The PRO-ACTIVE trial protocol: a randomized study comparing the effectiveness of PROphylACTic swallow InterVEntion for patients receiving radiotherapy for head and neck cancer.

BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).

Two decades of SPECT/CT - the coming of age of a technology: An updated review of literature evidence.

PURPOSE: Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication. METHODS: This review presents a critical assessment of the relevant literature published so far on the role of SPECT/CT in a variety of clinical conditions. It also includes an update on the established evidence demonstrating both the advantages and limitations of this modality. CONCLUSIONS: For the majority of applications, SPECT/CT should be a routine imaging technique, fully integrated into the clinical decision-making process, including oncology, endocrinology, orthopaedics, paediatrics, and cardiology. Large-scale prospective studies are lacking, however, on the use of SPECT/CT in certain clinical domains such as neurology and lung disorders. The review also presents data on the complementary role of SPECT/CT with other imaging modalities and a comparative analysis, where available.

Phase I study of concurrent and consolidation cisplatin and docetaxel chemotherapy with thoracic radiotherapy in non-small cell lung cancer.

BACKGROUND: We designed a phase i study of concurrent chemoradiotherapy (ccrt) with docetaxel (D) and cisplatin (C), followed by consolidation dc, for unresectable stage iii non-small cell lung cancer (nsclc). METHODS: Patients with histologically proven and unresectable stage iii nsclc were eligible. During ccrt, C was given every 3 weeks (75 mg/m2) and D given weekly. The starting dose of D was 20 mg/m2, escalated in cohorts of 3 to define the maximum tolerated dose (mtd). Radiotherapy was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidation dc, which were dose escalated if ccrt was tolerated. RESULTS: Twenty-six patients were enrolled, with 1 excluded following evidence of metastatic disease. Nineteen patients completed both phases of treatment. There were 7 grade 3 events during ccrt (5 esophagitis, 2 nausea), and 8 grade 3 events during consolidation (2 neutropenia, 2 leukopenia, 1 esophagitis, 2 nausea, and 1 pneumonitis). Three patients had grade 4 neutropenia. No patients died due to toxicities. The mtd of concurrent weekly D was 20 mg/m2. Consolidation D and C were each dose escalated to 75 mg/m2 in 8 patients. The median overall survival (os) and progression-free survival (pfs) of all patients were 33.6 months and 17.2 months, respectively, with median follow-up of 26.6 months (range 0.43-110.8). CONCLUSIONS: The use of docetaxel 20 mg/m2 weekly and cisplatin 75 mg/m2 every 3 weeks concurrent with thoracic radiotherapy, followed by consolidation docetaxel and cisplatin, both given at 75 mg/m2 every 3 weeks, appears to be safe in this phase i trial.

The impact of seasonal operating room closures on wait times for oral cancer surgery.

BACKGROUND: Operating room slowdowns occur at specific intervals in the year as a cost-saving measure. We aim to investigate the impact of these slowdowns on the care of oral cavity cancer patients at a Canadian tertiary care centre. METHODS: A total of 585 oral cavity cancer patients seen between 1999 and 2015 at the London Health Science Centre (lhsc) Head and Neck Multidisciplinary Clinic were included in this study. Operating room hours and patient load from 2006 to 2014 were calculated. Our primary endpoint was the wait time from consultation to definitive surgery. Exposure variables were defined according to wait time intervals occurring during time periods with reduced operating room hours. RESULTS: Overall case volume rose significantly from 2006 to 2014 (p < 0.001), while operating room hours remained stable (p = 0.555). Patient wait times for surgery increased from 16.3 days prior to 2003 to 25.5 days in 2015 (p = 0.008). Significant variability in operating room hours was observed by month, with lowest reported for July and August (p = 0.002). The greater the exposure to these months, the more likely patients were to wait longer than 28 days for surgery (odds ratio per day [or]: 1.07, 95% confidence interval [ci]: 1.05 to 1.10, p < 0.001). Individuals seen in consultation preceding a month with below average operating room hours had a higher risk of disease recurrence and/or death (hazard ratio [hr]: 1.59, 95% ci: 1.10 to 2.30, p = 0.014). CONCLUSIONS: Scheduled reductions in available operating room hours contribute to prolonged wait times and higher disease recurrence. Further work is needed to identify strategies maximizing efficient use of health care resources without negatively affecting patient outcomes.

