Current endodontic practice and use of newer technologies in Australia and New Zealand.

BACKGROUND: This study investigated endodontic clinical preferences, adoption of newer technologies and information sources among dentists and endodontists. METHODS: Dental and endodontic society members in Australia and New Zealand were surveyed online regarding their endodontic treatment preferences, armamentarium, information sources and continuing professional education (CPE) attendance. RESULTS: Complete responses were received from 71 endodontic specialists or postgraduates (Group E) and 139 general dentists (Group D). Most of Group E used dental operating microscopes (95.8%), endodontic cone-beam computed tomography (CBCT; 98.6%) and calcium silicate-based materials (CSBMs; 97.2%), significantly more (P < 0.001) than Group D (86.3% used loupes, <32% used CBCT for endodontics or CSBMs). Most respondents used dental dam always for endodontics (94.3%), electronic apex locators (EAL; 81.0%) and engine-driven nickel-titanium (NiTi) instruments (91.4%); Group E had more experience with engine-driven NiTi (P < 0.001). Endodontic CPE attendance was highest at dental association programs (P < 0.001) while hands-on NiTi training attendance was highest via commercial companies (P < 0.05). Online information sources were commonly used (38.8% of Group D, 59.2% of Group E). CONCLUSION: Dental dam, EAL and engine-driven NiTi were almost universally used. The endodontic group reported high adoption of newer endodontic technologies. Endodontic CPE and information sources should be further surveyed as online engagement evolves. © 2023 Australian Dental Association.

Hopes and fears regarding care robots: Content analysis of newspapers in East Asia and Western Europe, 2001-2020.

Background: As a type of welfare technology, care robotics is now widely seen as a potential aide to rehabilitation, increasing independence and enhancing the wellbeing of people with disabilities and older adults. Research into and development of care robots have both been vigorously promoted in North America, Europe and Asia, and the competition for technological advancement in robotics is becoming fierce. AI ethics and policy guidelines are being established. However, there are still differences in attitudes and perceptions, as well as national policies regarding this type of welfare technology. Moreover, despite the anticipated usefulness, it is believed that progress has been slow in the diffusion of care robots. Purpose: In order to explore how public discourses support technological innovation, such as care robots, while preparing society for potential risks and impact, we sought to ascertain whether public discourse on care robots varies from region to region. For example, what are the hopes and promises associated with care robots and what are the concerns? Methods: To address these questions, this article explored how care robots have been portrayed in five major broadsheet newspapers in five jurisdictions in Asia and Europe (France, Great Britain, Hong Kong SAR, Ireland and Japan). We obtained 545 articles for the period between January 2001 and September 2020, more than half of which originated in Japan. A thematic analysis was conducted of these articles written in four languages (Chinese, English, French and Japanese). Results: Positive and negative narratives were teased out, alongside other key prominent themes identified, such as Japan as the land of robots, the pandemic, and the impact of robots on the economy. As the number of robot-related articles grew from the year 2012 onwards, narratives became more nuanced in European newspapers, but not in Asian ones. Furthermore, recent articles began to address the social and relational impact of care robots, while providing concrete examples of improvements in the quality of life for users. Further careful examination will be necessary in the future in order to establish the impact of robotics use in rehabilitation for people with disabilities, older adults, their carers and society at large.

Dentists' preferences in implant maintenance and hygiene instruction.

