Georg Holgersson

Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer

The aim of the present study was to evaluate the potential predictive value of histology in non-small cell lung cancer (NSCLC) treated with curatively intended radiotherapy. In a collaborative effort among all the Swedish Oncology Departments, clinical data were collected for 1146 patients with a diagnosed non-small cell lung cancer subjected to curatively intended irradiation (⩾50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Only patients who did not have a histological diagnosis date and death date/last follow-up date were excluded (n=141). Among the 1146 patients with non-small cell carcinoma eligible for analysis, 919 were diagnosed with either adenocarcinoma (n=323) or squamous cell carcinoma (n=596) and included in this study. The median survival for the 919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients with adenocarcinoma had a significantly better overall survival compared with patients with squamous cell carcinoma (p=0.0062, log-rank test). When comparing different stages, this survival benefit was most pronounced for stages IIA-IIB (p<0.0001, log-rank test). The difference in survival between the two histological groups was statistically significant in a univariate Cox analysis (p=0.0063) as well as in two multivariate Cox analyses including demographic and treatment variables (p=0.037 and p=0.048, respectively). In this large population based retrospective study we describe for the first time that patients with adenocarcinoma have a better survival after curatively intended radiation therapy in comparison with squamous cell carcinoma patients, particularly those with clinical stages IIA-IIB.

Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer.

Abstract Background: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT). Material and methods: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m2 in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype. Patients were treated in the primary study treatment period for a maximum of four treatment cycles. Results: The 12-week PFS rate, median PFS and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did not show any statistically significant differences between the treatment groups. For the primary endpoint, the AXL group had a lower percentage of patients (25.9%) who were progression-free at Week 12 as compared to the DCT group (39.0%), although the difference was not statistically significant. The most notable difference in the incidence of treatment emergent adverse effects (TEAEs) was the lower incidence of treatment-related grade 3/4 neutropenia in patients treated with AXL. Conclusion: These results suggest neither of the treatments to be superior of the other when treating locally advanced or metastatic NSCLC. Considering the lower incidence of grade 3/4 neutropenia in the AXL group this treatment warrants further research.

Swedish Lung Cancer Radiation Study Group: predictive value of age at diagnosis for radiotherapy response in patients with non-small cell lung cancer.

Abstract Introduction. The aim of the present study was to investigate the impact of age at diagnosis on prognosis in patients treated with curatively intended radiotherapy for NSCLC. Material and methods. This is a joint effort among all the Swedish Oncology Departments that includes all identified patients with a diagnosed non-small cell lung cancer that have been subjected to curatively intended irradiation (≥50 Gy) treated during 1990 to 2000. Included patients had a histopathological/cytological diagnosis date as well as a death date or a last follow-up date. The following variables were studied in relation to overall and disease-specific survival: age, gender, histopathology, time period, smoking status, stage and treatment. Results. The median overall survival of all 1146 included patients was 14.7 months, while the five-year overall survival rate was 9.5%. Younger patients (<55 years), presented with a more advanced clinical stage but had yet a significantly better overall survival compared with patients in the age groups 55–64 years (p = 0.035) and 65–74 years (p = 0.0097) in a multivariate Cox regression analysis. The overall survival of patients aged ≥75 years was comparable to those aged <55 years. Conclusion. In this large retrospective study we describe that patients younger than 55 years treated with curatively intended radiotherapy for NSCLC have a better overall survival than patients aged 55–64 and 65–74 years and that younger patients seem to benefit more from the addition of surgery and/or chemotherapy to radiotherapy. Due to the exploratory nature of the study, these results should be confirmed in future prospective trials.

The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy

Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

End-of-life care: Where do cancer patients want to die? A systematic review

The importance to die at preferred death place is substantial among terminally ill cancer patients. Previously, several studies have investigated this issue, but no systematic review has been made for many years. This systematic review was made in order to investigate preferred death place among cancer patients. A systematic search was made in PubMed library and a total of 399 articles were found, of which 23 were eligible and included in the review. Preference of home death averaged by 59.9% (39.7–100%) across all studies. Information about actual death place was only reported in 12 studies with an average of 40.4% (14–65.2%); thus, the incongruence between preferred and actual death place seems to be substantial. This highlights the importance of health care providers to discuss the issue with the patients and their families. However, study designs must improve and publications of socioeconomic data should be unified to ease interpretation in future studies.

