Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy.

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Real-world use of nirmatrelvir-ritonavir in COVID-19 outpatients during BQ.1, BQ.1.1., and XBB.1.5 predominant omicron variants in three U.S. health systems: a retrospective cohort study.

Background: Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with in vitro activity against SARS-CoV-2, can reduce risk of progression to severe COVID-19 among high-risk individuals infected with earlier variants, but less is known about its effectiveness against omicron variants BQ.1/BQ.1.1/XBB.1.5. We sought to evaluate effectiveness of NMV-r in BQ.1/BQ.1.1/XBB.1.5 omicron variants by comparing hospitalisation rates to NMV-r treated patients during a previous omicron phase and to contemporaneous untreated patients. Methods: We conducted a retrospective observational cohort study of non-hospitalised adult patients with SARS-CoV-2 infection using real-world data from three health systems in Colorado and Utah, and compared hospitalisation rates in NMV-r-treated patients in a BA.2/BA.2.12.1/BA.4/BA.5 variant-predominant (first) phase (April 3, 2022-November 12, 2022), with a BQ.1/BQ.1.1/XBB.1.5 variant-predominant (second) phase (November 13, 2022-March 7, 2023). In the primary analysis, we used Firth logistic regression with a two-segment (phase) linear time model, and pre-specified non-inferiority bounds for the mean change between segments. In a pre-specified secondary analysis, we inferred NMV-r effectiveness in a cohort of treated and untreated patients infected during the second phase. For both analyses, the primary outcome was 28-day all-cause hospitalisation. Subgroup analyses assessed treatment effect heterogeneity. Findings: In the primary analysis, 28-day all-cause hospitalisation rates in NMV-r treated patients in the second phase (n = 12,061) were non-inferior compared to the first phase (n = 25,075) (198 [1.6%] vs. 345 [1.4%], adjusted odds ratio (aOR): 0.76 [95% CI 0.54-1.06]), with consistent results among secondary endpoints and key subgroups. Secondary cohort analyses revealed additional evidence for NMV-r effectiveness, with reduced 28-day hospitalisation rates among treated patients compared to untreated patients during a BQ.1/BQ.1.1/XBB.1.5 predominant phase (198/12,061 [1.6%] vs. 376/10,031 [3.7%], aOR 0.34 [95% CI 0.30-0.38), findings robust to additional sensitivity analyses. Interpretation: Real-world evidence from major US healthcare systems suggests ongoing NMV-r effectiveness in preventing hospitalisation during a BQ.1/BQ.1.1/XBB.1.5-predominant phase in the U.S, supporting its continued use in similar patient populations. Funding: U.S. National Institutes of Health.

Real-world evaluation of bebtelovimab effectiveness during the period of COVID-19 Omicron variants, including BA.4/BA.5.

OBJECTIVES: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. METHODS: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. RESULTS: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P <0.001), as well as COVID-19-related hospitalization (1.0% vs 2.0%, adjusted odds ratio: 0.44 [95% confidence interval: 0.30-0.64], P <0.001). Bebtelovimab appeared to be more beneficial in lowering the odds of hospitalization among patients with two or more comorbidities (interaction P = 0.03). CONCLUSION: During the Omicron BA.2/BA.2.12.1/BA.4/BA.5 variant phase, bebtelovimab was associated with lower hospitalization.

Real-world use of nirmatrelvir-ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study.