BACKGROUND: This study investigated the preferences of dentists in Australia in providing professional implant maintenance and implant-specific oral hygiene instructions (OHI). METHODS: General dentists were surveyed online about their preferences in peri-implant diagnostics, maintenance provision, armamentarium used, and implant OHI techniques and frequency. RESULTS: Most of the 303 respondents (96%) provided maintenance services; 87.6% reviewed implants regularly while 10.7% only performed diagnostics after detecting clinical signs/symptoms. Supragingival prosthesis cleaning was performed by 77.9% of respondents, 35.0% performed subgingival debridement, 41.9% treated peri-implant mucositis and 18.2% treated peri-implantitis. About 15% did not treat nor refer peri-implant disease, including significantly more non-implant providers and dentists without implant training. Maintenance armamentarium commonly included floss (76.3%), prophylaxis (73.9%), plastic curettes (43.3%) and stainless-steel ultrasonics (38.0%). Brushing (86.5%), flossing (73.9%) and interdental brush use (68.3%) were most commonly recommended. Implant OHI was repeated routinely by 57.4% of dentists who provided it. Dentists with greater implant training and experience were more likely to perform reviews and complex maintenance procedures. CONCLUSIONS: Peri-implant diagnostics performed, treatments provided and armamentarium varied among dentists. Implant providers and those with higher levels of training had more preventative approaches to implant OHI. Possible shortcomings in disease management and OHI reinforcement were identified.

Reimbursement recommendations for cancer drugs supported by phase II evidence in Canada.

Background: Phase ii data are increasingly being used as primary evidence for public reimbursement for oncologic drugs. We compared the frequency of reimbursement recommendations for phase ii and phase iii submissions and assessed for variables associated with a positive or conditional recommendation. Methods: We identified submissions made to the pan-Canadian Oncology Drug Review's Expert Review Committee (perc), of the Canadian Agency for Drugs and Technologies in Health, July 2011 to July 2019, that were supported only by phase ii data. We identified variables within the perc's deliberative framework, including clinical and economic factors, associated with the final reimbursement recommendation. We conducted a multivariable analysis with logistic regression for these variables: feasibility of phase iii study, hematologic indication, and unmet need. Results: We identified 139 submissions with a perc final recommendation. In 27 instances (19%), the submission had only phase ii evidence, and a positive recommendation was issued for 63% of them (the positive recommendation rate was 82% for submissions with phase iii evidence). Clinical benefit (p < 0.001), unmet need (p = 0.047), and patient alignment (p = 0.015) were associated with a positive recommendation. If a future phase iii study was deemed feasible for submissions with only phase ii evidence, then in univariable (p = 0.040) and multivariable analysis (p = 0.024), the perc was less likely to recommend reimbursement (odds ratio: 0.132). Conclusions: Although more than half the oncologic submissions with phase ii data were recommended for public reimbursement, compared with submissions having phase iii data, they were less likely to be recommended. A positive or conditional recommendation was more likely if clinical benefit and alignment with patient values was demonstrated. The perc was less likely to recommend reimbursement for submissions with phase ii evidence if a phase iii trial was deemed possible.

The generation of two specific cancer costing algorithms using Ontario administrative databases.

Cancer treatment and management have become increasingly economically burdensome. Consequently, to help with planning health service delivery, it is vital to understand the associated costs. Administrative databases can be used to help understand and generate real-world system-level costs. Using databases to generate costs can take one of two approaches: top-down or bottom-up. Top-down approaches disaggregate the total health care spending from a global health care budget by sector and provider. A bottom-up approach begins with individual-level health care use and its costs, which are then aggregated.

Implant education patterns and clinical practice of general dentists in Australia.

BACKGROUND: This study aimed to understand trends in dentists' implant training attendance and correlation to treatment provision. Implant-specific oral hygiene instruction coverage in training programs was investigated. METHODS: A cross-sectional web-survey of dentists registered in Australia was conducted. Respondents were asked about their background, implant training history and treatment provision. Results were analysed by implant provision characteristics and graduation decade. RESULTS: Three hundred and three responses from general dental practitioners (GDPs) were received and analysed. The highest implant training levels attained post-graduation were postgraduate non-specialist qualification (7.9% of respondents), continuing professional development (CPD) (73.6%) versus none (18.5%), with differences between implant providers and non-providers (P < 0.001), different graduation decades (P < 0.001) and those restoring implants or performing surgery as well (P < 0.001). University-based CPD was attended less than dental association/society or implant company CPD. Non-providers were significantly less likely to recall implant oral hygiene instruction sources (P < 0.001). Most GDPs (74.9%) provided implant services, with younger GDPs beginning earlier after graduation. About 16% of respondents did not provide implants once established career-wise. CONCLUSIONS: Dentists might be providing implant treatments increasingly earlier in their careers. Respondents with more training were significantly more likely to perform more complex procedures, while implant training attendance trends varied by graduation decade.

