Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population.

Modeling the Cost-Effectiveness of Adjuvant Osimertinib for Patients with Resected EGFR-mutant Non-Small Cell Lung Cancer.

INTRODUCTION: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib was recently approved for resected EGFR-mutant stages IB-IIIA non-small cell lung cancer due to improved disease-free survival (DFS) in this population compared with placebo. This study aimed to evaluate the cost-effectiveness (CE) of this strategy. MATERIALS AND METHODS: We constructed a Markov model using post-resection health state transitions with digitized DFS data from the ADAURA trial to compare cost and quality-adjusted life years (QALYs) of 3 years of adjuvant osimertinib versus placebo over a 10-year time horizon. An overall survival (OS) benefit of 5% was assumed. Costs and utility values were derived from Medicare reimbursement data and literature. A CE threshold of 3 times the gross domestic product per capita was used. Sensitivity analyses were performed. RESULTS: The incremental cost-effectiveness ratio for adjuvant osimertinib was $317 119 per QALY-gained versus placebo. Initial costs of osimertinib are higher in years 1-3. Costs due to progressive disease (PD) are higher in the placebo group through the first 6.5 years. Average pre-PD, post-PD, and total costs were $2388, $379 047, and $502 937, respectively, in the placebo group, and $505 775, $255 638, and $800 697, respectively, in the osimertinib group. Sensitivity analysis of OS gains reaches CE with an hazard ratio (HR) of 0.70-0.75 benefit of osimertinib over placebo. A 50% discount to osimertinib drug cost yielded an ICER of $115 419. CONCLUSIONS: Three-years of adjuvant osimertinib is CE if one is willing to pay $317 119 more per QALY-gained. Considerable OS benefit over placebo or other economic interventions will be needed to reach CE.

Analysis of composite endpoints with component-wise censoring in the presence of differential visit schedules.

Composite endpoints are very common in clinical research, such as recurrence-free survival in oncology research, defined as the earliest of either death or disease recurrence. Because of the way data are collected in such studies, component-wise censoring is common, where, for example, recurrence is an interval-censored event and death is a right-censored event. However, a common way to analyze such component-wise censored composite endpoints is to treat them as right-censored, with the date at which the non-fatal event was detected serving as the date the event occurred. This approach is known to introduce upward bias when the Kaplan-Meier estimator is applied, but has more complex impact on semi-parametric regression approaches. In this article we compare the performance of the Cox model estimators for right-censored data and the Cox model estimators for interval-censored data in the context of component-wise censored data where the visit process differs across levels of a covariate of interest, a common scenario in observational data. We additionally examine estimators of the cause-specific hazard when applied to the individual components of such component-wise censored composite endpoints. We found that when visit schedules differed according to levels of a covariate of interest, the Cox model estimators for right-censored data and the estimators for cause-specific hazards were increasingly biased as the frequency of visits decreased. The Cox model estimator for interval-censored data with censoring at the last disease-free date is recommended for use in the presence of differential visit schedules.

Cardiovascular risk factors, radiation therapy, and myocardial infarction among lymphoma survivors.

BACKGROUND: Mediastinal radiation is associated with increased risk of myocardial infarction (MI) among non-Hodgkin lymphoma (NHL) survivors. OBJECTIVE: To evaluate how preexisting cardiovascular risk factors (CVRFs) modify the association of mediastinal radiation and MI among a national population of NHL survivors with a range of CVRFs. MATERIAL AND METHODS: Using Danish registries, we identified adults diagnosed with lymphoma 2000-2010. We assessed MI from one year after diagnosis through 2016. We ascertained CVRFs (hypertension, dyslipidemia, and diabetes), vascular disease, and intrinsic heart disease prevalent at lymphoma diagnosis. We used multivariable Cox regression to test the interaction between preexisting CVRFs and receipt of mediastinal radiation on subsequent MI. RESULTS: Among 3151 NHL survivors (median age 63, median follow-up 6.5 years), 96 were diagnosed with MI. Before lymphoma, 32% of survivors had ≥1 CVRF. 8.5% of survivors received mediastinal radiation. In multivariable analysis, we found that mediastinal radiation (HR = 1.96; 95% CI = 1.09-3.52), and presence of ≥1 CVRF (HR = 2.71; 95% CI = 1.77-4.15) were associated with an increased risk of MI. Although there was no interaction on the relative scale (p = 0.14), we saw a clinically relevant absolute increase in risk for patients with CVRF from 10-year of MI of 10.5% without radiation to 29.5% for those undergoing radiation. CONCLUSION: Patients with CVRFs have an importantly higher risk of subsequent MI if they have mediastinal radiation. Routine evaluation of CVRFs and optimal treatment of preexisting cardiovascular disease should continue after receiving cancer therapy. In patients with CVRFs, mediastinal radiation should only be given if oncologic benefit clearly outweighs cardiovascular harm.