BACKGROUND: Nirmatrelvir is a protease inhibitor with in-vitro activity against SARS-CoV-2, and ritonavir-boosted nirmatrelvir can reduce the risk of progression to severe COVID-19 among individuals at high risk infected with delta and early omicron variants. However, less is known about the effectiveness of nirmatrelvir-ritonavir during more recent BA.2, BA2.12.1, BA.4, and BA.5 omicron variant surges. We used our real-world data platform to evaluate the effect of nirmatrelvir-ritonavir treatment on 28-day hospitalisation, mortality, and emergency department visits among outpatients with early symptomatic COVID-19 during a SARS-CoV-2 omicron (BA.2, BA2.12.1, BA.4, and BA.5) predominant period in Colorado, USA. METHODS: We did a propensity-matched, retrospective, observational cohort study of non-hospitalised adult patients infected with SARS-CoV-2 between March 26 and Aug 25, 2022, using records from a statewide health system in Colorado. We obtained data from the electronic health records of University of Colorado Health, the largest health system in Colorado, with 13 hospitals and 141 000 annual hospital admissions, and with numerous ambulatory sites and affiliated pharmacies around the state. Included patients had a positive SARS-CoV-2 test or nirmatrelvir-ritonavir medication order. Exclusion criteria were an order for or administration of other SARS-CoV-2 treatments within 10 days of a positive SARS-CoV-2 test, hospitalisation at the time of positive SARS-CoV-2 test, and positive SARS-CoV-2 test more than 10 days before a nirmatrelvir-ritonavir order. We propensity score matched patients treated with nirmatrelvir-ritonavir with untreated patients. The primary outcome was 28-day all-cause hospitalisation. FINDINGS: Among 28 167 patients infected with SARS-CoV-2 between March 26 and Aug 25, 2022, 21 493 met the study inclusion criteria. 9881 patients received treatment with nirmatrelvir-ritonavir and 11 612 were untreated. Nirmatrelvir-ritonavir treatment was associated with reduced 28-day all-cause hospitalisation compared with no antiviral treatment (61 [0·9%] of 7168 patients vs 135 [1·4%] of 9361 patients, adjusted odds ratio (OR) 0·45 [95% CI 0·33-0·62]; p<0·0001). Nirmatrelvir-ritonavir treatment was also associated with reduced 28-day all-cause mortality (two [<0·1%] of 7168 patients vs 15 [0·2%] of 9361 patients; adjusted OR 0·15 [95% CI 0·03-0·50]; p=0·0010). Using subsequent emergency department visits as a surrogate for clinically significant relapse, we observed a decrease after nirmatrelvir-ritonavir treatment (283 [3·9%] of 7168 patients vs 437 [4·7%] of 9361 patients; adjusted OR 0·74 [95% CI 0·63-0·87]; p=0·0002). INTERPRETATION: Real-world evidence reported during a BA.2, BA2.12.1, BA.4, and BA.5 omicron surge showed an association between nirmatrelvir-ritonavir treatment and reduced 28-day all-cause hospitalisation, all-cause mortality, and visits to the emergency department. With results that are among the first to suggest effectiveness of nirmatrelvir-ritonavir for non-hospitalised patients during an omicron period inclusive of BA.4 and BA.5 subvariants, these data support nirmatrelvir-ritonavir as an ongoing first-line treatment for adults acutely infected with SARS-CoV-2. FUNDING: US National Institutes of Health.

Real-World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) were authorized for the treatment of COVID-19 outpatients based on clinical trials completed early in the pandemic, which were underpowered for mortality and subgroup analyses. Real-world data studies are promising for further assessing rapidly deployed therapeutics. RESEARCH QUESTION: Did mAb treatment prevent progression to severe disease and death across pandemic phases and based on risk factors, including prior vaccination status? STUDY DESIGN AND METHODS: This observational cohort study included nonhospitalized adult patients with SARS-CoV-2 infection from November 2020 to October 2021 using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAb treatment under emergency use authorization. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and hospitalization severity. RESULTS: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 patients not receiving mAbs. Compared with mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR, 0.48; 95% CI, 0.38-0.60) and all-cause mortality (0.1% vs 0.9%; adjusted OR, 0.11; 95% CI, 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs 8.5 days) and lower risk of mechanical ventilation (4.6% vs 16.6%). Results were similar for preventing hospitalizations during the Delta variant phase (adjusted OR, 0.35; 95% CI, 0.25-0.50) and across subgroups. Number-needed-to-treat (NNT) to prevent hospitalization was lower for subgroups with higher baseline risk of hospitalization; for example, multiple comorbidities (NNT = 17) and not fully vaccinated (NNT = 24) vs no comorbidities (NNT = 88) and fully vaccinated (NNT = 81). INTERPRETATION: Real-world data revealed a strong association between receipt of mAbs and reduced hospitalization and deaths among COVID-19 outpatients across pandemic phases. Real-world data studies should be used to guide practice and policy decisions, including allocation of scarce resources.

Change in effectiveness of sotrovimab for preventing hospitalization and mortality for at-risk COVID-19 outpatients during an Omicron BA.1 and BA.1.1-predominant phase.