Development of an online, patient-centred decision aid for patients with oropharyngeal cancer in the transoral robotic surgery era.

BACKGROUND: Radiotherapy (rt) has been the standard treatment for early oropharyngeal cancer, achieving excellent outcomes, but with significant toxicities. Transoral robotic surgery (tors) has emerged as a promising alternative. A decision aid (da) can help to establish patient treatment preferences. METHODS: A da was developed and piloted in 40 healthy adult volunteers. Assuming equal oncologic outcomes of the treatments, participants indicated their preference. The treatment trade-off point was then established, and participant perceptions were elicited. RESULTS: More than 80% of participants initially selected tors for treatment, regardless of facilitator background. For all participants, the treatment trade-off point changed after an average 15% cure benefit. Treatment toxicities, duration, novelty, and perceptions all influenced treatment selection. All subjects valued the da. CONCLUSIONS: A da developed for early oropharyngeal cancer treatment holds promise in the era of shared decision-making. Assuming equal cure rates, tors was preferred over rt by healthy volunteers.

Identifying barriers to accrual in radiation oncology randomized trials.

BACKGROUND: Data about factors driving accrual to radiation oncology trials are limited. In oncology, 30%-40% of trials are considered unsuccessful, many because of poor accrual. The goal of the present study was to inform the design of future trials by evaluating the effects of institutional, clinician, and patient factors on accrual rates to a randomized radiation oncology trial. METHODS: Investigators participating in sabr-comet (NCT01446744), a randomized phase ii trial open in Canada, Europe, and Australia that is evaluating the role of stereotactic ablative radiotherapy (sabr) in oligometastatic disease, were invited to complete a survey about factors affecting accrual. Institutional ethics approval was obtained. The primary endpoint was the annual accrual rate per institution. Univariable and multivariable linear regression analyses were used to identify factors predictive of annual accrual rates. RESULTS: On univariable linear regression analysis, off-trial availability of sabr (p = 0.014) and equipoise of the referring physician (p = 0.014) were found to be predictive of annual accrual rates. The annual accrual rates were lower when centres offered sabr for oligometastases off-trial (median: 3.7 patients vs. 8.4 patients enrolled) and when referring physicians felt that, compared with having equipoise, sabr was beneficial (median: 4.8 patients vs. 8.4 patients enrolled). Multivariable analysis identified perceived level of equipoise of the referring physician to be predictive of the annual accrual rate (p = 0.023). CONCLUSIONS: The level of equipoise of referring physicians might play a key role in accrual to radiation oncology randomized controlled trials. Efforts to communicate with and educate referring physicians might therefore be beneficial for improving trial accrual rates.

[Extrathoracic manifestations of tuberculosis]. / Extrathorakale Manifestationen der Tuberkulose.

CLINICAL/METHODICAL ISSUE: Besides the lungs, tuberculosis (TB) can affect any organ system. In most cases, extrathoracic TB occurs in immunosuppressed patients as part of a severe illness via hematogenous spread. Extrathoracic involvement most commonly involves abdominal organs, especially the urogenital tract and less commonly the central nervous system (CNS) and the musculoskeletal system. Most frequently, computed tomography (CT) is used for detecting extrathoracic TB manifestations, except for CNS and musculoskeletal manifestations, where contrast-enhanced magnetic resonance imaging (MRI) is the gold standard. Extrathoracic manifestations of TB may be indistinguishable from inflammatory or malignant causes. Due to unspecific symptoms the diagnosis is often delayed. This article summarizes and discusses the various radiological manifestations of extrathoracic manifestation of TB. STANDARD RADIOLOGICAL METHODS: Radiological modalities for screening extrathoracic TB are CT and MRI. Conventional X­radiographs do not play a role in the diagnosis of extrathoracic TB. PRACTICAL RECOMMENDATIONS: The possibility of extrathoracic TB should be considered particularly in immunosuppressed patients, such as the homeless, alcoholics or drug addicts or in patients with an immigrant background from the endemic areas of TB. The most likely site of extrathoracic TB is the abdomen; however, infections of the CNS or musculoskeletal systems and multisystem infections can also occur. In patients with suspected extrathoracic TB, radiological modalities for screening are CT, especially for abdominal infections and lymphadenopathy and MRI with contrast media for the musculoskeletal system and the CNS.

