StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the overall efficacy of StrataXRT, a topical gel dressing, in preventing acute radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy (RT). METHODS: A systematic search was conducted on April 25, 2023 in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing the effectiveness of StrataXRT in preventing acute RD in breast cancer patients undergoing adjuvant RT to the breast or chest wall with or without regional nodes were included. Pooled incidence odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model, with analysis and forest plots generated in RevMan v5.4. RESULTS: The analysis included three RCTs with a total of 189 patients assessed using per-protocol analysis. Two RCTs compared StrataXRT to standard of care, while the third compared it with Mepitel film and was reported separately. In the former RCTs, the odds ratio (OR) for developing acute grade 3 RD favored StrataXRT at 0.05 (95% CI, 0.01-0.22; P < 0.0001). The OR for developing acute grades 2-3 RD was 0.32 (95% CI, 0.03-3.18; P = 0.33). The RCT comparing StrataXRT with Mepitel film showed insignificant ORs for grade 3 and grades 2-3 RD. One RCT reported significantly lower erythema index (P = 0.008) and melanin index (P = 0.015) in StrataXRT patients. The use of StrataXRT did not raise additional safety concerns. CONCLUSION: StrataXRT may help prevent severe acute RD in breast cancer RT patients. Further high quality, large-scale studies are needed to confirm these findings.

Photobiomodulation therapy for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Approximately 95% of patients undergoing radiotherapy (RT) experience radiation dermatitis (RD). Evidence has suggested that photobiomodulation therapy (PBMT) can stimulate skin renewal and minimize RD. The aim of the present paper was to investigate the efficacy of PBMT in RD prevention through a comprehensive literature review. METHODS: A literature search of Ovid MEDLINE, Embase, and Cochrane databases was conducted from 1980 to March 2021 to identify RCT on the use of PBMT for RD prevention. Forest plots were developed using RevMan software to quantitatively compare data between studies. RESULTS: Five papers were identified: four in breast and one in head and neck cancer patients. Patients receiving PBMT experienced less severe RD than the control groups after 40 Gray (Gy) of RT (grade 3 toxicity: Odds Ratio (OR): 0.57, 95% CI 0.14-2.22, p = 0.42) and at the end of RT (grade 0 + 1 vs. 2 + 3 toxicity: OR: 0.28, 95% CI 0.15-0.53, p < 0.0001). RT interruptions due to RD severity were more frequent in the control group (OR: 0.81, 95% CI 0.10-6.58, p = 0.85). CONCLUSION: Preventive PBMT may be protective against the development of severe grades of RD and reduce the frequency of RT interruptions. Larger sample sizes and other cancer sites at-risk of RD should be evaluated in future studies to confirm the true efficacy of PBMT, also in preventing the onset of RD and to finalize a standardized protocol to optimize the technique. At present, starting PBMT when RT starts is recommendable, as well as performing 2 to 3 laser sessions weekly.

Addressing antimicrobial resistance with the IDentif.AI platform: Rapidly optimizing clinically actionable combination therapy regimens against nontuberculous mycobacteria.

