher incidence of postoperative mortality in elderly patients. Given the lack of demonstrated benefit for the use of adjuvant radiotherapy, it is also not recommended in elderly patients. Elderly patients seem to derive the same benefit from adjuvant chemotherapy as younger patients do, with no significant increase in toxicity. For locally advanced NSCLC, concurrent chemoradiotherapy may be offered to selected elderly patients as there is a higher risk for toxicity reported in the elderly population. Third-generation single-agent treatment is considered the standard of care for patients with advanced/metastatic disease. Platinum-based combination chemotherapy needs to be evaluated in prospective trials. Unfortunately, with the exception of advanced/metastatic NSCLC, prospective elderly-specific NSCLC trials are lacking and the majority of recommendations made are based on retrospective data, which might suffer from selection bias. Prospective elderly-specific trials are needed.

End Points and Trial Design in Geriatric Oncology Research: A Joint European Organisation for Research and Treatment of Cancer–Alliance for Clinical Trials in Oncology–International Society of Geriatric Oncology Position Article

Selecting the most appropriate end points for clinical trials is important to assess the value of new treatment strategies. Well-established end points for clinical research exist in oncology but may not be as relevant to the older cancer population because of competing risks of death and potentially increased impact of therapy on global functioning and quality of life. This article discusses specific clinical end points and their advantages and disadvantages for older individuals. Randomized or single-arm phase II trials can provide insight into the range of efficacy and toxicity in older populations but ideally need to be confirmed in phase III trials, which are unfortunately often hindered by the severe heterogeneity of the older cancer population, difficulties with selection bias depending on inclusion criteria, physician perception, and barriers in willingness to participate. All clinical trials in oncology should be without an upper age limit to allow entry of eligible older adults. In settings where so-called standard therapy is not feasible, specific trials for older patients with cancer might be required, integrating meaningful measures of outcome. Not all questions can be answered in randomized clinical trials, and large observational cohort studies or registries within the community setting should be established (preferably in parallel to randomized trials) so that treatment patterns across different settings can be compared with impact on outcome. Obligatory integration of a comparable form of geriatric assessment is recommended in future studies, and regulatory organizations such as the European Medicines Agency and US Food and Drug Administration should require adequate collection of data on efficacy and toxicity of new drugs in fit and frail elderly subpopulations.

EORTC Elderly Task Force experts’ opinion for the treatment of colon cancer in older patients

As a result of an increasing life expectancy, the incidence of colon cancer in the older population is rising. As a consequence oncologists and their older patients commonly face the dilemma of whether or not to give/receive treatment for colon cancer. However, the paucity of large, well conducted prospective trials makes it difficult to provide evidence-based clinical recommendations for these patients. The current evidence supports the safety and efficacy of treatment for colon cancer in fit older patients and demonstrates that treatment outcome can be similar to that of their younger counterparts. However, it should be noted that these data are derived from retrospective studies which are likely to suffer from selection bias. Despite a growing body of data, further work is still needed to establish optimal strategies to care for this special population and prospective specific trials for older colon cancer patients are clearly needed.

Treatment of small-cell lung cancer in elderly patients.

Small‐cell lung cancer (SCLC) represents 15% to 20% of all lung carcinomas. Approximately 30% to 40% of these cases are diagnosed in patients older than 70 years of age. Staging of SCLC classifies patients as having either limited or extensive‐stage disease. The standard treatment for limited‐stage disease is platinum‐based chemotherapy, combined with external‐beam thoracic radiotherapy, whereas platinum‐based regimens alone represent the standard of care for extensive‐stage disease. In the elderly population, treatment of SCLC is more challenging given the decline in physiological organ reserve and the presence of comorbidities. The majority of data are drawn from retrospective studies, which are likely to suffer from selection bias. However, limited prospective data are available to guide treatment decisions in that special population. Nonetheless, these data demonstrate that standard approaches are feasible in carefully selected elderly patients. The purpose of this article is to review the currently available evidence on treatment of SCLC in patients older than 65‐70 years of age. Cancer 2010.

Completion of radiotherapy is associated with the Vulnerable Elders Survey-13 score in elderly patients with cancer

OBJECTIVES Vulnerability assessment of geriatric patients with cancer may contribute to improved anti-cancer treatment with maximal results and minimal side effects. The aim of the present study was to evaluate whether the Vulnerable Elders Survey-13 (VES-13) score is associated with completion of radiotherapy among elderly patients with cancer. MATERIALS AND METHODS This was a prospective observational study that included patients greater than age 75 with histologically confirmed cancer disease, referred to the Department of Radiation Oncology to receive radical or palliative radiotherapy, from 2010 to 2012. VES-13 forms were filled in before the initiation of radiotherapy and scores were assigned according to a standardized scoring procedure. RESULTS Of a total of 230 participants (median age 78.5 years), 41 (17.8%) did not complete radiotherapy. These patients had higher VES-13 scores (median with interquartile range: 5 [2-8.5]) compared to those who completed the treatment (3 [1-7]; P = 0.008). A VES-13 score >3 was associated with 2.14 times higher probability of not completing radiotherapy, whereas in patients with scores >7 this probability was 3.34 times higher. The association between higher VES-13 scores and non-completion of radiotherapy was independent of other factors, such as age, sex, comorbidities, type of radiotherapy, and presence of side effects. CONCLUSION Patients with higher VES-13 scores had increased probability of not completing radiotherapy in our study, and this effect was independent of other factors that might affect radiotherapy completion.

Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052)

BACKGROUND This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)(1) as primary end-point. METHODS Chemotherapy-naïve patients with histologically proven MPM and performance status (PS) 0/1, were treated with cisplatin 75 mg/m(2) on day 1 and bortezomib 1.3mg/m(2) on days 1, 4, 8, 11 every 3 weeks. The primary end-point validation utilised the landmark method. RESULTS Between 2007 and 2010 82 patients were entered. PFSR-18 was 53% (80% confidence intervals, CIs, 42-64%). The overall survival (OS) was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The median PFS was 5.1months (95% CI 3.3-6.5) and the response rate was 28.4% (95% CI 18.9-39.5%). The most frequent grade 3-4 toxicities were hyponatremia (46%), hypokalaemia (17%), fatigue (12.2%), thrombocytopenia (11%), neutropenia (9.7%) and neurotoxicity (motor, sensory, other: 1.2%, 8.5%, 2.4%). There were two toxic deaths (32 and 74days) due to acute pneumonitis and cardiac arrest. End-point validation showed that patients with no progression/progression at 18 weeks had median OS of 16.9/11.9 months, respectively. Hazard ratio was 0.46 (CI 0.32-0.67), logrank test and C-index were 0.007 and 0.60. CONCLUSION The 50% PFSR-18 for CB was contained within the 80% CI for (42-64%). Therefore the null hypothesis could not be rejected. Accordingly this combination does not warrant further investigation. PFSR-18 was confirmed as a strong predictor of survival.

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

Attitudes and referral patterns of lung cancer specialists in Europe to Specialized Palliative Care (SPC) and the practice of Early Palliative Care (EPC)

PurposeTo examine availability of Palliative Care (PC) services and referral patterns of European Lung cancer specialists to PC.MethodsAll members of the EORTC Lung Cancer Group (LCG) were asked via email to participate in an on-line survey.Results50 out of 170 (29.4%) replied: 24 medical oncologists, 14 radiation/clinical oncologists, 11 pulmonologists and 1 thoracic surgeon. All but two of respondents (96%) had access to at least one component of PC services. In terms of referral of patients to PC almost 75% of respondents would refer most of their patients when there were no treatment options or at the end of life, while only 22% would refer patients at earlier stages of disease. Barriers for referral to PC were negative attitudes of patients to PC (26%), lack of availability of PC services (20%), lack of expertise of PC physicians(18%), the belief that referral to PC signifies abandoning patients (8%), and that PC specialists discourage active oncological therapy (8%). Whilst most of the respondents expressed positive attitudes, 12-22% had overtly negative attitudes towards PC. Seventy-eight (78%) of respondents expressed an interest to participate in a trial of early PC (EPC).ConclusionDespite good availability of SPC services at institutions of members of the EORTC LCG, and most respondents expressing positive attitudes towards PC, their practice involved referral of patients to PC late in the disease trajectory, hence Lung Cancer specialists in Europe have not adopted the practice of EPC concurrent with active oncological care.

Is age a negative prognostic factor for the treatment of advanced/metastatic non-small-cell lung cancer?

As a result of an increasing life expectancy, the incidence of non-small-cell lung cancer (NSCLC) in the older population is rising. As a consequence oncologists and their older patients commonly face the dilemma of whether or not to give/receive treatment for NSCLC. The current evidence supports the safety and efficacy of treatment for NSCLC cancer in fit older patients and demonstrates that treatment outcome can be similar to that of their younger counterparts and that chronological age per se is not a negative prognostic factor. However, it should be noted that these data are derived from retrospective studies which are likely to suffer from selection bias. Prospective data support the use of third generation single-agent (vinorelbine, gemcitabine, docetaxel) as first-line treatment for older NSCLC patients. Although cisplatin-based doublets represent the cornerstone of chemotherapy treatment for advanced/metastatic NSCLC their role in the treatment of older patients needs to be further elucidated. Despite a growing body of data, further work is still needed to establish optimal strategies to care for this special population and prospective specific trials for older NSCLC patients are clearly needed.

High prevalence of osteoblastic bone reaction in computed tomography scans of an European Organisation for Research and Treatment of Cancer prospective randomised phase II trial in extensive stage small cell lung cancer

BACKGROUND Osteoblastic bone reaction is an important phenomenon defined by an increase in apparent bone density of previously known bone metastasis or development of new osteoblastic lesions in the presence of response in other tumour sites. Osteoblastic bone reaction in lung cancer has only been described in a few reports and mostly in patients with pre-existing bone metastasis. METHODS In this report we present the data of an independent, blinded and preplanned radiological review of the occurrence of osteoblastic lesions in patients with extensive stage small cell lung cancer (SCLC). The computed tomography (CT) scans of the chest and upper abdomen of 71/88 patients who had an investigator reported complete response (CR), partial response (PR) or stable disease (SD) were retrospectively analysed for the development of osteoblastic lesions. Furthermore, baseline exams were reviewed for the presence and location of bone metastasis and local radiological reports were reviewed for any knowledge of bone metastasis. RESULTS There were 14 patients with osteoblastic bone lesions in the reviewed follow-up CT scans. Three patients had known bone metastases at baseline, and 11 patients had no history or findings of bone metastases on the baseline scan. During the course of the disease, 13 out of 14 patients developed new osteoblastic lesions, while all responded in other sites. The prevalence of osteoblastic bone reaction in our study was 19.7%. CONCLUSION In this study osteoblastic bone reaction was observed in a larger number of patients without previously documented bone metastases, indicating a high prevalence of occult bone metastases in SCLC. If bone metastases are not documented at diagnosis, then osteoblastic bone reaction may cause confusion in a responding patient.