Machine learning radiomics can predict early liver recurrence after resection of intrahepatic cholangiocarcinoma
Jolissaint, Joshua S; Wang, Tiegong; Soares, Kevin C; Chou, Joanne F; Gönen, Mithat; Pak, Linda M; Boerner, Thomas; Do, Richard K G; Balachandran, Vinod P; D'Angelica, Michael I; Drebin, Jeffrey A; Kingham, T P; Wei, Alice C; Jarnagin, William R; Chakraborty, Jayasree
BACKGROUND:Most patients recur after resection of intrahepatic cholangiocarcinoma (IHC). We studied whether machine-learning incorporating radiomics and tumor size could predict intrahepatic recurrence within 1-year. METHODS:This was a retrospective analysis of patients with IHC resected between 2000 and 2017 who had evaluable computed tomography imaging. Texture features (TFs) were extracted from the liver, tumor, and future liver remnant (FLR). Random forest classification using training (70.3%) and validation cohorts (29.7%) was used to design a predictive model. RESULTS:138 patients were included for analysis. Patients with early recurrence had a larger tumor size (7.25Â cm [IQR 5.2-8.9] vs. 5.3Â cm [IQR 4.0-7.2], PÂ =Â 0.011) and a higher rate of lymph node metastasis (28.6% vs. 11.6%, PÂ =Â 0.041), but were not more likely to have multifocal disease (21.4% vs. 17.4%, PÂ =Â 0.643). Three TFs from the tumor, FD1, FD30, and IH4 and one from the FLR, ACM15, were identified by feature selection. Incorporation of TFs and tumor size achieved the highest AUC of 0.84 (95% CI 0.73-0.95) in predicting recurrence in the validation cohort. CONCLUSION/CONCLUSIONS:This study demonstrates that radiomics and machine-learning can reliably predict patients at risk for early intrahepatic recurrence with good discrimination accuracy.
Surgical Treatment after Neoadjuvant Systemic Therapy in Young Women with Breast Cancer: Results from a Prospective Cohort Study
Kim, Hee Jeong; Dominici, Laura; Rosenberg, Shoshana M; Zheng, Yue; Pak, Linda M; Poorvu, Philip D; Ruddy, Kathryn J; Tamimi, Rulla; Schapira, Lidia; Come, Steven E; Peppercorn, Jeffrey; Borges, Virginia F; Warner, Ellen; Vardeh, Hilde; Collins, Laura C; Gaither, Rachel; King, Tari A; Partridge, Ann H
OBJECTIVE:We aimed to investigate eligibility for breast-conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. BACKGROUND:Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NAC influences surgical decisions in young women. METHODS:The Young Women's Breast Cancer Study (YWS), a multicenter prospective cohort of women diagnosed with breast cancer at age â‰¤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response (cCR and pCR), and surgery were also assessed. RESULTS:Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (p < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%) and family history (5%). From 2006 to 2016, the rates of NST (p = 0.0012), cCR (p < 0.0001) and bilateral mastectomy (p < 0.0001) increased, but the rate of BCS did not increase (p = 0.34). CONCLUSION/CONCLUSIONS:While the proportion of young women eligible for BCS increased after NST, many patients choose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.
Addressing the problem of overtreatment in breast cancer
Pak, Linda M; Morrow, Monica
INTRODUCTION/UNASSIGNED:As breast cancer treatment options have multiplied and biologic diversity within breast cancer has been recognized, the use of the same treatment strategies for patients with early-stage and favorable disease, and for those with biologically aggressive disease, has been questioned. In addition, as patient-reported outcome measures have called attention to the morbidity of many common treatments, and as the cost of breast cancer care has continued to increase, reduction in the overtreatment of breast cancer has assumed increasing importance. AREAS COVERED/UNASSIGNED:Here we review selected aspects of surgery, radiation oncology, and medical oncology for which scientific evidence supports de-escalation for invasive carcinoma and ductal carcinoma in situ, and assess strategies to address overtreatment. EXPERT OPINION/UNASSIGNED:The problems of breast cancer overtreatment we face today are based on improved understanding of the biology of breast cancer and abandonment of the 'one-size-fits-all' approach. As breast cancer care becomes increasingly complex, and as our knowledge base continues to increase exponentially, these problems will only be magnified in the future. To continue progress, the move must be made from advocating the maximum-tolerated treatment to advocating the minimum-effective one.
