journal article
LitStream Collection
Home
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0245-8
There are four major types of lung carcinomas, small cell neuroendocrine carcinoma, squamous cell carcinoma, adenocarcinoma and large cell carcinomas (LC) [1]. Since the mid nineties the incidence of adenocarcinomas has increased; whereas squamous and small cell carcinomas have decreased dramatically [2, 3]. LC, however, remained constant at about 10–12% of all lung carcinomas. However, LC should not be mixed with large cell carcinoma variants including large cell neuroendocrine carcinoma, clear cell carcinoma, rhabdoid large cell carcinoma, basaloid, and lymphoepithelioma-like carcinoma, respectively. Whereas a lot of published data do exist for the LC variants, only few studies have investigated LC itself. Due to an increased use of differentiation markers in the diagnostic practice LC seems to decrease in frequency, and might even vanish. This review will try to explain the problems of LC diagnosis, the false use of this diagnosis, and reasons why LC is becoming a rare entity.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0248-5
Lung cancer remains the leading cause of cancer-related death in the developed countries. Surgical, anatomic resection (typically a lobectomy) is still a gold standard for patients who have early-stage non-small cell lung cancer. In the past 20 years, video-assisted thoracic surgery has been performed with increasing frequency in the surgical treatment of lung cancer worldwide. This article reviews several published reports suggesting potential advantages of VATS lobectomy over "open" thoracotomy in terms of mortality, morbidity, postoperative pain, complication rate and patient's quality of life. VATS lobectomy is a reasonable option for the management of early-stage non-small cell lung cancer. The advantages of this procedure over "open" lobectomy are of established value. Of great significance is also ability to apply this operation safely in high-risk patients.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0239-6
Adjuvant chemotherapy (CT) became the standard of care for patients with completely resected non-small cell lung cancer. However, the evidence supports this intervention for stages II-IIIA only. For stage IB, the randomized trials were not able co configure a clear-cut conclusion. Positive results have been published by the Japanese investigators using uracil-tegafur, whereas no survival benefit was observed in the trials using platinum-based CT. The new TNM staging system adopted in 2009 operated some modifications which partially included the former stage IB. Despite the fact that the new staging system is currently in use, the recommendations regarding adjuvant CT, as they appear in the guidelines, are based on the evidence built on the previous TNM classification. Subsequently, the issue regarding adjuvant CT in stage IB deserves a new perspective. This paper will address the new viewpoint regarding adjuvant CT in stage IB, defined according to the current evidence and the amendments of new TNM staging system.
Rothschild, S. I.; Gautschi, O.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0242-y
Most patients with non-small cell lung cancer (NSCLC) present with advanced, metastatic disease. Although treatment of these patients was recently improved with the discovery of EGFR and ALK targeting, molecular targeted drugs, most patients require chemotherapy. The outcome of patients with advanced NSCLC lacking EGFR or ALK mutations remains disappointing, with a median overall survival of 12–14 months. To improve survival and quality of life, the concept of maintenance therapy after first-line chemotherapy has gained interest, especially in the light of efficacious and better tolerable drugs and the results of recent clinical trials. However, the topic of maintenance therapy remains controversial and complex. Therefore, we give an overview on the current evidence and discuss our personal recommendations for clinical practice.
