Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases.

PURPOSE: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. PATIENTS AND METHODS: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. RESULTS: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). CONCLUSION: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

[State of art of photobiomodulation in the management of radiotherapy adverse events: Indications and level of evidence]. / État de l'art de la photobiomodulation dans la prise en charge des effets secondaires de la radiothérapie : indications et niveaux de preuve.

PURPOSE: To evaluate the current and potential indications of photobiomodulation (PBM) and their level of evidence in the prevention or management of radiation therapy-related side effects. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that have assessed PBM in the prevention or management of radiotherapy-related side effects. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "hyposalivation"; "trismus"; "bone necrosis"; "osteoradionecrosis"; and "radiation induced fibrosis". Prospective studies were included, whereas retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has demonstrated efficacy in randomized controlled trials in the prevention and management of radiotherapy-related side effects, especially acute oral mucositis, acute radiation dermatitis, and upper extremity lymphedema. The level of evidence associated with PBM was heterogeneous, but overall was still moderate. The main shortcomings were the diversity and lack of detail in treatment protocols, which could have compromised efficiency and reproducibility of PBM results. CONCLUSION: The published data suggest that PBM may be considered as a full-fledged supportive care for patients treated with radiotherapy, or at least in the setting of a therapeutic clinical trial. However, until strong evidence has been published on its long-term safety, the use of PBM should be considered with caution, specifically when applied near areas with proven or potential tumors. The patient should be informed of the theoretical benefits and risks of PBM in order to obtain his informed consent before treatment.

The risk of epilepsy in children with celiac disease: a population-based cohort study.

BACKGROUNDAND PURPOSE: The purpose was to estimate the risk of epilepsy in a cohort of young individuals with celiac disease (CD) compared to that of matched references. METHODS: The cohort consisted of 213 635 individuals born during 1989-2011 and residing in Friuli-Venezia Giulia (Italy). 1215 individuals affected by CD and 6075 reference individuals matched by sex and age were identified. Epilepsy was defined by means of hospital diagnosis or drug prescriptions. Conditional logistic regression was used to estimate the odds ratios (ORs) of having epilepsy amongst individuals with CD, before CD diagnosis and in the entire period, compared with those of their matched references. Cox regression was used to calculate the hazard ratios for epilepsy diagnosed after CD diagnosis. Different definitions of epilepsy were used for sensitivity analyses. RESULTS: Thirty-one (2.6%) individuals with CD and 78 (1.3%) reference individuals had epilepsy [adjusted OR 2.03; 95% confidence interval (CI) 1.33-3.10]. The risk of epilepsy was increased prior to CD (adjusted OR 2.29; 95% CI 1.33-3.94), with similar estimates after CD diagnosis (adjusted hazard ratio 1.96; 95% CI 0.95-4.02). The increased risk of epilepsy was not explained by a peak in epilepsy diagnosis just around CD diagnosis. Sex stratification found a significantly higher risk of epilepsy amongst female individuals with CD. Sensitivity analyses confirmed the positive association between CD and epilepsy. CONCLUSION: Children and youths with CD were at increased risk of epilepsy. Patients with epilepsy without a clear etiology should be screened for CD since an early diagnosis and treatment might improve the response to antiepileptic therapies.

Whole brain radiotherapy with concurrent temozolomide in multifocal and/or multicentric newly diagnosed glioblastoma.

The standard medical care of glioblastoma (GBM) patients with good performance status is based on focal brain radiotherapy (40-60 Gy) with concurrent temozolomide (TMZ) followed by adjuvant TMZ. Newly diagnosed multifocal and/or multicentric GBM (M/M GBM) cases are usually treated with TMZ alone: whole brain chemoradiotherapy (CRT) is avoided for safety reasons. To our knowledge, no study has investigated the safety and efficacy of whole-brain radiotherapy (WBRT) with concurrent TMZ in M/M GBM patients. This retrospective study sought to assess the role of WBRT associated with concurrent TMZ followed by TMZ alone in this population. Eleven patients with pathologically proven M/M GBM (≥3 lobes) were treated with WBRT between April 2009 and September 2017. The median age was 50 years [34-74]. The median dose of radiotherapy was 45 Gy at 1.8 Gy per fraction over 37 days [29-41], with concurrent daily TMZ at the dose of 75 mg/m2. This treatment was followed by adjuvant monthly TMZ (150 mg/m2-D1-D5). All pathology slides and radiology images were reviewed. The median overall and progression-free survival times for all patients were 10 months [4-25] and 5 months [3-21], respectively. There was no grade 3-4 toxicity due to radiotherapy. One patient stopped the TMZ during the radiochemotherapy period and 9 patients received adjuvant TMZ with a median number of 5 cycles [2-8]. Our study supports the safety and the efficacy of WBRT with TMZ in newly diagnosed M/M GBM. Larger prospective studies are needed to support our results.

