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Radiometric calibration has become important pre-processing with increasing use of unmanned aerial vehicle (UAV) images in various applications. In order to convert the digital number (DN) to reflectance, vicarious radiometric calibration is widely used including relative radiometric calibration. Some UAV sensor systems can measure irradiance for precise relative radiometric calibration. However, most of UAV sensor systems cannot measure irradiance and therefore precise relative radiometric calibration is needed to produce reflectance map with vicarious calibration. In this study, an optimal image selection method is proposed to improve quality of relative radiometric calibration. The method, relative calibration by the optimal path (RCOP), uses filtered tie points acquired in geometric calibration based on selection optimal image by Dijkstra algorithm. About 100 multispectral images were acquired with a RedEdge-M camera and a fixed-wing UAV. The reflectance map was produced using RCOP and vicarious calibration using ground reference panels. A validation data was processed using irradiance for precise relative radiometric calibration. As a result, the RCOP method showed root mean square error (RMSE) of 0.03–0.10 reflectance to validation data. Therefore, the proposed method can be used to produce precise reflectance map by vicarious calibration.

Objective The aim of this study was to compare the survival rates of Korean females aged 40 to 49 years with breast cancer detected by supplemental screening ultrasound (US) or screening mammography alone. Materials and methods This single-institution retrospective study included 240 patients with breast cancer (mean age, 45.1 ± 2.8 years) detected by US or mammography who had undergone breast surgery between 2003 and 2008. Medical records were reviewed for clinicopathologic characteristics and detection methods. Disease-free survival (DFS) and overall survival (OS) were compared between patients with breast cancer in the US and mammography groups using the log-rank test. Multivariable cox regression analysis was used to identify independent variables associated with DFS and OS. Results Among the 240 cases of breast cancer, 43 were detected by supplemental screening US and 197 by screening mammography (mean follow-up: 7.4 years, 93.3% with dense breasts). There were 19 recurrences and 16 deaths, all occurring in the mammography group. While the US group did not differ from the mammography group in tumor stage, the patients in this group were more likely to undergo breast-conserving surgery and radiation therapy than the mammography group. The US group also showed better DFS (p = 0.016); however, OS did not differ between the two groups (p = 0.058). In the multivariable analysis, the US group showed a lower risk of recurrence (hazard ratio, 0.097; 95% confidence interval, 0.001-0.705) compared to the mammography group. Conclusion Our study found that Korean females aged 40-49 years with US-detected breast cancer showed better DFS than those with mammography-detected breast cancer. However, there were no statistically significant differences in OS.

Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose delays or reductions due to afebrile grade 3 neutropenia. A consecutive cohort of ER( +)/HER2( −) advanced breast cancer patients who received palbociclib between 2017 and 2018 was analyzed. The patients were classified into Group 1 (patients who maintained palbociclib dose with afebrile grade 3 neutropenia), Group 2 (patients who experienced any dose modification with afebrile grade 3 neutropenia), and Group 3 (patients without afebrile grade 3 neutropenia). The primary endpoint was febrile neutropenia incidence; other toxicities were compared with those of the PALOMA-2 trial. Among the 107 patients, 54.2%, 22.4%, and 23.4% were classified into Groups 1, 2, and 3, respectively. There was no febrile neutropenia in Groups 1 and 2 during palbociclib treatment. Group 1 showed higher incidence of thrombocytopenia (all-grade, 32.8%; grade 3–4, 8.6%) than Group 2 and the PALOMA-2 data, but there was no bleeding related to thrombocytopenia. Group 1 showed higher incidence of all-grade non-hematologic adverse events than Group 2; only one grade 3 non-hematologic toxicity was observed in Group 1. There were no treatment-related hospitalizations or deaths in Group 1. Thus, omitting palbociclib dose modification with afebrile grade 3 neutropenia is safe and tolerable without febrile neutropenia events. This scheme could be useful to avoid unnecessary reductions in palbociclib doses in future practice.

Background Postoperative lymphedema in breast cancer survivors is a serious complication that develops from axillary lymph node dissection (ALND), chemotherapy, and radiation therapy. Axillary reverse mapping (ARM) was recently introduced to reduce lymphedema. This pilot study aimed to investigate the feasibility of preserving the ARM node using fluorescence imaging for patients at high risk of lymphedema. Methods We prospectively screened patients with breast cancer who had pathologic node-positive disease at diagnosis and were scheduled for neoadjuvant chemotherapy (NCT). The sentinel lymph node (SLN) was identified using blue dye and radioisotope, while the ARM node was traced using indocyanine green (ICG). In cases in which SLN was negative on the intraoperative frozen section examination, the ARM node and lymphatics were preserved. Results Of the 20 screened patients, six whose metastatic axillary lymph node (ALN) was converted to clinically node-negative disease after NCT were enrolled. No patients experienced recurrence at 24 months postoperative. Four patients who had a preserved ARM node did not develop lymphedema. One patient whose ARM node was not preserved due to SLN identification failure did not develop postoperative lymphedema. One patient who underwent ALND without ARM node conservation because of metastatic SLN on frozen section examination developed postoperative lymphedema. Conclusions ARM is oncologically safe, decreases the incidence of postoperative lymphedema, and allows for the early detection of postoperative lymphedema in patients who underwent ALND. Ultimately, ARM may help improve the quality of life of patients with pathologic node-positive breast cancer.