Tumor phenotype and concordance in synchronous bilateral breast cancer in young women
Pak, Linda M; Gaither, Rachel; Rosenberg, Shoshana M; Ruddy, Kathryn J; Tamimi, Rulla M; Peppercorn, Jeffrey; Schapira, Lidia; Borges, Virginia F; Come, Steven E; Warner, Ellen; Snow, Craig; Collins, Laura C; King, Tari A; Partridge, Ann H
PURPOSE/OBJECTIVE:Synchronous bilateral breast cancer is uncommon, and its pattern and incidence among younger women is unknown. Here we report the incidence, phenotypes, and long-term oncologic outcomes of bilateral breast cancer in women enrolled in the Young Women's Breast Cancer Study (YWS). METHODS:The YWS is a multi-center, prospective cohort study of women with breast cancer diagnosed at ageâ€‰â‰¤â€‰40Â years. Those with synchronous bilateral breast cancer formed our study cohort. Tumor phenotypes were categorized as luminal A (hormone receptor (HR)+/HER2-/grade 1/2), luminal B (HR+â€‰/HER2+â€‰or HER2- and grade 3), HER2-enriched (HR-/HER2+), or basal-like (HR-/HER2-). Descriptive statistics were used to evaluate tumor phenotypes of bilateral cancers for concordance. RESULTS:Among 1302 patients enrolled in the YWS, 21 (1.6%) patients had synchronous bilateral disease. The median age of diagnosis was 38Â years (range 18-40Â years). Seventeen (81.0%) underwent genetic testing with 6 found to have pathogenic germline mutations in BRCA1, BRCA2, or TP53. The majority of patients (76.2%) underwent bilateral mastectomy. On pathology, 2 patients had bilateral in-situ disease, 6 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, 10 (76.9%) had bilateral luminal tumors and, when fully characterized, 6 were of the same luminal subtype. Only 1 patient had bilateral basal-like breast cancer. At median follow-up of 8.2Â years, 14 patients are alive with no recurrent disease. CONCLUSIONS:Bilateral breast cancer is uncommon among young women diagnosed with breast cancer at ageâ€‰â‰¤â€‰40. In our cohort, the majority of invasive tumors were of the luminal phenotype, though some differed by grade or HER2 status. These findings support the need for thorough pathologic workup of bilateral disease when it is found in young women with breast cancer to determine risk and tailor treatment.
Non-clinical Drivers of Variation in Preoperative MRI Utilization for Breast Cancer
Pak, Linda M; Banaag, Amanda; Koehlmoos, Tracey P; Nguyen, Louis L; Learn, Peter A
BACKGROUND:Preoperative magnetic resonance imaging (MRI) utilization in breast cancer treatment has increased significantly over the past 2 decades, but its use continues to have interprovider variability and disputed clinical indications. OBJECTIVE:The aim of this study was to evaluate non-clinical factors associated with preoperative breast MRI utilization. METHODS:This study utilized TRICARE claims data from 2006 to 2015. TRICARE provides health benefits for active duty service members, retirees, and their dependents at both military (direct care with salaried physicians) and civilian (purchased care under fee-for-service structure) facilities. We studied patients aged 25-64Â years with a breast cancer diagnosis who had undergone mammogram/ultrasound (MMG/US) alone or with subsequent breast MRI prior to surgery. Facility characteristics included urban-rural location according to the National Center for Health Statistics classification. Adjusted multivariable logistic regression tests were used to identify independent factors associated with preoperative breast MRI utilization. RESULTS:Of the 25,392 identified patients, 64.7% (nâ€‰=â€‰16,428) received preoperative MMG/US alone, while 35.3% (nâ€‰=â€‰8964) underwent additional MRI. Younger age, Charlson Comorbidity Index scoreâ€‰â‰¥â€‰2, active duty or retired beneficiary category, officer rank (surrogate for socioeconomic status), Air Force service branch, metropolitan location, and purchased care were associated with an increased likelihood of preoperative MRI utilization. Non-metropolitan location and Navy service branch were associated with decreased MRI use. CONCLUSION/CONCLUSIONS:After controlling for expected clinical risk factors, patients were more likely to receive additional MRI when treated at metropolitan facilities or through the fee-for-service system. Both associations may point toward non-clinical incentives to perform MRI in the treatment of breast cancer.