The Prognostic Value of Pre-Treatment Leukocytosis in Patients with Previously Treated, Stage IIIB/IV Non-Small Cell Lung Cancer Treated with the IGF-1R Pathway Modulator AXL1717 or Docetaxel; a Retrospective Analysis of a Phase II Trial

Background: The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC. Methods: A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline. These hematological parameters were studied in relation to overall survival using Kaplan–Meier product-limit estimates and multivariate Cox proportional hazards regression models. Results: The median overall survival for all patients was 8.9 months. Patients with leukocytosis (WBC > 9 x 109/L) had a significantly shorter median overall survival (4.2 months) as compared with those with a WBC ≤ 9 x 109/L at baseline (12.3 months) with a corresponding of HR 2.10 (95% CI: 1.29-3.43). Patients with anemia (Hgb < 110 g/L) had a non-significant (p = 0.097) shorter median overall survival (6.1 months) as compared with their counterparts with Hgb ≥ 110 g/L at baseline (9.4 months). As for thrombocytosis (Plt > 350 x 109/L), there was no statistically significant impact on overall survival. Leukocytosis retained its prognostic significance in a multivariate model where other clinical factors such as age, sex and WHO performance status were taken into consideration (HR: 1.83, 95% CI: 1.06-3.13, p = 0.029). Conclusion: Pre-treatment leukocytosis is a strong and independent prognostic marker for shorter overall survival in previously treated stage IIIB or IV NSCLC patients receiving docetaxel or AXL1717. Combined use of pre-treatment leukocytosis assessments together with established prognostic factors such as performance status could be of help when making treatment decisions in this clinical setting.

The role of income in brain tumor patients: a descriptive register-based study

Socioeconomic status (SES) and its association with cancer in general have been thoroughly studied in the last decades. Several studies have shown associations between SES and many types of cancer such as lung cancer, breast cancer, and prostate cancer. For gliomas, no clear occupational or exposure risk factors have been identified, although some possible risk factors such as use of cellular telephone are still controversial. The aim in the present study is to analyze whether there is an association between SES and development of brain cancer. Data from 1999 through 2013 were collected from the Swedish Cancer Registry and from the National Statistics of Sweden. Age-standardized incidence rates for people with different income were calculated using linear regression model. A total of 11,892 patients were included, of which 5675 were meningiomas, 1216 low-grade gliomas, and 5001 high-grade gliomas. No clear trend between increasing incidence rates and higher income was seen in neither of the investigated brain tumor histologies. In conclusion, the results should be interpreted with caution, but there does not seem to be a correlation in this material between increased income and development of brain cancer.

Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer

OBJECTIVES Cancer-testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. MATERIALS AND METHODS To comprehensively analyze autoantibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. RESULTS Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analyzed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against cancer-testis antigen family 47; member A (CT47A) genes, P antigen family member 3 (PAGE3), variable charge X-linked (VCX), melanoma antigen family B1 (MAGEB1), lin-28 homolog B (LIN28B) and chromosome 12 open reading frame 54 (C12orf54) were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients. CONCLUSION We identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.

Incidence trends in high-grade primary brain tumors in males and females

The focus of the present review is to investigate whether there is a variation in the incidence rates between male and female patients with high-grade primary brain tumors and if there are altered incidence rates associated with the time at which they were diagnosed. Previous studies identified in internationally peer-reviewed journals were identified using a systematic search of the PubMed database. Due to the difficulties in data interpretation, studies that exclusively included patient data classified prior to the 2nd edition of the World Health Organization histological classification system of brain tumors were excluded. The overall incidence rates and incidence trends of male and female patients were analyzed separately. The mean age-adjusted overall incidence rate in the male population was 1.27 per 100,000 compared with 0.89 per 100,000 in the female population. The variance between the two genders differed and a Wilcoxon rank-sum test indicated that there was no significant difference in the incidence rate of high-grade primary brain tumors between males and females (P=0.3658). Furthermore, there was no significant difference in incidence rate trend between 1996-2004 and 2005-2010 for male or female populations (P=0.101 and P=0.472, respectively). The results from the present systematic review did not demonstrate a significant difference in incidence rate between the two genders. Therefore, the results from the current study are considered to be preliminary and further studies are required to elucidate this issue.