Abstract Breast cancer survivorship guidelines recommend at least annual follow-up visits, yet the degree to which this occurs in clinical practice is uncertain. Claims data from a US commercial insurance database (OptumLabs) were used to identify women treated with curative intent surgery for newly diagnosed breast cancer between 2006 and 2014. In 25 035 women, median follow-up was 3 years. In the second year after surgery, 9.6% of the patients did not visit a primary care provider, an oncologist, or a surgeon (guideline-nonadherent). The guideline-nonadherent proportion increased from 7.8% in women diagnosed in 2006 to 12.2% in those diagnosed in 2014 (two-sided Wald P < .001). During years 2–6, guideline-nonadherence was also associated with older age, nonwhite race, no radiation, no chemotherapy, no endocrine therapy, and increasing time after surgery. There is a substantial and increasing rate of inadequate follow-up among breast cancer survivors. This has the potential to impair outcomes.
A Randomized Phase III Trial of Thalidomide and Prednisone as Maintenance Therapy Following Autologous Stem Cell Transplantation (ASCT) In Patients with Multiple Myeloma (MM): The NCIC CTG MY.10 Trial
Abstract Abstract 39 Three randomized trials have previously reported a progression-free survival (PFS) advantage for patients receiving thalidomide (T) maintenance post ASCT in MM. Two trials reported an overall survival (OS) advantage but the largest trial reported shows no OS advantage and in very high risk MM the use of T was deleterious. Recent trial reports demonstrate a PFS but not yet an OS advantage for patients receiving maintenance lenalidomide. We report results of NCIC CTG MY.10 which compared treatment with T (200 mg daily) and prednisone (50 mg alternate days) (T/P) until progression versus observation alone when used as maintenance therapy following ASCT. Importantly, OS was the 1ry endpoint of this study, 2ry endpoints were PFS, quality of life (QoL), toxicity, and the incidence of venous thromboembolism events (VTE). Eligibility: Patients with MM who had ASCT within 1 year of beginning initial treatment for their disease. Patients were randomized 60–100 days post ASCT and had no other medical condition precluding long term use of T/P. Results: 332 patients were enrolled. Median age was 58 years and the arms were balanced. Patients were stratified by age (<60 or >60), and CR status post transplant. Median follow up is 4 years. Only 14% of patients were in CR post transplant. 111 patients died (50 versus 61 in T/P vs. observation). The median OS was 5 years for observation, and has not yet been reached for T/P, however T/P maintenance therapy did not significantly prolong OS: p = 0.18, HR of maintenance vs. observation 0.77 (95% CI 0.53–1.13). The 4 year survival rate was 68% for T/P and 60% for observation. Age and response to transplant had no significant association with OS (p=0.21), while higher disease stage was associated with shorter OS (p=0.03). The median PFS was 28 months for T/P versus 17 months for observation: p<0.0001, HR of T/P vs. observation 0.56 (95% CI 0.43 – 0.73). The 4 year PFS rate was 32% for T/P treated patients versus 14% for patients on observation. At relapse, treatment by arm (T/P vs observation) included lenalidomide (39 vs 34%), T (13 vs 22%) or bortezomib (50 versus 46%). Non hematologic toxicities were seen in more patients with treatment (Grade 3: 92% T/P vs 49% observation, grade 4: 16% vs 7%). Common toxicities of all grades that were significantly higher in T/P treated patients included hyperglycemia, edema, hypertension, fatigue, Cushingoid appearance, constipation, mouth dryness, dyspepsia, anxiety, memory loss, sensory neuropathy, tremor, blurred vision, depressed consciousness, cataracts, dyspnea and bruising. 7% of patients on maintenance T/P developed a VTE in the absence of prophylaxis versus 0% on observation. NCIC CTG standardized response analysis was use to compare QoL data between the 2 treatment arms. Overall, patients on T/P had worse QoL specifically in physical (p=0.07), role (p=0.08), cognitive (p = 0.01) and global (p=0.06) domains, and worse symptoms with dyspnea (p = 0.0007), constipation (p<0.0001), thirst (p=0.003), swelling in leg (p=0.03), numbness (p=0.02), dry mouth (p<0.0001), and balance problems (p<0.0001). However, patients on T/P reported improvement in appetite (p 0.02), and sleep (p=0.04). Conclusions: T/P maintenance did not improve overall survival, the primary objective of this trial, although a trend in favor of T/P was seen. In contrast, PFS was significantly improved in the T/P arm while toxicity was demonstrably increased and quality of life diminished. Disclosures: Stewart: Millennium: Consultancy; Celgene: Honoraria. Trudel:Celgene: Honoraria. Bahlis:Celgene: Honoraria, Research Funding, Speakers Bureau. White:Celgene: Honoraria, Research Funding. Meyer:Celgene: Honoraria.
