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..

Stereotactic Ablative Radiotherapy in the Treatment of Early-Stage Lung Cancer - A Done Deal?

Stereotactic ablative radiotherapy (SABR) is an important curative-intent treatment option for early-stage non-small cell lung cancer. It offers good cancer control without invasive surgery and has become the standard of care for medically inoperable patients. The literature on SABR for early-stage non-small cell lung cancer is substantial and continues to grow. However, there remain areas of controversy where data are limited - notably the use of SABR in medically operable patients. Other areas of some debate include the treatment of central/ultra-central and large (>5 cm) lesions, as well as treatment with co-existing interstitial lung disease. This review article provides an overview of the current literature together with a discussion of future directions.

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).

Clinical characteristics and long-term outcome of E. coli-associated granulomatous ileocolitis in dogs: five cases (2010-2014).

OBJECTIVES: To describe the clinical characteristics and long-term outcome of Escherichia coli-associated granulomatous ileocolitis in dogs. METHODS: Retrospective review of medical records from dogs with periodic acid-Schiff positive (PAS+) granulomatous ileocolitis and mucosally invasive E. coli in the ileum and colon. Initial bacterial colonisation was evaluated using fluorescence in situ hybridization (FISH) in all dogs and corroborated with colonic and/or ileal culture, when performed. RESULTS: Four boxer dogs and 1 French Bulldog with PAS+ granulomatous ileocolitis (GIC) were evaluated. All dogs had chronic diarrhoea refractory to empirical therapy. Ileocolonoscopy revealed mucosal haemorrhage and ulceration in the ileum (3/4) and colon (5/5). E. coli were visualised as clusters within the ileal and colonic mucosa. Complete (CR, 4/5) or partial (PR, 1/5) clinical response to fluoroquinolones was noted in all dogs within 30 days. CR was sustained in three of four dogs (median disease-free interval 40 months, range 16 to 60). Two dogs relapsed while receiving fluoroquinolones. Repeat biopsy isolated multidrug-resistant, mucosally invasive E. coli in the ileum (1/2) and colon (2/2). Targeted antimicrobial therapy was associated with long-term PR (78 months) in both dogs. CLINICAL SIGNIFICANCE: Concurrent E. coli-associated granulomatous inflammation in the ileum and colon did not impart a poor clinical outcome or lack of response to the conventional standard of care for granulomatous colitis in dogs that were aggressively diagnosed and treated. Clinical outcome was influenced by antimicrobial resistance, with response dependent upon antimicrobial therapy informed by susceptibility testing.

Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay.

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting. Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients. Results: The average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site. Conclusions: At our tertiary care cancer centre, a patient's clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system.

Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) represent non-invasive, efficacious and safe radiation treatments for the ablation of intracranial and extracranial metastases. Although the use of SRS has been established by level 1 evidence for patients presenting with up to three or four brain metastases for at least a decade, the paradigm of ablating a limited number of extracranial metastases (typically up to five, known as oligometastatic disease) has yet to be proven beyond the few reported but highly encouraging phase II randomised trials. In this overview, we summarise the phase III randomised controlled trials evaluating SRS for intact brain metastases and postoperative surgical cavities and introduce the limited literature and future concepts for treating patients with more than five intracranial metastases. Next, we summarise the published phase II randomised controlled trials specific to SBRT and oligometastatic disease, while briefly describing and contrasting the technical principles and biological mechanisms of SBRT versus conventional radiation. Phase III evidence for SBRT is needed, and we summarise ongoing trials in this overview. Ultimately, SRS and SBRT have become cornerstone therapeutic options for patients with oligometastatic disease and the future is bright for these patients, considering that not so long ago they were considered incurable and relegated to palliation alone.

Does free nicotine replacement improve smoking cessation rates in cancer patients?

Background: Cigarette smoking is carcinogenic and has been linked to inferior treatment outcomes and complication rates in cancer patients. Here, we report the results of an 18-month pilot smoking cessation program that provided free nicotine replacement therapy (nrt). Methods: In January 2017, the smoking cessation program at our institution began offering free nrt for actively cigarette-smoking patients with cancer. The cost of 4 weeks of nrt was covered by the program, and follow-up was provided by smoking cessation champions. Results: From January 2017 to June 2018, 8095 patients with cancer were screened for cigarette use, of whom 1135 self-identified as current or recent smokers. Of those 1135 patients, 117 enrolled in the program and accepted a prescription for nrt. The rates of patient referral and patients attending a referral appointment were significantly higher in 2018-2018 than they had been in 2015-2016 (100% vs. 80.3%, p < 0.001, and 27.6% vs. 11.3%, p < 0.001, respectively). Median follow-up was 9.0 months (25%-75% interquartile range: 5.7-11.6 months). Of the patients who accepted nrt and who also had complete data (n = 71), 25 (35.2%) reported complete smoking cessation, and 32 (45.1%) reported only decreased cigarette smoking. On univariable analysis, no factors were significantly predictive of smoking cessation, although initial cigarette use (>10 vs. ≤10 initial cigarettes) was significantly predictive of smoking reduction (odds ratio: 5.04; 95% confidence interval: 1.46 to 17.45; p = 0.011). Conclusions: This pilot study of free nrt demonstrated rates of referral and acceptance of nrt that were improved compared with historical rates, and most referred patients either decreased their use of cigarettes or quit entirely.