Background: Lymphopenia is frequently observed in advanced cancer patients even before initiation of systemic anti-cancer treatment. The aim of this study is to investigate the pre-treatment lymphopenia as a prognostic factor for breast cancer specific survival (BCSS), distant recurrence free survival (DRFS) in patients with early breast cancer (EBC) and overall survival (OS), OS2 (from diagnosis with stage IV to death) with metastatic breast cancer (MBC) in large-scaled early and metastatic breast cancer database cohort. Methods: We reviewed demographic, clinical, pathologic, and survival data from Yonsei Breast Cancer Center Registry. In large scaled database, 5252 patients who underwent surgery with stage I-III EBC at the Yonsei Cancer Center between 2006 and 2015 were included and 1481 patients who were newly diagnosed de novo or recurrent MBC were included. The pre-treatment lymphocyte count was obtained from complete blood count (CBC) assay before the initiation of any treatment. Lymphopenia was defined as an absolute lymphocyte count (ALC) < 1000/mm3. Clinicopathologic factors, such as human epidermal growth factor 2 (HER2) receptor, hormone receptor (HR) status and metastatic site, were reviewed. To evaluate the prognostic factors, Kaplan-Meier, log-rank, and Cox regression analysis were performed. Results: Of 5211 eligible EBC patients, 2690 (51.6%) stage I and 1857 (35.6%) stage II patients was included. De novo and recurrent MBC patients were 260 (31.0%) and 576 (69.0%). The incidences of pre-treatment lymphopenia were 3.0% (154/5211) in EBC and 14.5% (121/836) in MBC: 10 (3.9%) in de novo stage IV and 117 (19.3%) in recurrent stage IV. There was no difference in pre-treatment lymphopenia incidence among histologic subtypes in EBC cohort, but it was significantly higher in triple negative breast cancer (TNBC) in MBC. EBC patients with HBsAg positive showed higher incidence of pre-treatment lymphopenia than HBV negative patients (7.3% vs. 2.9%, p=0.003). In MBC cohort, patients with early distant recurrent (less than 2 year) disease (35.8%, p Conclusions: In this large-scaled and retrospectively analyzed a dataset, we showed highest incidence of pre-treatment lymphopenia in recurrent MBC, not affected by previous chemotherapy exposure. Pre-treatment lymphopenia was a significant poor prognostic factor in recurrent stage IV MBC, but not in EBC or de novo stage IV MBC. Citation Format: Jee Hung Kim, Min Hwan Kim, Gun Min Kim, Byeong-Woo Park, Young Up Cho, Seung Il Kim, Seho Park, Hyung Seok Park, Ji Ye Kim, Hyun Cheol Chung, Soonmyung Paik, Joohyuk Sohn. Comprehensive analysis of lymphopenia in large-scaled early and metastatic breast cancer database cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-43.

Background The antibody-drug conjugate targeting HER2, DS8201 has shown clinical activity against breast cancer with low-level HER2 expression in early clinical trial. In this study, we investigated the clinical implication and prognostic impact of intermediate HER2 expression in the prospectively collected ER (+) early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. Methods We analyzed the prospectively collected database of EBC and MBC cohort patients in Yonsei Cancer Center. We defined patients with HER2 immunohistochemistry (IHC) 0~1+ as HER2-negative group, and IHC 2+ and in situ hybridization (ISH) negative as HER2-intermediate group. Only ER (+) patients with complete HER2 IHC and ISH status were selected, excluding HER2 IHC 3+ or ISH+ patients. A total of 2,657 early breast cancer and 535 metastatic breast cancer patients were finally analyzed. The clinical and pathological characteristics and survival outcome of the patients were compared between HER2-negative and HER2-intermediate group in each cohort. Results The 654 (24.6%) EBC patients and 166 (31.0%) MBC patients were classified as HER2-intermediate group. The HER2-intermediate patients were more common in PR negative (30.4% versus 22.6%, p< 0.001) and higher nuclear grade (grade 2 or 3) patients (25.7% versus 17.4%, p = 0.001) in EBC cohort and in age ≥ 55 patients (36.7% versus 27.4%, p = 0.001) in MBC cohort. Other characteristics were not different between two groups in both cohorts. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) than HER2-negative patients in EBC patients (p = 0.044), although the prognostic impact was not significant in the multivariate analysis. Of note, intermediate HER2 expression was associated with significantly poorer RFS in EBC patients (p = 0.007) of age ≥ 55, but did not affect the RFS in patients of age < 55. The intermediate HER2 expression independently predicted poorer RFS of EBC patients of age ≥ 55 (Hazard ratio [HR], 1.95; 95% Confidence interval [CI], 1.03-3.73; p = 0.042) in multivariate Cox regression analysis with adjustment of other prognostic factors, T stage, N stage, PR status, and histologic grade. In line with result of EBC cohort, intermediate HER2 expression was associated with poorer overall survival (OS) in MBC patients of age ≥ 55 (p = 0.037), not affecting OS in MBC patients of age < 55. Intermediate HER2 expression predicted significantly poorer OS in MBC patients of age ≥ 55 (HR, 1.45; 95% CI, 1.01-2.07; p = 0.044) independent from PR status, disease status (recurrent versus de novo stage IV), and visceral metastasis. Conclusion Our analysis demonstrates intermediate HER2 expression as an independent poor prognostic factor for ER (+) breast cancer patients with age ≥ 55 in both EBC and MBC cohorts. The clinical efficacy of new HER2-targeting antibody-drug conjugates needs to be validated in this high-risk subset of ER (+) breast cancer patients. Citation Format: Min Hwan Kim, Gun Min Kim, Jee Hung Kim, Ji Ye Kim, Hyung Seok Park, Seho Park, Young Up Cho, Byeong Woo Park, Seung Il Kim, Joo-Hyuk Sohn. Intermediate HER2 expression predicts poor prognosis in ER (+) breast cancer patients aged 55 and older [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-33.