Background: Current standard of care (SOC) regimens against nontuberculous mycobacteria (NTM) usually result in unsatisfactory therapeutic responses, primarily due to multi-drug resistance and antibiotic susceptibility-guided therapies. In the midst of rising incidences in NTM infections, strategies to develop NTM-specific treatments have been explored and validated. Methods: To provide an alternative approach to address NTM-specific treatment, IDentif.AI was harnessed to rapidly optimize and design effective combination therapy regimens against Mycobacterium abscessus (M. abscessus), the highly resistant and rapid growth species of NTM. IDentif.AI interrogated the drug interaction space from a pool of 6 antibiotics, and pinpointed multiple clinically actionable drug combinations. IDentif.AI-pinpointed actionable combinations were experimentally validated and their interactions were assessed using Bliss independence model and diagonal measurement of n-way drug interactions. Results: Notably, IDentfi.AI-designed 3- and 4-drug combinations demonstrated greater %Inhibition efficacy than the SOC regimens. The platform also pinpointed two unique drug interactions (Levofloxacin (LVX)/Rifabutin (RFB) and LVX/Meropenem (MEM)) that may serve as the backbone of potential 3- and 4-drug combinations like LVX/MEM/RFB, which exhibited 58.33±4.99 %Inhibition efficacy against M. abscessus. Further analysis of LVX/RFB via Bliss independence model pointed to dose-dependent synergistic interactions in clinically actionable concentrations. Conclusions: IDentif.AI-designed combinations may provide alternative regimen options to current SOC combinations that are often administered with Amikacin, which has been known to induce ototoxicity in patients. Furthermore, IDentif.AI pinpointed 2-drug interactions may also serve as the backbone for the development of other effective 3- and 4-drug combination therapies. The findings in this study suggest that this platform may contribute to NTM-specific drug development.

Advances in radiotherapy in bone metastases in the context of new target therapies and ablative alternatives: A critical review.

In patients with bone metastases (BM), radiotherapy (RT) is used to alleviate symptoms, reduce the risk of fracture, and improve quality of life (QoL). However, with the emergence of concepts like oligometastases, minimal invasive surgery, ablative therapies such as stereotactic ablative RT (SABR), radiosurgery (SRS), thermal ablation, and new systemic anticancer therapies, there have been a paradigm shift in the multidisciplinary approach to BM with the aim of preserving mobility and function survival. Despite guidelines on using single-dose RT in uncomplicated BM, its use remains relatively low. In uncomplicated BM, single-fraction RT produces similar overall and complete response rates to RT with multiple fractions, although it is associated with a higher retreatment rate of 20% versus 8%. Complicated BM can be characterised as the presence of impending or existing pathologic fracture, a major soft tissue component, existing spinal cord or cauda equina compression and neuropathic pain. The rate of complicated BM is around 35%. Unfortunately, there is a lack of prospective trials on RT in complicated BM and the best dose/fractionation regimen is not yet established. There are contradictory outcomes in studies reporting BM pain control rates and time to pain reduction when comparing SABR with Conventional RT. While some studies showed that SABR produces a faster reduction in pain and higher pain control rates than conventional RT, other studies did not show differences. Moreover, the local control rate for BM treated with SABR is higher than 80% in most studies, and the rate of grade 3 or 4 toxicity is very low. The use of SABR may be preferred in three circumstances: reirradiation, oligometastatic disease, and radioresistant tumours. Local ablative therapies like SABR can delay change or use of systemic therapy, preserve patients' Qol, and improve disease-free survival, progression-free survival and overall survival. Moreover, despite the potential benefit of SABR in oligometastatic disease, there is a need to establish the optial indication, RT dose fractionation, prognostic factors and optimal timing in combination with systemic therapies for SABR. This review evaluates the role of RT in BM considering these recent treatment advances. We consider the definition of complicated BM, use of single and multiple fractions RT for both complicated and uncomplicated BM, reirradiation, new treatment paradigms including local ablative treatments, oligometastatic disease, systemic therapy, physical activity and rehabilitation.

A Flexi-PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy.

Near-infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless-based phototherapies by converting deep-tissue-penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep-sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA-approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5-aminolevulinic acid (5-ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR-based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep-tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep-tissue light delivery.

Mepitel Film and Mepilex Lite for the prophylaxis and treatment of skin toxicities from breast radiation.

Despite the prevalence of radiation dermatitis in breast cancer patients, current practice guidelines for its treatment are limited. We aimed to discuss the quality of evidence for the barrier-forming Mepitel Film for prophylaxis of radiation dermatitis, and argue for further investigation into evidence-based management of skin toxicities. Two studies assessing Mepitel Film were critically evaluated. Both reported that Mepitel Film decreased radiation dermatitis; moreover, patient-reported outcomes significantly favoured Mepitel Film. However, there has not been global adoption of barrier-forming films such as Mepitel, in part due to the absence of multi-centred randomised trials and the heterogeneity of study designs.