[Thoracic manifestation of tuberculosis]. / Thorakale Manifestation der Tuberkulose.

CLINICAL ISSUE: Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. In the majority of cases patients have thoracic TB, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. Due to the rise in incidence of TB in central Europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary TB, particularly to be able to discriminate active from inactive TB. Due to the use of molecular techniques entailing DNA fingerprinting, the traditional classification of TB in primary and postprimary TB is being challenged. These genetic studies have revealed that variations in the clinical and radiographic appearance of TB are mainly affected by the immune status of the patients. Due to the low prevalence of TB in central Europe and the wide variation of radiological presentations, the diagnosis and therapy of TB is often delayed. In this article, the radiographic manifestations of thoracic TB are summarized and discussed. STANDARD RADIOLOGICAL METHODS: Together with the medical history and bacteriological tests, chest X­ray imaging and computed tomography (CT) play a major role not only in the detection of TB but also in the follow-up during and after therapy. PRACTICAL RECOMMENDATIONS: Chest X­radiographs should be the primary diagnostic method in patients with suspected TB in screening as well as for diagnosis and therapy monitoring. The use of CT is more sensitive than chest radiographs and is frequently performed after chest radiographs to obtain detailed information about subtle parenchymal changes or lymph node manifestation. When active TB is suspected CT should be performed. Tree in bud, lobular consolidations, centrilobular nodules, cavities and ground-glass opacification are typical changes in active TB.

Prevalence of simple nodular goiter and Hashimoto's thyroiditis in current, previous, and never smokers in a geographical area with mild iodine deficiency.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis.Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

[Orbital emphysema after Valsalva maneuver. Report of one case]. / Enfisema orbitario espontáneo tras la maniobra de Valsalva.

Orbital emphysema is a rare complication of orbital and facial trauma, involving the sinuses and occasionally the nasal cavity. Most cases occur as a result of trauma but spontaneous orbital emphysema has been reported. Clinical manifestations are often delayed until the upper airway pressure increases as when blowing or coughing. Along with the fracture, the rupture of the underlying mucosa is essential for emphysema to manifest. We report a 29-years-old male who consulted in the emergency room due to eyelid swelling after a Valsalva maneuver, a couple of hours after suffering a facial injury secondary to a fall. In the presence of eyelid emphysema, the patient underwent craniofacial imaging studies, confirming an ethmoidal lamina papyracea fracture.

Renal radionuclide imaging, an evergreen forty years old.

Urinary tract congenital abnormalities (UCA) and febrile infections (UTI) are, respectively, 2 of the commonest congenital and acquired health problems in childhood. In both, radionuclide imaging still represent a cornerstone of diagnostic imaging, although the involved techniques are more or less the same from the early '80 s. During the last 2 decades, published papers focused on a deep revision about the optimal use and usefulness of such imaging tools in affected children, with the aim of reducing invasiveness, radiation burden and costs without losing efficacy. This approach leads to different results. In UCA, no consensus for a diagnostic algorithm was up to now reached, whilst, about febrile UTIs, guidelines were published in 2007 by the UK's National Institute for Clinical Excellence (NICE) and by the European Society of Paediatric Radiology (ESPR), in 2011 by the American Academy of Paediatrics (AAP), and in 2012 by the Italian Society of Paediatric Nephrology (SINP). Nevertheless, new data continuously arise and the scientific debate always revives. Every imaging tool now available has its own strengths and weaknesses, and so all published guidelines. All this body of knowledge must be critically analysed for obtaining a complete, up-to-date and flexible overview about these "always hot" topics.