An antibody–drug conjugate targeting HER2, DS8201, has shown clinical activity against breast cancer with low-level HER2 expression. We aimed to evaluate the prognostic impact of intermediate HER2 expression in estrogen receptor (ER)+ early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. We analyzed prospectively collected data from EBC and MBC cohorts at Yonsei Cancer Center. Patients with HER2 immunohistochemistry (IHC) 0 ~ 1+ were assigned to the HER2-negative group, and patients with IHC 2+ and in situ hybridization (ISH)-negativity were assigned to the HER2-intermediate group. After the exclusion of HER2 IHC 3+ or ISH+ patients, a total of 2657 EBC and 535 MBC patients were analyzed. In total, 654 (24.6%) EBC and 166 (31.0%) MBC patients were classified in the HER2-intermediate group. The HER2-intermediate patients more frequently tended to have progesterone receptor (PR)-negativity and higher nuclear grade in the EBC cohort, and showed a higher proportion of patients aged ≥ 55 years compared with the HER2-negative group in the MBC cohort. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) compared to the HER2-negative patients in the EBC cohort (p = 0.044). Notably, intermediate HER2 expression predicted poorer RFS in EBC patients aged ≥ 55 years (hazard ratio 1.95; p = 0.042) in multivariate Cox analysis but did not affect RFS in those aged

Background Self-management is becoming essential for breast cancer survivors, but evidence about the effectiveness of self-management support (SMS) intervention is lacking. To address this issue, we developed a theory-based SMS intervention, the ‘EMPOWER’, aimed at empowering breast cancer survivors. Here we describe the rationale of the intervention and its development. Methods The conceptual framework of this study is the Chronic Care Model, which posits that SMS can influence patient-provider relationships and ultimately improve health outcomes. We will conduct a multi-center, 2-armed randomized controlled trial to assess the effectiveness of EMPOWER among post-treatment breast cancer survivors in South Korea. The trial will include 94 women who completed primary breast cancer treatment within the last 6 months. Participants will be randomly assigned to the intervention group or the wait-list control group (1:1). The intervention group will receive a 7-week partnership-based and needs-tailored SMS intervention via telephone counseling. The primary outcome is empowerment. The secondary outcomes include self-efficacy for post-treatment self-management behaviors, mental adjustment, psychological distress, and health-related quality of life (HRQOL). Data will be collected by self-reported questionnaire at baseline, post-intervention, and 3-month follow-up. Discussion We believe that the EMPOWER intervention could improve HRQOL of post-treatment breast cancer survivors by enhancing their empowerment. If found successful, it could aid clinicians engaged in the long-term care of breast cancer survivors. Trial registration Clinical Research Information Service, KCT0004794. Registered 5 March 2020.

Seeking smaller and indistinct incisions, physicians have attempted endoscopic breast surgery in breast cancer patients. Unfortunately, there are some limitations in the range of movement and visualization of the operation field. Potentially addressing these limitations, we investigated the outcomes of gas and gasless robot-assisted nipple-sparing mastectomy (RANSM) with immediate breast reconstruction (IBR). Ten patients underwent 12 RANSM with IBR between November 2016 and April 2018. Patients with tumors measuring5 cm in diameter, tumor invasion of the skin or nipple-areolar complex, proven metastatic lymph nodes, or planned radiotherapy were excluded. Age, breast weight, diagnosis, tumor size, hormone receptor status, and operation time were retrospectively collected. Postoperative outcomes including postoperative complications and final margin status of resected were analyzed. The median total operation time and console time were 351 min (267-480 min) and 51 min (18-143 min), respectively. The learning curve presented as a cumulative sum graph showed that the console time decreased and then stabilized at the eighth case. There was no open conversion or major postoperative complication. One patient had self-resolved partial nipple ischemia, and two patients experienced partial skin ischemia. We deemed that RANSM with IBR is safe and feasible for early breast cancer, benign disease of the breast, and BRCA 1/2 mutation carriers. RANSM is an advanced surgical method with a short learning curve.

