Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Importance: Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. Objective: To assess whether xerostomia is a toxic effect of WBRT. Design, Setting, and Participants: This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Main Outcomes and Measures: Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Results: Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use. Conclusions and Relevance: Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

PURPOSE: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. PATIENTS AND METHODS: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. RESULTS: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. CONCLUSION: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. CLINICAL TRIAL: (NCT01305941).

Erratum: Multidisciplinary Management of Breast Cancer During Pregnancy.

[This corrects the article DOI: 10.1634/theoncologist.2016-0208.].

Heart dosimetric analysis of three types of cardiac toxicity in patients treated on dose-escalation trials for Stage III non-small-cell lung cancer.

BACKGROUND AND PURPOSE: To assess associations between radiation dose/volume parameters for cardiac subvolumes and different types of cardiac events in patients treated on radiation dose-escalation trials. MATERIAL AND METHODS: Patients with Stage III non-small-cell lung cancer received dose-escalated radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective trials from 1996 to 2009. Volumes analyzed included whole heart, left ventricle (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into three categories: pericardial (symptomatic effusion and pericarditis), ischemia (myocardial infarction and unstable angina), and arrhythmia. Univariable competing risks analysis was used. RESULTS: 112 patients were analyzed, with median follow-up 8.8 years for surviving patients. Nine patients had pericardial, seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial events were correlated with whole heart, RA, and LA dose (eg, heart-V30 [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart-V30 [p=0.048]). Arrhythmic events showed borderline significant associations with RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30 [p=0.051]). Cardiac events were associated with decreased survival on univariable analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased survival on multivariable analysis. CONCLUSIONS: Cardiac events were heterogeneous and associated with distinct heart subvolume doses. These data support the hypothesis of distinct etiologies for different types of radiation-associated cardiotoxicity.

The use of psychological supportive care services and psychotropic drugs in patients with early-stage breast cancer: a comparison between two institutions on two continents.

The aim of this study was to evaluate the mental health consumption among patients with early-stage breast cancer in two radiation oncology departments in two countries (USA and Italy). Data were extracted from the medical records of consecutive patients treated between 2014 and 2015 in two centers. Extracted data included patient's demographics, treatment, referral to psychological supportive care programs, and prescribed psychotropic drugs. Data from the two centers were compared using Student's t, Wilcoxon, Fisher's exact, and Jonckheere-Terpstra tests. Adjusted relative risks (RR) were estimated using Poisson regression. A total of 231 (Italy = 110, USA = 121) patients were included, with a mean age of 60 years. The crude rate of psychological supportive care visits was similar in the US versus the Italian cohort (28.9 vs. 21.8%, p = 0.23). The crude rate of prescribed psychotropic drug was higher in the US cohort versus Italian cohort (43.8 vs. 18.2%, p < 0.0001). These differences remained significant after adjusting for breast cancer subtype, stage, and treatment (RR 1.8, 95 CI 1.17-2.76). Between 20 and 30% of patients receive psychological supportive care during treatment for breast cancer. The use of psychotropic medication was higher in the US cohort than the cohort from Italy. The reasons for these differences might be related to social and cultural differences and the method of prescribing medication.

Early cardiac perfusion defects after left-sided radiation therapy for breast cancer: is there a volume response?

PURPOSE: Cardiac single-photon emission computed tomography (SPECT) is often used to identify defects in myocardial perfusion due to atherosclerotic coronary artery disease. It was also used in studies to evaluate radiation therapy (RT)-associated cardiac abnormalities. In the current review, we aim to evaluate the rates of post-RT cardiac SPECT early perfusion abnormalities and relate this to the irradiated left ventricular volume. METHODS: The studies cited in this systematic review were identified using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: Six studies between 1996 and 2016 fulfilled the inclusion criteria. The reported perfusion defects in these studies were seen in the apical and anterolateral aspects of the left ventricle. Three studies show correlation between the percent of the left ventricle within the RT-field and percent of patients with early perfusion defects on cardiac SPECT. In two studies that used cardiac sparing techniques (such as deep inspiration), that resulted in a low mean heart dose, no perfusion defects were noted. CONCLUSIONS: Data suggest that incidental irradiation of the heart in cases of left breast/chest wall RT can result in early post-RT perfusion defects on cardiac SPECT. There appears to be strong dose/volume dependence to the risk, and hence techniques to reduce cardiac exposure are recommended.

The incidence of radiation necrosis following stereotactic radiotherapy for melanoma brain metastases: the potential impact of immunotherapy.