[From bunker construction to patient treatment: quality controls applied to modern radiotherapy techniques]. / De la construction du bunker à la prise en charge du patient : contrôles qualité des techniques modernes de radiothérapie.

Installation and use of a new radiotherapy device require an adequate quality and safety policy. The process leading to the commissioning of an accelerator following the construction of a bunker includes, among other tasks, the installation of the accelerator, the verification of compliance with the specifications, the signature of the acceptance specification as well as the process of characterization and modeling of the accelerator before its clinical use. The emergence of modern radiotherapy techniques, such as intensity modulated conformational radiotherapy and stereotactic radiotherapy, has resulted in more complex quality controls. The purpose of this article is to explain the different stages of the implementation of innovative radiotherapy techniques and to specify their features.

[Chemoradiation for oesophageal cancer: A critical review of the literature]. / Chimioradiothérapie des cancers de l'œsophage : revue critique de la littérature.

Locally advanced oesophageal cancer treatment requires a multidisciplinary approach with the combination of chemotherapy and radiotherapy for preoperative and definitive strategy. Preoperative chemoradiation improves the locoregional control and overall survival after surgery for locally advanced oesophageal cancer. Definitive chemoradiation can also be proposed for non-resectable tumours or medically inoperable patients. Besides, definitive chemoradiation is considered as an alternative option to surgery for locally advanced squamous cell carcinomas. Chemotherapy regimen associated to radiotherapy consists of a combination of platinum derived drugs (cisplatinum or oxaliplatin) and 5-fluorouracil or a weekly scheme combination of carboplatin and paclitaxel according to CROSS protocol in a neoadjuvant strategy. Radiation doses vary from 41.4Gy to 45Gy for a preoperative strategy or 50 to 50.4Gy for a definitive treatment. The high risk of lymphatic spread due to anatomical features could justify the use of an elective nodal irradiation when the estimated risk of microscopic involvement is higher than 15% to 20%. An appropriate delineation of the gross tumour volume requires an exhaustive and up-to-date evaluation of the disease. Intensity-modulated radiation therapy represents a promising approach to spare organs-at-risk. This critical review of the literature underlines the roles of radiotherapy for locally advanced oesophageal cancers and describes doses, volumes of treatment, technical aspects and dose constraints to organs-at-risk.

[Quality and safety policy implementation for a new radiotherapy device]. / Mise en place d'une politique de qualité et de sécurité lors de l'installation d'un nouvel équipement dans un service de radiothérapie.

Modern radiotherapy techniques (intensity-modulated radiotherapy, volumetric-modulated arctherapy, image-guided radiotherapy) or stereotactic radiotherapy are in expansion in most French cancer centres. The arrival of such techniques requires updates of existing equipment or implementation of new radiotherapy devices with adapted options. With the arrival of these new devices, there is a need to develop a quality and safety policy. This is necessary to ease the process from the setup to the first treated patient. The quality and safety policy is maintained to ensure the quality assurance of the radiotherapy equipment. We conducted a review of the literature on the quality and safety policy in the French legal framework that can be proposed when implementing a new radiotherapy device.

Predictors of oropharyngeal cancer survival in Europe.

OBJECTIVES: HPV16-positive oropharyngeal cancer (OPC) patients experience better outcomes compared to HPV16-negative patients. Currently, strategies for treatment de-escalation are based on HPV status, smoking history and disease stage. However, the appropriate cut-point for smoking and the role of other non-clinical factors in OPC survival remains uncertain. MATERIALS AND METHODS: We examined factors associated with OPC outcome in 321 patients recruited in a large European multi-center study. Seropositivity for HPV16 E6 was used as a marker of HPV16 positive cancer. Hazard ratios (HR) and confidence intervals (CI) were estimated using Cox proportional models adjusted for potential confounders. RESULTS: Overall 5-year survival following OPC diagnosis was 50%. HPV16-positive OPC cases were at significantly lower risk of death (aHR = 0.51, 95% CI: 0.32-0.80). A significant effect on OPC survival was apparent for female sex (aHR 0.50: 95% CI: 0.29-0.85) and being underweight at diagnosis (aHR: 2.41, 95% CI: 1.38-4.21). A 10 pack year smoking history was not associated with overall survival. Higher stage at diagnosis appeared as the only factor significantly associated with OPC recurrence (aHR: 4.88, 95% CI: 2.12-11.21). CONCLUSION: This study confirms that HPV16 status is an independent prognostic factor for OPC survival while female sex lowers risk of death and being underweight at diagnosis increases the risk of death. Smoking was not an independent predictor of OPC survival.