This study aimed to develop a post-traumatic growth (PTG) program, based on the PTG promotion resources suggested by Cahlhoun, Cann, and Tedeschi, and to apply it to breast cancer patients to determine its effect.A non-equivalent control group pretest-posttest experimental design was used. In total, 74 participants were enrolled in this study, with 37 in the experimental group and 37 in the control group. The PTG program developed in this study consisted of writing and self-reflection for self-analysis, talking and sharing for self-disclosure, and participation in a self-help group for social support. The instruments used for this study were the Korean version of the Event Related Rumination Inventory, the Korean version of the Hospital Anxiety and Depression Scale, and the Korean version of the Post-traumatic Growth Inventory. The data were analyzed with the χThe experimental group that underwent a PTG program had a lower emotional distress score than the control group (anxiety: t = -3.84, p = .001; depression: t = -3.22, p = .002). The experimental group had a lower intrusive rumination (t = -3.55, p = .001) and had higher deliberate rumination score than the control group (t = 2.10, p = .039). The experimental group had a higher PTG score than the control group (t = 2.34, p = .022).The PTG program developed in this study for breast cancer patients has the potential to contribute to the promotion of PTG in breast cancer patients.

This study aimed to examine the prevalence and trends of breast cancer-related risk factors and characteristics in premenopausal underweight Korean women according to birth year cohort. Socioeconomic and breast cancer-related risk factors were investigated in 13,415 premenopausal women using nationwide cross-sectional surveys performed between 2007 and 2015. Underweight was defined as body mass index

“BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test.

Purpose Dose-dense chemotherapy (DD-CT) is a preferred (neo)adjuvant regimen in early breast cancer (BC). Although the results of reported randomized trials are conflicting, a recent metaanalysis showed improved overall and disease-free survival with DD-CT compared to conventional schedules. However, no DD-CT safety data for Korean BC patients are available. This phase II study was conducted to evaluate the safety and efficacy of pegteograstim in Korean BC patients receiving DD-CT. Materials and methods Patients with operable (stage I-III), histologically confirmed BC received four cycles of intravenous doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 every 2 weeks as neoadjuvant or adjuvant therapy. Pegteograstim (6.0 mg) was administered subcutaneously on day 2 of each cycle. The primary endpoint was the incidence of febrile neutropenia (FN). The secondary endpoints were safety and tolerability. Results Of 63 patients, one (1.6%) developed FN during all cycles of DD-CT. Dose delay was observed in four patients (6.3%) and dose reduction in two (3.2%) during DD-CT. Frequent adverse events (AEs) were nausea, alopecia, generalized muscle weakness, myalgia, mucositis, anorexia, dyspepsia, and diarrhea; most AEs were related to chemotherapy. Grade 3-4 AEs were reported in five of 63 patients (7.9%), and all grade 3 and 4 AEs were related to chemotherapy. Adverse drug reactions possibly linked to pegteograstim were abdominal pain, bone pain, myalgia, generalized muscle weakness, and headache in five of 63 patients (7.9%). Conclusion Dose-dense AC (doxorubicin/cyclophosphamide) chemotherapywith pegteograstim support is a tolerable and safe regimen in Korean early BC patients.

Purpose Sentinel lymph node biopsy (SLNB) can be performed when node-positive disease is converted to node-negative status after neoadjuvant chemotherapy (NCT). Tattooing nodes might improve accuracy but supportive data are limited. This study aimed to investigate the feasibility of charcoal tattooing metastatic axillary lymph node (ALN) at presentation followed by SLNB after NCT in breast cancers. Materials and methods Twenty patientswith cytology-proven node metastases prospectively underwent charcoal tattooing at diagnosis. SLNB using dual tracers and axillary surgery after NCT were then performed. The detection rate of tattooed node and diagnostic performance of SLNB were analyzed. Results All patients underwent charcoal tattooingwithout significant morbidity. Sentinel and tattooed nodes could be detected during surgery after NCT. Nodal pathologic complete response was achieved in 10 patients. Overall sensitivity, false-negative rate (FNR), negative predictive value, and accuracy of hot/blue SLNB were 80.0%, 20.0%, 83.3%, and 90.0%, respectively. Retrieving more nodes and favorable nodal response were associated with improved performance. The best accuracy was observed when excised tattooed node was calculated together (FNR, 0.0%). Cold/non-blue tattooed nodes of five patients were removed during non-sentinel axillary surgery but clinicopathological parameters did not differ compared to patients with hot/blue tattooed node detected during SLNB, suggesting the importance of the tattooing procedure itself to improve performance. Conclusion Charcoal tattooing of cytology-confirmed metastatic ALN at presentation is technically feasible and does not limit SLNB after NCT. The tattooing procedure without additional preoperative localization is advantageous for improving the diagnostic performance of SLNB in this setting.

Purpose We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. Methods Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into "either sufficient" or "both deficient" groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. Results Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. Conclusion Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.

This study was to investigate a hierarchical prognostic model using clinicopathological factors and 18F‐fludeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) for recurrence‐free survival (RFS) in patients with early breast cancer who underwent surgery without neoadjuvant chemotherapy. A total of 524 patients with early breast cancer were included. The Cox proportional hazards model was used with clinicopathological variables and maximum standardized uptake value (SUVmax) on PET/CT. After classification and regression tree (CART) modeling, RFS curves were estimated using the Kaplan–Meier method and differences in each risk layer were assessed using the log‐rank test. During a median follow‐up of 46.2 months, 31 (5.9%) patients experienced recurrence. The CART model identified four risk layers: group 1 (SUVmax ≤6.75 and tumor size ≤2.0 cm); group 2 (SUVmax ≤6.75 and Luminal A [LumA] or TN tumor >2.0 cm); group 3 (SUVmax ≤6.75 and Luminal B [LumB] or human epidermal growth factor receptor 2 [HER2]‐enriched] tumor >2.0 cm); group 4 (SUVmax >6.75). Five‐year RFS was as follows: 95.9% (group 1), 98% (group 2), 82.8% (group 3), and 85.4% (group 4). Group 3 or group 4 showed worse prognosis than group 1 or group 2 (group 1 vs. group 3: P = 0.040; group 1 vs. group 4: P 6.75) in primary breast cancer was an independent factor for poor RFS. In patients with low SUVmax, LumB or HER2‐enriched tumor >2 cm was also prognostic for poor RFS, similar to high SUVmax.