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.

Voiding cystourethrography and 99MTC-MAG3 renal scintigraphy in pediatric vesicoureteral reflux: what is the role of indirect cystography?

BACKGROUND: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS: 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.

Percutaneous Lung Tumor Biopsy Under CBCT Guidance with PET-CT Fusion Imaging: Preliminary Experience.

PURPOSE: The aim of this study is to evaluate the feasibility of percutaneous lung tumor biopsy under cone beam-computed tomography (CBCT) with PET-CT imaging fusion. MATERIALS AND METHODS: Eleven patients (four women and seven men) underwent C-arm CBCT lung biopsy with PET-CT fusion imaging. A preprocedural PET-CT scan was manually fused with procedural CBCT based on anatomical landmarks; using real-time fluoroscopy, the coregistered PET-CT and CBCT images were overlaid to guide the needle trajectory. Technical success, accuracy, sensibility and specificity were evaluated. Mean total procedure time and time required for image elaboration were recorded. RESULTS: Technical success, diagnostic accuracy, sensitivity and specificity were 100%. The mean procedure time was 38 min. The average time of PET-CT/CBCT image fusion elaboration was 3.53 min for planning and 3.42 min for needle positioning check. CONCLUSION: CBCT-guided percutaneous lung biopsy with PET-CT fusion imaging is a feasible and effective procedure, with the potential to further improve diagnostic yield by targeting the most metabolically active portion of a lesion, whether it is morphologically altered or normal.

The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively?

Oligoprogressive disease is a relatively new clinical concept describing progression at only a few sites of metastasis in patients with otherwise controlled widespread disease. In the era of well-tolerated targeted treatments, resistance inevitably occurs and overcoming this is a challenge. Local ablative therapy for oligoprogressive disease may allow the continuation of systemic treatments by overcoming the few sub-clones that have developed resistance. Stereotactic body radiotherapy is now frequently used in treating oligometastatic disease using ablative doses with minimally invasive techniques and acceptable toxicity. We discuss the current retrospective clinical evidence base supporting the use of local ablative therapy for oligoprogression in metastatic patients on targeted treatments within multiple tumour sites. As there is currently a lack of published prospective data available, the best management for these patients remains unclear. We discuss current trials in recruitment and the potential advancements in treating this group of patients with stereotactic radiotherapy.

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.

Incidence of High-Risk Radiologic Features in Patients Without Local Recurrence After Stereotactic Ablative Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: To investigate, in the setting of stereotactic ablative radiation therapy (SABR) for early-stage non-small cell lung cancer, the incidence and patterns of change in high-risk radiologic features (HRFs) in patients known to have no local recurrence. METHODS AND MATERIALS: Computed tomography (CT) scans of patients treated using volumetric modulated arc therapy SABR between 2008 and 2013 were eligible if follow-up scans were available for 2 years and no local recurrences were diagnosed. All scans were reviewed at a workstation using an add-on tool for ClearCanvas (Synaptive Medical). Five clinicians who were blinded to clinical outcomes scored the presence of HRFs: enlarging opacity (EO), sequential enlarging opacity, enlarging opacity after 12 months (EO12), bulging margin, loss of linear margins, cranio-caudal growth, and loss of air bronchogram. After each review, clinicians recommended follow-up procedures based on published recommendations. RESULTS: A total of 88 patients (747 CT scans) were evaluated. The HRFs most frequently recorded by ≥3 observers on at least 1 follow-up scan were EO (64.8%), EO12 (50.0%), and sequential enlarging opacity (13.6%). Fifty-six patients developed EO within the first year after SABR, and of these, 46 also developed subsequent EO (EO12). In 76 patients who developed EO after 1 year of follow-up, 30 had not manifested EO previously. Three or more HRFs have been associated with recurrences, and this was observed on CT scan in 22.7% of patients. In their routine care, 6 patients had undergone a positron emission tomography scan because of a suspected local recurrence, and 4 underwent an attempt at biopsy. CONCLUSIONS: More than 50% of patients without a local recurrence after SABR develop HRFs. Because ≥3 HRFs were present in nearly 25% of patients, further refinement of follow-up recommendations are necessary.

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.