Stage-specific survival has improved for young breast cancer patients since 2000: but not equally.

PURPOSE: The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. METHODS: Using Norwegian registry data, we assessed stage-specific breast cancer survival by education and income level of 7501 patients (2317 localized, 4457 regional, 233 distant and 494 unknown stage) aged 30-48 years at diagnosis during 2000-2015. Using flexible parametric models and national life tables, we compared excess mortality up to 12 years from diagnosis and 5-year relative survival trends, by education and income as measures of socioeconomic status (SES). RESULTS: Throughout 2000-2015, regional and distant stage 5-year relative survival improved steadily for patients with high education and high income (high SES), but not for patients with low education and low income (low SES). Regional stage 5-year relative survival improved from 85 to 94% for high SES patients (9% change; 95% confidence interval: 6, 13%), but remained at 84% for low SES patients (0% change; - 12, 12%). Distant stage 5-year relative survival improved from 22 to 58% for high SES patients (36% change; 24, 49%), but remained at 11% for low SES patients (0% change; - 19, 19%). CONCLUSIONS: Regional and distant stage breast cancer survival has improved markedly for high SES patients, but there has been little survival gain for low SES patients. Socioeconomic status matters for the stage-specific survival of young breast cancer patients, even with universal health care.

Socioeconomic inequalities in stage-specific breast cancer incidence: a nationwide registry study of 1.1 million young women in Norway, 2000-2015.

BACKGROUND: Women with high socioeconomic status (SES) have the highest incidence rates of breast cancer. We wanted to determine if high SES women only have higher rates of localized disease, or whether they also have higher rates of non-localized disease. To study this, we used data on a young population with universal health care, but not offered screening. MATERIAL AND METHODS: Using individually linked registry data, we compared stage-specific breast cancer incidence, by education level and income quintile, in a Norwegian cohort of 1,106,863 women aged 30-48 years during 2000-2015 (N = 7531 breast cancer cases). We calculated stage-specific age-standardized rates and incidence rate ratios and rate differences using Poisson models adjusted for age, period and immigration history. RESULTS: Incidence of localized and regional disease increased significantly with increasing education and income level. Incidence of distant stage disease did not vary significantly by education level but was significantly reduced in the four highest compared to the lowest income quintile. The age-standardized rates for tertiary versus compulsory educated women were: localized 28.2 vs 19.8, regional 50.8 vs 40.4 and distant 2.3 vs 2.6 per 100,000 person-years. The adjusted incidence rate ratios (tertiary versus compulsory) were: localized 1.40 (95% CI 1.25-1.56), regional 1.25 (1.15-1.35), distant 0.90 (0.64-1.26). The age-standardized rates for women in the highest versus lowest income quintile were: localized 28.9 vs 17.7, regional 52.8 vs 41.5 and distant 2.3 vs 3.2 per 100,000 person-years. The adjusted incidence rate ratios (highest versus lowest quintile) were: localized 1.63 (1.42-1.87), regional 1.27 (1.09-1.32), distant 0.64 (0.43-0.94). CONCLUSION: Increased breast cancer rates among young high SES women is not just increased detection of small localized tumors, but also increased incidence of tumors with regional spread. The higher incidence of young high SES women is therefore real and not only because of excessive screening.

Norwegian reference data on the Fatigue Questionnaire and the Patient Health Questionnaire-9 and their interrelationship.

BACKGROUND: Population-based reference data on frequently used questionnaires are important for comparative purposes. Due to changes in health and lifestyles, such data should be updated every other decade. The objectives of this study were to establish Norwegian population-based reference data on the Fatigue Questionnaire (FQ) and the Patient Health Questionnaire-9 (PHQ-9) on depression, to compare the FQ-scores with our previous reference data from 1996, and to explore the relationship between the scores on these two instruments. METHODS: In 2015, a representative sample of 6,012 Norwegians aged 18-80 years was mailed a questionnaire including the FQ and the PHQ-9, and 36% responded. Complete FQ-scores were delivered by 2,041 subjects, and complete PHQ-9 scores by 2,086 subjects. The scores are displayed according to sex and 10-year age groups. RESULTS: Few 2015 mean scores of mental, physical, and total fatigue differed significantly from those of 1996, and the same was found for the prevalence rates of chronic fatigue. The exception was a significantly lower prevalence in 2015 of mean fatigue scores and prevalence of chronic fatigue in females ≥ 60 years. The prevalence of major depressive episode (MDE) based on the PHQ-9 sum score cut-off ≥ 10 was 5.9% for males and 9.8% for females, and 2.5% and 3.8% using a DSM-based algorithm with at least five endorsed criteria including either anhedonia or depressed mood. The correlation between the FQ and the PHQ-9 was 0.59, implying 36% shared variance. CONCLUSIONS: This study showed considerable interrelationship between the FQ and the PHQ-9 constructs. The reference data show that scores on the FQ have only improved significantly in persons aged 60 or more years between 1996 and 2015. Our prevalence findings of MDE based on the PHQ-9 are in accordance with the findings from other countries. The FQ and the PHQ-9 should be used together in epidemiological and clinical studies.