PURPOSE/OBJECTIVE(S) Radiographic density changes in normal lung parenchyma are a function of radiation dose, are associated with inflammation, and vary among patients. The purpose of this study is to evaluate these radiation-induced changes quantitatively in different patient cohorts treated with PD-1 Immune Checkpoint Inhibitors (ICI) and investigate them as possible RT-related imaging biomarker for outcome. MATERIALS/METHODS We looked at two groups of non-small cell lung cancer (NSCLC) patients drawn from two institutions: patients with metastatic disease treated with non-curative intent and normal lung in the radiation field, and patients receiving definitive chemo-radiation (CRT) followed by adjuvant PD-L1 blockade (durvalumab), some of which received durvalumab also concurrently. Normal lung parenchyma on the first post-treatment chest computer tomography (CT) scans (median time 3 months post RT) was deformably registered to the treatment plan to analyze lung density changes as function of dose, normalized to 2Gy-equivalent, and quantified as Hounsfield Unit (HU)/Gy. Differences between groups were assessed using Wilcoxon's rank sum test, correlation to progression-free and overall survival using Cox regression. RESULTS We analyzed a total of 26 patients treated with non-curative intent RT and 60 patients who received CRT. For metastatic patients, RT delivered concurrently with ICI (n = 16) led to significantly larger changes compared to patients receiving RT before initiation of ICI (median 2.21 vs 0.27 HU/Gy, P = 0.02), even though the former received significantly lower doses to the normal lung (median 27.6 vs 55.8 Gy, P = 0.02). Fraction sizes were smaller when RT was delivered concurrently with ICI (median 3.3 vs 5.5 Gy/fraction). Number of patients and events in metastatic patients were too low for survival analysis. During CRT, patients receiving concurrent durvalumab (n = 20) did not show significant lung density changes compared to those that did not (median 1.39 vs 1.28 HU/Gy, P = 0.99). All CRT patients received 1.8-2.2 Gy/fraction. The amount of change in each patient did not correlate with progression-free or overall survival (HR = 0.91, 95% CI [0.71-1.16] and HR = 0.92, [0.72-1.17] respectively). CONCLUSION RT delivered concurrently with PD-1 ICI leads to significantly increased normal lung density changes in metastatic patients but not in locally advanced patients treated with CRT, possibly related to the different fraction size. For CRT patients treated with adjuvant durvalumab, normal lung changes after CRT do not correlate with outcome. The correlation of lung density changes to oncologic outcomes in metastatic patients' needs to be studied in larger cohorts.

Purpose/Objective(s) There is a paucity of data studying the significance of neutrophil-to-lymphocyte ratio (NLR) in peripheral blood of patients with locally advanced rectal cancer (LARC) planning to undergo preoperative RT. We aimed to investigate the prognostic impact of NLR in patients with LARC and whether there are modifiable factors in RT which influencing the level of NLR. Materials/Methods We studied 1366 patients treated with neoadjuvant RT with concurrent or sequential chemotherapy for LARC from 2006 to 2019. Most (97.8%) were treated with long-course RT (50-50.4 Gy in 25-28 fractions) with 3DCRT (n = 851) or helical tomotherapy (n = 504). Short-course RT (25 Gy in 5 fractions, followed by 6-week XELOX) was used in 30 cases (NCT03676517). The absolute neutrophil and lymphocyte counts were obtained from the sample collected at the time of initial diagnosis, before and during the course of preoperative RT and before surgery. The primary endpoint was distant metastasis-free survival (DMFS). Results With the median follow-up time of 61.3 months (4.1-173.7 months), the 5-year DMFS was 80.1%. 5-year DMFS was significantly associated with the level of NLR after RT, but not with the level of NLR before RT. In Cox multivariate model, post-RT NLR greater than 4 was independently correlated with worse DMFS (HR 1.37, 95% CI, 1.08-1.73), along with higher icT stage, ypT stage and ypN stage. The 5-year OS of patients with post-RT NLR > 4.0 was 83.2%, compared to 94.4% in post-RT NLR ≤ 4 patients (P 4.0) was more frequently developed after long-course RT (OR, 2.77, P = 0.032) or helical tomotherapy (OR, 1.29, P .05). Conclusion Elevation of NLR after neoadjuvant RT is associated with increased risk of DM development and poor OS in LARC. Development of high NLR following RT is directly related to RT fractionation and delivery modality, and tumor characteristics. Incorporation of SCRT with 3D-CRT or active bone marrow sparing-IMRT may be a modifiable factor that can indirectly affect DMFS by means of attenuating NLR in LARC patients, which needs further investigations.