ASO Author Reflections: Preoperative Breast MRI and Provider-Induced Demand
Pak, Linda M; Learn, Peter A
Racial Differences in Extremity Soft Tissue Sarcoma Treatment in a Universally Insured Population
Pak, Linda M; Kwon, Nicollette K; Baldini, Elizabeth H; Learn, Peter A; Koehlmoos, Tracey; Haider, Adil H; Raut, Chandrajit P
BACKGROUND:In prior reports from population-based databases, black patients with extremity soft tissue sarcoma (ESTS) have lower reported rates of limb-sparing surgery and adjuvant treatment. The objective of this study was to compare the multimodality treatment of ESTS between black and white patients within a universally insured and equal-access health care system. METHODS:Claims data from TRICARE, the US Department of Defense insurance plan that provides health care coverage for 9 million active-duty personnel, retirees, and dependents, were queried for patients younger than 65Â y with ESTS who underwent limb-sparing surgery or amputation between 2006 and 2014 and identified as black or white race. Multivariable logistic regression analysis was used to evaluate the impact of race on the utilization of surgery, chemotherapy, and radiation. RESULTS:Of the 719 patients included for analysis, 605 patients (84%) were white and 114 (16%) were black. Compared with whites, blacks had the same likelihood of receiving limb-sparing surgery (odds ratio [OR], 0.861; 95% confidence interval [95% CI], 0.284-2.611; PÂ =Â 0.79), neoadjuvant radiation (OR, 1.177; 95% CI, 0.204-1.319; PÂ =Â 0.34), and neoadjuvant (OR, 0.852; 95% CI, 0.554-1.311; PÂ =Â 0.47) and adjuvant (OR, 1.211; 95% CI, 0.911-1.611; PÂ =Â 0.19) chemotherapy; blacks more likely to receive adjuvant radiation (OR, 1.917; 95% CI, 1.162-3.162; PÂ =Â 0.011). CONCLUSIONS:In a universally insured population, racial differences in the rates of limb-sparing surgery for ESTS are significantly mitigated compared with prior reports. Biologic or disease factors that could not be accounted for in this study may contribute to the increased use of adjuvant radiation among black patients.
Prediction of Discharge Destination Following Major Hepatectomy
Mahvi, David A; Pak, Linda M; Fields, Adam C; Urman, Richard D; Gold, Jason S; Whang, Edward E
BACKGROUND:Anatomic hepatectomies can be associated with complicated post-operative recoveries, often with discharge to post-acute care facilities. This study identifies preoperative and intraoperative factors associated with increased risk for non-home discharge destination after major hepatectomy. METHODS:Patients undergoing major hepatectomy were identified in the NSQIP Targeted Hepatectomy Dataset (2014-2016). Multivariable logistic regression was performed. Patients from 2014 to 2015 were used for training cohort with nomogram generation and 2016 for validation cohort. RESULTS:Overall, 226 of 3750 patients (6.0%) were discharged to rehab, skilled care, or acute care facilities. Preoperative factors associated with non-home discharge on multivariable analysis were outside patient transfers, older age, presence of ascites, ASA physical status 3 or higher, and low preoperative hematocrit (all pÂ <Â 0.05). Intraoperative factors significantly predictive were concurrent lysis of adhesions, Pringle maneuver, and biliary reconstruction (all pÂ <Â 0.05). Predictors from testing cohort were validated in validation cohort. Nomograms based on preoperative variables alone and both preoperative and intraoperative variables were generated. CONCLUSION:We identify several preoperative and intraoperative factors that are associated with increased risk for non-home discharge after major hepatectomy. Preoperative anemia represents a potentially modifiable risk factor. Nomograms for preoperative planning as well as immediately following surgery were generated.
