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BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-respon

AIM: It is well established that (i) magnetic resonance imaging, (ii) multidisciplinary cancer conference (MCCs), (iii) preoperative radiotherapy, (iv) total mesorectal excision surgery and (v) pathological assessment as described by Quirke are key processes necessary for high quality, rectal cancer care. The objective was to select a set of multidisciplinary quality indicators to measure the uptake of these clinical processes in clinical practice. METHOD: A multidisciplinary panel was convened and a modified two-phase Delphi method was used to select a set of quality indicators. Phase 1 included a literature review with written feedback from the panel. Phase 2 included an in-person workshop with anonymous voting. The selection criteria for the indicators were strength of evidence, ease of capture and usability. Indicators for which ≥90% of the panel members voted 'to keep' were selected as the final set of indicators. RESULTS: During phase 1, 68 potential indicators were generated from the literature and an additional four indicators were recommended by the panel. During phase 2, these 72 indicators were discussed; 48 indicators met the 90% inclusion threshold and included eight pathology, five radiology, 11 surgical, six radiation oncology and 18 MCC indicators. CONCLUSION: A modified Delphi method was used to select 48 multidisciplinary quality indicators to specifically measure the uptake of key processes necessary for high quality care of patients with rectal cancer. These quality indicators will be used in future work to identify and address gaps in care in the uptake of these clinical processes.

Contains fulltext : 220003.pdf (Publisher’s version ) (Closed access), BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is associated with an increased risk of gallbladder cancer (GBC). Gallbladder polyps potentially harbour malignancy and thus international guidelines recommend prophylactic cholecystectomy for gallbladder polyps of any size in patients with PSC. To best inform patient care we sought to quantify the malignant risk of gallbladder polyps in patients with PSC. METHODS: A retrospective cohort study of patients followed in secondary and tertiary care settings in two large PSC clinics in North America was performed. RESULTS: In total, 453 patients were included with a median (IQR) follow-up time of 7.7 (4.1-12) years. A gallbladder polyp was radiographically detected in 16% (n = 71) with median size (range) of 4 (2-18) mm. In this group, post-cholecystectomy histology (n = 17) reported benign or no polyp in 77% (n = 13), dysplasia in 5.9% (n = 1) and malignancy in 18% (n = 3). The GBC rate was 8.8 (95% CI 1.8-25.7) per 1000 person-years in patients with a radiographically detected gallbladder polyp. GBC was associated with polyps >10 mm, interval growth or mass-like lesions on pre-operative imaging. In patients who did not have cholecystectomy (n = 50), the polyp was only transiently seen in 80% (n = 40), remained stable or decreased in size in 10% (n = 5) and increased in size in 6% (n = 3). The majority of gallbladder polyps did not show significant growth over time (0.041 mm/year [95% CI -0.017 to 0.249]). CONCLUSIONS: Most gallbladder polyps in patients with PSC are benign. Short-term surveillance imaging may be considered prior to recommending immediate cholecystectomy in patients with PSC without high-risk imaging features.

BACKGROUND: Over the last 2 decades, the use of multimodal strategies, including total mesorectal excision (TME) surgery, preoperative chemotherapy, multidisciplinary case conference, pelvic magnetic resonance imaging, and pathologic assessment using Quirke method, has led to significant improvements in oncologic outcomes for patients with rectal cancer. Although the literature supports claims on the effectiveness of these multimodal strategies, the uptake of these multimodal strategies varies considerably among centers, suggesting that the best evidence is not always implemented into clinical practice. OBJECTIVE: This study aims to perform a quality improvement initiative to (1) identify existing gaps in care for these multimodal strategies and (2) implement knowledge translation (KT) interventions to close these gaps to optimize quality of care for patients with rectal cancer across high-volume centers in Canada. METHODS: Process indicators for the selected multimodal strategies to optimize rectal cancer care will be selected and prospectively collected for all patients with stages 1 to 3 rectal cancer undergoing TME surgery. KT interventions, including audit and feedback, opinion leaders, and community of practice, will be implemented to increase the uptake of these clinical strategies. RESULTS: The uptake of the process indicators over time and the effect of the uptake of the process indicators on short- and long-term oncologic outcomes will be evaluated for each multimodal strategy. CONCLUSIONS: This quality improvement initiative will identify existing gaps in care for the selected multimodal strategies and implement KT interventions to close these gaps. The results of this study will inform further efforts to optimize rectal cancer care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15535.