Alcohol and cigarette consumption predict mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: This study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC. PATIENTS AND METHODS: We conducted a pooled analysis, including 4759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis. RESULTS: Five-year OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined: 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI 1.01-6.38, for high school or lower versus college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, 95% CI 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, 95% CI 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, 95% CI 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity. CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, whereas pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.

[Clinical research for rectal carcinoma: State of the art and objectives]. / Acquis et objectifs de la recherche clinique sur le cancer du rectum.

The treatment of rectal carcinoma is based on multidisciplinary strategy and multimodal approaches including gastrointestinal tract specialists, medical oncologists, radiation oncologists and surgery. The different objectives should be declined according to the characteristics of the tumours. The aim of the therapist would be to select the best strategy offering to the patient to be cured with as less as possible late adverse toxicity. The challenge of the treatment of small tumours is to maintain a functional anal sphincter while minimizing the risk of local recurrence. The standard treatment of locally advanced disease is aiming firstly to cure the patient and secondly to prevent late complications. Each of these clinical presentations of the disease has to be considered as a whole taking into account the new surgical techniques and a personalized approach adapted to the tumour. Nowadays they should be studied with dedicated clinical trials.

Pelvic radiotherapy in the setting of rheumatoid arthritis: Refining the paradigm.

PURPOSE: Conflicting results concerning the toxicity of radiotherapy in the setting of rheumatoid arthritis were reported in literature. This work describes the toxicity profiles of patients with rheumatoid arthritis undergoing pelvic radiotherapy for gynecologic malignancies at our institution. PATIENTS AND METHODS: Charts of patients with rheumatoid arthritis who underwent pelvic radiotherapy for cervical or endometrial cancer in a curative intent at the Gustave-Roussy Cancer Campus between 1990 and 2015 were reviewed for treatment-related toxicities. Acute and late effects were graded as per the Common Terminology Criteria for Adverse Events version 4.0 scoring system. RESULTS: Eight patients with cervical cancer and three with endometrial cancer were identified. Median follow-up was 56 months. Median external beam radiotherapy dose was 45Gy. All patients received a brachytherapy boost using either pulse- or low-dose rate technique. Concomitant chemotherapy was used in seven cases. Median time from rheumatoid arthritis diagnosis to external beam radiation therapy was 5 years. No severe acute gastrointestinal or genitourinary toxicity was reported. One patient had grade 3 dermatitis. Any late toxicity occurred in 7 /11 patients, and one patient experienced severe late toxicities. One patient with overt systemic rheumatoid arthritis symptoms at the time of external beam radiation therapy experienced late grade 3 ureteral stenosis, enterocolitis and lumbar myelitis. CONCLUSION: Pelvic radiotherapy, in the setting of rheumatoid arthritis, appears to be feasible, with potentially slight increase in low grade late events compared to other anatomic sites. Patients with overt systemic rheumatoid arthritis manifestation at the time of radiotherapy might be at risk of potential severe toxicities.

[Chordoma]. / Les chordomes.