Lifestyle behavior among lymphoma survivors after high-dose therapy with autologous hematopoietic stem cell transplantation, assessed by patient-reported outcomes.

Introduction: High-dose therapy with autologous stem cell transplantation (HD-ASCT) is associated with an increased risk of late effects. Our aim was to assess lifestyle behavior and factors associated with unhealthy lifestyle among HD-ASCT-treated lymphoma survivors (HD-ASCT-LS). Materials and methods: We conducted a national cross-sectional study of HD-ASCT-LS treated during 1987-2008. Among 399 eligible participants, 312 (78%) completed patient-reported outcome measures (PROMs) on lifestyle behavior (physical activity, overweight, smoking and alcohol consumption), chronic fatigue (CF) and somatic and mental illness. We assessed lifestyle according to WHO recommendations. Multivariable logistic regression models were used to study associations between variables. A comparison to the general population was performed. Results: Mean age at survey was 54.6 years, 60% were men, 55% sedentary, 55% overweight, 18% smokers and 5% had unhealthy alcohol consumption. Being sedentary was positively associated with older age, low household income, CF and higher somatic burden (≥4 self-reported somatic conditions). Overweight was positively associated with male gender and negatively associated with increased number of chemotherapy regimens prior to HD-ASCT. Current smoking was positively associated with living alone and CF, and negatively associated with older age. Male gender, CF and higher somatic burden increased the risk of an unhealthier lifestyle whereas the increased number of chemotherapy regimens prior to HD-ASCT decreased the risk. HD-ASCT-LS were significantly less sedentary, less overweight, and had a lower likelihood of smoking than the controls. Discussion: Assessed by PROMs, unhealthy habits were frequent among HD-ASCT-LS and associated with comorbidity. Nevertheless, compared with controls significantly more HD-ASCT-LS met lifestyle recommendations. These results indicate that the HD-ASCT-LS may consist of two groups, the adhering group with less comorbidity and the non-adhering group with more comorbidity. Our findings illustrate the necessity of recommendations and support for improving health-related behavior in cancer survivorship plans in order to empower survivors in their life beyond cancer.

The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma--differences in histological subtypes.

BACKGROUND: Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC. METHODS: Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients. Expression of the let-7 microRNA family was performed in 78 adenocarcinomas and 16 matching normal lung tissue samples using microarrays. The protein levels of HMGA2 were determined by immunohistochemistry in 156 tumour samples and the protein expression was correlated with gene expression. Associations between clinical data, including time to recurrence, and expression of mRNA, protein and microRNAs were analysed. RESULTS: Compared to adenocarcinomas, squamous cell carcinomas had a median 5-fold increase in mRNA expression of HMGA2 (p = 0.003). A positive correlation (r = 0.513, p < 0.010) between HMGA2 mRNA expression and HMGA2 protein expression was seen. At the protein level, 90% of the squamous cell carcinomas expressed high levels of the HMGA2 protein compared to 47% of the adenocarcinomas (p < 0.0001). MYCN was positively correlated with HMGA2 (p < 0.010) and DICER1 mRNA expression (p < 0.010), and the expression of the let-7 microRNAs seemed to be correlated with the genes studied. MYCN expression was associated with time to recurrence in multivariate survival analyses (p = 0.020). CONCLUSIONS: A significant difference in HMGA2 mRNA expression between the histological subtypes of NSCLC was seen with a higher expression in the squamous cell carcinomas. This was also found at the protein level, and we found a good correlation between the mRNA and the protein expression of HMGA2. Moreover, the expression of MYCN, HMGA2, and DICER1 seems to be correlated to each other and the expression of the let7-genes impacted by their expression. MYCN gene expression seems to be of importance in time to recurrence in this patient cohort with resected NSCLC.

Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters.

BACKGROUND: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.

Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy.

BACKGROUND: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). MATERIAL AND METHODS: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. RESULTS: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. CONCLUSIONS: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.

Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown. OBJECTIVE: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes. METHODS: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO2peak), limiting factors for VO2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention. RESULTS: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025. CONCLUSIONS: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45244.

Correction: Effects of Aerobic Exercise on Cardiorespiratory Fitness, Cardiovascular Risk Factors, and Patient-Reported Outcomes in Long-Term Breast Cancer Survivors: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/45244.].

A study of high neuroticism in long-term survivors of childhood, adolescence, and young adult cancers.