PURPOSE/OBJECTIVE(S) Sarcopenia, defined as the loss of skeletal muscle mass, is known to be associated with poor treatment outcome, treatment-related toxicity, and high mortality. The association between sarcopenia, the prognostic nutritional index, and survival is not well defined in patients with advanced biliary tract cancer. In this study, we aimed to evaluate the impact of a combination of the prognostic nutritional index and sarcopenia with survival in patients with advanced biliary tract cancer. MATERIALS/METHODS In this study, we assessed the impact of the prognostic nutritional index (PNI) and sarcopenia, determined using computed tomography, on overall survival (OS) in advanced biliary tract cancer (BTC). We reviewed patients with either recurrent or metastatic BTC treated at a single institution between 2007 and 2016. RESULTS In total, 533 patients were included with a median follow-up of 9.30 months (inter-quartile range [IQR]; 4.10-16.70). The median PNI was 46.5 (IQR; 40.60-51.55). Those with a high PNI showed significantly superior 1-year OS than the low PNI group (30.8% vs 48.3%, P < 0.001). The sarcopenia cut-off value for males and females was 44 cm2/m2 and 37 cm2/m2, respectively. The OS was significantly higher in the non-sarcopenia group (34.4% vs 44.2%, P = 0.007). We categorized patients into 3 groups: patients with both sarcopenia and low PNI, patients with either sarcopenia or low PNI, and non-sarcopenic patients with high PNI. The OS was significantly different between groups (1-year OS; 7% vs 38.3% vs 46.5%, P < 0.001), and group was a significant contributor to OS in multivariate analysis. CONCLUSION In conclusion, a low PNI and sarcopenia indicate patients with a poor nutritional status and systemic inflammation and are associated with poor OS in advanced BTC.

Objectives To investigate predictors of occult nipple-areolar complex (NAC) involvement in patients with carcinoma in situ (CIS) and to validate an online probability calculator (CancerMath; www.lifemath.net/cancer/breastcancer/nipplecalc/index.php). Methods Mastectomized patients with CIS (n = 104) were retrospectively selected. Clinicopathology and preoperative mammography, ultrasound, and magnetic resonance imaging (MRI) findings were analyzed. Results Histopathological NAC-positivity was confirmed in 20 (19.2%) patients. Short nipple-tumor distance and suspicious extension to the nipple by mammography were significant but ultrasound was not significant to predict NAC involvement. NAC-positive cases had MRI findings of shorter nipple-tumor distance in both the early and delayed phases. Multivariable regression model showed age >50 years and shorter tumor-nipple distance on the delay phase of MRI were statistically significant predictors of NAC involvement. Area under the receiver operating characteristics curve (AUC) was 0.618 when calculated by CancerMath; however, an AUC of 0.954 was achieved when distance and age were applied together as predictor. Conclusions Mammographic and MRI findings were significant for predicting NAC involvement, with distance of the tumor from the nipple in delay phase MRI the most significant predictor of NAC involvement. Therefore, breast MRI could be beneficial for planning nipple-sparing mastectomy in patients with CIS.

Purpose: Accelerated partial breast irradiation (A-PBI) in Korean women has been considered impracticable, owing to small breast volume and lack of high-precision radiotherapy experience. We present the first experience of stereotactic-PBI (S-PBI) with CyberKnife M6 to investigate feasibility of use and early toxicities in Korean women with early breast cancers. Materials and Methods: A total of 104 breasts receiving S-PBI at our institution between September 2017 and October 2018 were reviewed. Patients were selected based on the American Society for Radiation Oncology (ASTRO), American Brachytherapy Society, American Society of Breast Surgeons, and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology guidelines. A dose of 30 Gy in 5 fractions (NCT01162200) was used. Gold fiducials were routinely inserted near the tumor bed for tracking. Constraints regarding organs-at-risk followed the NSABP-B39/RTOG 0413 protocol. Results: Median follow-up was for 13 months. Patients were categorized as "suitable" (71.2%) or "cautionary" (28.8%) according to 2017 the ASTRO guidelines. No tracking failure of inserted gold fiducials occurred. Median planning target volume (PTV) and PTV-to-whole breast volume ratio was 73.6 mL (interquartile range, 58.8-103.9 mL) and 17.0% (13.3-19.1%), respectively. Median PTV V95%, PTV Dmax, and ipsilateral breast V50% were 97.8% (96.2-98.8%), 105.3% (104.2-106.4%), and 35.5% (28.3-39.8%), respectively. No immediate post-S-PBI toxicity ≥ grade 2 was reported, except grade 2 induration in three breasts. All patients remain disease-free to date. Conclusion: The first use of S-PBI in Korean women was feasible and safe for selected early breast cancer. Based on these results, we have initiated a prospective study (NCT03568981) to test S-PBI in whole-breast irradiation for low-risk early breast cancer.

Background The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18–30, particularly those with RS 26–30, are not known. Methods Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18–30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox’s proportional hazards model. Results Among the breast cancer patients with the RS 18–30, 21% of them had RS 26–30. Compared to breast cancer patients with RS 18–25, patients with RS 26–30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26–30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47–0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44–0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor. Conclusions The 21-gene RS of 18–30 showed heterogeneous outcomes, and the RS 26–30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26–30 and should be considered for patients, especially younger patients or patients with high-grade tumors.