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic.

PURPOSE: Radiation-induced nausea and vomiting (RINV) is a common side effect of radiotherapy and can affect up to 50-80% of patients, potentially causing detrimental effects to physical health, clinical efficacy, and patient quality of life. Antiemetic drugs act on receptors involved in the emesis pathway to block the uptake of neurotransmitters and inhibit stimulation of vomiting centers in the brain to prevent and treat RINV. The most commonly prescribed antiemetics for RINV are 5-hydroxytryptamine receptor antagonists (5-HT3 RA). Guidelines describing the optimal management of RINV are produced by the Multinational Association for Supportive Care in Cancer, the European Society of Medical Oncology, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. This review will present findings from research on antiemetic management for RINV conducted at our center. METHODS: A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed. RESULTS: Several studies investigating the efficacy of different routes of administration, new antiemetic drug types, and novel combinations of antiemetics have been tested at our clinic to elucidate which approach provides the best response. These include studies on the use of ondansetron rapidly dissolving film, palonosetron, and the addition of a neurokinin-1 receptor antagonist to traditional 5-HT3 RA regimens. CONCLUSIONS: These studies provide a framework for future research and could potentially inform changes to future guidelines to include the use of these novel regimens and techniques.

Radiation-induced nausea and vomiting: a comparison between MASCC/ESMO, ASCO, and NCCN antiemetic guidelines.

PURPOSE: Radiation-induced nausea and vomiting (RINV) can affect 50-80% of patients undergoing radiotherapy and negatively impacts quality of life. This review aimed to compare the most recent RINV antiemetic guidelines produced by the Multinational Association for Supportive Care in Cancer (MASCC), the European Society of Clinical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Future improvements to the guidelines and the need for further research in RINV were also discussed. METHODS: Antiemetic guidelines produced by MASCC/ESMO, ASCO, and NCCN were examined to identify similarities, differences, and inadequacies within the guidelines. RESULTS: Areas of dissension within the guidelines include the addition of dexamethasone to moderate-risk antiemetic regimens, the prophylactic treatment of RINV in the low-risk categories, and the appropriate treatment for breakthrough emesis. The guidelines are in accordance that high-risk radiotherapy regimens should be treated prophylactically with a serotonin receptor antagonist and for those undergoing concurrent chemotherapy and radiotherapy, antiemetic treatment should be prescribed according to the emetic risk associated with their respective chemotherapy regimen. Low- and minimal-risk recommendations are based on low-level evidence and informal consensus. CONCLUSION: RINV is a frequent and distressing side effect of radiotherapy and requires further research to establish effective antiemetic guidelines and ensure optimal treatment outcomes.

ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in adult patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with a variety of early- and end-stage malignancies. In light of recent changes in the optimal management of CINV, we undertook this narrative review to compare the latest guidelines published by ASCO (2017), NCCN (2018), and MASCC/ESMO (2016). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, and MASCC/ESMO guidelines for the treatment and prevention of CINV share many fundamental similarities, literature surrounding low and minimal emetic risk regimens is lacking. Data regarding the use of complementary alternative medicine for CINV is particularly scarce and in need of further investigation.

Modulating the endocannabinoid pathway as treatment for peripheral neuropathic pain: a selected review of preclinical studies.