Bayesian basket trial design with false-discovery rate control.

BACKGROUND: Recent advances in developing "tumor agnostic" oncology therapies have identified molecular targets that define patient subpopulations in a manner that supersedes conventional criteria for cancer classification. These successes have produced effective targeted therapies that are administered to patients regardless of their tumor histology. Trials have evolved as well with master protocol designs. By blending translational and clinical science, basket trials in particular are well-suited to investigate and develop targeted therapies among multiple cancer histologies. However, basket trials intrinsically involve more complex design decisions, including issues of multiple testing across baskets, and guidance for investigators is needed. METHODS: The sensitivity of the multisource exchangeability model to prior specification under differing degrees of response heterogeneity is explored through simulation. Then, a multisource exchangeability model design that incorporates control of the false-discovery rate is presented and a simulation study compares the operating characteristics to a design where the family-wise error rate is controlled and to the frequentist approach of treating the baskets as independent. Simulations are based on the original design of a real-world clinical trial, the SUMMIT trial, which investigated Neratinib treatment for a variety of solid tumors. The methods studied here are specific to single-arm phase II trials with binary outcomes. RESULTS: Values of prior probability of exchangeability in the multisource exchangeability model between 0.1 and 0.3 provide the best trade-offs between gain in precision and bias, especially when per-basket sample size is below 30. Application of these calibration results to a re-analysis of the SUMMIT trial showed that the breast basket exceeded the null response rate with posterior probability of 0.999 while having low posterior probability of exchangeability with all other baskets. Simulations based on the design of the SUMMIT trial revealed that there is meaningful improvement in power even in baskets with small sample size when the false-discovery rate is controlled as opposed to the family-wise error rate. For example, when only the breast basket was active, with a sample size of 25, the power was 0.76 when the false-discovery rate was controlled at 0.05 but only 0.56 when the family-wise error rate was controlled at 0.05, indicating that impractical sample sizes for the phase II setting would be needed to achieve acceptable power while controlling the family-wise error rate in this setting of a trial with 10 baskets. CONCLUSION: Selection of the prior exchangeability probability based on calibration and incorporation of false-discovery rate control result in multisource exchangeability model designs with high power to detect promising treatments in the context of phase II basket trials.

Patterns of invasive recurrence among patients originally treated for ductal carcinoma in situ by breast-conserving surgery versus mastectomy.

PURPOSE: Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy. METHODS: From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy. RESULTS: 452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p < 0.001) compared with the BCS group. A higher proportion of invasive recurrences were local after BCS (93%; 343/367), whereas 88% (75/85) of recurrences after mastectomy were regional or distant (p < 0.001). The median time to first invasive recurrence was not different between surgical groups (BCS: 6.4 years vs. mastectomy: 5.5 years; p = 0.12). CONCLUSIONS: Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.

Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer. METHODS: Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method. RESULTS: Of 132 MBC patients, those with heterologous mesenchymal MBC (n = 45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78-0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32-0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6-3.3; p < 0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response. CONCLUSIONS: Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC's unique biology.

Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes.