Seeking smaller and indistinct incisions, physicians have attempted endoscopic breast surgery in breast cancer patients. Unfortunately, there are some limitations in the range of movement and visualization of the operation field. Potentially addressing these limitations, we investigated the outcomes of gas and gasless robot-assisted nipple-sparing mastectomy (RANSM) with immediate breast reconstruction (IBR). Ten patients underwent 12 RANSM with IBR between November 2016 and April 2018. Patients with tumors measuring >5 cm in diameter, tumor invasion of the skin or nipple-areolar complex, proven metastatic lymph nodes, or planned radiotherapy were excluded. Age, breast weight, diagnosis, tumor size, hormone receptor status, and operation time were retrospectively collected. Postoperative outcomes including postoperative complications and final margin status of resected were analyzed. The median total operation time and console time were 351 min (267–480 min) and 51 min (18–143 min), respectively. The learning curve presented as a cumulative sum graph showed that the console time decreased and then stabilized at the eighth case. There was no open conversion or major postoperative complication. One patient had self-resolved partial nipple ischemia, and two patients experienced partial skin ischemia. We deemed that RANSM with IBR is safe and feasible for early breast cancer, benign disease of the breast, and BRCA 1/2 mutation carriers. RANSM is an advanced surgical method with a short learning curve.

This study assessed the effectiveness of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), regarding cancer-related fatigue (CRF), quality of life (QOL), physical activity, and psychosocial characteristics. Forty-eight BCS with moderate or high (≥ 4) CRF participated in this randomized control trial (intervention group n = 23, control group n = 25). The intervention group participated in small group sessions to activate social capital while targeting CRF in supervised physical exercises supplemented by home-based physical exercises. The control group was only given written information on exercise. A questionnaire was used to assess CRF, QOL, physical activity, depression, anxiety, sleep quality, and social capital. The majority of participants had undergone surgery less than 2 years ago. After participating in BLESS, the CRF behavioral/severity domain significantly decreased (t = 2.642, p = 0.011) and physical activity significantly increased (t = − 2.049, p = 0.046) in the intervention group, in comparison with the control group; there were no significant post-intervention differences in the control group. Both groups showed improvements in sleep quality, depression, anxiety, and QOL. The BLESS program decreased behavioral/severity in the CRF and increased physical activity after 12 weeks among BCS. Future research needs to evaluate whether the promising results on physical activity and behavioral fatigue observed in the short term will persist over time. Also, longer-term effects should be examined.

International audience; OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk. Copyright

Background Cancer treatment-induced bone loss is an important long-term effect in breast cancer survivors, but evidence regarding lifestyle interventions for preventing cancer treatment-induced bone loss is lacking. Objective The aim of this study was to investigate the feasibility, safety, and effects of a 6-month combined home-based exercise and calcium and vitamin D supplements (EX + SUPP) intervention compared with calcium and vitamin D supplements alone (SUPP) on bone health of osteopenic breast cancer survivors. Methods In this pilot randomized controlled trial, we enrolled 43 women with breast cancer who were diagnosed as osteopenic through bone mineral density screening. Women were randomly assigned to the EX + SUPP group (n = 23) or the SUPP group (n = 20). Results The rates of participant retention (90.7%) and of counseling calls delivered to the EX + SUPP group (90.3%) were high. The average exercise adherence rate was 69.5% for weight-bearing exercise and 48.5% for resistance exercise. The EX + SUPP group reported no injuries or adverse events. Despite positive findings of adherence and safety, no significant group differences were observed for bone mineral density, bone turnover marker, or physical performance. Conclusions A home-based exercise program for bone health among osteopenic breast cancer survivors is feasible and safe. There was no significant additive effect of exercise on bone outcomes under the conditions studied, however, suggesting the need for a larger trial. Implications for practice Effective exercise intervention may require more intensive components such as higher loading forces and longer duration for improving bone health among this population.

In the original publication of the article, under the Results section, subheading "Patient survival", the second sentence that reads as "The 6-month PFS was 92.4%, 81.8%, and 93.3% and the one-year PFS was 72.0%, 88.9%, and 78.9% in Groups 1-3, respectively." should read as "The 6-month PFS was 82.8%, 75.0%, and 68.0% and the one-year PFS was 77.0%, 62.0%, and 63.8% in Groups 1-3, respectively.".

Background Cancer treatment-induced bone loss is an important long-term effect among breast cancer survivors. Little is known, however, about the pattern of bone loss and the factors associated with it. Objective The aim of this study was to examine annual bone health changes and factors associated with bone loss for 3 years after diagnosis among women with breast cancer. Methods Ninety-nine newly diagnosed women with breast cancer (mean age, 51.1 years) were enrolled in a prospective longitudinal study. Bone mineral density (BMD) was measured with dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Results During the 3-year follow-up, the proportion of women who had osteopenia or osteoporosis increased from 33.3% to 62.5%. The BMD of the participants significantly decreased 6.8% in the lumbar spine, 4.6% in the femur neck, and 3.5% in the total hip, with bone loss the greatest in the first year. In multiple linear regression analysis, chemotherapy was significantly associated with bone loss at all sites, and premenopausal status at diagnosis was significantly related to bone loss at the lumbar spine. We found no significant relationship between health behavior status and BMD change at any site. Conclusion Women newly diagnosed with breast cancer can lose up to 6.8% of BMD during a 3-year follow-up. Chemotherapy and premenopausal status are important risk factors for bone loss. Implications for practice Identification of premenopausal women at diagnosis and monitoring BMD before and after chemotherapy are key for promoting bone health in women with breast cancer.

