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Background and purpose An earlier prospective randomised multicentre study (ARTSCAN) in head and neck cancer patients that compared conventionally fractionated radiotherapy (CF) with accelerated radiotherapy (AF) was inconclusive. In the subgroup of oral cavity squamous cell cancer (OCSCC) a large absolute, but not statistically significant, difference in local control was seen in favour of AF. This difference was more pronounced in resectable tumours. The finding raised the hypothesis that AF could be beneficial for OCSCC patients. In addition, the longstanding controversy on pre- or postoperative radiotherapy was addressed. Materials and methods Patients with OCSCC, judged to withstand and likely benefit from combined therapy, were recruited. Subjects were randomised to either preoperative AF with 43 fractions given as a concomitant boost with two fractions/day to the tumour bearing volume to a total dose of 68 Gy in 4.5 weeks followed by surgery, or primary surgery with postoperative CF, total dose 60 or 66 Gy in 6–7 weeks. For patients whose tumours had high-risk features, 66 Gy and concomitant cisplatin was prescribed. Results 250 patients were randomised. Median follow-up was 5 years for locoregional control (LRC) and 9 years for overall survival (OS). There were no statistically significant differences between the two treatment arms regarding LRC and OS. LRC at five years was 73% (95% CI, 65–82) in preoperative AF and 78% (95% CI, 70–85) in postoperative CF. Toxicity was more pronounced in preoperative AF. Conclusion This study does not support that AF prior to surgery improves outcome in oral cavity cancer compared with postoperative CF.

Background Results from studies addressing age-related patterns of cancer care have found evidence of unjustified differences in management between younger and older patients. Methods We examined associations between age and clinical presentation, management and mortality in patients diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2016. Analyses were adjusted for comorbidity and other factors that may have affected management decisions and outcomes. Results The study population encompassed 40,026 patients with NSCLC. Stage at diagnosis did not differ between age groups <= 84. The diagnostic intensity was similar in age groups <80 years. In patients with stage IA-IIB disease and PS 0-2, surgery was more common in the youngest age groups and decreased with increasing age, and was rarely performed in those >= 85 years. The use of stereotactic body radiotherapy (SBRT) increased with age (<= 69 years 5.4%; >= 85 years 35.8%). In patients with stage IIIA disease and PS 0-2, concurrent chemoradiotherapy was more common in younger patients (<= 69 years 55.3%; >= 85 years 2.2%). In stage IA-IIIA disease, no major differences in treatment-related mortality was observed. In stage IIIB-IV and PS 0-2, chemotherapy was more common in patients <80 years. However, 58.1% of patients 80-84 years and 30.3% >= 85 years received treatment. In stage IA-IIIA, overall and cause-specific survival decreased with increasing age. No age-differences in survival were observed in patients with stage IIIB-IV NSCLC. Conclusion Treatments were readily given to older patients with metastatic disease, but to a lesser degree to those with early stage disease. Significant differences in cause specific survival were observed in early, but not late stage disease. Our findings underscore the importance of individualized assessment of health status and life expectancy. Our results indicate that older patients with early stage lung cancer to a higher extent shoul