Stereotactic radiotherapy (SRT) is the standard treatment for patients with limited number of brain metastases. In the past few years, newer immunotherapies (immune checkpoint inhibitors) have been proven to prolong survival in patients with metastatic melanoma. The safety of the combination of SRT and immunotherapy for brain metastases is unknown. We retrospectively identified patients with melanoma brain metastases treated with SRT between 2007 and 2015. Patients who did not have at least 3 months of follow-up with imaging after SRT were excluded from the analysis. Outcomes were compared between patients who were treated with or without immunotherapy. A total of 58 patients were included; of these, 29 were treated with SRT and immunotherapy. MAPK inhibitors (BRAF, MEK inhibitors) were used more often in the immunotherapy group (nine vs. two patients). There was a higher incidence of intracranial complications in patients treated with immunotherapy and SRT. Eight patients had radiation necrosis; all occurred in patients who were treated with immunotherapy. Nine patients had hemorrhage, of which seven occurred in patients who were treated with immunotherapy (P=0.08). However, patients treated with immunotherapy and SRT had a significant overall survival advantage compared with SRT without immunotherapy (15 vs. 6 months, P=0.0013). Patients treated with SRT and immunotherapy have a higher incidence/risk of intracranial complications, but a longer overall survival.

Utility of Deep Inspiration Breath Hold for Left-Sided Breast Radiation Therapy in Preventing Early Cardiac Perfusion Defects: A Prospective Study.

PURPOSE: To evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH). METHODS AND MATERIALS: We performed a prospective single-institution single-arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (± internal mammary nodes). The DIBH was done by use of a controlled surface monitoring technique (AlignRT, Vision RT Ltd, London, UK). The RT was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall motion changes were assessed by pre-RT and 6-month post-RT SPECT scans. A cumulative SPECT summed-rest score was used to quantify perfusion in predefined left ventricle segments. The incidence of wall motion abnormalities was assessed in each of these same segments. RESULTS: A total of 20 patients with normal pre-RT scans were studied; their median age was 56 years (range, 39-72 years). Seven (35%) patients also received irradiation to the left internal mammary chain, and 5 (25%) received an additional RT field to supraclavicular nodes. The median heart dose was 94 cGy (range, 56-200 cGy), and the median V25Gy was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities. CONCLUSIONS: Our results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.

The prognostic value of pre-diagnosis health-related quality of life on survival: a prospective cohort study of older Americans with lung cancer.

PURPOSE: Health-related quality of life (HRQOL) after cancer diagnosis is prognostic for overall survival (OS). However, no studies have assessed if HRQOL before diagnosis is predictive for OS. The objective of this study was to determine the association between pre-lung cancer diagnosis HRQOL and OS. METHODS: Our prospective cohort study used surveillance, epidemiology, and end results linked to the Medicare Health Outcomes Survey. We included 6290 individuals 65 years or older diagnosed with incident lung cancer from 1998 to 2013. We assessed the prognostic value of (1) short-form 36 summary component and domain-specific scores, (2) activities of daily living (ADL), and (3) two global HRQOL questions. Cox-proportional hazards models were used to examine associations between HRQOL and OS, adjusting for demographics, comorbid conditions, and clinical characteristics. RESULTS: Worse pre-diagnosis HRQOL was significantly associated with greater risk of death across HRQOL measures. An above average physical or mental component summary score was associated with 16 and 24% decreases in the hazard of death, respectively (p < 0.0001). Being unable to perform ADLs, such as bathing oneself, was associated with an 89% increased hazard of death (p < 0.0001). Reporting "poor" versus "excellent" health was associated with a 74% increase in the hazard of death (p < 0.0001). CONCLUSION: This population-based study reinforces the importance of self-reported health status as a predictor for OS. Routine HRQOL screening may identify patients who could benefit from early interventions to improve HRQOL. Future studies should explore associations between changes in HRQOL before and after cancer diagnosis and OS.

Multidisciplinary Management of Breast Cancer During Pregnancy.

BACKGROUND: Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16-49 years), management decisions are challenging to both the patient and the multidisciplinary team. MATERIALS AND METHODS: Experts in breast cancer at the University of North Carolina conducted a targeted literature search regarding the multidisciplinary treatment approaches to BCDP: medical, surgical, and radiation oncology. Supportive care, including antiemetic agents, and imaging approaches were also reviewed. RESULTS: Review of the literature revealed key points in the management of BCDP. Surgical management is similar to that in nonpregnant patients; pregnant patients may safely undergo breast-conserving surgery. Recommendations should be tailored to the individual according to the clinical stage, tumor biology, genetic status, gestational age, and personal preferences. Anthracycline-based chemotherapy can be safely initiated only in the second and third trimesters. The rate of congenital abnormalities in children exposed to chemotherapy is similar to the national average (approximately 3%). Dosing of chemotherapy should be similar to that in the nonpregnant patient (i.e., actual body surface area). Antihuman epidermal growth factor receptor 2 therapy, radiation, and endocrine treatment are contraindicated in pregnancy and lactation. Care should include partnership with obstetricians. The literature regarding prognosis of BCDP is mixed. CONCLUSION: To maximize benefit and minimize risk to the mother and fetus, an informed discussion with the patient and her medical team should result in an individualized treatment plan, taking into account the timing of the pregnancy and the stage and subtype of the breast cancer. Because BCDP is rare, it is essential to collect patient data in international registries. The Oncologist 2017;22:324-334 IMPLICATIONS FOR PRACTICE: Breast cancer during pregnancy is a major ethical and professional challenge for both the patient and the multidisciplinary treatment team. Although the oncologic care is based on that of the non-pregnant breast cancer patient, there are many challenges from regarding the medical, surgical and radiation oncology and obstetrical aspects of care that need to be considered to deliver the safest and best treatment plan to both the mother and developing fetus.