Tropism of influenza B viruses in human respiratory tract explants and airway organoids.

Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract.Physiologically relevant ex vivo explant cultures of human bronchus and lung, human airway organoids, and in vitro cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included.The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs.Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.

Conditional approval of cancer drugs in Canada: accountability and impact on public funding.

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010-2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug-indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.

Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East Respiratory Syndrome Coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication. In both culture systems the combined treatment was more effective than either agent used alone in reducing MERS-CoV replication. PCR SuperArray analysis showed that the reduction of virus replication was associated with a greater induction of interferon stimulated genes. As these therapeutic agents are already licensed for clinical use, it may be relevant to investigate their use for therapy of human MERS-CoV infection.

Examining the medical resource utilization and costs of relapsed and refractory chronic lymphocytic leukemia in Ontario.

PURPOSE: The purpose of the present study was to collect medical resource utilization data and costs in Ontario for the management of patients with relapsed or refractory chronic lymphocytic lymphoma (cll) who have undergone at least 1 treatment course and have been stratified by Rai staging. METHODS: This retrospective longitudinal cohort study, conducted by chart review, analyzed anonymized patient records from two cancer centres in Ontario. Comprehensive records of 86 patients meeting the inclusion criteria were used to obtain resource utilization, which, multiplied by unit costs, were used to determine overall and mean costs. Descriptive statistics are presented for patient demographics, medical resource utilization, and costing data. RESULTS: The total cost for the cohort was $2.2 million over a mean follow-up period of 4.7 years. The mean total cost per patient (regardless of follow-up) was $25,736. In terms of Rai staging, overall mean costs were highest for stage iv patients. Almost 50% of the total cost was attributable to cll treatments, among which fludarabine-based treatments had the highest utilization. CONCLUSIONS: For this Canadian cll cohort, medical resource utilization and costs were determined to be $2.2 million, with cll treatments accounting for about half the cost. Costs generally increased with Rai stage.

Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: 'Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone'; 'chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma'; 'The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival'. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients' point of view.

Interest in dental implantology and preferences for implant therapy: a survey of Victorian dentists.

BACKGROUND: The purpose of this study was to gauge dentists' interest, knowledge and training in implantology, and to compare their treatment preferences with current literature. Subsequently, this information may be used to evaluate implantology education pathways. METHODS: A cross-sectional postal survey of 600 randomly selected dentists registered with the Dental Practice Board of Victoria was conducted. Respondents were asked about background, interest and training in implantology, and implant treatment preferences. Results were analysed according to primary practice location, decade of graduation and attendance at continuing professional development (CPD) programmes. RESULTS: One hundred and seventy-six questionnaires were included for analysis. In general, dentists rate their implant knowledge, interest and enjoyment in restoring implants favourably. No differences were found between city and country practitioners, and different graduation decades. The level of CPD significantly influenced treatment preferences. Practitioners were generally unwilling to treat patients taking bisphosphonates, or to perform grafting procedures. Most dentists provide common services to treat peri-implant conditions. Direct-to-fixture is the most popular fixture-abutment connection. CONCLUSIONS: Overall, there is a high level of implant knowledge corresponding to current evidence in the literature. Level of CPD attendance is the most important factor in dentists' willingness to provide more implant therapy options.