Objectives: While studies have found lower cancer risks and better cancer survival in immigrant populations, it is debated whether cancer care is offered on equal terms to all residents regardless of background. Our aim was to study patterns of care and outcomes in immigrants in a country with a tax-financed universal health care system. Material and methods: We used a population-based database to compare clinical presentation, management and mortality between Swedish-born and immigrant patients with non-small cell lung cancer (NSCLC). Analyses were adjusted for potential confounders. Results: We identified 40,075 patients diagnosed with NSCLC of which 84% were born in Sweden, 7% in Nordic and 9% in Non-Nordic countries. Non-Nordic immigrants were to a higher extent male, smokers, younger at diagnosis, had a better performance status and a higher educational level. No differences were seen regarding comorbidity burden or stage at diagnosis. Non-Nordic immigrants more often underwent positron emission tomography (PET) (aHR 1.32; 95% CI 1.19-1.45) and were more often discussed in a multidisciplinary team setting (aHR 1.30; 95% CI 1.17-1.44). There were no differences in treatment modalities following adjustment for age, with the exception of concurrent chemoradiotherapy in stage IIIA disease which was more common in Non-Nordic immigrants (aOR 1.34; 95% CI 1.03-1.74). Both overall and cause specific survival in non-metastatic disease were higher among Non-Nordic immigrants. Overall mortality in stage I-II: HR 0.81; 95% CI 0.73-0.90 and stage IIIA: HR 0.75; 95% CI 0.65-0.86. Following full adjustments, cause-specific mortality in stage I-II was aHR 0.86, 95% CI 0.75-0.98. Conclusion: Taken together, only minor differences in management and outcomes were observed between Swedish-born and immigrant patients. We conclude that lung cancer care is offered on equal terms. If anything, outcomes were better in Non-Nordic immigrants with early stage NSCLC.

Background/Aim: Previous studies have shown discrepancies between patient's desired and actual death place. As planning of family support and involvement of palliative home care teams seem to improve the chance to meet patients preferences, geographical availability of specialized palliative home care could influence place of death. Patients and Methods: Data of patients diagnosed and deceased between January 2011 until December 2014 with lung, brain, colorectal, breast and prostate cancer was collected from Swedish national registers and multiple regression analyses were performed. Results: Patients with lung, brain, colorectal, and prostate cancer who resided in rural municipalities had a higher likelihood of dying at home than dying in hospital settings, compared to those who lived in urban areas. Conclusion: Patients in Sweden, with the exception of breast cancer patients, have a higher likelihood of home death than inpatient hospital death when residing in rural areas compared to when residing in urban areas.

The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB-IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010-2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient-, tumor-related factors with OS. Of 9,992 Stage IIIB-IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less >= 1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non-TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010-2011; 14.4 months 2012-2013; 18.6 months 2014-2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.

Objectives: We examined associations between educational level and clinical presentation, patterns of management and mortality in patients with non-small cell lung cancer (NSCLC) in Sweden, a country with a National Health Care System. Materials and Methods: We identified 39,671 patients with a NSCLC diagnosis 2002-2016 in Lung Cancer Data Base Sweden (LCBaSe), a population-based research database. In analyses adjusted for comorbidity and other prognostic factors, odds Ratios (OR) and hazard Ratios (HR) were estimated to examine associations between patients' educational level and aspects of management and mortality. Results: Stage at diagnosis and waiting times did not differ between educational groups. In multivariable analysis, the likelihood to undergo PET/CT and assessment in a multidisciplinary team setting were higher in patients with high compared to low education (aOR 1.14; CI 1.05-1.23 and aOR 1.22; CI 1.14-1.32, respectively). In patients with early stage IA-IIB disease, the likelihood to undergo stereotactic radiotherapy was elevated in patients with high education (aOR 1.40; CI 1.03-1.91). Both all-cause (aHR 0.86; CI 0.77-0.92) and cause specific mortality (aHR 0.83; CI 0.74-0.92) was lower in patients with high compared to low education in early stage disease (IA-IIB). In higher stage NSCLC no differences were observed. Patterns were similar in separate assessments stratified by sex and histopathology. Conclusions: While stage at diagnosis and waiting times did not differ between educational groups, we found socioeconomic differences in diagnostic intensity, multidisciplinary team assessment, stereotactic radiotherapy and mortality in patients with NSCLC. These findings may in part reflect social gradients in implementation and use of novel diagnostic and treatment modalities. Our findings underscore the need for improved adherence to national guidelines.

Background/Aim: The main objective of this study was to evaluate if there was an increased incidence of brain tumours between years 1980-2012, a time period when mobile phone usage has increased substantially. Materials and Methods: From the Swedish Cancer Registry, cases of meningiomas, low-grade gliomas (LGG) and high-grade gliomas (HGG) were identified in patients between 1980-2012. Direct age-standardised incidence rates were used to calculate incidence trends over time. Results: A total of 13,441 cases of meningiomas, 12,259 cases of high-grade gliomas and 4,555 cases of LGG were reported to the register during the study period. The results suggest that there may be a negative development in the trend for LGG of -0,016 cases per 100,000 and year, corresponding to a mean reduction of approximately 1% per year. Conclusion: The present study was not able to demonstrate an increased incidence of glioma during the past 30 years in Sweden.

Publicerad 2019-05-28 på www.lakartidningen.se

Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0–1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011–2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).

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.

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.

Background: Coexisting disease constitutes a challenge for the provision of optimal cancer care. The influence of comorbidity on lung cancer management and prognosis remains incompletely understood. We assessed the influence of comorbidity on treatment intensity and prognosis in a population-based setting in patients with nonsmall cell lung cancer.Material and methods: Our study was based on information available in Lung Cancer Data Base Sweden (LcBaSe), a database generated by record linkage between the National Lung Cancer Register (NLCR) and several other population-based registers in Sweden. The NLCR includes data on clinical characteristics on 95% of all patients with lung cancer in Sweden since 2002. Comorbidity was assessed using the Charlson Comorbidity Index. Logistic regression and time to event analysis was used to address the association between comorbidity and treatment and prognosis.Results: In adjusted analyses encompassing 19,587 patients with a NSCLC diagnosis and WHO Performance Status 0-2 between 2002 and 2011, those with stage-IA-IIB disease and severe comorbidity were less likely to be offered surgery (OR: 0.45; 95% CI: 0.36-0.57). In late-stage disease (IIIB-IV), severe comorbidity was also associated with lower chemotherapy treatment intensity (OR: 0.76; 95% CI: 0.65-0.89). In patients with early, but not late-stage disease, severe comorbidity in adjusted analyses was associated with an increased all-cause mortality, while lung cancer-specific mortality was largely unaffected by comorbidity burden.Conclusions: Comorbidity contributes to the poor prognosis in NSCLC patients. Routinely published lung cancer survival statistics not considering coexisting disease conveys a too pessimistic picture of prognosis. Optimized management of comorbid conditions pre- and post-NSCLC-specific treatment is likely to improve outcomes.

BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors. MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing. RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.

Background: Complementary alternative medicine (CAM) is widely used among patients with cancer. This usage may have potentially harmful effects, especially when combined with anticancer drugs. However, some complementary methods may benefit patients. This review investigated the prevalence of CAM use among patients with cancer in Scandinavia and secondly studied the educational levels of CAM users compared to non-users. Materials and Methods: A systematic search of the PubMed library was carried out to locate articles published between January 2000 and October 2015 that investigated prevalence of CAM use among Scandinavian patients with cancer. Results: Twenty-two articles were found, of which nine were included in the review. The prevalence of CAM use was 7.9% to 53%, with an average of 36.0% across all studies. Conclusion: Use of CAM is widespread among patients with cancer. Knowledge about CAM should be disseminated to both patients and staff in order to optimise discussions about CAM in clinical practice.

Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.

Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000. Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

The work-up process for lung cancer patients consists of several steps from suspicion of malignant disease to start of treatment. Delays between these steps should be minimized. Data in the Swedish National Lung Cancer Register show that the work-up times for lung cancer patients vary greatly between different counties in central Sweden. In order to reduce delays, a trial of implementing patient guides (Sw: patientlotsar) for patients referred to the hospital was conducted. When comparing the work-up times before and after implementation of patient guides the median waiting time from suspicion of lung cancer to start of treatment in the region was reduced from 71 to 45 days. Furthermore, the duration of most of the steps in the work-up process were shortened despite more complex investigation procedures, e.g. increased use of PET/CT in the guided patient group.