Chemotherapy-induced neuropathic pain is a distressing and commonly occurring side effect of many commonly used chemotherapeutic agents, which in some cases may prevent cancer patients from being able to complete their treatment. Cannabinoid based therapies have the potential to manage or even prevent pain associated with this syndrome. Pre-clinical animal studies that investigate the modulation of the endocannabinoid system (endogenous cannabinoid pathway) are being conducted to better understand the mechanisms behind this phenomenon. Five recent pre-clinical studies identified from Medline published between 2013 and 2016 were selected for review. All studies evaluated the effect of small-molecule agonists or antagonists on components of the endocannabinoid system in rats or mice, using cisplatin or paclitax-el-induced allodynia as a model of chemotherapy-induced neuropathic pain. Activation of the cannabinoid receptor-2 (CB-2) receptor by AM1710 blocked paclitaxel-induced mechanical and cold allodynia in one study. Four studies investigating the activation of both cannabinoid receptor-1 (CB-1) and CB-2 receptors by dual-agonists (WIN55,21 and CP55,940), or by the introduction of inhibitors of endocannabinoid metabolisers (URB597, URB937, JZL184, and SA-57) showed reduction of chemotherapy-induced al-lodynia. In addition, their results suggest that anti-allodynic effects may also be mediated by additional receptors, including TRPV1 and 5-hydroxytryptamine (5-HT1A). Pre-clinical studies demon-strate that the activation of endocannabinoid CB-1 or CB-2 receptors produces physiological effects in animal models, namely the reduction of chemotherapy-induced allodynia. These studies also provide in-sight into the biological mechanism behind the therapeutic utility of cannabis compounds in managing chemotherapy-induced neuropathic pain, and provide a basis for the conduct of future clinical studies in patients of this population.

Effects of circadian rhythms and treatment times on the response of radiotherapy for painful bone metastases.

BACKGROUND: Previous studies have observed how the time of radiotherapy delivery can impact toxicities and outcomes. The goal of this study was to determine whether treatment time influenced radiotherapy response for bone metastases. METHODS: Patients who received radiation treatment to painful bone metastases from January 2000 to December 2010 were included in our analysis. Demographic and treatment information including performance status, primary site, treatment dose and fraction, and response were collected prospectively. Treatment times were extracted from patient medical records. Patients were allocated to 8:00 AM-11:00 AM, 11:01 AM-2:00 PM, or 2:01 PM-5:00 PM cohorts based on their treatment times. To compare treatment response between the three cohorts, the Fisher exact test was used. A two-sided P value of <0.05 was considered statistically significant. Analysis was repeated with males and females separately. RESULTS: A total of 194 patients were included. The median age was 68 years and 55.5% of patients responded to treatment. The dose and fraction of radiation received differed significantly between treatment cohorts using all allocation methods. Females in the 11:01 AM-2:00 PM cohort exhibited a significantly higher response rate (P=0.02) and differing proportions of response types (P=0.03) compared to the 8:00 AM- 11:00 AM and 2:01 PM-5:00 PM cohorts when allocated using all treatment times. No significant differences in response were seen between cohorts when all patients were analysed together or analysed for males only. CONCLUSIONS: Treatment time may affect response in female patients receiving radiotherapy for painful bone metastases. Subsequent chronotherapy studies in radiation should investigate these gender differences.

Could time of whole brain radiotherapy delivery impact overall survival in patients with multiple brain metastases?

OBJECTIVE: Whole brain radiotherapy (WBRT) is commonly used to treat brain metastases. Previous studies have explored how radiotherapy treatment time can affect response. The present study evaluated the influence of treatment time on overall survival (OS) for cancer patients receiving WBRT. METHODS: Patients who received WBRT from 2004 to 2016 were included. Demographic information including age, performance status, primary site, dose, fraction, treatment time, and date of death were collected. Based on different percentages of treatment times falling into one time frame (i.e., 100%, ≥80%, ≥70%, or ≥60%), patients were allocated to three cohorts (8:00-11:00 AM, 11:01 AM-2:00 PM, 2:01-5:00 PM). Demographics were compared among cohorts using the Kruskal-Wallis nonparametric test and Fisher exact test. To control the multiple comparisons on select demographic variables a Bonferroni adjusted P value was considered statistically significant. Kaplan-Meier curves were created for OS. Univariate and multivariate Cox proportional hazard (PH) model were used to find predictive factors of OS in all patients, females and males. RESULTS: A total of 755 patients were included with a median age of 66 years. The actuarial median OS was 2.37 months. Treatment time was not associated with OS for all patients or males only. In elderly female patients (>65 years), a significant difference in OS was found among treatment cohorts (P=0.02). Treatment time (when ≥80% or ≥70% of treatment times were in one time frame), age, and Karnofsky performance status (KPS) were significant predictive factors of OS in univariate analysis for females. Only age and KPS remained significant in multivariate analysis. CONCLUSIONS: Time of WBRT delivery for brain metastases was significantly related to OS upon univariate analyses in females only. Future investigations should be conducted prospectively with homogenous patient groups to elucidate the effect of chronotherapy in palliative brain metastases patients as time of WBRT administration may affect OS in specific subsets of patients.