PURPOSES: To review in the literature, all the epidemiological, clinical, radiological, histological and therapeutic data regarding chordomas as well as various notochordal entities: ecchordosis physaliphora, intradural and intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and extra-axial chordomas. To identify different types of chordomas, including familial forms, associations with tuberous sclerosis, Ollier's disease and Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data regarding molecular biology and progress in targeted therapy. To compare the different types of radiotherapy, especially protontherapy and their therapeutic effects. To review the largest series of chordomas in their different localizations (skull base, sacrum and mobile spine) from the literature. MATERIALS: The series of 136 chordomas treated and followed up over 20 years (1972-2012) in the department of neurosurgery at Lariboisière hospital is reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly, 31 chordomas in children (less than 18 years of age), observed in the departments of neurosurgery of les Enfants-Malades and Lariboisière hospitals, are presented. They were observed between 1976 and 2010 and were located intracranially (n=22 including 13 with cervical extension), 4 at the craniocervical junction level and 5 in the cervical spine. METHODS: In the entire Lariboisière series and in the different groups of localization, different parameters were analyzed: the delay of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death, the number of primary patients and patients referred to us after progression or recurrence and the number of deaths, recurrences and metastases. The influence of the quality of resection (total, subtotal and partial) on the prognosis is also presented. Kaplan-Meier actuarial curves of overall survival and disease free survival were performed in the entire series, including the different groups of localization based on the following 4 parameters: age, primary and secondary patients, quality of resection and protontherapy. In the pediatric series, a similar analysis was carried-out but was limited by the small number of patients in the subgroups. RESULTS: In the Lariboisière series, the mean delay of diagnosis is 10 months and the mean follow-up is 80 months in each group. The delay before recurrence, metastasis and death is always better for the skull base chordomas and worse for those of the craniocervical junction, which have similar results to those of the cervical spine. Similar figures were observed as regards the number of deaths, metastases and recurrences. Quality of resection is the major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after total resection as compared to 52.5 % and 47.5 % after subtotal resection. This is still more obvious in the group of skull base chordomas. Adding protontherapy to a total resection can still improve the results but there is no change after subtotal resection. The actuarial curve of overall survival shows a clear cut in the slope with some chordomas having a fast evolution towards recurrence and death in less than 4 years and others having a long survival of sometimes more than 20 years. Also, age has no influence on the prognosis. In primary patients, disease free survival is better than in secondary patients but not in overall survival. Protontherapy only improves the overall survival in the entire series and in the skull base group. Total resection improves both the overall and disease free survival in each group. Finally, the adjunct of protontherapy after total resection is clearly demonstrated. In the pediatric series, the median follow-up is 5.7 years. Overall survival and disease free survival are respectively 63 % and 54.3 %. Factors of prognosis are the histological type (atypical forms), localization (worse for the cervical spine and better for the clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many different pathologies derived from the notochord can be observed: some are remnants, some may be precursors of chordomas and some have similar features but are probably not genuine chordomas. To-day, immuno-histological studies should permit to differentiate them from real chordomas. Improving knowledge of molecular biology raises hopes for complementary treatments but to date the quality of surgical resection is still the main factor of prognosis. Complementary protontherapy seems useful, especially in skull base chordomas, which have better overall results than those of the craniocervical junction and of the cervical spine. However, we are still lacking an intrinsic marker of evolution to differentiate the slow growing chordomas with an indolent evolution from aggressive types leading rapidly to recurrence and death on which more aggressive treatments should be applied.

[Radiotherapy in central neurocytoma and review of literature]. / Place de la radiothérapie dans les neurocytomes centraux et revue de la littérature.

Central neurocytoma is a rare primary central nervous system tumour of young adults with good prognosis. Typical and atypical forms are described according to various histologic and histopathologic parameters. Central neurocytoma develops in the periventricular areas and is revealed by increased intracranial pressure. The tumour exhibits typical characteristics on CT scan and MRI and a characteristic peak of glycine on spectroscopy-MRI. The main treatment is total resection, which is achievable only in half of the cases. External beam therapy improves local control of partially resected and/or atypical central neurocytoma. Many studies show that stereotactic radiotherapy can be used in the therapeutic management as exclusive treatment, in postoperatives residues and in case of distant recurrence. Chemotherapy is the last line of treatment in refractory forms, especially in the forms with extracranial and/or neuromeningeal spread and in recurrent forms after treatment with surgery and/or radiotherapy.

[Radiation therapy of sinonasal natural killer/T-cell lymphoma]. / Radiothérapie des lymphomes NK/T localisés aux fosses nasales.

Natural killer (NK)/T-cell lymphoma are part of lymphoproliferative diseases, they are rare in Europe and the United States but relatively common in Asia and South America. Natural killer (NK)/T-cell lymphoma present clinically as destructive lesions of the upper aerodigestive tract with perforation of deep structures of the face, destruction of the palate or an invasion of orbits. Treatment modalities of these lymphomas are still discussed because of the lack of available studies and the rarity of this disease. Radiotherapy provides a rapid control of the disease and is positioned as a major treatment of localized stages of NK/T-cell lymphoma of the nasal cavity. We therefore studied the different forms of radiation therapy in the early stages of nasal NK/T-cell lymphoma.

Validation of a stoma-specific quality of life questionnaire in a sample of patients with colostomy or ileostomy.