Factors associated with referrals for directly observed treatment and unsuccessful treatment.

To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment.This was a multicentre observational study based on a prospective follow-up of patients over 18 years old diagnosed with TB between 2006 and 2019 from the registry of the Programa Integrado de Investigación en Tuberculosis (PII-TB). Sociodemographic and clinical variables were collected. Adjusted odds ratios (aORs) were calculated for the indication of DOT and for having an unsuccessful treatment.A total of 7,883 patients were included. The indication of DOT was associated with being homeless (aOR 5.93, 95% CI 3.03-11.59), inactivity status (aOR 2.55, 95% CI 2.02-3.23), alcohol consumption (aOR 1.94, 95% CI 1.51-2.48), parenteral drug use (aOR 1.77, 95% CI 1.06-2.95) and HIV diagnosis (aOR 1.96, 95% CI 1.16-3.29). Unsuccessful treatment was associated with having an HIV diagnosis (aPR 2.31, 95% CI 1.31-4.08), having a worse clinical and radiological evolution (clinical progression: APR 15.59, 95% CI 8.21-29.60; radiological progression: aPR 12.84, 95% CI 6.46-25.52), need for hospitalisation (aPR 1.73, 95% CI 1.10-2.73), unsatisfactory tolerability (aPR 2.82, 95% CI 1.49-5.29), the existence of difficulties in understanding the prescribed treatment (aPR 1.92, 95% CI 1.21-3.06), as well as worse treatment satisfaction (aPR 7.27, 95% CI 4.32-12.24).The prioritisation of vulnerable populations is a key aspect to carry out the new Global Plan to End TB 2023-2030. In these groups DOT indication should be increased to ensure adherence and patient follow-up and outcomes..

Scale-independent roughness value of cell membranes studied by means of AFM technique.

The roughness of cell membrane is a very interesting indicator of cell's health state. Atomic Force Microscopy allows us to investigate the roughness of cell membrane in great detail, but the obtained roughness value is scale-dependent, i.e. it strongly depends on measurement parameters, as scanning area and step size. The scale-dependence of the roughness value can be reduced by means of data filtration techniques, that are not standardized at nanometric scale, especially as far as biological data are concerned. In this work, a new method, based on the changes of values of some roughness parameter (root mean square roughness and skewness) as a function of filtration frequencies, has been implemented to optimize data filtering procedure in the calculation of cell membrane roughness. In this way, a root mean square roughness value independent of cell shape, membrane micro-irregularities and measurement parameters can be obtained. Moreover, different filtration frequencies selected with this method allow us to discriminate different surface regimes (nominal form, waviness and roughness) belonging to the raw cell profile, each one related to different features of the cell surface.

Stage I-II non-small-cell lung cancer treated using either stereotactic ablative radiotherapy (SABR) or lobectomy by video-assisted thoracoscopic surgery (VATS): outcomes of a propensity score-matched analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched analysis to compare locoregional control (LRC). PATIENTS AND METHODS: VATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board. RESULTS: The matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different. CONCLUSION: This retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.

Multidisciplinary assessment of fitness to drive in brain tumour patients in southwestern Ontario: a grey matter.