Rapid access palliative radiation therapy programs: an efficient model of care.

Palliating symptoms of advanced and metastatic cancers are one of the most common indications for radiation therapy (RT), and the demand for palliative RT is increasing. Dedicated rapid access palliative RT programs improve access to care, and can deliver RT in a more efficient and evidence-based manner than standard RT programs. In this narrative review, we discuss the role of palliative RT in comprehensive cancer care, and challenges that have faced patients trying to access it. We describe how rapid access programs developed to address these challenges and provide an overview of dedicated programs worldwide. Finally, we show how these programs can serve as models for multidisciplinary care and education, and sources of exciting research opportunities in clinical care and advanced technologies.

Cancer nanomedicine: from drug delivery to imaging.

Nanotechnology-based chemotherapeutics and imaging agents represent a new era of "cancer nanomedicine" working to deliver versatile payloads with favorable pharmacokinetics and capitalize on molecular and cellular targeting for enhanced specificity, efficacy, and safety. Despite the versatility of many nanomedicine-based platforms, translating new drug or imaging agents to the clinic is costly and often hampered by regulatory hurdles. Therefore, translating cancer nanomedicine may largely be application-defined, where materials are adapted only toward specific indications where their properties confer unique advantages. This strategy may also realize therapies that can optimize clinical impact through combinatorial nanomedicine. In this review, we discuss how particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano.

Factors influencing health related quality of life in cancer patients with bone metastases.

OBJECTIVE: Health related quality of life (HRQOL) is a multidimensional concept that is especially important for cancer patients with bone metastases, as maintaining and improving HRQOL is often the main focus of treatment. This study aims to determine factors that may influence HRQOL, which may in turn influence treatment and care of patients. METHODS: Patients (n=396) completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Bone Metastases module (BM22) at baseline. The EORTC QLQ-BM22 consists of four scales: painful site (PS), pain characteristics (PC), functional interference (FI), and psychosocial aspect (PA) scales. EORTC QLQ-BM22 data, together with sociodemographic and medical factors were analyzed by univariate analysis of variance (ANOVA). Items of significance were determined through backward selection, which were then put through multivariate analysis to determine further significance. RESULTS: Through ANOVA analysis, KPS>80 and breast primary histology were predictive of better HRQOL in the PS scale, while KPS>80, female gender, and breast primary histology were predictive of better HRQOL in the PC and FI scales. KPS>80 and prostate primary histology were predictive of better HRQOL in the PA scale. KPS>80 and primary cancer site were confirmed as significant predictive factors in multivariate analysis. RECOMMENDATIONS: This study identified baseline factors of gender, performance status, and primary histology as determinants of HRQOL in patients with bone metastases. Further study focusing on current treatment (chemotherapy, bisphosphonates, and radiotherapy) and spiritual well-being may identify additional factors affecting HRQOL. Understanding the influence of these factors will allow health care professionals to provide more effective palliative care.

Pain Management Needs Assessment: A Survey of Radiation Therapists at a Large Academic Comprehensive Cancer Centre.