Neuroticism is a basic personality trait concerning negative feelings under stressful conditions. Our purpose was to examine the rate of high neuroticism and factors associated with high neuroticism in long-term (≥ 5 years) survivors of childhood, adolescent, and young adult cancer (CAYACSs). Norwegian CAYACSs aged 0-39 years when diagnosed and treated between 1985 and 2009 for cancer in childhood/adolescence (0-18 years), or as young adults (19-39 years) and alive in 2015 were mailed a questionnaire. Data from 1629 CAYACSs (481 children/adolescents and 1148 young adults) were analyzed. High neuroticism was found in 44% of survivors of childhood/adolescent cancers versus 34% in survivors of young adult cancer (p < 0.001). The rate of high neuroticism in female CAYACSs was 40% and in males 30% (p < 0.001). The corresponding difference between male survivor group was non-significant. In multivariable analysis, young age at survey, more adverse effects, poor self-rated health, female sex, chronic fatigue, and increased depression remained significantly associated with high neuroticism. Cancer treatment, comorbidity, and lifestyle were significant in bivariate analyses. Cancer at earlier age could increase the risk of high neuroticism among adult survivors. Screening for neuroticism could identify CAYACSs at risk for experiencing multiple health concerns and needing special follow-up attention.

A Controlled Study of Major Depressive Episodes in Long-Term Childhood, Adolescence, and Young Adult Cancer Survivors (The NOR-CAYACS Study).

BACKGROUND: A major depressive episode (MDE) is typically self-rated by screening forms identifying probable MDE (pMDE). This population-based cross-sectional questionnaire study examined the prevalence rates of pMDE identified by the PHQ-9 screener in long-term survivors of childhood and adolescence (CACSs) and young adult cancer (YACSs) and a normative sample (NORMs). METHODS: Data from 488 CACSs, 1202 YACSs, and 1453 NORMs were analyzed, and pMDE was defined both by cut-off ≥10 on the total PHQ-9 score and by an algorithm. RESULTS: The prevalence rates of pMDE among CACSs were 21.5%, 16.6% in YACSs, and 9.2% among NORMs using the cut-off definition. With the algorithm, the prevalence rates of pMDE were 8.0% among CACSs, 8.1% among YACSs, and 3.9% among NORMs. Independent of definition, CACSs and YACSs had significantly increased prevalence rates of pMDE compared to NORMs. Psychosocial factors and self-rated health were significantly associated with both definitions of pMDE in multivariable analyses, while survivor groups, cancer types, and adverse events were not. CONCLUSION: Since pMDE has negative health consequences and is amenable to treatment, healthcare providers should be attentive and screen for pMDE in young cancer survivors. For PHQ-9, the preferred type of definition of pMDE should be determined.

Sexual dysfunction is prevalent in female lymphoma survivors after autologous stem-cell transplantation and is associated with younger age, chronic fatigue, and mental distress.

Sexual function in female lymphoma survivors after high-dose therapy with autologous stem-cell transplantation (auto-SCT) is largely unstudied. Female lymphoma survivors treated with auto-SCT in Norway 1987-2008 were eligible participants (n = 157). A multi-item questionnaire including a complete Sexual Activity Questionnaire was returned by 70% (n = 110) of the women. A comparison to age-matched normative controls was performed. Sexual inactivity was equal among survivors and controls. The survivors reported personal issues more frequent as reason for inactivity compared with controls (44% vs. 28%, p = 0.04). The sexually active survivors reported more sexual discomfort, greater reduction in frequency of sexual activity, and more sex-related tiredness compared with controls (p value and effect size [95% confidence interval]; p ≤ 0.001, 0.70 [0.44, 0.97], p = 0.03, -0.29 [-0.55, -0.03] and p ≤ 0.001, 0.64 [0.37, 0.90], respectively). Sexual activity was related to older age (odds ratio (OR) 0.58 [0.43, 0.82] per 10 years), being in a relationship (OR 28.6 [6.9, 118.9]) and hormonal replacement therapy (OR 6.0 [1.49, 24.2]). Tiredness in relation to sexual activity was associated with younger age, chronic fatigue and mental distress. Sexual inactivity due to personal issues was more frequent and among those sexually active, a higher rate of sexual dysfunction exists among auto-SCT survivors compared with controls. Hence, sexual function should be addressed at regular timepoints during the cancer trajectory.

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.

Sexual function in long-term male lymphoma survivors after high-dose therapy with autologous stem-cell transplantation.