BACKGROUND: The development of novel therapies for the myelodysplastic syndromes (MDS) is hampered by inadequate trial recruitment. Factors contributing to low trial accrual are incompletely understood. METHODS: This study analyzed a pooled patient database from institutions of the US MDS Clinical Research Consortium to compare the characteristics of participants in interventional trials with those of patients who did not enroll in a trial. RESULTS: Data were identified for 1919 patients with MDS, and 449 of these patients (23%) participated in an interventional clinical trial. The median age of all patients was 68 years, and 64% were male. Patients who participated in trials were significantly younger than nonparticipants (P = .014), and men were more likely to participate in a trial (71% of trial participants were male, whereas 61% of nonparticipants were; P < .001). Race and ethnicity were not associated with trial enrollment. Patients in more affluent ZIP codes had a higher participation rate (P < .001). Patients with intermediate- and high-risk disease according to the revised International Prognostic Scoring System were overrepresented (P = .004), and trial participants less frequently had treatment-related disease (P < .001). In multivariable analyses, participation in a clinical trial was associated with a reduced hazard of death (P = .004). Even at large referral centers, only a minority of patients with MDS enrolled in interventional trials. CONCLUSIONS: Restrictive trial eligibility criteria that exclude patients with MDS on account of age, comorbidities, or a history of another cancer are limit enrollment of MDS patients to clinical trials. Gaining insight into the barriers to trial accrual may help investigators and study sponsors to design trials that will accrue more rapidly and augment treatment options for patients with MDS.

Axillary management for young women with breast cancer varies between patients electing breast-conservation therapy or mastectomy.

PURPOSE: Axillary treatment strategies for the young woman with early-stage, clinically node-negative breast cancer undergoing upfront surgery found to have 1-3 positive sentinel lymph nodes (SLNs) differ significantly after BCT and mastectomy. Here we compare axillary lymph node dissection (ALND) and regional nodal irradiation (NRI) rates between women electing breast-conservation therapy (BCT) versus mastectomy. METHODS: From 2010 to 2016, women age < 50 years with clinical T1-T2N0 breast cancer having upfront surgery and found to have a positive SLN were identified. ALND and/or NRI receipt were compared between groups. RESULTS: 192 women undergoing BCT and 165 undergoing mastectomy were identified (median age: 44 years). 5.2% (10/192) of women undergoing BCT had an ALND versus 87% (144/165) of women undergoing mastectomy (p < 0.01). NRI was given to 48% (78/165) of mastectomy patients compared to 30% (57/192) of BCT patients (p < 0.01). Of the 75 mastectomy patients with 1-2 total positive lymph nodes after completion ALND, 44% received NRI. Women undergoing mastectomy were significantly more likely to receive both ALND and NRI than women undergoing BCS (45% vs 6%, p < 0.01). CONCLUSION: Young cT1-2N0 breast cancer patients found to have 1-3 SLN metastases received ALND, NRI, and combined ALND/NRI more frequently if they elected mastectomy over BCT. Use of both ALND and postmastectomy radiotherapy (PMRT) in this population could be reduced in the future by omitting ALND in patients for whom the need for PMRT is clear with the finding of 1-2 SLN metastases.

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. Patient summary: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.

Contralateral Prophylactic Mastectomy Use After Neoadjuvant Chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) for breast cancer increases breast-conserving surgery (BCS) rates, but many women opt for mastectomy with contralateral prophylactic mastectomy (CPM). Here we evaluate factors associated with CPM use in women undergoing mastectomy post-NAC. METHODS: A retrospective institutional NAC database review identified women with clinical stage I-III, unilateral invasive breast cancer undergoing unilateral mastectomy (UM) or CPM mastectomy from 9/2013 to 12/2017. Clinical/pathologic characteristics, imaging, and presence of contraindications to BCS post-NAC were compared, with subset analysis of BCS candidates. The multivariable analysis was adjusted for potential confounders. RESULTS: Five hundred sixty-nine women underwent mastectomy after NAC, 297 (52%) UM and 272 (48%) CPM. On univariable analysis, younger age, BRCA+, lower pre-NAC clinical stage, pathologic complete response, and axillary surgery extent were associated with CPM (all p < 0.01). Favorable post-NAC clinical factors of no residual palpable disease, clinically negative nodes, complete response on breast imaging, and no post-NAC contraindication to BCS were also associated with CPM (all p < 0.01). On multivariable analysis, young age (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.91-0.95), lower pre-NAC stage (OR 0.51, 95% CI 0.34-0.77), and no contraindication to BCS (OR 3.12, 95% CI 2.02-4.82) were significantly associated with CPM. Among the 203 (35%) women who had no contraindications to BCS post-NAC, 145 (71%) underwent CPM. BRCA+ and family history were reasons more frequently cited for mastectomy among CPM than UM (p < 0.001). CONCLUSIONS: CPM was performed in 48% of women undergoing mastectomy after NAC; younger women with earlier-stage cancers were more likely to undergo CPM. While increased use of CPM in women with more favorable disease is medically appropriate, our findings indicate a lost opportunity for use of BCS.