Cardiac Toxicity After Radiotherapy for Stage III Non-Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy.

Purpose The significance of radiotherapy (RT) -associated cardiac injury for stage III non-small-cell lung cancer (NSCLC) is unclear, but higher heart doses were associated with worse overall survival in the Radiation Therapy Oncology Group (RTOG) 0617 study. We assessed the impact of heart dose in patients treated at our institution on several prospective dose-escalation trials. Patients and Methods From 1996 to 2009, 127 patients with stage III NSCLC (Eastern Cooperative Oncology Group performance status, 0 to 1) received dose-escalated RT to 70 to 90 Gy (median, 74 Gy) in six trials. RT plans and cardiac doses were reviewed. Records were reviewed for the primary end point: symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, pericarditis, significant arrhythmia, and heart failure). Cardiac risk was assessed by noting baseline coronary artery disease and calculating the WHO/International Society of Hypertension score. Competing risks analysis was used. Results In all, 112 patients were analyzed. Median follow-up for surviving patients was 8.8 years. Twenty-six patients (23%) had one or more events at a median of 26 months to first event (effusion [n = 7], myocardial infarction [n = 5], unstable angina [n = 3], pericarditis [n = 2], arrhythmia [n = 12], and heart failure [n = 1]). Heart doses (eg, heart mean dose; hazard ratio, 1.03/Gy; P = .002,), coronary artery disease ( P < .001), and WHO/International Society of Hypertension score ( P = .04) were associated with events on univariable analysis. Heart doses remained significant on multivariable analysis that accounted for baseline risk. Two-year competing risk-adjusted event rates for patients with heart mean dose < 10 Gy, 10 to 20 Gy, or ≥ 20 Gy were 4%, 7%, and 21%, respectively. Heart doses were not associated with overall survival. Conclusion Cardiac events were relatively common after high-dose thoracic RT and were independently associated with both heart dose and baseline cardiac risk. RT-associated cardiac toxicity after treatment of stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized.

Adoption of Stereotactic Body Radiotherapy for Stage IA Non-Small Cell Lung Cancer Across the United States.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a treatment option for stage I non-small cell lung cancer (NSCLC), providing a potentially curative therapy for patients who are nonsurgical candidates. This study describes the adoption of SBRT vs other treatment options across the United States, as well as commonly used dose-fractionation regimens. METHODS: We analyzed patients in the National Cancer Data Base. A total of 107 233 stage IA NSCLC patients diagnosed from 2008 to 2013 were included. We described the proportions of patients who received different surgical and radiation treatment options by year. A multivariable model was constructed to assess factors associated with patients receiving SBRT. In patients who received SBRT, we described the proportion of patients who received common dose/fractionation regimens. RESULTS: Use of SBRT increased from 6.7% to 16.3% from 2008 to 2013, with a corresponding decrease in lobectomy/pneumonectomy (49.5% to 43.7%). The rates of wedge resection, conventional radiotherapy, and no treatment remained relatively constant. Adoption of SBRT was lowest in small community centers (8.6% of patients by 2013). On multivariable analysis, older age and treatment at larger centers were associated with higher SBRT receipt, and black race and higher comorbidity were associated with lower SBRT receipt. There was statistically significant geographic variation. Common SBRT schemes were 10 Gy × 5 (19%), 18-20 Gy × 3 (31%), and 12 Gy × 4 (16%). CONCLUSIONS: SBRT adoption has been modest over time and has not substantially replaced less curative treatments. Lack of access to this technology in smaller cancer centers may have partly contributed to the slow adoption.

Evaluating the Effectiveness of Neoadjuvant Chemotherapy in Reducing Mastectomy for Women With Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. METHODS: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. RESULTS: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. CONCLUSIONS: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment.

Multidisciplinary Management of Breast Cancer Brain Metastases.

This review summarizes the most up-to-date approach to the multidisciplinary management of patients with breast cancer brain metastases. A brief overview of the epidemiology and biology of breast cancer brain metastasis is provided. The perspectives of radiation oncology, neurosurgery, and medical oncology-and landmark studies from each discipline-are all discussed. We also offer practical tips to help guide the treating physician, including data on antiseizure medications. Finally, we introduce the concept of a multidisciplinary clinic that combines input from medical and radiation oncology, neurosurgery, and support services, which we developed at the University of North Carolina as a coordinated and optimal approach to the management of patients with this complex disease.

Neoadjuvant Systemic Therapy Use for Younger Patients with Breast Cancer Treated in Different Types of Cancer Centers Across the United States.

BACKGROUND: Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. STUDY DESIGN: Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. RESULTS: Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). CONCLUSIONS: Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment.