Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

How physiotherapists attend to the human aspects of care when working with people with low back pain: a thematic analysis.

Pain is a multidimensional experience. Physiotherapy has attempted to enhance earlier biomedical approaches to patient care through approaches like the 'biopsychosocial' model. Nevertheless, physiotherapy continues to focus on biomedical and/or behavioural aspects of care. We critically investigated how physiotherapists attend to human (psychosocial, emotional, existential, and moral) aspects of low back pain care. We co-analysed ethnographic data with researchers, patients, and physiotherapists using concepts of conforming, tinkering and abandoning 'scripts'. Data included observations of 28 physiotherapy interactions between 26 patients and 10 physiotherapists and 7 researcher-clinician dialogues. Analysis suggests when conforming to scripts, clinicians have difficulty recognising and responding to emotions; time pressure limited clinicians focus, and a biological focus often distracted from psychosocial aspects of people's back pain experiences. In contrast, tinkering with or abandoning scripts allowed space to broaden the focus. Drawing from theorists such as Butler (1999) and Gibson et al. (2020) our analysis contributes to health sociology, arguing that 'tinkering' with or 'abandoning' scripts can foster more humanistic, flexible and reflexive approaches to care. Although health sociologists have explored tinkering, abandoning is new; within physiotherapy, it encapsulates being able to respond with agility to non-physical elements of care without constraint from traditional ways of thinking and doing.

Uncertainty in low back pain care - insights from an ethnographic study.

PURPOSE: To explore how uncertainty plays out in low back pain (LBP) care and investigate how clinicians manage accompanying emotions/tensions. MATERIALS AND METHODS: We conducted ethnographic observations of clinical encounters in a private physiotherapy practice and a public multidisciplinary pain clinic. Our qualitative reflexive thematic analysis involved abductive thematic principles informed by Fox and Katz (medical uncertainty) and Ahmed (emotions). RESULTS: We identified three themes. (1) Sources of uncertainty: both patients and clinicians expressed uncertainty during clinical encounters (e.g., causes of LBP, mismatch between imaging findings and presentation). Such uncertainty was often accompanied by emotions - anger, tiredness, frustration. (2) Neglecting complexity: clinicians often attempted to decrease uncertainty and associated emotions by providing narrow answers to questions about LBP. At times, clinicians' denial of uncertainty also appeared to deny patients the right to make informed decisions about treatments. (3) Attending to uncertainty?: clinicians attended to uncertainty through logical reasoning, reassurance, acknowledgement, personalising care, shifting power, adjusting language and disclosing risks. CONCLUSIONS: Uncertainty pervades LBP care and is often accompanied by emotions, emphasising the need for a healthcare culture that recognises the emotional dimensions of patient-clinician interactions and prepares clinicians and patients to be more accepting of, and clearly communicate about, uncertainty.IMPLICATIONS FOR REHABILITATIONUncertainty pervades LBP care and is often accompanied by emotions.Neglecting complexity in LBP care may compromise person-centred care.Acknowledging uncertainty can enhance communication, balance patient-clinician relationships and address human aspects of care.

Validation of the Prognostic Utility of ESTRO/EORTC Oligometastatic Disease Classification: A Secondary Analysis From the Population-Based Phase II SABR-5 Trial.

PURPOSE: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme. METHODS AND MATERIALS: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling. RESULTS: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS. CONCLUSIONS: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required.

The Effect of Breast Cancer Subtype on Symptom Improvement Following Palliative Radiotherapy for Bone Metastases.

AIM: To assess the relationship between breast cancer subtypes and patient-reported outcomes (PRO) following palliative radiotherapy for bone metastases. MATERIALS AND METHODS: Prospectively collected PRO for all breast cancer patients treated with palliative, bone metastasis-directed radiotherapy from 2013 to 2016 in the province of British Columbia were analysed. The PRO questionnaire scored pain severity, level of function and symptom frustration at baseline and at 3-4 weeks following palliative radiotherapy using a 12-point scale. The primary outcome was the rate of overall response (any improvement in score); the secondary outcome was the rate of complete improvement in PRO (final PRO score of 0). Multivariate logistic analysis was used to compare response rates between molecular subgroup approximations of luminal A (LumA), luminal B (LumB), HER2-enriched (HER2) and triple negative (TN), as defined by grade and immunohistochemical staining. RESULTS: There were 376 patients who underwent 464 courses of palliative radiation for bone metastases. Subtypes included: 243 LumA, 146 LumB, 46 HER2 and 29 TN. There were 216 multifraction radiotherapy courses (median dose 20 Gy) and 248 single-fraction radiotherapy courses (median dose 8 Gy). The overall response rate was 85% and the complete response rate was 25%. In comparison with LumA breast cancers, TN breast cancers were associated with a lower rate of overall response (69% versus 86%, P = 0.021) and a lower rate of complete response (10% versus 28.8%, P = 0.045) on multivariate analyses. CONCLUSION: Patients with TN breast cancer have lower rates of pain, function and symptom frustration improvement following palliative radiation for bone metastases.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Spine and Non-spine Bone Metastases - Current Controversies and Future Direction.

