Initial Definitive Management Research Articles

Is Prostate Brachytherapy a Dying Art? Evidence of Increasing Utilization in Ontario, Canada

A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumor-, and provider-factors on treatment utilization over time. There were 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 (p<0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p<0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 (p<0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p<0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p<0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p<0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p<0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p<0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.

Is prostate brachytherapy a dying art? Trends and variation in the definitive management of prostate cancer in Ontario, Canada

Background and purposeDeclining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. Materials and methodsMen with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. Results61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22–1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02–1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93–0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11–6.26, p < 0.01) and 2.88 (95% CI: 2.60–3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. ConclusionWe found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.

Is prostate brachytherapy a dying art? Evidence of increasing utilization in Ontario, Canada.

e17608 Background: A worldwide decline in prostate brachytherapy (BT) utilization has been reported in multiple health care settings/jurisdictions, despite strong evidence for efficacy and safety compared to other alternatives. We sought to evaluate contemporary trends in BT, EBRT and prostatectomy utilization in a publicly funded healthcare system. Methods: Men with localized prostate cancer diagnosed and treated between 2007 and 2017 in Ontario, Canada were identified using administrative data from the Institute for Clinical Evaluative Sciences. Men were coded to have received EBRT, BT (monotherapy or boost) or prostatectomy as initial definitive management. Trends were evaluated using the Cochran-Armitage test. Multivariate logistic regression was used to evaluate patient-, tumour-, and provider-factors on treatment utilization over time. Results: 57,655 men were included in our study. Prostate BT use increased from 7.5% of all treatments in 2007 to 15.4% in 2017 ( p&lt; 0.01), primarily due to increased use of BT boost (1.7% in 2007 to 10.4% in 2017, p &lt; 0.01). Relative to EBRT, BT use increased from 17.9% in 2007 to 28.1% in 2017 ( p&lt; 0.01). On multivariate analysis (MVA), BT boost use increased by 28% per year (OR 1.28, 95% CI 1.26–1.31, p&lt; 0.01) and BT monotherapy use increased by 12% per year (OR 1.12, 95% CI 1.10–1.14, p&lt; 0.01), offset by decreasing prostatectomy use (12% per year, OR 0.88, 95% CI 0.87–0.89, p&lt; 0.01). Comparing BT to EBRT, the strongest predictors of receiving BT were geographic residence (OR 27.6, 95% CI: 20.3–37.6, p&lt; 0.01 between highest/lowest Local Health Integration Networks) and whether the first consulting radiation oncologist performed BT (OR 3.46, 95% CI: 3.15–3.80, p&lt; 0.01). Other significant factors predicting BT use vs. EBRT included lower age, lower PSA, lower Charlson comorbidity score and increasing neighborhood income quintile. Low-intermediate, high-intermediate and high-risk groups were predictive of receiving BT boost, whereas BT monotherapy was predominantly used in low-risk disease. Conclusions: Contrary to trends observed in other jurisdictions, utilization of prostate BT is increasing over time in Ontario. However, substantial variation in BT utilization was found, strongly driven by both geographic region and radiation oncologist BT practice patterns. To our knowledge, this is the first study to report increasing BT utilization in the era of dose-escalated EBRT, with Ontario potentially serving as a model to promote BT utilization elsewhere.

PET/MRI and prostate cancer

Advances in medical imaging are needed to support the general goal of personalized patient-centric care. This is particularly true for prostate cancer, which frequently presents as the initial multifocal disease with variable significance and outcome, and, when aggressive, can recur after the initial definitive management. The combined simultaneous acquisition of multi-parametric magnetic resonance imaging and positron emission tomography (PET) can provide combined structural, metabolic, and functional imaging information regarding prostate cancer status in a whole-body single session examination. As described in this review article, combining PET and MRI appears particularly useful for pelvic disease assessments, as PET and MRI provide complementary information, which can be best obtained with hybrid PET/MR scanners. While there is growing interest in the field of prostate cancer imaging regarding the value of PET/MRI, the current literature in this field is sparse and insufficient for a systematic analysis. This article, therefore, highlights available evidence and future perspectives of PET/MRI for the initial diagnosis, staging, and restaging of prostate cancer with choline-based radiotracers as well as ligands to target prostate-specific membrane antigen.

Timeliness of lung cancer care in Victoria: a retrospective cohort study.

To assess factors associated with second-line delays in the management of patients diagnosed with lung cancer. A retrospective cohort study, conducted in six public and two private Victorian hospitals, of 1417 patients aged 18 years or more who were diagnosed between July 2011 and October 2014 with an incident case of lung cancer identified by International Classification of Diseases, 10th revision codes (C34.0-C34.9, Z85.1, Z85.2) on the basis of either a clinical or pathological diagnosis. Time intervals between referral, diagnosis and initial definitive management. The median time from referral to diagnosis was 15 days (interquartile range [IQR], 5-36); from diagnosis to initial definitive management, 30 days (IQR, 6-84); and from referral to initial definitive management, 53 days (IQR, 25-106). Factors that were significantly associated with delay between referral and initial definitive management include declining or not being referred to palliative care (hazard ratio [HR], v patients referred for palliation, 0.73; 95% CI, 0.62-0.86; P < 0.001), and being treated in a public hospital (HR, v patients managed in a private hospital, 0.55; 95% CI, 0.48-0.64; P < 0.001). The median time from referral to initial definitive management in public and private hospitals was 61 days (IQR, 35-118) and 30 days (IQR, 13-76) respectively; 48% of patients in public hospitals waited longer than the British National Health Service target of a maximum 62 days between referral and first definitive treatment. There are significant delays at various stages of the patient journey after referral for initial definitive management. Having a greater understanding of these delays will enable strategies to be developed that improve the timeliness of care for patients with lung cancer.

Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation - a follow-up study.

Non-functioning pituitary adenomas (NFA) are the commonest type of pituitary macroadenoma. Although the initial definitive management of these tumours is almost always trans-sphenoidal surgery, the use of postoperative radiotherapy remains controversial. Radiotherapy has been shown to significantly reduce the risk of tumour regrowth. An audit of patients with NFAs treated with trans-sphenoidal surgery without irradiation was performed at our centre five years ago, and suggested that careful selection and follow-up could avoid the need for adjuvant radiotherapy. We have repeated this audit to assess the longer term effects of this management strategy. The case notes and imaging of the original cohort of 65 of 73 patients (50 males, mean age 52) who had undergone trans-sphenoidal surgery (TSA) for NFA between July 1979 and 1992, had not received irradiation and were followed up by imaging were reviewed. Tumour regrowth was defined as enlargement of the pituitary tumour. Mean follow-up was 76 months (range 12-173). Pituitary tumour regrowth has occurred in 21 of the 65 patients (32%) during a mean follow-up of 76 months compared with 8/73 (11%) in 1994 (P = 0.002). The tumour regrowth was detected at a mean of 5.4 years (range 2-14 years). Lifetable analysis of the whole unirradiated group showed 82% recurrence free survival at 5 years (95% confidence limits 72-92%), and 56% at 10 years (95% confidence limits 38-74%). Eight (12%) patients required a second surgical procedure (6 TSA and 2 craniotomies). There was no relationship between recurrence and whether a total surgical removal was thought to have been performed. Despite careful selection of patients with non-functioning pituitary adenomas, tumour regrowth occurs in a significant proportion. These results show that continued follow-up in these patients is essential as significantly more patients showed evidence of tumour regrowth at this second assessment compared with the 1994 data. Until we are able to predict which tumours are likely to regrow postoperatively, radiotherapy should be considered for all patients with non-functioning pituitary adenomas as even in carefully selected cases, the regrowth rate is approaching 50% at 10 years.

On-line assurance in the initial definitive management of multiple trauma: evaluating system potential

The TraumAID system has been designed to provide on-line decision support throughout the initial definitive management of injured patients. Here we describe its retrospective evaluation and the use we subsequently made of judges comments on the validation data to evaluate TraumaTIQ, a new critiquing interface for TraumAID, investigating the question of whether, with timely recording of information, a system could produce commentary in line with that of human experts. Our results show that (1) comparable commentary can be produced, and (2) validation studies, which take great time and effort to conduct, can produce useful data beyond their original design goals.

Flexible support for trauma management through goal-directed reasoning and planning

We describe a system, TRAUMAID, which has been designed to provide decision support throughout the initial definitive management of severely injured patients (i.e. after their initial evaluation, resuscitation, and stabilization). Over the course of initial definitive management, TraumAID recommends appropriate procedures to be carried out, based on currently available evidence and on the complexity and urgency of the situation. TraumAID's ability to deal flexibly with complex and often urgent situations comes from its ability to reason separately about the management goals that should be achieved and about the means that are situationally appropriate for achieving them. In this paper, we describe TraumAID's approach to trauma management in more detail, showing in particular how it enables TraumAID to adapt its reasoning and recommendations to the urgency with which a patient's condition must be addressed.

Transnasal permanent interstitial implantation for carcinoma of the nasopharynx

A technique for transnasal permanent interstitial implantation of the nasopharynx with 125I seeds is described. This technique allows the precise placement of radioactive sources into mucosal and submucosal tumors, without the need for palatal fenestration. Preliminary results in 10 patients treated by this technique for recurrent nasopharyngeal carcinoma are presented. In the future we also hope to employ this technique for delivering “boost” irradiation to the primary site, in the initial definitive management of carcinoma of the nasopharynx.

Permanent iodine-125 implants in head and neck cancer

One hundred twenty-four patients were treated with advanced recurrent head and neck cancer for palliation with radioactive permanent Iodine-125 (125I) implants. Complete regression occurred in 71% of the 118 lesions for which evaluation was possible and greater than 50% regression occurred in 18%; no meaningful regression occurred in 11%. Local recurrence of cancer was subsequently seen in 21% of the lesions which had regressed completely, in 55% of those which had regressed incompletely, and in 100% of those which had not regressed. The incidence of serious complications was 5.5%. Overall, in 64% of the instances the implanted lesions remained controlled until the patient's death, usually due to progression of cancer elsewhere in the body. It is concluded that permanent 125I implants offer useful palliation to the patient with recurrent head and neck cancer with a minimum of toxicity and inconvenience. Because of their low toxicity even after prior full-course external radiation therapy, the authors are currently investigating their use as planned adjunct to external radiation therapy and chemotherapy in the initial definitive management of patients with locally advanced head and neck cancer.