Szutowicz, E.; Konopa, K.; Jassem, J.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0243-x
The progress in molecular oncology has resulted in developing numerous targeted anticancer agents, some of which have emerged as therapeutic options in non-small cell lung cancer (NSCLC). The largest clinical experience in this malignancy concerns inhibitors of epidermal growth factor receptor (EGFR), including small molecular tyrosine kinase inhibitors (erlotinib and gefitinib), and monoclonal antibody cetuximab. Of those, erlotinib and gefitinib are routinely used in first-line, second-line and maintenance therapy of advanced NSCLC. Another targeting agent approved in advanced NSCLC is a humanized anti-VEGF monoclonal antibody bevacizumab. Until so far, no valuable clinical efficacy has been documented for small-molecule VEGFR kinase inhibitors and anti-IGF-1R agents. Most recently, an impressive activity of crizotinib, an EML4-ALK inhibitor has been reported. Several other targeted agents are currently being tested in clinical trials. This article critically reviews the current achievements and failures in the targeted treatment of advanced NSCLC, with particular focus on the importance of molecular testing and treatment individualization.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0240-0
As interest in biomarkers, staging and treatment of NSCLC has dramatically increased in the past years, the opposite is true for SCLC. The number of abstracts dealing with SCLC presented during the past ASCO meetings amounts to only one-eighth of the number of abstracts on NSCLC. Some specific reasons may be responsible for the decrease in applied research in SCLC. The incidence of SCLC has dropped over the last decades mainly due to changes in smoking habits, whereas efforts to improve survival by means of systemic treatment have been stagnating for years. One of the rare appreciable improvements impacting survival of patients with ES-SCLC was made with prophylactic cranial irradiation (PCI) treatment. On the basis of recently published data, it seems that revisiting past experience with surgery in LS-SCLC may be one of the most promising perspectives to regain interest in tailored therapy in SCLC. In many malignancies targeted therapies have been successfully applied in the meantime. Developments in targeted therapy aiming at SCLC are lagging far behind, for example NSCLC. None of the abstracts concerning SCLC presented at this year's ASCO showed an improvement in survival and even worse is that only one phase III trial was presented in the lung cancer session and this trial showed negative results.
Stenger, I.; Tomala, C.; Pietsch, M.; Olgemoeller, U.; Koerber, W.; Fischer, B.; Sebastian, M.; Truemper, L.; Overbeck, T.; Griesinger, F.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0246-7
BACKGROUND: Cisplatin-based chemotherapy in combination with thoracic radiotherapy is frequently used as a standard treatment for patients with unresectable NSCLC stage IIIA/IIIB disease. Within three years up to 70% of these patients develop a disease recurrence and a subgroup relapses within the radiation field. Therapy is challenging for this patient group, since a high degree of tumour hypoxia often makes these tumours resistant to chemotherapy, even if small portions of normoxic regions, in particular in the outer regions of the tumour, might still exist. As Mitomycin is known to be effective under hypoxic conditions, a combination of Mitomycin with Vinorelbine or Cisplatin was used to treat relapses that occur in the radiation field. Simultaneously, erythropoietin was applied to decrease tumour hypoxia. METHODS: Fifteen patients pretreated with definitive radio- or radio-chemotherapy who developed a symptomatic relapse within the radiation field were enrolled in the study: 5 patients with stage IIIB and 10 with stage IV. Patients received Mitomycin 8 mg/m2 on day 1 with either Vinorelbine 25 mg/m2 (in case of Cisplatin pretreatment) on days 1 and 8 or Cisplatin 40 mg/m2 on days 1 and 8 of a 21-day cycle to a maximum of 4 cycles. 40,000 IE Erythropoietin was administered s.c. every 7 days to maintain Hb levels between 12 and 13.0 g/dl. Response (WHO criteria), time to progression, survival, toxicities and Hb values were evaluated. RESULTS: A median of 2 cycles was administered (1–4). Fourteen patients were assessable for clinical response, one died before first tumour response evaluation. One patient achieved a partial response, stable disease was observed in 6 patients. Median time to progression was 2.3 months (95% CI, 1.20–5.60 months) and median survival was 4.6 months (95% CI, 3.42–6.54 months). Main Grade 3/4 toxicities included leucocytopenia (4/15) and neutropenia (4/15). One patient died of a pulmonary fibrosis probably due to Mitomycin medication. Median Hb levels were maintained above 11 g/dl. CONCLUSION: This is the first trial investigating a standardised treatment of pretreated patients with a relapse within the radiation field. The therapeutic concept including Mitomycin for the treatment of recurrent disease in the radiation field offers an active regimen with modest toxicity. Stable disease was observed in 43%, partial response in 7% of the patients and reaches a similar rate as known from chemotherapy results of pretreated patients. Median survival was poor, but may be due to the limited prognosis of this selected patient cohort. There was a trend to better results in patients with performance status 0 or 1 and response to previous radio-chemotherapy. Further studies for patients with radiation field relapses are warranted.