The Tyrer-Cuzick Model Inaccurately Predicts Invasive Breast Cancer Risk in Women With LCIS.

BACKGROUND: The Tyrer-Cuzick model has been shown to overestimate risk in women with atypical hyperplasia, although its accuracy among women with lobular carcinoma in situ (LCIS) is unknown. We evaluated the accuracy of the Tyrer-Cuzick model for predicting invasive breast cancer (IBC) development among women with LCIS. METHODS: Women with LCIS participating in surveillance from 1987 to 2017 were identified from a prospectively maintained database. Tyrer-Cuzick score (version 7) was calculated near the time of LCIS diagnosis. Patients with prior or concurrent breast cancer, a BRCA mutation, receiving chemoprevention, or with pleomorphic LCIS were excluded. Invasive cancer-free probability was estimated using the Kaplan-Meier method. RESULTS: A total of 1192 women with a median follow-up of 6 years (interquartile range [IQR] 2.5-9.9) were included. Median age at LCIS diagnosis was 49 years (IQR 45-55), 88% were white; 37% were postmenopausal, 28% had ≥ 1 first-degree family member with breast cancer, and 13% had ≥ 2 second-degree family members with breast cancer. In total, 128 patients developed an IBC; median age at diagnosis was 54 years (IQR 49-61). Five- and 10-year cumulative incidences of invasive cancer were 8% (95% confidence interval [CI] 6-9%) and 14% (95% CI 12-17%), respectively. The median Tyrer-Cuzick 10-year risk score was 20.1 (IQR 17.4-24.3). Discrimination measured by the C-index was 0.493, confirming that the Tyrer-Cuzick model is not well calibrated in this patient population. CONCLUSIONS: The Tyrer-Cuzick model is not accurate and may overpredict IBC risk for women with LCIS, and therefore should not be used for breast cancer risk assessment in this high-risk population.

Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer?

BACKGROUND: The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists. METHODS: This retrospective review included all premenopausal women diagnosed at our institution with stage 0-III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed. RESULTS: A total of 334 women were identified. Median age was 35 years (interquartile range 32-38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the most frequent referring service (n = 194, 58.1%), with significantly more REI referrals compared to Breast Medicine and Genetics services (p = 0.002). Nulliparity was associated with REI referral (p < 0.0001). Adjuvant chemotherapy (p = 0.003) was associated with pursuing REI referral, whereas NAC (p < 0.001) was associated with declining REI referral. CONCLUSIONS: Most women elected to consult with an REI specialist, confirming strong interest in fertility preservation among premenopausal women with breast cancer. However, women receiving NAC more frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.

Correction to: Is Low-Volume Disease in the Sentinel Node After Neoadjuvant Chemotherapy an Indication for Axillary Dissection?

The following are corrections to the original article.

Do Body Mass Index and Breast Density Impact Cancer Risk Among Women with Lobular Carcinoma In Situ?

PURPOSE: Both body mass index (BMI) and breast density impact breast cancer risk in the general population. Whether obesity and density represent additive risk factors in women with lobular carcinoma in situ (LCIS) is unknown. METHODS: Patients diagnosed with LCIS from 1988 to 2017 were identified from a prospectively maintained database. BMI was categorized by World Health Organization classification. Density was captured as the mammographic Breast Imaging Reporting and Data System (BIRADS) value. Other covariates included age at LCIS diagnosis, menopausal status, family history, chemoprevention, and prophylactic mastectomy. Cancer-free probability was estimated using the Kaplan-Meier method, and Cox regression models were used for univariable and multivariable analyses. RESULTS: A total of 1222 women with LCIS were identified. At a median follow-up of 7 years, 179 women developed breast cancer (121 invasive, 58 ductal carcinoma in situ); 5- and 10-year cumulative incidences of breast cancer were 10% and 17%, respectively. In multivariable analysis, increased breast density (BIRADS C/D vs. A/B) was significantly associated with increased hazard of breast cancer (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.52-3.88), whereas BMI was not. On multivariable analysis, chemoprevention use was associated with a significantly decreased hazard of breast cancer (HR 0.49, 95% CI 0.29-0.84). Exploratory analyses did not demonstrate significant interaction between BMI and menopausal status, BMI and breast density, BMI and chemoprevention use, or breast density and chemoprevention. CONCLUSIONS: Breast cancer risk among women with LCIS is impacted by breast density. These results aid in personalizing risk assessment among women with LCIS and highlight the importance of chemoprevention counseling for risk reduction.

