Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy on pathologic complete response rate in HER2-negative breast cancer patients.

PURPOSE: Data exploring optimal sequencing of anthracyclines and taxanes as neoadjuvant chemotherapy (NACT) for breast cancer are limited and inconsistent. The objective of this study was to assess the real-world impact of sequence order on pathologic complete response (pCR) and clinical outcomes from NACT. METHODS: Patients with HER2-negative breast cancer treated with NACT from May 2012 to April 2020 were identified from a prospectively collected institutional database. The primary endpoint was to compare rates of pCR (ypT0/isN0) between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Additional endpoints of interest included clinical complete response, downstaging, Neo-Bioscore, conversion to breast-conserving surgery eligibility, relapse-free survival, and overall survival between groups. RESULTS: Of the 283 patients who met eligibility criteria, 187 (66%) received AC-T and 96 (34%) received T-AC. Sequence order did not influence the primary endpoint of pCR rate (19% for AC-T vs. 21% for T-AC, p = 0.752). There were also no significant differences in secondary NACT efficacy outcomes between groups. In the overall cohort, pCR rate was higher in patients with triple-negative breast cancer (TNBC) (32% vs. 13% in hormone-positive cancer, p < 0.001) and grade 3 tumors (31% vs. 12% for grade 1-2 tumors, p < 0.001). CONCLUSIONS: In this real-world analysis of HER2-negative breast cancer patients, there was no differential impact on pCR rate or clinical outcomes from NACT with sequence order of anthracyclines and taxanes. This supports the current variation in prescribing practice.

Tyrosine kinase inhibitors significantly improved survival outcomes in patients with metastatic gastrointestinal stromal tumour: a multi-institutional cohort study.

Background: The real-world impact of tyrosine kinase inhibitors (tkis) in clinical practice for gastrointestinal stromal tumour (gist) has not been extensively reported. We sought to assess how outcomes have changed over the eras and to evaluate the effect of access to imatinib and sunitinib on survival in patients with unresectable or metastatic gist in British Columbia. Methods: Patients with metastatic or unresectable gist were allocated to one of three eras: pre-2002, 2002-2007, and post-2007 based on treatment availability (pre-imatinib, post-imatinib, and post-sunitinib). Overall survival (os) and progression-free survival (pfs) were compared between eras. Univariate and multivariate analyses were performed to determine the effects of tumour, patient, and treatment characteristics on survival outcomes. Results: Of 657 patients diagnosed with gist throughout British Columbia during 1996-2016, 196 had metastatic disease: 23 in the pre-imatinib era, 67 in the post-imatinib era, and 106 in the post-sunitinib era. A significant increase in os, by 53.6 months (p = 0.0007), and pfs, by 29.1 months (p = 0.044), was observed after the introduction of imatinib. The introduction of sunitinib did not significantly affect os or pfs. Conclusions: Implementation of tkis has drastically improved survival outcomes for patients with metastatic gist by up to 4.55 years in the real-world setting. Our study demonstrates that implementation of tkis in clinical practice has outperformed their benefit predicted in clinical trials.

Impact of Recurrence Score on type and duration of chemotherapy in breast cancer.

Background: The use of Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) testing has been shown to change treatment decisions in approximately 30% of breast cancer (bca) cases, but research on how Recurrence Score testing has affected the type of chemotherapy offered is limited. We sought to determine if the availability of Oncotype dx testing resulted in a change to the type and duration of chemotherapy regimens used in the treatment of early-stage hormone receptor-positive bca. Methods: In a population-based cohort study, patients treated in the 2 years before the availability of Oncotype dx testing were compared with patients treated in the 2 years after testing availability. Charts were audited and divided into 2 groups: pre-Oncotype dx and post-Oncotype dx. The groups were compared for differences in duration of chemotherapy (12 weeks vs. >12 weeks), types of agents used (anthracycline vs. non-anthracycline), and myelosuppressive potential of the chosen regimen. Results: Of 834 patients who fulfilled the enrolment criteria, 360 fell into the pre-Oncotype dx era, and 474, into the post-Oncotype dx era. An increase of 11.2 percentage points, to 69.5% from 58.3%, was observed in the proportion of patients receiving short-course compared with long-course chemotherapy (p = 0.068). The proportion of patients prescribed anthracycline-containing regimens declined in the post-Oncotype dx era (47.7% pre vs. 32.2% post, p = 0.016). The selection of more-myelosuppressive chemotherapy protocols increased in the post-Oncotype dx era (67.4% pre vs. 78.8% post, p = 0.044). Conclusions: In the present study, the availability of Oncotype dx testing was observed to influence the choice of chemotherapy type in the setting of early-stage bca.

Fluoroscopy-guided placement of nasoenteral tubes in children using intermittent digital pulse fluoroscopy and last image save/grab technique.