Granulocyte colony-stimulating factor in secondary prophylaxis for advanced-stage Hodgkin lymphoma treated with ABVD chemotherapy: a cost-effectiveness analysis.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to patients with Hodgkin lymphoma (HL) with neutropenia. We constructed a decision-analytic model to compare the cost-effectiveness of secondary prophylaxis with G-CSF to a strategy of 'no G-CSF' in response to severe neutropenia for adults with advanced-stage HL treated with ABVD. A Canadian public health payer's perspective was considered and costs were presented in 2013 Canadian dollars. The quality-adjusted life years (QALYs) attained with the G-CSF and 'no G-CSF' strategies were 1.403 and 1.416, respectively. Costs for the strategies with and without G-CSF were $38,971 and $33,982, respectively. In the base case analysis, the 'no G-CSF' strategy was associated with cost savings and improved QALYs; therefore, 'no G-CSF' was the dominant approach. For patients with severe neutropenia during ABVD chemotherapy for advanced-stage HL, a strategy without G-CSF support is associated with improved quality-adjusted outcomes, cost savings, and is the preferred approach.

The experiences of cancer survivors while transitioning from tertiary to primary care.

PURPOSE: In current fiscally constrained health care systems, the transition of cancer survivors to primary care from tertiary care settings is becoming more common and necessary. The purpose of our study was to explore the experiences of survivors who are transitioning from tertiary to primary care. METHODS: One focus group and ten individual telephone interviews were conducted. Data saturation was reached with 13 participants. All sessions were audio-recorded, transcribed verbatim, and analyzed using a qualitative descriptive approach. RESULTS: Eight categories relating to the main content category of transition readiness were identified in the analysis. Several factors affected participant transition readiness: how the transition was introduced, perceived continuity of care, support from health care providers, clarity of the timeline throughout the transition, and desire for a "roadmap." Although all participants spoke about the effect of their relationships with health care providers (tertiary, transition, and primary care), their relationship with the primary care provider had the most influence on their transition readiness. CONCLUSIONS: Our study provided insights into survivor experiences during the transition to primary care. Transition readiness of survivors is affected by many factors, with their relationship with the primary care provider being particularly influential. Understanding transition readiness from the survivor perspective could prove useful in ensuring patient-centred care as transitions from tertiary to primary care become commonplace.

Impact of country-specific EQ-5D-3L tariffs on the economic value of systemic therapies used in the treatment of metastatic pancreatic cancer.

BACKGROUND: Previous Canadian cost-effectiveness analyses in cancer based on the EQ-5D-3L (EuroQoL, Rotterdam, Netherlands) have commonly used U.K. or U.S. tariffs because the Canadian equivalent only just recently became available. The implications of using non-Canadian tariffs to inform decision-making are unclear. We aimed to reevaluate an earlier cost-effectiveness analysis of therapies for metastatic pancreatic cancer (originally performed using U.S. tariffs) with tariffs from Canada and various other countries to determine the impact of using non-country-specific tariffs. METHODS: We used tariffs from Canada, the United States, the United Kingdom, Denmark, France, Germany, Japan, the Netherlands, and Spain to derive EQ-5D-3L utilities for the 10 health states in the pancreatic cancer model. Quality-adjusted life years (qalys) and incremental cost-effectiveness ratios (icers) were generated, and probabilistic sensitivity analyses (psas) were performed. RESULTS: Canadian utilities are generally lower than the corresponding U.S. utilities and higher than those for the United Kingdom. Compared with the Canadian-valued scenarios, U.S. and U.K. estimates were statistically different for 3 and 9 scenarios respectively. Overall, 35% of the non-Canadian utilities (28 of 80) were significantly different, clinically, from the Canadian values. Canadian qalys were 6% lower than those for the United States and 6% higher than those for the United Kingdom. When comparing the qalys of each treatment with those of gemcitabine alone, the average percent change was +6.8% for a U.S. scenario and -7.5% for a U.K. scenario compared with a Canadian scenario. Consequently, Canadian icers were approximately 5.4% greater than those for the United States and 8.6% lower than those for the United Kingdom. Based on the psas and compared with the Canadian threshold value, the minimum willingness-to-pay threshold at which the combination chemotherapy regimen of gemcitabine-capecitabine is the most cost-effective is $5,239 less than in the United States and $11,986 more than in the United Kingdom. CONCLUSIONS: The use of non-country-specific tariffs leads to significant differences in the derived utilities, icers, and psa results. Past Canadian EQ-5D-3L-based cost-effectiveness analyses and related funding decisions might need to be re-visited using Canadian tariffs.