OBJECTIVES: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection. METHODS: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021, to March 10, 2022, using electronic health records from a statewide health system. We propensity-matched patients not receiving authorized treatment for each patient treated with sotrovimab. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. We also propensity-matched sotrovimab-treated patients from the Omicron and Delta phases. Logistic regression was used to determine sotrovimab effectiveness during Omicron and between variant phases. RESULTS: Of 30,247 SARS-CoV-2 Omicron variant infected outpatients, we matched 1542 receiving sotrovimab to 3663 not receiving treatment. Sotrovimab treatment was not associated with reduced odds of 28-day hospitalization (2.5% vs 3.2%; adjusted odds ratio [OR] 0.82, 95% CI 0.55, 1.19) or mortality (0.1% vs 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). Between phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs 0.39, respectively; interaction P-value = 0.053). CONCLUSION: Real-world evidence demonstrated that sotrovimab was not associated with reduced 28-day hospitalization or mortality among COVID-19 outpatients during the Omicron BA.1 phase.

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. METHODS: This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. RESULTS: COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52-5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01-3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20-3.82), obesity (OR 1.79, 95% CI 1.36-2.34), one comorbidity (OR 1.68, 95% CI 1.11-2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13-2.35), and male sex (OR 1.56, 95% CI 1.21-2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). CONCLUSIONS: Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection. METHODS: In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021-11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. RESULTS: Of 10 036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% vs 5.7%; adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], .19-.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% vs 1.0%; aOR, 0.11; 95% CI, .0-.79), and may reduce respiratory disease severity among those hospitalized. CONCLUSIONS: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

Background: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is effective against the SARS-CoV-2 Delta variant to prevent progression to severe disease and mortality. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1 st 2021 - December 11 th 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. Results: Of 10,036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1,563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% versus 5.7%; adjusted OR 0.37, 95% CI 0.19-0.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% versus 1.0%; adjusted OR 0.11, 95% CI 0.0-0.79), and may reduce respiratory disease severity among those hospitalized. Conclusion: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Real World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) are authorized for early symptomatic COVID-19 patients. Whether mAbs are effective against the SARS-CoV-2 Delta variant, among vaccinated patients, or for prevention of mortality remains unknown. OBJECTIVE: To evaluate the effectiveness of mAb treatment in preventing progression to severe disease during the Delta phase of the pandemic and based on key baseline risk factors. DESIGN SETTING AND PATIENTS: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from November 2020-October 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAbs. EXPOSURE: Neutralizing mAb treatment under emergency use authorization. MAIN OUTCOMES: The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. RESULTS: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 not receiving mAbs. Compared to mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR 0.48, 95%CI 0.38-0.60) and all-cause mortality (0.1% vs. 0.9%; adjusted OR 0.11, 95%CI 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs. 8.5 days) and lower risk of mechanical ventilation (4.6% vs. 16.6%). Relative effectiveness was similar in preventing hospitalizations during the Delta variant phase (adjusted OR 0.35, 95%CI 0.25-0.50) and across subgroups. Lower number-needed-to-treat (NNT) to prevent hospitalization were observed for subgroups with higher baseline risk of hospitalization (e.g., multiple comorbidities (NNT=17) and not fully vaccinated (NNT=24) vs. no comorbidities (NNT=88) and fully vaccinated (NNT=81). CONCLUSION: Real-world evidence demonstrated mAb effectiveness in reducing hospitalization among COVID-19 outpatients, including during the Delta variant phase, and conferred an overall 89% reduction in 28-day mortality. Early outpatient treatment with mAbs should be prioritized, especially for individuals with highest risk for hospitalization.

De-implementation of Axillary Dissection in Women With Breast Cancer is Largely Driven By Site-level Contextual Effects.

OBJECTIVE: To assess the contribution of unknown institutional factors (contextual effects) in the de-implementation of cALND in women with breast cancer. SUMMARY OF BACKGROUND DATA: Women included in the National Cancer Database with invasive breast carcinoma from 2012 to 2016 that underwent upfront lumpectomy and were found to have a positive sentinel node. METHODS: A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and institutional variables on the risk of cALND. Reference effect measureswere used to describe and compare the contribution of contextual effects to the variation in cALND use to that of measured variables. RESULTS: By 2016, cALND was still performed in at least 50% of the patients in a quarter of the institutions. Black race, younger women and those with larger or hormone negative tumors were more likely to undergo cALND. However, the width of the 90% reference effect measures range for the contextual effects exceeded that of the measured site, tumor, time, and patient demographics, suggesting institutional contextual effects were the major drivers of cALND de-implementation. For instance, a woman at an institution with low-risk of performing cALND would have 74% reduced odds of havinga cALND than if she was treated at a median-risk institution, while a patient at a high-risk institution had 3.91 times the odds. CONCLUSION: Compared to known patient, tumor, and institutional factors, contextual effects had a higher contribution to the variation in cALND use.