Arzt, L.; Kothmaier, H.; Quehenberger, F.; Halbwedl, I.; Popper, H. H.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0241-z
PURPOSE: STAT1 and STAT3 are dysregulated in human malignant mesothelioma (MM), an aggressive cancer, with poor knowledge about predictive factors of outcome. Asbestos exposure is the main cause. Since microRNAs (miRNAs) are known to regulate the expression of target mRNAs, the aim of the study was to quantify selected miRNAs in MM which are thought to be involved in the STAT signalling pathway to gain more insight into a possible regulatory mechanism. PATIENTS: RNA was obtained from 35 formalin-fixed and paraffin-embedded tumour tissue samples. MATERIAL AND METHODS: MiRNAs were selected via in silico target prediction tools. Quantitative real-time PCR was used to assess the expression levels of the miRNAs. The reference gene RNU6B was used for normalization. An immunohistochemical (IHC) staining with 5 antibodies was performed on tissue microarray sections to correlate it with the results of the miRNA detection. RESULTS: MiR-106a (targeting STAT3) expression was increased in 63% of cases. MiR-155, miR-19a and miR-30d* (targeting SOCS1, SOCS1 and STAT1, respectively) were downregulated in all cases. Due to very low expression levels, miR-196a*, miR-608 and miR-765 (targeting SOCS6, PIAS1, and SOCS3, respectively) were not detected. Positive IHC staining was achieved for STAT1, pSTAT1(Ser727), STAT3 and PIAS1. STAT1 was higher expressed than STAT3; SOCS1 was not detected by IHC. CONCLUSION: An inverse correlation was found for pSTAT1 and miR-30d* (p = 0.014) and this miRNA may interact with STAT1 (p = 0.062). STAT3 is not affected by miR-106a (p = 0.53) although this miRNA is expected to play an important role in MM.
Simanek, R.; Walczuk, J.; Geissler, K.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0247-6
Increasing life expectancy results in an increased number of elderly cancer patients. Comorbidity is one of several domains in the Comprehensive Geriatric Assessment (CGA), which supports the appraisal of the patient's individual health characteristics, especially due to the fact that chronological age does not always correlate with the patient's health. The Society of Geriatric Oncology (SIOG) recommends the CGA in cancer patients older than seventy years. Comorbidities influence patients' risk for malignancy and their prognosis when suffering from cancer. Secondly, organ dysfunctions as renal, hepatic, cardiac and bone marrow insufficiencies have to be considered while planning and administering a systemic antineoplastic therapy due to an increased probability of toxicity and side effects. Renal and hepatic impairment often result in dose reduced antineoplastic treatment, whereas in patients with cardiac insufficiency liposomal substances and in patients with decreased bone marrow function growth factors are available. Nevertheless, an early consultation of palliative care experts simultaneously to anti-cancer therapy is advisable.
Edlinger, M.; Nagel, G.; Hilbe, W.; Diem, G.; Concin, H.; Strasak, Alexander M.; Ulmer, H.
2011 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-011-0249-4
The Vorarlberg Health Monitoring and Promotion Programme (VHM&PP), based on prospectively gathered, repeated routine health examination data from a cohort of more than 175,000 adults, is one of the largest ongoing population-based risk factor surveillance programmes worldwide. Among others, the so far widely unknown associations of serum uric acid (SUA) and gamma-glutamyltransferase (GGT) with cancer were investigated. Both SUA and GGT are known to be related to the metabolic syndrome and furthermore considered as markers of oxidative stress. After controlling for several confounding factors, it was found that elevated SUA levels were statistically significantly related to overall cancer mortality and several site-specific malignancies in both men and women. Additionally, a J-shaped effect of SUA levels on risk of overall cancer incidence appeared in men, with significantly increased cancer risk at high levels of SUA. Likewise, in accordance with some experimental evidence, among men and women elevated GGT increased cancer risk overall and for several lifestyle-related malignancies. On the basis of these findings, and considering the routine measurement in clinical practice, SUA and GGT might function as a valuable marker to identify patients with an increased risk to develop malignant diseases.