Combined radio- and chemotherapy for non-small cell lung cancer: systematic review of landmark studies based on acquired citations

The important role of combined chemoradiation for several groups of patients with nonsmall cell lung cancer (NSCLC) is reflected by the large number of scientific articles published during the last 30 years. Different measures of impact and clinical relevance of published research are available, each with its own pros and cons. For this review, article citation rate was chosen. Highly cited articles were identified through systematic search of the citation database Scopus. Among the 100 most often cited articles, meta-analyses (nD5) achieved a median of 203 citations, guidelines (nD7) 97, phase III trials (nD29) 168, phase II trials (nD21) 135, phase I trials (nD7) 88, and others combined 115.5 (p D0.001). Numerous national and international cooperative groups and several single institutions were actively involved in performing often cited, high-impact trials, reflecting the fact that NSCLC is a world-wide challenge that requires research collaboration. Platinum-containing combinations have evolved into a standard of care, typically administered concurrently.The issue of radiotherapy fractionation and total dose has also been studied extensively, yet with less conclusive results. Differences in target volume definition have been addressed. However, it was not possible to test all theoretically possible combinations of radiotherapy regimens, drugs, and drug doses (lower radiosensitizing doses compared to higher systemically active doses).That is why current guidelines offer physicians a choice of different, presumably equivalent treatment alternatives. This review identifies open questions and strategies for further research

Presentation and course of brain metastases from breast cancer in a paranoid-schizophrenic patient: A case report

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Palliative radiotherapy with or without additional care by a multidisciplinary palliative care team in patients with newly diagnosed cancer: A retrospective matched pairs comparison

License: Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)Purpose: To analyze survival after early palliative radiotherapy (RT) in patients managed exclusively by regular oncology staff or a multidisciplinary palliative care team (MPCT) in addition. Methods: Retrospective matched pairs analysis. Comparison of two groups of 29 patients each: MPCT versus none. Early RT started within three months after cancer diagnosis. Results: Bone and brain metastases were common RT targets. No significant differences in baseline characteristics were observed between both groups. Twelve patients in each group had non-small cell lung cancer. Median performance status was 2 in each group. Twenty-seven patients in each group had distant metastases. Median survival was not significantly different. In multivariate analysis, MPCT care was not associated with survival, while performance status and liver metastases were. Rate of radiotherapy during the last month of life was comparable. Only one patient in each group failed to complete radiotherapy. Conclusions: MPCT care was not associated with survival in these two matched groups of patients. The impact of MPCT care on other relevant endpoints such as symptom control, side effects and quality of life should be investigated prospectively

Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer

In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer) in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years). Actuarial survival analyses were performed. During the first 3 years, two patients (1.1%) died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4%) was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI) scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition). The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis). However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis

Contribution of Case Reports to Brain Metastases Research: Systematic Review and Analysis of Pattern of Citation

Research activity related to different aspects of prevention, prediction, diagnosis and treatment of brain metastases has increased during recent years. One of the major databases (Scopus) contains 942 scientific articles that were published during the 5-year time period 2006–2010. Of these, 195 (21%) reported on single patient cases and 12 (1%) were reports of 2 cases. Little is known about their influence on advancement of the field or scientific merits. Do brain metastases case reports attract attention and provide stimuli for further research or do they go largely unrecognized? Different measures of impact, visibility and quality of published research are available, each with its own pros and cons. For the present evaluation, article citation rate was chosen. The median number of citations overall and stratified by year of publication was 0, except for the year 2006 when it was 2. As compared to other articles, case reports remained more often without citation (p<0.05 except for 2006 data). All case reports with 10 or more citations (n = 6) reported on newly introduced anticancer drugs, which commonly are prescribed to treat extracranial metastases, and the responses observed in single patients with brain metastases. Average annual numbers of citations were also calculated. The articles with most citations per year were the same six case reports mentioned above (the only ones that obtained more than 2.0 citations per year). Citations appeared to gradually increase during the first two years after publication but remained on a generally low or modest level. It cannot be excluded that case reports without citation provide interesting information to some clinicians or researchers. Apparently, case reports describing unexpected therapeutic success gain more attention, at least in terms of citation, than others

Can prophylactic breast irradiation contribute to cardiac toxicity in patients with prostate cancer receiving androgen suppressing drugs?

<p>Abstract</p> <p>Background</p> <p>Androgen suppression treatment (AST) might increase the risk of cardiac morbidity in prostate cancer patients. Possible explanations were provided, however, they disregard the potential contribution of prophylactic radiotherapy to the mamillary regions (PMRT, prescribed to avoid gynecomastia).</p> <p>Methods</p> <p>We studied the exposure of the heart in a typical electron beam PMRT setting by evaluating computed tomography (CT) scans in 40 non-cancer patients (age 65 and 75 years in 50% each) and 17 prostate cancer patients. Five of the younger, 7 of the older and 4 of the cancer patients had significant cardiac disease.</p> <p>Results</p> <p>The median distance between skin and outer heart contour decreased with age. In all three groups, patients with cardiac morbidity had smaller distances. When using the CT-determined PMRT beam energy, 10% of the younger, 15% of the older and none of the prostate cancer patients would receive approximately 50% of the prescription dose to a part of the heart (2 had no history of cardiac disease). When using the clinically rather than CT-determined beam energy, as often done in daily practice, an additional 12.5% of the non-cancer and 12% of the prostate cancer patients would be exposed to comparably high doses.</p> <p>Conclusion</p> <p>The present data provide preliminary evidence that PMRT might be a factor that contributes to cardiac side effects. Previous studies that established a relationship between AST and cardiac morbidity did not include information on delivery of PMRT.</p

A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer

Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated

Confirmatory analysis of QUARTZ study results: Survival prolongation after whole-brain radiotherapy

Background/Aim: The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points). Patients and Methods: We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy). Results: All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal. Conclusion: In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features

Continous controversy about radiation oncologists' choice of treatment regimens for bone metatases: should we blame doctors, canser-related features, or design of previous clinical studies

Recent studies from Italy, Japan and Norway have confirmed previous reports, which found that a large variety of palliative radiotherapy regimens are used for painful bone metastases. Routine use of single fraction treatment might or might not be the preferred institutional approach. It is not entirely clear why inter-physician and interinstitution differences continue to persist despite numerous randomized trials, meta-analyses and guidelines, which recommend against more costly and inconvenient multi-fraction regimens delivering total doses of 30 Gy or more in a large number of clinical scenarios. In the present mini-review we discuss the questions of whether doctors are ignoring evidence-based medicine or whether we need additional studies targeting specifically those patient populations where recent surveys identified inconsistent treatment recommendations, e.g. because of challenging disease extent. We identify open questions and provide research suggestions, which might contribute to making radiation oncology practitioners more confident in selecting the right treatment for the right patient