Moyamoya disease versus moyamoya syndrome: comparison of presentation and outcome in 338 hemispheres
OBJECTIVE Phenotypic differences between moyamoya disease (MMD) and moyamoya syndrome (MMS) remain unclear. The purpose of this study was to evaluate whether such differences exist when presentation, procedure-related, and outcome variables are compared quantitatively. METHODS The study cohort included 185 patients with moyamoya presenting to the Johns Hopkins Medical Institutions between 1994 and 2015. Baseline demographic, angiographic, and clinical characteristics were compared between patients with MMS and MMD, in addition to procedure-related complications and length of stay (LOS) after surgery. Stroke-free survival was compared between both disease variants after diagnosis. Kaplan-Meier analysis and Cox proportional hazards regression were used to compare stroke-free survival between surgically treated and conservatively managed hemispheres in both types of disease, while evaluating interaction between disease variant and management. RESULTS The cohort consisted of 137 patients with MMD (74%) with a bimodal age distribution and 48 patients with MMS (26%) who were mostly under 18 years of age (75%). Underlying diseases included sickle cell disease (48%), trisomy 21 (12%), neurofibromatosis (23%), and other disorders (17%). Patients with MMS were younger (p < 0.001) and less likely to be female (p = 0.034). Otherwise, baseline characteristics were statistically comparable. The rate of surgical complications was 33% in patients with MMD and 16% in patients with MMS (p = 0.097). Both groups of patients had a similar LOS after surgery (p = 0.823). Survival analysis (n = 330 hemispheres) showed similar stroke-free survival after diagnosis (p = 0.856) and lower stroke hazard in surgically managed patients in both MMD (hazard ratio [HR] 0.29, p = 0.028) and MMS (HR 0.62, p = 0.586). The disease variant (MMD vs MMS) did not affect the relationship between management approach (surgery vs conservative) and stroke hazard (p = 0.787). CONCLUSIONS MMD and MMS have largely comparable clinical and angiographic phenotypes with analogously favorable responses to surgical revascularization.
Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century
Background Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan‐Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. Results A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast‐conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor–positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node–negative, estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)‐negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy ( P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor–positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. Conclusions Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.
Ethics of Artificial Intelligence in Radiology: Summary of the Joint European and North American Multisociety Statement
This is a condensed summary of an international multisociety statement on ethics of artificial intelligence (AI) in radiology produced by the ACR, European Society of Radiology, RSNA, Society for Imaging Informatics in Medicine, European Society of Medical Imaging Informatics, Canadian Association of Radiologists, and American Association of Physicists in Medicine. AI has great potential to increase efficiency and accuracy throughout radiology, but it also carries inherent pitfalls and biases. Widespread use of AI-based intelligent and autonomous systems in radiology can increase the risk of systemic errors with high consequence and highlights complex ethical and societal issues. Currently, there is little experience using AI for patient care in diverse clinical settings. Extensive research is needed to understand how to best deploy AI in clinical practice. This statement highlights our consensus that ethical use of AI in radiology should promote well-being, minimize harm, and ensure that the benefits and harms are distributed among stakeholders in a just manner. We believe AI should respect human rights and freedoms, including dignity and privacy. It should be designed for maximum transparency and dependability. Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future. The radiology community should start now to develop codes of ethics and practice for AI that promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes.
Use of a Wearable EEG Headband as a Meditation Device for Women With Newly Diagnosed Breast Cancer: A Randomized Controlled Trial
Background: Breast cancer diagnosis and treatment affect quality of life and stress and are associated with fatigue. Meditation interventions are effective strategies for patients with breast cancer but are often limited by poor access, high cost, substantial time commitment, and poor adherence. In this feasibility study, we investigated the use of a portable, wearable, electroencephalographic device for guided meditation practices by breast cancer patients during the period from breast cancer diagnosis until 3 months after surgical treatment. Methods: We enrolled women (age = 20-75 years) who had received a recent diagnosis of breast cancer and planned to undergo surgical treatment. Participants were randomly assigned to perform guided meditation with the device (intervention group) or receive CD-based stress-reduction education (control group). Surveys were used to measure stress, quality of life, and fatigue at baseline, within 4 days before surgery, up to 14 days after surgery, and at 3 months after surgery. Results: In the intervention group, 15 of 17 participants (88.2%) completed the study; in the control group, 13 of 13 participants completed the study (100%). Participants in both groups had less fatigue and stress and improved quality of life at 2 weeks and 3 months after surgery compared with baseline, but there were no significant intergroup differences at any time point. Conclusion: The use of this wearable electroencephalographic device for meditation is a feasible strategy for patients with breast cancer.