The Z0011 trial demonstrated that axillary dissection (ALND) could be omitted during breast-conserving therapy for cT1-2N0 breast cancers with 1–2 metastatic SLNs. However, that result has not been validated in a larger cohort and the significance of the small number of SLNs remains unclear. This study aimed to validate the Z0011 results within an Asian Z0011-eligible cohort and determine whether the number of sentinel lymph nodes (SLNs) influenced the Z0011-based outcomes. Data from Asian patients who fulfilled the Z0011 criteria were collected from five hospitals. Disease recurrence (DR) was compared between patients who underwent ALND or SLN dissection (SLND) alone. Propensity-score matching was performed to reduce the effects of potential selection biases. During 2010–2016, 1750 Asian patients had 1–2 SLN metastases and fulfilled the Z0011 criteria. These patients included 707 cases treated using SLND alone (40%) and 967 patients with ≤ 2 SLNs (55%). Ninety-five patients (5.4%) experienced DR at a median interval of 50 months, although the rates of DR were similar in the ALND and SLND groups. The adjusted hazard ratios for DR after ALND omission were 0.95 (95% CI 0.55–1.64) among the entire cohort and 0.83 (95% CI 0.34–2.03) among patients with ≤ 2 SLNs. In this Asian Z0011-eligible cohort, ALND omission did not increase risk of DR, even among patients with ≤ 2 SLNs. Therefore, the Z0011 strategy might be safely applied in Asia, and a small number of SLNs did not significantly influence this strategy.

Purpose The aim of this study was to describe distinct coping styles of women newly diagnosed with breast cancer and to determine whether there is an association between those styles and the women's long-term health-related quality of life (HRQOL). Methods Using a prospective longitudinal study design, we enrolled 101 women recently diagnosed with breast cancer in South Korea and asked them to complete a questionnaire that included the Mini-Mental Adjustment to Cancer (Mini-MAC) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Results From the baseline data, we identified two coping style clusters. The first (“FS cluster”) had higher scores on the fighting spirit subscale and lower scores on the helpless-hopeless and anxious preoccupation subscales (n = 52, 51.5%), while the second (“HHAP cluster”) scored higher on the helpless-hopeless and anxious preoccupation subscales and lower on the fighting spirit subscale (n = 49, 48.5%). In the longitudinal analysis, the FS cluster had a better HRQOL then the HHAP cluster for 2 years after diagnosis, but the HRQOLs did not differ significantly 3 years after diagnosis. Conclusions Maladaptive coping at diagnosis may predict poor HRQOL in women with breast cancer. Regular screening of coping style and interventions to improve poor coping style should be considered for at least 2 years post initial diagnosis.

Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors (BCS), with severe impact on quality of life. CRF can be reduced through exercise, but conversely, is also a barrier to exercising. The aim of this article was to apply the intervention mapping protocol (IMP) to develop an exercise adherence intervention for BCS with CRF. The program was developed using the IMP, which consists of six steps. Based on the data from focus group interviews and literature review, we produced a logic model of change. Two performance objectives (survivors adopt and maintain exercise and survivors cope with fatigue) and 17 change objectives were generated. Also, we designed theory-based methods of change, and strategies for practical application. A structured program plan that includes intervention content and methods, ranges, and program data was proposed. Finally, an implementation and evaluation plan was developed. The IMP provided a useful framework to systematically plan an exercise adherence program. This study resulted in a theory and practice-based exercise adherence program, based on behavioral change theories, and practice-based knowledge that fits the needs of BCS with CRF.

This study investigated the impact of pN1mi disease on the survival of T1 breast cancer patients and examined the clinical usefulness of the online PREDICT tool and updated staging system. The node stages of 2344 patients were divided into pN0, pN1mi, and pN1a. Clinicopathological parameters and survival outcomes were retrospectively analyzed. Data for 111 micrometastatic diseases were applied to the PREDICT version 2.0 and re-classified using the 8th edition of the cancer staging manual. Univariable analyses demonstrated worse disease-free and overall survival rates for patients with node-positive cancer; however, the significance was not maintained in multivariable analyses. Chemotherapy improved outcomes in patients with node-positive and non-luminal A-like subtype cancers. The PREDICT tool demonstrated good performance when estimating the 5-year overall survival for pN1mi disease (area under the receiver operating characteristic curve, 0.834). According to the updated staging system, 74% of cases were down-staged to IA, and clearly splitting survival curves were identified. pN1mi disease alone did not adversely affect survival outcomes. Biologic and treatment factors determined outcomes in cases of small-volume node micrometastasis. The PREDICT tool or new staging classification could help predict the survival of patients with micrometastatic sentinel nodes.

Purpose There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. Methods Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. Results All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p

Purpose IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. Materials and Methods The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of 10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. Results The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. conclusions IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.