OBJECTIVE: To determine the knowledge of pain management among the radiation therapists (RTs) at the Odette Cancer Centre (OCC) to aid in the development of a formalized education strategy. METHODS: A needs assessment survey comprising eight topics pertaining to pain management was distributed to 130 RTs at the OCC. Survey topics were ranked using a 4-point Likert scale based on preference for further education, familiarity with the topic, and relevance to practice. RESULTS: RTs rated topics pertaining to the undertreatment, pathophysiology, assessment, diagnosis, and treatment of pain as the most relevant topics requiring further education. RTs were most unfamiliar with topics concerning opioids and addiction, but did not find a need for further education. They also felt that breakthrough cancer pain was the most significant topic for further education. CONCLUSION: Implementation of an educational intervention for RTs to more effectively and efficiently address pain management for their patient population is needed. Topics of most clinical relevance include: undertreatment of pain, pathophysiology of pain, assessment and diagnosis of acute and chronic pain as well as its treatment.

A review of recently published radiotherapy treatment guidelines for bone metastases: Contrasts or convergence?

Bone metastases are a common manifestation of malignancy, and external beam radiotherapy (EBRT) effectively and safely palliates the pain caused by this clinical circumstance. The myriad of EBRT dosing schemes and complexities involved with coordinating radiotherapy with other interventions necessitated the need for bone metastases treatment guidelines. Here we compare and contrast the bone metastases radiotherapy treatment guidelines recently published by the American Society for Radiation Oncology (ASTRO) and the American College of Radiology (ACR). These evaluations acknowledge current controversies in treatment approaches, they evaluate the nuances of ASTRO and ACR task force decision-making regarding standard approaches to care, and they project the upcoming research results that may clarify approaches to palliative radiotherapy for bone metastases. The results of these two dedicated radiotherapy guidelines are compared to the brief mentions of radiotherapy for bone metastases in the National Comprehensive Cancer Network (NCCN) guidelines. Finally, the paper describes how treatment guidelines may influence patterns of care and reimbursement by their use as quality measures by groups such as the National Quality Forum (NQF).

Palliative care and oncology: integration leads to better care.

The timely integration of palliative care services into standard oncology care is essential to providing comprehensive individualized care for patients with advanced and incurable cancer and their families. Herein we discuss five important areas in which this integration is critical to optimize management, namely: symptom management, transitioning from disease-focused care to palliative care, discussing goals of care and advance care planning, community care, and psychosocial support for the patient and family.

Utilization of palliative radiotherapy for breast cancer patients with bone metastases treated with bisphosphonates-Toronto Sunnybrook Regional Cancer Centre experience.

BACKGROUND: The use of both bisphosphonates and palliative radiotherapy for the prevention and treatment of skeletal complications in women with bone metastases from breast cancer is well established. We undertook an evaluation of palliative radiotherapy utilization rates in breast cancer patients who received bisphosphonates for the treatment of bone metastases in a major Canadian cancer center. METHODS: Charts and electronic files of breast cancer patients with bone metastases who had received either clodronate or pamidronate at any time between January 2000 and December 2001 at our center were retrospectively reviewed. The utilization rates of palliative radiotherapy in these patients were examined. RESULTS: The percentage of patients receiving bisphosphonates for the treatment of bone metastases who also received palliative radiotherapy to bone remained relatively constant over our study period in the range of 70%. In patients commenced on bisphosphonates before 1998, 42.9% received palliative radiotherapy as initial therapy for bone metastases, whereas in 2001 only 27.8% of patients received palliative radiotherapy before commencing bisphosphonate therapy. There has been a marked improvement in the time between the diagnosis of bone metastases and the commencement of bisphosphonates from a median of 446 days before 1998 to 21 days in 2001. At the same time, there was also an improvement in time between diagnosis of bone metastases and initiation of palliative radiotherapy from a median of 265 days before 1998 to 49 days in 2001. CONCLUSION: Use of bisphosphonates has not reduced the utilization rates of palliative radiotherapy in breast cancer patients with bone metastases. There is a trend of initiating bisphosphonates before delivery of palliative radiotherapy. The latter was also delivered earlier in the course of bone metastases.