Reduced sexual function may have negative implications on health related quality of life among lymphoma survivors. A national cross-sectional study among long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplantation auto-SCT treated during 1987-2008 was conducted in 2012-2014. The current study explored sexual functioning among these survivors. Sixty-six percent (n = 159) of eligible men with complete questionnaire data were included, median age was 55 years. The Brief Sexual Function Inventory (BSFI) was used to assess sexual function and sexual satisfaction, compared with age-matched controls. In addition, sexual problems were defined based on predetermined cutoff values for BSFI domain scores. Sexual drive and erections firm enough to have sexual intercourse were reported to be present only a few days or less last month among 30% and 41% of survivors, respectively. Sexual satisfaction was reported by 39% of survivors. The survivors had significantly lower scores on all BSFI domains and an increased risk of problems with sexual drive and erection compared with controls. In multivariable models, cardiovascular disease was significantly associated with worse erectile function, while age > 55 years, chronic fatigue, and physical inactivity were significantly associated with lower sexual functioning overall. Chronic fatigue and anxiety were related to lower sexual satisfaction.

Employment Status and Work Ability in Long-Term Young Adult Cancer Survivors.

Purpose: In young adult cancer survivors (YACSs) to explore the rate of being nonemployed and having low work ability, and to identify factors associated with these two outcomes. Methods: All Norwegian YACSs (N = 3558) diagnosed at ages 19-39 years and treated between 1985 and 2009 for breast or colorectal cancer, leukemia, non-Hodgkin lymphoma, or melanoma, and alive in 2015, were mailed a questionnaire. The response rate was 42%. For treatment, a minimal surgery-only group (N = 198) was defined as reference group, and 1000 YACSs represented the local, systemic, and systemic plus other treatment groups. Work status was compared with normative data. Results: The sample included 63% females. Median age at survey was 49 years (range 27-65), and median time since first cancer diagnosis was 16 years (range 6-31). At survey, 25% (95% confidence interval [CI]: 22-27) of YACSs were nonemployed, and 38% (95% CI: 35-41) reported low work ability. The rate of being nonemployed was similar to normative data. More female YACSs held disability pension compared with normative data. In multivariable analyses, an increasing number of adverse effects (AEs), cardiovascular diseases, lower basic education, reduced level of self-rated health, and increased level of depression were significantly associated with both being nonemployed and having low work ability. Conclusions: In YACSs surveyed at median 49 years of age, 25% were nonemployed and 38% had low current work ability. An increased mean number of long-term AEs and several other health-related factors were significantly associated with both these outcomes. Health care providers responsible for YACSs should be attentive to such factors and work ability.

Non-small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease.

Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD. Unsupervised hierarchical clustering and non-parametric analyses were performed. False discovery rate was used to adjust for multiple testing. Clustering of cytokine and MMP concentrations in the serum revealed a distinct separation of the NSCLC patients from the COPD group. Individual concentrations of thymus and activation-regulated cytokine (C-C motif chemokine ligand 17), Gro-b (C-X-C motif chemokine ligand 2 (CXCL2)), CXCL13, interleukin (IL)-1ra, IL-6, IL-8 (CXCL8), IL-16, IL-17A, macrophage migration inhibitory factor (MIF), granulocyte colony-stimulating factor, platelet-derived growth factor subunit B, MMP-2, MMP-8 and MMP-12 were significantly different in serum from NSCLC and COPD patients. Moreover, the interferon-γ/IL-10 ratio was lower in cancer patients compared with COPD patients, consistent with a cytokine milieu favouring tumour tolerance. Our results suggest that NSCLC is characterised by a distinct inflammatory signature in serum. The different cytokine profiles in NSCLC and COPD patients may represent tumour-promoting and tumour-suppressing immune responses developing in response to mucosal inflammation and mutations induced by smoking.

Hormonal dysfunction is frequent in cancer survivors treated with radiotherapy to the head and neck region.

PURPOSE: Cancer treatment may lead to hormonal dysfunction. Therefore, we assessed the prevalence of dysfunction in four hormonal axes among long-term cancer survivors who received radiotherapy to the head and neck region and analyzed associations between hormonal status and clinical variables. METHODS: We included 140 cancer survivors who received radiotherapy to the head and neck region, either locally or through total body irradiation after a diagnosis of lymphoma, plasmacytoma/multiple myeloma, or carcinoma of the epipharynx. Radiation doses to the pituitary gland and thyroid gland were estimated, and blood samples were collected to analyze hormonal levels. RESULTS: At a median of 16 years after their cancer diagnosis, 46% of cancer survivors showed dysfunction in one hormonal axis, 24% had dysfunction in two axes, and 3% had dysfunction in three axes. Twenty cancer survivors (14%) had hormone levels consistent with pituitary dysfunction. Cancer survivors who had received an estimated 30 Gray (Gy) or more to the pituitary gland had an increased risk for pituitary dysfunction in one of the hormonal axes (odds ratio [OR] 3.16, confidence interval [CI] 1.02-9.87, p = 0.047) and for growth hormone dysfunction alone (OR 2.96, CI 1.02-8.55, p = 0.045). CONCLUSIONS: Abnormal hormone values are frequent after radiotherapy to the head and neck region. IMPLICATIONS FOR CANCER SURVIVORS: Screening for hormonal dysfunction during follow-up might be indicated.