Discharge destination following pancreaticoduodenectomy: A NSQIP analysis of predictive factors and post-discharge outcomes
Mahvi, David A; Pak, Linda M; Urman, Richard D; Gold, Jason S; Whang, Edward E
INTRODUCTION:Pancreaticoduodenectomy is a complex surgical procedure. The purpose of this study was to identify factors associated non-home discharge destination and to characterize outcomes after non-home discharge. METHODS:10,719 pancreaticoduodenectomy cases contained in the National Surgical Quality Improvement Program (NSQIP) Targeted Pancreatectomy dataset (years 2014-2016) were examined with univariate and multivariate logistic regression. RESULTS:1336 patients (12.5%) were discharged to rehabilitation, skilled care, or acute care facilities. Preoperative factors significantly associated with non-home discharge on multivariate analysis were female gender, older age, elevated BMI, poor functional status or dyspnea, smoking, low albumin, COPD, and ascites. Intraoperative factors significantly associated with non-home discharge destination on multivariate analysis were longer operative time, open surgery, softer pancreatic texture, drain placement, and jejunostomy tube placement. A nomogram was generated for estimating probability of non-home discharge immediately after surgery. CONCLUSION:Preoperative and intraoperative factors can be used to predict probability of non-home discharge immediately after completion of pancreaticoduodenectomy.
Fast-Track Pancreaticoduodenectomy: Factors Associated with Early Discharge
Mahvi, David A; Pak, Linda M; Bose, Sourav K; Urman, Richard D; Gold, Jason S; Whang, Edward E
BACKGROUND:Pancreaticoduodenectomy is a complex surgery frequently associated with prolonged hospitalizations. However, there are a subset of patients discharged within 5Â days from surgery; the preoperative and intraoperative characteristics of this subset are unknown. METHODS:The NSQIP Targeted Pancreatectomy Dataset was used from 2014 to 2016. Patients who died within 30Â days were excluded. A total of 10,741 patients undergoing pancreaticoduodenectomy were identified. Univariable and multivariable logistic regression analyses were performed for preoperative and intraoperative ACS-NSQIP variables to identify predictors of early discharge. Early discharge was defined as discharge 3-5Â days after surgery. RESULTS:A total of 1105 patients (10.3%) were discharged within 5Â days following pancreaticoduodenectomy. On multivariable analysis, preoperative factors associated with early discharge included younger age (OR 0.988, pâ€‰<â€‰0.001), non-obesity (OR 0.737, pâ€‰=â€‰0.001), those receiving neoadjuvant chemotherapy (OR 1.424, pâ€‰<â€‰0.001), and lack of COPD (OR 0.489, pâ€‰=â€‰0.005) or hypertension (OR 0.805, pâ€‰=â€‰0.007). Intraoperative factors associated with early discharge on multivariable analysis were shorter operation duration (OR 0.999, pâ€‰=â€‰0.002), minimally invasive surgery (OR 3.537, pâ€‰<â€‰0.001), and hard pancreatic texture (OR 1.480, pâ€‰<â€‰0.001). Intraoperative factors associated with non-early discharge were epidural placement (OR 0.485, pâ€‰<â€‰0.001), drain placement (OR 0.308, pâ€‰<â€‰0.001), and jejunostomy tube placement (OR 0.278, pâ€‰<â€‰0.001). Patients discharged within 5Â days had a 14.7% readmission rate compared to 17.0% for later discharges (pâ€‰=â€‰0.047). CONCLUSIONS:Multiple preoperative and intraoperative factors, including some that are potentially modifiable, were significantly associated with early discharge after pancreaticoduodenectomy. Patients with these characteristics may benefit from enhanced recovery after surgery programs and expedited disposition planning postoperatively.