A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Prolonged clinical remissions in patients with relapsed or refractory follicular lymphoma treated with autologous stem cell transplantation incorporating rituximab.

Three sequential phase II trials were conducted with different immunotherapy approaches to enhance the outcome of autologous transplant (high-dose therapy and autologous stem cell transplantation (HDT/ASCT)) for recurrent follicular lymphoma. Seventy-three patients were enrolled from 1996 to 2009. Patients received HDT/ASCT combined with (1) interferon-α 3 MU/m(2) subcutaneously (SC) three times per week (TIW) for 2 years post-ASCT, (2) rituximab (R) 375 mg/m(2) for in vivo purging 3-5 days pre-stem cell collection and 2 × 4 weekly R at 2 and 6 months post-ASCT, respectively, or (3) three infusions of R pre-stem cell collection followed by 6× R weekly and interferon-α 3 MU/m(2) SC TIW. Although not statistically significant, progression-free survival (PFS) for patients who received rituximab was 56.4 and 49.1% at 5 and 10 years compared to 36 and 21% in those who did not receive rituximab. Molecular relapse post-HDT/ASCT was the strongest predictor of PFS in a multivariate analysis. Molecular relapse was coincident with or preceded clinical relapses in 84% of patients who relapsed­median of 12 months (range 0-129 months). Adverse events included secondary malignancy, transformation to diffuse large B cell lymphoma, prolonged mostly asymptomatic hypogammaglobulinemia, and pulmonary fibrosis. The long-term toxicity profile must be considered when selecting patients for this treatment.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

Bortezomib in multiple myeloma: systematic review and clinical considerations.

We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We searched medline, embase, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult mm patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects. Twenty-six unique studies met the inclusion criteria. For patients with previously untreated mm and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (hr): 0.48, p < 0.001; and hr: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (hr compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016). In relapsed or refractory mm, overall survival (p = 0.03), time to progression (hr: 1.82; p = 0.000004), and progression-free survival (hr: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (hr: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001). In previously untreated or in relapsed or refractory mm patients, bortezomib-based therapy has improved disease control and, in some patients, overall survival.

Bortezomib in multiple myeloma: a practice guideline.

AIMS: Bortezomib (Velcade™, PS-341), a first-in-class proteasome inhibitor, has been extensively studied either alone or in combination with other agents for the treatment of multiple myeloma. We created a provincial guideline for the use of bortezomib, in newly diagnosed individuals (both eligible and ineligible for transplant) and in individuals with relapsed or refractory multiple myeloma. MATERIALS AND METHODS: A systematic review was conducted searching MEDLINE, EMBASE, the Cochrane Library and relevant meeting abstracts. Outcomes of interest were survival, disease control, response rate, response duration, quality of life and adverse effects. Members of the Cancer Care Ontario Hematology Disease Site Group (CCO HDSG), comprising physicians with content expertise, epidemiologists and consumers, developed a guideline through a systematic process that involved assessment of the best available evidence, consensus interpretation of the evidence and a validation process involving practitioners across the province. RESULTS: The CCO HDSG recommends the use of bortezomib-based combinations in previously untreated patients with multiple myeloma who are candidates for autologous stem cell transplantation and in individuals who are ineligible for autologous stem cell transplantation. The group further recommends the use of bortezomib, alone or in combination, for patients with relapsed/refractory disease. The evidence did not establish a subgroup of patients with myeloma that should be uniquely targeted for therapy with bortezomib. Qualifying statements by the HDSG address alternative dosing options, the management of cytopenias and the prevention of toxicities, including herpes zoster reactivation. CONCLUSIONS: Bortezomib alone or in combination with other agents can be recommended for both previously untreated or relapsed/refractory patients with multiple myeloma. Guidelines for monitoring and reducing toxicity are provided.