Bone is a common site of metastases in advanced cancers. The main symptom is pain, which increases morbidity and reduces quality of life. The treatment of bone metastases needs a multidisciplinary approach, with the main aim of relieving pain and improving quality of life. Apart from systemic anticancer therapy (hormonal therapy, chemotherapy or immunotherapy), there are several therapeutic options available to achieve palliation, including analgesics, surgery, local radiotherapy, bone-seeking radioisotopes and bone-modifying agents. Long-term use of non-steroidal analgesics and opiates is associated with significant side-effects, and tachyphylaxis. Radiotherapy is effective mainly in localised disease sites. Bone-targeting radionuclides are useful in patients with multiple metastatic lesions. Bone-modifying agents are beneficial in reducing skeletal-related events. This overview focuses on the role of surgery, including minimally invasive treatments, conventional radiotherapy in spinal and non-spinal bone metastases, bone-targeting radionuclides and bone-modifying agents in achieving palliation. We present the clinical data and their associated toxicity. Recent advances are also discussed.

A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

Observation of persistent species temperature separation in inertial confinement fusion mixtures.

The injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.

The role of multiple ionization of H2O in heavy ion collisions.

Collisional ionization processes involving H2O molecules and C6+, O8+, Si13+ ions are studied by means of the classical trajectory Monte Carlo method using molecular orbital calculations to define the ionization stages of the water molecule. Net total and single-differential cross sections in energy and angle are obtained by using a newly developed model that goes beyond the commonly applied one-active electron approximation. This model allows us to access the fraction of electron emission arising from single and multiple electron ionization. Calculated cross sections are contrasted and benchmarked against available experimental data at impact energies in the MeV/u range. The present results highlight the important role of multiple ionization in the emission of electrons where we find the majority of electrons emitted with energies greater than ~50 eV arise from multiple ionization collisions.

A novel method to test non-exclusive hypotheses applied to Arctic ice projections from dependent models.

A major conundrum in climate science is how to account for dependence between climate models. This complicates interpretation of probabilistic projections derived from such models. Here we show that this problem can be addressed using a novel method to test multiple non-exclusive hypotheses, and to make predictions under such hypotheses. We apply the method to probabilistically estimate the level of global warming needed for a September ice-free Arctic, using an ensemble of historical and representative concentration pathway 8.5 emissions scenario climate model runs. We show that not accounting for model dependence can lead to biased projections. Incorporating more constraints on models may minimize the impact of neglecting model non-exclusivity. Most likely, September Arctic sea ice will effectively disappear at between approximately 2 and 2.5 K of global warming. Yet, limiting the warming to 1.5 K under the Paris agreement may not be sufficient to prevent the ice-free Arctic.

Metabolic tumour volume is prognostic in patients with non-small-cell lung cancer treated with stereotactic ablative radiotherapy.

Introduction: Stereotactic ablative radiotherapy (sabr) is a relatively new technique for the curative-intent treatment of patients with inoperable early-stage non-small-cell lung cancer (nsclc). Previous studies have demonstrated a prognostic value for positron emission tomography-computed tomography (pet/ct) parameters, including maximal standardized uptake value (suvmax), metabolic tumour volume (mtv), and total lesion glycolysis (tlg) in lung cancer patients. We aimed to determine which pet/ct parameter is most prognostic of local control (lc) and overall survival (os) in patients treated with sabr for nsclc. Methods: We conducted a retrospective review of patients treated with sabr for stage I inoperable nsclc at BC Cancer between 2009 and 2013. The Akaike information criterion was used to compare the prognostic value of the various pet/ct parameters. Results: The study included 134 patients with a median age of 76 years. Median tumour diameter was 2.2 cm, gross tumour volume was 8.1 mL, suvmax was 7.9, mtv was 2.4 mL, and tlg was 10.9 suv·mL. The 2-year lc was 92%, and os was 66%. On univariate and multivariate analysis, imaging variables including tumour size, gross tumour volume, suvmax, mtv, and tlg were all associated with worse lc. Tumour size was not associated with significantly worse os, but other imaging variables were. The pet/ct parameter most prognostic of lc was mtv. Compared with suvmax, tlg and mtv were more prognostic of os. Conclusions: In patients with early-stage nsclc treated with sabr, mtv appears to be prognostic of lc and os.

