The results of this study indicate that the RS assay impacts medical oncologist adjuvant treatment recommendations, patient treatment choice, and patient anxiety.

I-SPY2 Trial ConsortiumIMPORTANCE Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in the context of a phase 2 neoadjuvant platform trial.OBJECTIVE To evaluate the association of pCR with event-free survival (EFS) and pCR with distant recurrence-free survival (DRFS) in subpopulations of women with high-risk operable breast cancer treated with standard therapy or one of several novel agents. DESIGN, SETTING, AND PARTICIPANTSMulticenter platform trial of women with operable clinical stage 2 or 3 breast cancer with no prior surgery or systemic therapy for breast cancer; primary tumors were 2.5 cm or larger. Women with tumors that were ERBB2 negative/hormone receptor (HR) positive with low 70-gene assay score were excluded. Participants were adaptively randomized to one of several different investigational regimens or control therapy within molecular subtypes from March 2010 through 2016. The analysis included participants with follow-up data available as of February 26, 2019.INTERVENTIONS Standard-of-care neoadjuvant therapy consisting of taxane treatment with or without (as control) one of several investigational agents or combinations followed by doxorubicin and cyclophosphamide.MAIN OUTCOMES AND MEASURES Pathologic complete response and 3-year EFS and DRFS. RESULTSOf the 950 participants (median [range] age, 49 [23-77] years), 330 (34.7%) achieved pCR. Three-year EFS and DRFS for patients who achieved pCR were both 95%. Hazard ratios for pCR vs non-pCR were 0.19 for EFS (95% CI, 0.12-0.31) and 0.21 for DRFS (95% CI, 0.13-0.34) and were similar across molecular subtypes, varying from 0.14 to 0.18 for EFS and 0.10 to 0.20 for DRFS. CONCLUSIONS AND RELEVANCEThe 3-year outcomes from the I-SPY2 trial show that, regardless of subtype and/or treatment regimen, including 9 novel therapeutic combinations, achieving pCR after neoadjuvant therapy implies approximately an 80% reduction in recurrence rate. The goal of the I-SPY2 trial is to rapidly identify investigational therapies that may improve pCR when validated in a phase 3 confirmatory trial. Whether pCR is a validated surrogate in the sense that a therapy that improves pCR rate can be assumed to also improve long-term outcome requires further study.

Background Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings. MethodsIn this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, from patients (aged ≥18 years) with primary stage I-III breast cancer treated with neoadjuvant chemotherapy followed by surgery. We assessed the association between the continuous RCB score and the primary study outcome, event-free survival, using mixed-effects Cox models with the incorporation of random RCB and cohort effects to account for betweenstudy heterogeneity, and stratification to account for differences in baseline hazard across cancer subtypes defined by hormone receptor status and HER2 status. The association was further evaluated within each breast cancer subtype in multivariable analyses incorporating random RCB and cohort effects and adjustments for age and pretreatment clinical T category, nodal status, and tumour grade. Kaplan-Meier estimates of event-free survival at 3, 5, and 10 years were computed for each RCB class within each subtype. FindingsWe analysed participant-level data from 5161 patients treated with neoadjuvant chemotherapy between Sept 12, 1994, and Feb 11, 2019. Median age was 49 years (IQR 20-80). 1164 event-free survival events occurred during follow-up (median follow-up 56 months [IQR 0-186]). RCB score was prognostic within each breast cancer subtype, with higher RCB score significantly associated with worse event-free survival. The univariable hazard ratio (HR) associated with one unit increase in RCB ranged from 1•55 (95% CI 1•41-1•71) for hormone receptor-positive, HER2-negative patients to 2•16 (1•79-2•61) for the hormone receptor-negative, HER2-positive group (with or without HER2-targeted therapy; p<0•0001 for all subtypes). RCB score remained prognostic for eventfree survival in multivariable models adjusted for age, grade, T category, and nodal status at baseline: the adjusted HR ranged from 1•52 (1•36-1•69) in the hormone receptor-positive, HER2-negative group to 2•09 (1•73-2•53) in the hormone receptor-negative, HER2-positive group (p<0•0001 for all subtypes).Interpretation RCB score and class were independently prognostic in all subtypes of breast cancer, and generalisable to multiple practice settings. Although variability in hormone receptor subtype definitions and treatment across patients are likely to affect prognostic performance, the association we observed between RCB and a patient's residual risk suggests that prospective evaluation of RCB could be c...

