Evidence-Based Follow-up for Adults With Cancer.

BACKGROUND: The objectives of follow-up care for cancer patients include psycho- social assistance and the detection of health problems. The concept of follow-up care rests on the assumption that the early detection of cancer recurrences and disease- or treatment-related complications is beneficial to patients. In this article, we provide an overview of the scientific evidence supporting current recommen- dations for the follow-up care of patients with colorectal cancer, lung cancer, and lymphoma. METHODS: This review is based on pertinent publications that were retrieved by a selective search in PubMed, supplemented by the authors' own experience in patient care and guideline creation. RESULTS: As recurrences usually arise soon after initial treatment, the recommended follow-up interval is shorter in the first two years (3-6 months) and longer thereafter (6-12 months). The question of which particular follow-up studies should be per- formed has only been systematically analyzed in a few cases. For patients with colorectal cancer, colonoscopy is the most important study. Intensive follow-up care is associated with a statistically non-significant increase in the survival rate compared to minimal follow-up care (77.5% versus 75.8%). Intensive diagnostic follow-up studies have been found to lead to a doubling of the frequency of operations for recurrence with curative intent, yet without any effect on the average survival time. The findings in lung cancer are similar. However, after tumor resection with curative intent, regularly repeated CT scanning leads to a survival advantage. In lymphoma patients, the longer the interval from primary treatment, the greater the likelihood of treatment-related secondary illnesses. It is not yet known how follow-up care should be provided to these patients in order to help them best. CONCLUSION: The evidence supporting the efficacy of currently recommended modalities of follow-up care for cancer patients is weak. Until more data from clinical studies become available, the current guidelines should be followed.

[Chemotherapy in the Elderly with Non-Small Cell Lung Cancer: A Non-Interventional, Prospective, Multicentric Observational Study]. / Chemotherapie beim älteren Patienten mit nicht kleinzelligem Lungenkarzinom: Eine nicht-interventionelle, prospektive, multizentrische Beobachtungsstudie.

Background Elderly patients (70 years or older) with non-small cell lung cancer (NSCLC) do benefit from systemic chemotherapy as shown in many studies. We prospectively collected multicentric data on therapeutic decisions from patients 70 years or older to reflect the reality in the German health care system. Material and Methods Patients 70 years or older with NSCLC Stage IIIB or IV were eligible. No more than 20 consecutive patients from each center were included. Comorbidities, weighted by the Charlson-comorbidity-index, and survival data were collected. Results 253 patients were documented. Median age was 75.5 years (range 70 to 92) and 75 % were male. 2 % had no comorbidities, 5 % one, 15 % two, 24 % three and 55 % more than three. 237 patients (94 %) received systemic chemotherapy: 172 (73 %) as a combination and 58 (24 %) as monotherapy. Data from seven patients regarding therapy are missing. Combination regimens were in 66 % carboplatin- and in 30 % cisplatin-based. The most frequently given monotherapy was vinorelbin in 50 % of cases. In the group of the patients older than 80 years (n = 38), 53 % received mono therapy, 29 % a carboplatin-based regimen and 16 % no chemotherapy. Cisplatin was not administered in this age group. Median overall survival (OS) was 16.9 months. Patients with a Charlson-score ≤ 6 had 17.9 months, those > 6 12.0 months. With combination chemotherapy median OS was 23.5 months. Patients > 80 years had a median OS of 5.7 months. Conclusion A high percentage of patients older than 70 years received systemic therapy. Survival depended more on comorbidities than on age.

An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as a First-Line Therapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer.

INTRODUCTION: Type 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting. METHODS: In this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m2 pemetrexed, and 75 mg/m2 cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed. RESULTS: The mean age of the intent-to-treat population (n = 172) was 59 years (range 32-83). Median progression-free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81-1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64-1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred. CONCLUSIONS: Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.

Neuroendocrine tumors of the bronchopulmonary system (typical and atypical carcinoid tumors): current strategies in diagnosis and treatment. Conclusions of an expert meeting February 2011 in Weimar, Germany.

Neuroendocrine tumors (NETs; syn. carcinoid tumors) are highly or moderately differentiated neoplasms. They comprise a large variety of rare and heterogeneous tumors with an estimated incidence of 3-5/100,000/year. They can arise in virtually every internal organ, but mainly occur in the gastroenteropancreatic and bronchopulmonary systems. Around 25% of the NETs are localized in the bronchopulmonary system. Approximately 2% of all lung tumors are NETs. According to the World Health Organization (WHO) classification of lung tumors, bronchopulmonary NETs are subdivided into typical carcinoids (TCs) and atypical carcinoids (ACs). The parameter with the highest impact on NET behavior and prognosis is the histological classification and staging according to the tumor/node/metastasis (TNM) system. The diagnosis of NETs is established by histological examination and the immunohistochemical detection of general neuroendocrine markers, such as chromogranin A (CgA) and synaptophysin. Serum markers and the use of functional imaging techniques are important additive tools to establish the diagnosis of a NET. The only curative option for lung NETs is complete surgical resection. Beyond that, the currently available interdisciplinary therapeutic options are local ablation, biotherapy (somatostatin analogues), or chemotherapy. New therapeutic options such as peptide receptor radionuclide therapy (PRRT) and molecularly targeted therapies achieve promising results and are under further evaluation. This report is a consensus summary of the interdisciplinary symposium 'Neuroendocrine Tumors of the Lung and of the Gastroenteropancreatic System (GEP NET) - Expert Dialogue' held on February 25-26, 2011 in Weimar, Germany. At this conference, a panel of 23 German experts shared their knowledge and exchanged their thoughts about research, diagnosis, and clinical management of NETs, whereby special attention was paid to NETs of the respiratory tract.