BACKGROUND: Neurocognitive impairments from brain tumours may interfere with the ability to drive safely. In 9 of 13 Canadian provinces and territories, physicians have a legal obligation to report patients who may be medically unfit to drive. To complicate matters, brain tumour patients are managed by a multidisciplinary team; the physician most responsible to make the report of unfitness is often not apparent. The objective of the present study was to determine the attitudes and reporting practices of physicians caring for these patients. METHODS: A 17-question survey distributed to physicians managing brain tumour patients elicited Respondent demographicsKnowledge about legislative requirementsExperience of reportingBarriers and attitudes to reporting Fisher exact tests were performed to assess differences in responses between family physicians (fps) and specialists. RESULTS: Of 467 physicians sent surveys, 194 responded (42%), among whom 81 (42%) were specialists and 113 (58%) were fps. Compared with the specialists, the fps were significantly less comfortable with reporting, less likely to consider reporting, less likely to have patients inquire about driving, and less likely to discuss driving implications. A lack of tools, concern for the patient-physician relationship, and a desire to preserve patient quality of life were the most commonly cited barriers in determining medical fitness of patients to drive. CONCLUSIONS: Legal requirements to report medically unfit drivers put physicians in the difficult position of balancing patient autonomy and public safety. More comprehensive and definitive guidelines would be helpful in assisting physicians with this public health issue.

Assessing fitness to drive in brain tumour patients: a grey matter of law, ethics, and medicine.

BACKGROUND: Neurocognitive deficits from brain tumours may impair the ability to safely operate a motor vehicle. Although certain jurisdictions in Canada legally require that physicians report patients who are unfit to drive, criteria for determining fitness are not clearly defined for brain tumours. METHODS: Patients receiving brain radiotherapy at our institution from January to June 2009 were identified using the Oncology Patient Information System. In addition to descriptive statistics, details of driving assessment were reviewed retrospectively. The Fisher exact test was used to determine factors predictive of reporting a patient to the Ontario Ministry of Transportation (mto) as unfit to drive. A logistic regression model was constructed to further determine factors predictive of reporting. RESULTS: Of the 158 patients available for analysis, 48 (30%) were reported to the mto, and 64 (41%) were advised to stop driving. With respect to the 53 patients with seizures, a report was submitted to the mto for 30 (57%), and a documented discussion about the implications of driving was held with 35 (66%). On univariate analysis, younger age, a central nervous system primary, higher brain radiotherapy dose, unifocal disease, and the presence of seizures were predictive of physician reporting (p < 0.05). On logistic regression modelling, the presence of seizures (odds ratio: 3.9) and a higher radiotherapy dose (odds ratio: 1.3) remained predictive of reporting. INTERPRETATION: Physicians frequently do not discuss the implications of driving with brain tumour patients or are not properly documenting such advice (or both). Clear and concise reporting guidelines need to be drafted given the legal, medical, and ethical concerns surrounding this public health issue.

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population.

BACKGROUND: Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. METHODS: Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. RESULTS: Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. INTERPRETATION: The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.

Early-stage lung cancer in elderly patients: a population-based study of changes in treatment patterns and survival in the Netherlands.

BACKGROUND: Elderly patients with stage I non-small-cell lung cancer are less likely to undergo curative treatment. However, the introduction of new treatment options such as stereotactic ablative radiotherapy (SABR) may improve treatment rates. We evaluated time trends in treatment patterns and survival in the entire Netherlands population for patients diagnosed between 2001 and 2009. PATIENTS AND METHODS: Details of 4605 elderly Dutch patients were obtained from the Netherlands Cancer Registry, containing data on all cancer patients in a population of 16 million. Three consecutive time periods were studied: 2001-2003 (A, before SABR became available), 2004-2006 (B, increasing availability), and 2007-2009 (C, full availability). RESULTS: Between period A and C, there was a 7% absolute reduction in patients going untreated, corresponding to an 8-month improvement in median survival (P < 0.001). Radiotherapy utilization increased from 31% to 38%, whereas surgical utilization remained constant (37%). Significant improvements in survival were observed in the radiotherapy subgroup (P < 0.001) and surgery subgroup (P < 0.001), not in patients going untreated. There was no evidence of stage migration. CONCLUSIONS: Population-based increases in survival of elderly stage I lung cancer patients were seen between 2001 and 2009. The introduction of SABR correlated with a decline in the number of untreated patients.

Hyperleptinemia is associated with hypertension, systemic inflammation and insulin resistance in overweight but not in normal weight men.

BACKGROUND AND AIM: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity. METHODS AND RESULTS: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables. CONCLUSIONS: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.