AIM: To document the radiation exposure metrics, including fluoroscopic radiation time and radiation dose-area product, in children <18 years of age who undergo nasoenteral tube placement using fluoroscopic guidance with maximal dose-reduction techniques. MATERIALS AND METHODS: Following institutional review board approval, the age, gender, anatomical information, immediate procedure-related complications if any, fluoroscopy time, and radiation dose-area product were collected retrospectively in all paediatric patients who underwent fluoroscopically guided nasoenteral tube placement during a 5-year period. Three paediatric radiology faculty members, a radiologist assistant, and trainee residents during their paediatric radiology rotation performed the procedures on two different digital fluoroscopic machines using radiation-minimising techniques. Median values of the fluoroscopy time and radiation dose-area product were calculated and compared to values reported in the literature using the Wilcoxon procedure. RESULTS: There were 41 male and 33 female patients with a median age of 4 years and 6 months. Median fluoroscopy time used for placing a nasoenteral tube was 1.25 minutes with a median radiation exposure dose-area product of 0.245 Gy·cm(2). All patients had successful placement of nasoenteral tube without immediate procedure-related complications. CONCLUSION: Fluoroscopy-guided nasoenteral feeding tube placement can be performed successfully with minimal radiation exposure without compromising procedural success.

A Canadian national expert consensus on neoadjuvant therapy for breast cancer: linking practice to evidence and beyond.

BACKGROUND: Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. METHODS: A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. RESULTS: Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. CONCLUSIONS: A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

Comparison of international breast cancer guidelines: are we globally consistent? cancer guideline AGREEment.

BACKGROUND: Evidence-based guidelines are used in health care systems throughout the world to aid in treatment decisions and to ensure quality and consistency in patient care. In breast oncology, guidelines for care are published by several internationally recognized organizations, including those from the United States, Canada, and the United Kingdom. The present study compared clinical breast cancer guidelines from the American Society of Clinical Oncology (ASCO, United States), Cancer Care Ontario (CCO, Canada), and the National Institute for Health and Clinical Excellence (NICE, United Kingdom) to determine the quality and consistency of content across international organizations. METHODS: We searched for breast cancer guidelines published by ASCO, CCO, and NICE. Guidelines on the same theme were identified across organizations and appraised by 4 independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Content of each guideline was also scored for consistency in overall recommendations across organizations and for consistency in cited evidence. RESULTS: The quality of breast cancer guidelines produced by the targeted organizations was consistently good in the areas of Scope and Purpose, Rigor of Development, and Clarity and Presentation, but variable in the domains of Stakeholder Involvement, Applicability, and Editorial Independence. The content of the guidelines varied slightly in the strength of their recommendations. CONCLUSIONS: Our review demonstrated consistency in quality and content for breast cancer practice guidelines published by various organizations. Future guidelines developed by these organizations should focus on how to implement and measure uptake of a guideline.

Vascular endothelial growth factor activity after switching of bisphosphonate treatment for metastatic breast cancer.

BACKGROUND: Recent data have shown a fall in vascular endothelial growth factor (VEGF) concentrations after bisphosphonate (BP) treatment in BP-naïve patients. It has therefore been proposed that BPs may have in vivo anti-VEGF effects. AIMS: To explore whether VEGF concentrations change after administration of a more potent BP in patients receiving long-term BP treatment. METHODS: 31 patients with breast cancer who had progressive metastatic bone disease despite treatment with early-generation BPs were switched to zoledronic acid. Serum VEGF concentrations were measured at baseline, and weeks 1, 2, 3, 4, 8 and 12. RESULTS: VEGF concentration per platelet count did not change significantly at any time during the 12 weeks after treatment with zoledronic acid. CONCLUSIONS: Switching to zoledronic acid did not suppress circulating serum VEGF concentrations in BP-pretreated patients. Novel approaches to assess the effect of BPs on the bone milieu may provide further insight into the possible antiangiogenic properties of BPs.

Arachidonic acid metabolism, prostaglandins and the kidney.

Renal prostaglandins are gaining increasing recognition as important modulators of hemodynamics and excretory function in the mammalian kidney. Synthesis of these unsaturated fatty acids from arachidonate precursors is closely regulated by intrarenal factors, and circulating angiotensin II, catecholamines, arginine vasopressin and bradykinin. Endogenous prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state, but inhibition of arachidonate metabolism when renal perfusion is impaired causes marked alterations in these parameters. Renal salt and water excretion is modified by the effects of prostaglandins on glomerular filtration rate, proximal tubule fluid reabsorption, medullary solute gradients, and the intrinsic water and ion reabsorptive properties of distal nephron segments. Prostaglandins also mediate renin release under basal conditions and in response to intravascular volume depletion. Abnormalities of renal prostaglandins are evident in various clinical disorders of renal function including hypertension, ureteral obstruction, Bartter syndrome, hypokalemic nephropathy and drug-induced disorders of water metabolism. Appropriate clinical use of nonsteroidal anti-inflammatory agents requires consideration of the potential renal consequences of inhibiting prostaglandin biosynthesis.