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer.

BACKGROUND: Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. METHODS: Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137. FINDINGS: 558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p<0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]). INTERPRETATION: In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided. FUNDING: German Cancer Aid (Bonn, Germany).

[Geriatric assessment and diagnosis in elderly patients]. / Geriatrische Assessments und Diagnostik beim älteren Patienten.

As is the case with younger patients, the treatment decisions for elderly patients with thoracic tumours are primarily based on the results of the usual routine diagnostics. Standardised assessments of existing comorbidities and geriatric assessments may provide information which are of particular relevance for intensive and/or complex therapy modalities and which may require early corresponding intervention or measures for support.

Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years'-follow-up results from a randomised phase III trial.

PURPOSE: Based on the promising activity of paclitaxel in small-cell lung cancer (SCLC) we conducted a randomized phase III trial to evaluate whether a combination of paclitaxel, carboplatin and etoposide phosphate (TEC) improves survival and time to progression as well as tolerability and quality of life (QoL) compared to a regimen of carboplatin, etoposide phosphate and vincristine (CEV) in SCLC patients. PATIENTS AND METHODS: Six hundred and fourteen patients with stages I-IV SCLC were randomly assigned between January 1998 and December 1999 to both treatment arms. All patients were evaluated for response rate, survival, side effects and quality of life with overall survival (OS) serving as primary endpoint. A final analysis was done after a six-year follow-up. Survival curves were estimated using Kaplan-Meier curves and tested with the log-rank test. Quality of life data were assessed in using the EORTC QLQ-C30 questionnaire and evaluated by calculating and comparing the mean scores as well as applying longitudinal techniques. RESULTS: Six hundred and eight patients were evaluable for efficacy and toxicity. The long-term follow-up confirms the significant survival benefit for the paclitaxel, etoposide, carboplatin (TEC) regimen with a median OS of 12.5 months compared to 11.7 months for the CEV arm (HR, 1.21; 95% CI, 1.02-1.43; P=.030). The 5-year survival rates were 14% for the experimental versus 6 % for the CEV arm. Significant survival prolongation was also observed in the subgroup of patients with stage IV disease (HR, 1.27; 95% CI, 1.00-1.60; P=.047). The previously reported clinical benefit in form of an overall reduction of grade 3/4 toxicity was backed by the results of the comprehensive QoL analysis we report hereby. TEC significantly improves the relevant QoL parameters like global overall QoL or physical functioning. CONCLUSION: When administered in combination with etoposide and carboplatin, paclitaxel is able to offer in SCLC patients with extensive disease a survival benefit without additional toxicities, but with gains in patient-reported quality of life. In terms of efficient palliative care, TEC might be seen as an alternative to standard cisplatin plus etoposide in patients requesting a powerful palliative regimen not compromising any survival benefit.

Lung cancer screening--where we are in 2004 (take home messages).

The best prognosis for lung cancer can be expected by diagnosis at an early stage of the disease. Long-term survival may be improved by increasing the number of early-stage diagnoses. At the present time, three different screening tools for lung cancer are available: Low-dose CT scanning, sputum analysis and fluorescence bronchoscopy. Each of these tools has a different screening target. Low-dose CT scanning focusses on small pulmonary nodules, sputum analysis has the potential of detecting lung cancer of the central airways, and fluorescence bronchoscopy can identify pre-malignancy, carcinoma in situ and minimally invasive squamous cell carcinoma. The best way forward appears to be a combination of all techniques. Sputum analysis can be used to define a better-characterised risk population, and subsequently this population can undergo low-dose CT and fluorescence bronchoscopy.

Randomized phase III trial of paclitaxel, etoposide, and carboplatin versus carboplatin, etoposide, and vincristine in patients with small-cell lung cancer.

BACKGROUND: Paclitaxel administered in combination with a topoisomerase-II inhibitor (such as etoposide) and carboplatin is an effective and safe first-line treatment for patients with small-cell lung cancer (SCLC). We conducted a randomized phase III multicenter trial to determine whether paclitaxel plus etoposide plus carboplatin improves the outcome of patients with primary SCLC relative to standard chemotherapy (carboplatin, etoposide, and vincristine). METHODS: Between January 1998 and December 1999, 614 patients with SCLC stages I-IV were randomly assigned to the standard arm (309 patients) or the experimental arm (305 patients). Treatment courses were repeated every 21 days for a maximum of six courses. All patients were evaluated for response rate, survival, and toxicities every two courses. The primary endpoint was survival. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. All statistical tests were two-sided. RESULTS: A total of 608 patients were evaluable for all endpoints (standard arm 307 patients, experimental arm 301 patients). The hazard ratio [HR] of death for patients receiving the standard treatment was statistically significantly higher than that for patients receiving the experimental treatment (HR = 1.22, 95% confidence interval [CI] = 1.03 to 1.45; P =.024). Progression-free survival was also statistically significantly shorter for patients in the standard arm relative to that of patients in the experimental arm (HR = 1.21, 95% CI = 1.03 to 1.42). There were no differences in the response rates (complete and partial combined) to the treatments (standard arm: 69.4%, 95% CI = 63.9% to 74.5%; experimental arm: 72.1%, 95% CI = 66.7% to 77.1%; difference = 2.7%, 95% CI = 4.5% to 9.9%). Rates of severe grade of anemia, leukocytopenia, neutropenia, and thrombocytopenia were lower in the experimental arm than in the standard arm. CONCLUSION: Patients with previously untreated SCLC who received paclitaxel, etoposide, and carboplatin showed improved overall and progression-free survival and less frequent hematologic toxicities than those who received the standard therapy.