A Transcriptionally Definable Subgroup of Triple-Negative Breast and Ovarian Cancer Samples Shows Sensitivity to HSP90 Inhibition
Abstract Purpose: We hypothesized that integrated analysis of cancer types from different lineages would reveal novel molecularly defined subgroups with unique therapeutic vulnerabilities. On the basis of the molecular similarities between subgroups of breast and ovarian cancers, we analyzed these cancers as a single cohort to test our hypothesis. Experimental Design: Identification of transcriptional subgroups of cancers and drug sensitivity analyses were performed using mined data. Cell line sensitivity to Hsp90 inhibitors (Hsp90i) was tested in vitro. The ability of a transcriptional signature to predict Hsp90i sensitivity was validated using cell lines, and cell line- and patient-derived xenograft (PDX) models. Mechanisms of Hsp90i sensitivity were uncovered using immunoblot and RNAi. Results: Transcriptomic analyses of breast and ovarian cancer cell lines uncovered two mixed subgroups comprised primarily of triple-negative breast and multiple ovarian cancer subtypes. Drug sensitivity analyses revealed that cells of one mixed subgroup are significantly more sensitive to Hsp90i compared with cells from all other cancer lineages evaluated. A gene expression classifier was generated that predicted Hsp90i sensitivity in vitro, and in cell line- and PDXs. Cells from the Hsp90i-sensitive subgroup underwent apoptosis mediated by Hsp90i-induced upregulation of the proapoptotic proteins Bim and PUMA. Conclusions: Our findings identify Hsp90i as a potential therapeutic strategy for a transcriptionally defined subgroup of ovarian and breast cancers. This study demonstrates that gene expression profiles may be useful to identify therapeutic vulnerabilities in tumor types with limited targetable genetic alterations, and to identify molecularly definable cancer subgroups that transcend lineage.
Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update
PURPOSE To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor–positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines .
Infections following Immediate Implant-Based Breast Reconstruction: A Case-Control Study over 11 Years
Background: Surgical-site infection after implant-based breast reconstruction adversely affects surgical outcomes and increases health care costs. This 11-year case-control study examines risk factors specific for surgical-site infection after immediate tissue expander/implant-based breast reconstruction. Methods: The authors performed a retrospective review to identify all consecutive patients with breast implant infections between 2006 and 2016. Patients who developed surgical-site infection after immediate tissue expander/implant-based breast reconstruction were included. Surgical-site infection was defined using the Centers for Disease Control and Prevention criteria; specifically, infections requiring hospital admission, intravenous antibiotics, or surgical intervention were included. The authors matched a control patient to each infection case by patient age and date of surgery. Patient demographics, medical comorbidities, and perioperative surgical variables were examined. Univariate and multivariable conditional logistic regression models were constructed. Results: A total of 270 breasts in 252 patients were evaluated. On multivariate analysis, patients with a higher body mass index (OR, 1.1 per 1 body mass index point increase; 95 percent CI, 1.0 to 1.2; p = 0.02), hypertension (OR, 6.5; 95 percent CI, 1.9 to 22.3; p = 0.002), neoadjuvant chemotherapy (OR, 2.6; 95 percent CI, 1.0 to 6.3; p = 0.04), axillary lymph node dissection (OR, 7.1; 95 percent CI, 1.7 to 29.2; p = 0.006), seroma formation (OR, 15.34; 95 percent CI, 3.7 to 62.5; p = 0.0001), and wound healing complications (OR, 23.91; 95 percent CI, 6.1 to 93.4; p < 0.0001) were significantly associated with surgical-site infection. Conclusions: Women with obesity, women with hypertension, and those treated with neoadjuvant chemotherapy are at increased risk of surgical-site infection. Further risks are also associated with postoperative seroma and wound complications. This may help patient selection and counseling, adjusted based on risk factors regarding complications of immediate implant-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
Two-Staged Implant-Based Breast Reconstruction: A Long-Term Outcome Study in a Young Population
Background and objectives: Differences in patient anatomy and physiology exist between young and older patients undergoing breast reconstruction after mastectomy. Breast cancer has been described as being more aggressive, more likely to receive radiation, contralateral mastectomy, as well as bilateral reconstruction in young patients. Our purpose is to report long-term experience on two-staged implant-based breast reconstruction (IBR) in young females, with complication sub-analysis based on obesity and adjuvant radiation. Materials and Methods: Retrospective chart review of all consecutive young patients who underwent two-staged IBR at our institution, between 2000 and 2016, was performed. Patients between 15 and 40 years old with least 1-year follow-up were included. Univariate logistic regression models and receiver operating characteristic (ROC) curves were created. Results: Overall 594 breasts met our inclusion criteria. The mean age was 34 years, and the median follow-up was 29.6 months. Final IBR was achieved in 98% of breasts. Overall, 12% of breasts had complications, leading to explantations of 5% of the devices. Adjuvant radiation was followed by higher rates of total device explantations (p = 0.003), while obese patients had higher rates of total complications (p < 0.001). For each point increase in BMI, the odds of developing complications increased 8.1% (p < 0.001); the cutoff BMI to predict higher complications was 24.81 kg/m2. Conclusions: This population demonstrates high successful IBR completion and low explantation rates. These data suggest that obese women and those with planned adjuvant radiation deserve special counseling about their higher risk of complications.