Prescribing practices of endocrine therapy for ductal carcinoma in situ in British Columbia.

Purpose: The mainstay of treatment for ductal carcinoma in situ (dcis) involves surgery in the form of mastectomy or lumpectomy. Inconsistency in the use of endocrine therapy (et) for dcis is evident worldwide. We sought to assess the variation in et prescribing for patients with dcis across a population-based radiotherapy (rt) program and to identify variables that predict its use. Methods: Data from a breast cancer database were obtained for women diagnosed with dcis in British Columbia from 2009 to 2014. Associations between et use and patient characteristics were assessed by chi-square test and multilevel multivariate logistic regression. The Kaplan-Meier method, with propensity score matching and Cox regression analysis, was used to assess the effects of et on overall survival (os) and relapse-free survival (rfs). Results: For the 2336 dcis patients included in the study, et use was 13% in dcis patients overall, and 17% in patients with estrogen receptor-positive (er+) tumours treated with breast-conserving surgery and rt. Significant variation in et use by treatment centre was observed (range: 8%-23%; p < 0.001), and prescription of et by individual oncologists varied in the range 0%-40%. After controlling for confounding factors, age less than 50 years [odds ratio (or): 1.72; p = 0.01], treatment centre, er+ status (or: 5.33; p < 0.001), and rt use (or: 1.77; p < 0.001) were significant predictors of et use. No difference in os or rfs with the use of et was observed. Conclusions: In this population-based analysis, 13% of patients with dcis in British Columbia received et, with variation by treatment centre (8%-23%) and individual oncologist (0%-40%). Age less than 50 years, er+ status, and rt use were most associated with et use.

Factors affecting radiotherapy prescribing patterns in the post-mastectomy setting.

Background: Radiation therapy (rt) after mastectomy for breast cancer can improve survival outcomes, but has been associated with inferior cosmesis after breast reconstruction. In the literature, rt dose and fractionation schedules are inconsistently reported. We sought to determine the pattern of rt prescribing practices in a provincial rt program for patients treated with mastectomy and reconstruction. Methods: Women diagnosed with stages 0-iii breast cancer between January 2012 and December 2013 and treated with curative-intent rt were identified from a clinicopathology database. Patient demographic, tumour, and treatment information were extracted. Of the identified patients, those undergoing mastectomy were the focus of the present analysis. Results: Of 4016 patients identified, 1143 (28%) underwent mastectomy. The patients treated with mastectomy had a median age of 57 years, and 37% of them underwent reconstruction. Treatment with more than 16 fractions of rt was associated with autologous reconstruction [odds ratio (or): 37.2; 95% confidence interval (ci): 11.2 to 123.7; p < 0.001], implant reconstruction (or: 93.3; 95% ci: 45.3 to 192.2; p < 0.001), and treating centre. Hypofractionated treatment was associated with older age (or: 0.94; 95% ci: 0.92 to 0.96; p < 0.001), and living more than 400 km from a treatment centre (or: 0.37; 95% ci: 0.16 to 0.86; p = 0.02). Conclusions: Prescribing practices in breast cancer patients undergoing mastectomy are influenced by reconstruction intent, age, nodal status, and distance from the treatment centre. Those factors should be considered when making treatment decisions.

Assessing post-radiotherapy handover notes from a family physician perspective.

BACKGROUND: Across our province, post-radiotherapy (rt) handover notes are sent to family physicians (fps) after rt. Based on previous fp feedback, we created a revised post-radiotherapy handover note with more information requested by fps. The purpose of this study was to determine whether the revised handover note improved the note as a communication aid. METHODS: Potential common and rare treatment side effects, oncologist contact information, and treatment intent were added to the revised handover note. Both versions were sent alongside a questionnaire to fps. Paired t-tests were carried out to compare satisfaction differences. RESULTS: There was a response rate of 37% for the questionnaires. Significantly greater clarity in the following categories was observed: responsibility for patient follow-up (mean score improvement of 1.2 on a 7-point Likert scale, p < 0.001), follow-up schedule (1.1, p < 0.001) as well as how and when to contact the oncologist (1.4, p = 0.001). Family physicians were also more content with how the institute transitioned care back to them (1.5, p = 0.012). Overall, fps were generally satisfied with the content of the revised post-rt handover note and noted improvement over the previous version. The frequency of investigations and institute supports initiated such as counselling services were suggested further additions. CONCLUSIONS: The inclusion of potential treatment side effects, oncologist contact information, treatment intent and a well-laid out follow-up schedule were essential information needed by fps for an effective post-rt completion note. With these additions, the revised post-rt handover note showed significant improvement.

Patient-reported outcome use in oncology: a systematic review of the impact on patient-clinician communication.

PURPOSE: Patient-reported outcomes (PROs) are an increasingly popular tool to optimize care and bridge the gap between patient experience and clinician understanding. The aim of this review was to identify mechanisms through which PROs facilitate patient-clinician communication in the adult oncology population. METHODS: We conducted a systematic review of the published literature using the following data sources: MEDLINE, EMBASE, CINAHL, PsycINFO, Cab Direct, and CDSR. Studies included in this review reported on the outcomes of PRO use, used PROs as an intervention and not as a study outcome measurement tool, included cancer patients or survivors as study participants, and analyzed patient-clinician communication. RESULTS: We identified 610 unique records, of which 43 publications met the inclusion and exclusion criteria. Synthesis of the reviewed studies provided evidence of the usefulness of PROs in facilitating patient-clinician communication on a variety of topics. We identified mechanisms though which PROs influenced patient-clinician communication to include increasing symptom awareness, prompting discussion, streamlining consultations, and facilitating inter-professional communication. Barriers to PRO use in communication improvement include technical problems impeding its administration and completion, compliance issues due to lack of incentive or forgetfulness, and use of PROs that do not appropriately assess issues relevant to the patient. Facilitators include increased education on PRO use, using PRO tools that patients find more acceptable, and providing patient data summaries in an easily accessible format for clinicians. CONCLUSIONS: Our review suggests that PROs facilitate patient-clinician communication through various mechanisms that could perhaps contribute to improvements in symptom management and survival. The impact of PROs on clinical outcomes, however, remains poorly studied.

Neoadjuvant systemic therapy in breast cancer: use and trends in radiotherapy practice.

BACKGROUND: The use of neoadjuvant systemic therapy (nast) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (rt) in that setting is uncertain. We sought to review and report the use of nast, its trends over time, and its relationship with the prescribing patterns of locoregional rt in a provincial cancer system. METHODS: Patients with stages i-iii breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of nast. Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received nast. Use of nast was more frequent in stage iii patients (53%) than in stages i and ii patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of nast and of nodal rt after nast, but pathologic nodal status after nast was not associated with use of nodal rt. A statistically significant survival difference was observed between patients in the nast and no-nast groups, but that significance disappeared in a multivariable Cox regression analysis. CONCLUSIONS: This population-based study demonstrated 5% use of nast for breast cancer. Most patients received nodal rt after nast, and nodal rt was not associated with pathologic stage after nast. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature.

Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial.

OBJECTIVE: Evaluate the efficacy and safety/tolerability of cryoneurolysis for reduction of pain and symptoms associated with knee osteoarthritis (OA). DESIGN: Randomized, double-blind, sham-controlled, multicenter trial with a 6-month follow-up in patients with mild-to-moderate knee OA. Patients were randomized 2:1 to cryoneurolysis targeting the infrapatellar branch of the saphenous nerve (IPBSN) or sham treatment. The primary endpoint was the change from baseline to Day 30 in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score adjusted by the baseline score and site. Secondary endpoints, including visual analogue scale (VAS) pain score and total WOMAC score, were tested in a pre-defined order. RESULTS: The intent-to-treat (ITT) population consisted of 180 patients (n = 121 active treatment, n = 59 sham treatment). Compared to the sham group, patients who received active treatment had a statistically significant greater change from baseline in the WOMAC pain subscale score at Day 30 (P = 0.0004), Day 60 (P = 0.0176), and Day 90 (P = 0.0061). Patients deemed WOMAC pain responders at Day 120 continued to experience a statistically significant treatment effect at Day 150. Most expected side effects were mild in severity and resolved within 30 days. The incidence of device- or procedure-related adverse events was similar in the two treatment groups with no occurrence of serious or unanticipated adverse device effects (ADE). CONCLUSIONS: Cryoneurolysis of the IPBSN resulted in statistically significant decreased knee pain and improved symptoms compared to sham treatment for up to 150 days, and appeared safe and well tolerated.