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Context. Immune checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancers, but comparatively little is known about patient-reported outcomes (PROs) and health-related quality of life (HRQoL) among patients receiving these novel therapies.Objectives. We performed a systematic review to examine PROs and HRQoL among cancer patients receiving ICIs as compared to other anticancer therapies.Methods. We systematically searched PubMed, CINAHL, Embase, Web of Science, and Scopus, using search terms representing ICIs, PROs, and HRQoL on August 10, 2018. Eligible articles were required to involve cancer patients treated with ICIs and to report PROs and/or HRQoL data.Results. We screened 1453 references and included 15 publications representing 15 randomized controlled trials in our analysis. Studies included several cancer types (melanoma, lung cancer, genitourinary cancer, and head/neck cancer), used four different ICIs (nivolumab, pembrolizumab, atezolizumab, and ipilimumab), and compared ICIs to a wide range of therapies (chemotherapy, targeted therapies, other immunotherapy strategies, and placebo). Studies used a total of seven different PROs to measure HRQOL, most commonly the European Organisation for the Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) (n ¼ 12, 80%). PRO data were reported in a variety of formats and at a variety of time points throughout treatment, which made direct comparison challenging. Some trials (n ¼ 11, 73%) reported PROs on specific symptoms. In general, patients receiving ICIs had similar-to-improved HRQoL and experiences when compared to other therapies.Conclusion. Despite the broad clinical trials experience of ICI therapies across cancer types, relatively few randomized studies reported PROs and patient HRQoL data. Available data suggest that ICIs are well tolerated in terms of HRQoL compared to other anticancer therapies although the conclusions are limited by the heterogeneity of trial designs and outcomes. Currently used instruments may fail to capture important symptomatology unique to ICIs, underscoring a need for PROs designed specifically for ICIs.

The 70-GS provides clinically actionable information regarding patients classified as intermediate risk by the 21-GA and was associated with a change in treatment decision in 282 of these patients (33.6%). Chemotherapy was added or withheld by the treating physician based on the results of the 70-GS test. Physicians reported more confidence with their treatment recommendation after receiving 70-GS results.

Gastrointestinal stromal tumors are rare tumors of the gastrointestinal tract. Gastrointestinal stromal tumors involving the rectum are uncommon. We describe a case of a 43-year-old female with a gastrointestinal stromal tumor of the rectum who declined abdominoperineal resection. Neoadjuvant treatment with imatinib decreased her tumor size, permitting sphincter-sparing transanal excision. She had no evidence of disease for 24 months postoperatively until she recurred with lung metastases. Microdissection genotyping of the recurrent lesion revealed a deletion in exon 11. Further mutational analysis showed that her metastatic lesion was concordant with her primary rectal lesion, suggesting that systemic micrometastasis was previously present at initial diagnosis. Deletion in exon 11 predicts for response with imatinib treatment and is associated with a longer event-free and overall survival. Current studies are underway that may help us optimize the treatment for patients with gastrointestinal stromal tumors.

Context. Although the literature on transitions from hospital to the community is extensive, little is known about this experience within the context of palliative care (PC).Objective. We conducted a systematic review to investigate the impact of receiving palliative care in hospital on the transition from hospital to the community.Methods. We systematically searched MEDLINE, Embase, ProQuest, and CINAHL from 1995 until April 10, 2018, and extracted relevant references. Eligible articles were published in English, included adult patients receiving PC as inpatients, and explored transitions from hospital to the community.Results. A total of 1514 studies were identified and eight met inclusion criteria. Studies were published recently (>2012; n ¼ 7, 88%). Specialist PC interventions were delivered by multidisciplinary care teams as part of inpatient PC triggers, discharge planning programs, and transitional care programs. Common outcomes reported with significant findings consisted of length of stay (n ¼ 5), discharge support (n ¼ 5), and hospital readmissions (n ¼ 6) for those who received inpatient PC. Most studies were at high risk of bias.Conclusion. Heterogeneity of study designs, outcomes, findings, and poor methodological quality renders it challenging to draw conclusions regarding PC's impact on the transition from hospital to home. Further research should use standardized outcomes with randomized controlled trial and/or propensity matched cohort designs.