Increase in Utilization of Nipple-Sparing Mastectomy for Breast Cancer: Indications, Complications, and Oncologic Outcomes.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. METHODS: From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. RESULTS: Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24-75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p < 0.001). There was no difference in family history, genetic mutations, smoking status, neoadjuvant chemotherapy, prior radiation, nodal involvement, or tumor subtype. Twenty-one (4.5%) nipple excisions were performed, of which 14 were performed for cancer at the nipple margin. Forty-four breasts (9.4%) had complications that required re-operation. Fifteen patients had locoregional recurrence or distant metastasis. CONCLUSIONS: NSM use for invasive carcinoma has doubled at our institution since 2011, while postoperative complications and recurrence rates remain low. Our experience supports the selective use of NSM in the malignant setting with careful patient selection.

Guidelines for Reporting of Figures and Tables for Clinical Research in Urology.

In an effort to improve the presentation of and information within tables and figures in clinical urology research, we propose a set of appropriate guidelines. We introduce six principles: (1) include graphs only if they improve the reader's ability to understand the study findings; (2) think through how a graph might best convey information, do not just select a graph from preselected options on statistical software; (3) do not use graphs to replace reporting key numbers in the text of a paper; (4) graphs should give an immediate visual impression of the data; (5) make it beautiful; and (6) make the labels and legend clear and complete. We present a list of quick "dos and don'ts" for both tables and figures. Investigators should feel free to break any of the guidelines if it would result in a beautiful figure or a clear table that communicates data effectively. That said, we believe that the quality of tables and figures in the medical literature would improve if these guidelines were to be followed. PATIENT SUMMARY: A set of guidelines were developed for presenting figures and tables in urology research. The guidelines were developed by a broad group of statistical experts with special interest in urology.

Prediagnostic serum polychlorinated biphenyl concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

BACKGROUND: Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the 1970s, they are highly persistent in the environment and bioaccumulate. Whether PCBs are associated with liver cancer risk at general population levels is unknown. METHODS: This study consisted of 136 incident liver cancer cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the Norwegian Janus cohort. Sera collected in the 1960s-1980s were measured for 37 PCB congeners and markers of hepatitis B (HBV) and C (HCV) infection. Odds ratios (OR) and 95% confidence intervals (CI) for tertiles of each lipid-adjusted PCB were estimated from conditional logistic regression. We also examined the molar sum of congeners in groups: total PCBs; low, medium, and high chlorination; and Wolff functional groups. RESULTS: Concentrations of individual congeners from the 1960s/1970s sera ranged from 1.3-123.0 and 1.4-116.0 ng/g lipid among MHC cases and controls, respectively, and from 1.9-258.0 and 1.9-271.0 ng/g lipid among Janus cases and controls, respectively. Among MHC participants with sera from the 1960s, collected an average of 27 years before diagnosis among cases, the top tertile of PCBs 151, 170, 172, 177, 178, 180, and 195 was significantly associated with elevated odds of liver cancer (OR range = 2.01-2.38); most of these congeners demonstrated exposure-response trends. For example, ORtertile 3vs1 = 2.38 (95% CI: 1.22-4.64, p-trend = 0.01) for PCB 180. As a group, Wolff group 1b congeners, which are biologically persistent and weak phenobarbital inducers, were associated with increased odds. In MHC participants, ever vs. never HBV or HCV infection modified the PCB-liver cancer associations. There was little evidence of an association between PCBs and odds of liver cancer among the Janus cohort. DISCUSSION: We observed associations between a number of PCB congeners and increased odds of liver cancer among MHC, but not Janus, participants with sera from the 1960s/1970s.

Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.