AIM: The aim of this study was to determine how socio-demographic and clinical variables affect quality of life (QoL) and to assess the validity of a 20-item scale in a sample of Italian subjects with colostomy, ileostomy and multiple stomata. METHOD: A cross-sectional multicentre survey was carried out in Italy between 2009 and 2010 in 73 stoma centres coordinated by the University of Padova. Patients aged 18 years old and above with a history of nontemporary stoma were included in the study. The Stoma Care QoL scale was measured and validated using a Rasch model. Socio-demographic and clinical characteristics were considered in the analyses. RESULTS: Two hundred and fifty-one patients were recruited for the study; the mean age was 62 years, 58% were men, 72% had colostomy and 25% ileostomy; approximately 70% of patients had intestinal cancer requiring a stoma, 13% a complication and 10% an inflammatory disease. No significant differences were observed throughout strata in the Stoma Care QoL scale index, except for geographical area, where subjects from south Italy showed a significantly lower index than subjects living in other parts of Italy (P < 0.01). Colostomy and ileostomy patients reported very similar QoL. Cronbach's alpha for the Stoma Care QoL scale was 0.90 (95% CI 0.88-0.92). Rasch analysis supported the viability of the Stoma Care QoL scale questionnaire and showed acceptable goodness-of-fit. Three under-fitted items were observed. CONCLUSION: The study confirms the validity of the 20-item Stoma Care QoL scale questionnaire as a research tool for stoma patients but the number of items could be reduced.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Personal exposure to particulate matter is associated with worse health perception in adult asthma.

BACKGROUND: Epidemiological studies have shown positive associations between particulate matter (PM) air pollution and short-term mortality and morbidity for asthma. The hypothesis that lung inflammation is responsible for these effects has been tested in panel and controlled exposure studies in asthmatic adults, with inconsistent results. OBJECTIVES: We investigated whether personal exposure to PM10 and PM2.5 were related to changes in the clinical course of asthma and to lung inflammatory responses in adult asthmatics. METHODS: A cohort of 32 asthmatic patients was followed for 2 years. Asthma control test (ACT) and St George's Respiratory Questionnaire (SGRQ) scores, forced expired volume in the first second (FEV1), exhaled nitric oxide (Fe(NO)), and pH of exhaled breath condensate (EBC) were determined on 6 occasions during different seasons. Personal exposure to PM was measured for 24 hours prior to clinical assessments. RESULTS: A 10 microg/m3 increase in PM10 personal exposure was associated with an increase in SGRQ scores (regression coefficient beta = 0.22; 95% confidence interval [CI], -0.005 to 4.451; P =.055) and with a decrease in ACT scores (beta = -0.022; 95% CI, -0.045 to 0.001; P = .060), whereas no associations were found between PM10 and FEV1, Fe(NO), or EBC pH. A positive association was detected between Fe(NO) and outdoor O3 (P = .042) and SO2 (P = .042) concentrations in the subgroup of nonsmoking asthmatics. CONCLUSIONS: We concluded that increments in personal exposure to PM10 are associated with a decrease in asthma control and health-related quality of life. However, this study does not provide evidence that 24-hour exposures to PM are associated with short-term changes in lung function or inflammatory responses of the lung.

Mortality, incidence of cardiovascular diseases, and educational level among the diabetic and non-diabetic populations in two large Italian cities.

AIMS: We investigated if diabetes modifies the effect of the association of education with mortality and incidence of cardiovascular diseases. METHODS: We identified 44,889 diabetics using multiple data sources. They were followed up from January 2002 up to December 2005, and their mortality, incidence of myocardial infarction and stroke, by educational level were analysed, and compared with those of the local non-diabetic population. RESULTS: The all-cause Standardized Mortality Ratios among diabetics, compared with non-diabetics, were 170 for men and 175 for women. Standardized Incidence Ratios were 199 for myocardial infarction, and 183 for stroke in men and, respectively, 281, and 179 in women. Among non-diabetics there was a clear inverse relation with educational level for all outcomes, whereas among diabetics no significant social difference in incidence was found; slight social differences in mortality were present among men, but not among women. The effect of diabetes on social differences was enhanced in the youngest population. CONCLUSIONS: Diabetes increases the risk of death and the incidence of vascular diseases, but reduces their inverse association with education. This is likely related to the high accessibility and good quality of health care provided by the local networks of diabetic centres and primary care.

Life course social mobility and risk of upper aerodigestive tract cancer in men.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Socioeconomic factors associated with risk of upper aerodigestive tract cancer in Europe.

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.