bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiographic paradoxical response in patients with metastatic castrate-resistant prostate cancer (mCRPC) undergoing treatment with second-generation hormone therapy (second-HT).
Authors: Alamiri Jamal , Ahmed Mohamed E. , Andrews Jack R. , Dundar Ayca , Motterle Giovanni , Karnes Jeffrey , Kwon Eugene D. , Bryce Alan Haruo , Kendi Ayse T. , Bold Michael S. 
Published: May 2020

5577 Background: Prostate specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. A post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve mCRPC patients on enzalutamide had radiographic progression on conventional imaging with non-rising PSA. In this study, we sought to retrospectively compare PSA levels with C-11 choline positron emission tomography/ computed tomography (PET/CT) images in patients with m-CRPC on 2nd-HT with prior use of chemotherapy. Methods: We identified 123 patients with mCRPC on 2nd-HT following prior use of docetaxel chemotherapy (Abiraterone, n = 106; Enzalutamide, n = 17). Patients underwent serial PSA testing and C-11 choline PET/ CTs every 3–6 months. Disease progression was defined by the increase in blood pool corrected maximum standardized uptake value (SUVmax) of the index lesion on C-11 choline PET/CT scan. Suspicious lesions were confirmed by biopsy and/or conventional imaging. Results: Approximately 43% (n = 53) of patients had radiographic disease progression while on 2nd-HT. At time of radiographic progression, 60.4% of patients showed a parallel rise in PSA (Group-A), while 39.6% showed a paradoxical response; defined as radiographic progression with stable or down-trending PSA (Group-B). Median PSA at time of progression was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p-value = 0.0176). Median SUVmax was the same (4.9 Group-A, 4.6 Group-B; p-value = 0.6072). Bone-predominance progression was more significant in Group-B (90%) versus Group-A (65%) (p-value = 0.0309). The median time for radiographic progression was 9.5 months versus 3.9 months for Group-A and Group-B, respectively (Log-Rank = 0.0063). Conclusions: Metabolic imaging is a useful tool that should complement PSA in the evaluation of treatment response and disease progression in mCRPC patients on 2nd-HT, especially considering the paradoxical response observed in our data.
Treatment patterns and outcomes of patients with penile squamous-cell carcinoma (PSCC) undergoing inguinal lymph node dissection (ILND): An analysis of a multicenter contemporary database.
Authors: Bandini Marco , Zhu Yao , Ye Dingwei , Ornellas Antonio Augusto , Watkin Nick , Ager Michael , Hakenberg Oliver W. , Heidenreich Axel , Raggi Daniele , Haidl Friederike , Marandino Laura , Pederzoli Filippo , Briganti Alberto , Montorsi Francesco , Chipollini Juan , Azizi Mounsif , Albersen Maarten , Spiess Philippe E. , Necchi Andrea 
Published: May 2020

5585 Background: PSCC is a rare tumor and the administration of guidelines-based therapies is still problematic in real-world practice. Survival outcomes remain suboptimal in patients (pts) with ILN involvement. Multinational analyses of real-world patterns are needed. Methods: Within an international, multicenter database of 965 PSCC pts who received ILND from 1980-2019, 630 had complete information for the variables of interest, from USA (N=81), Europe (EU, N=355), South America (SA, N=90), and China (Ch, N=104). Descriptive analyses according to geographical and ethnicity/race distribution were made. Comparisons of outcomes were made with Kaplan-Meier analyses and corresponding logrank tests. Results: Median age at diagnosis was 59 yrs, with no differences worldwide and according to ethnicity/race. Pts from SA presented with more advanced cT-stage (cT3-4: 26.7% vs. 17.3% USA vs. 7.6% EU) while EU pts presented with more advanced cN-stage (cN3: 14.9% vs. 11% USA vs. 7.8% SA vs. 5.8% Ch) as well as pathological (p)N-stage: pN3 pts were 53% in EU, 33.3% in USA, 20% in SA, and 18.3% in Ch. Perioperative chemotherapy (pCT) was more frequently administered in EU (53.8%) vs. USA (34.6%) SA (5.6%) Ch (7.7%). cT-stage was more frequently advanced in black pts (cT3-4: 33.3% vs. 12% Caucasian, 6.2% Hispanic/latino, 0% Asian) and the same was for cN-stage (cN3: 25% in black, 13% in Caucasian, 6.2% in Hispanic/latino, 6% in Asian). Conversely, pN3 pts were more frequently Caucasian (45.6%) vs. black (25%), Hispanic/latino (19%), and Asian (18%). pCT was more frequently administered in Caucasian pts (45%) vs. black (8.3%), Hispanic/latino (0), and Asian (8%). No significant differences in overall survival (OS) were observed according to geographical region or ethnicity/race, in the total pts and in the subgroups according to cT, cN, pN-stages and pCT. Median OS after pCT and ILND was 95 months. Bilateral ILN involvement was equally observed regardless of geographical region and ethnicity/race. In the total population, pCT significantly prolonged OS in pts with bilateral ILN (p=0.04), but not in pts with pelvic LN. Conclusions: Treatment patterns for PSCC undergoing ILND remain heterogeneous worldwide, and adherence to guidelines is seemingly poor. However, long-term outcomes with pCT remain uniformly suboptimal with <50% pts alive at 10 yrs. Further collaborative efforts are needed in this orphan disease to harmonize the therapeutic paradigm.
Clinical utility of 18F-FDG-PET/CT in staging localized breast cancer prior to initiating preoperative systemic therapy.
Authors: Ko Heidi , Baghdadi Yaser , Love Charito , Sparano Joseph A. 
Published: May 2020

563 Background: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) is recommended as an optional study in current National Comprehensive Cancer Network (NCCN) guidelines after computerized tomography and bone scan (CTBS) in patients with stage IIA-IIIC breast cancer. We evaluated our experience with use of PET/CT in this setting prior to beginning primary systemic therapy (PST) before planned surgery. Methods: We performed medical record abstractions to identify all adult female patients with clinical stage IIA to IIIC breast cancer diagnosed at Montefiore Medical Center from January 1, 2014 to January 1, 2019 who underwent PET/CT. We calculated the proportion of patients upstaged after PET/CT, stratified by their initial clinical stages and use of PST, and examined the cost and radiation exposure associated with PET/CT compared with CTBS. Results: 227 patients with 230 breast cancers (bilateral disease in 3) met the study inclusion criteria. PET/CT was the only staging done in 195 patients (86%); 32 patients had PET/CT based on suspicious findings from prior CTBS. Among these 195 patients with 196 breast cancers (bilateral disease in 1) that had PET/CT as the only staging done, the overall upstaging rate for regional nodal and/or distant metastasis was 37% (73/196), including 24% for stage IIA (9/38), 39% for IIB (31/79), 54% for IIIA (22/41), 27% for IIIB (8/30), and 37% for IIIC (3/8). The overall upstaging rate to stage IV was 14% (27/196), including 0% for stage IIA, 13% for IIB (10/79), 22% for IIIA (9/41), 17% for IIIB (5/30), and 37% for IIIC (3/8). The sensitivity and specificity of PET/CT in detecting distant metastasis was 100% and 94%, respectively. Our institution's total Medicare reimbursement rate of PET/CT is $1604.37 whereas CTBS is $1679.94. Radiation dose for PET/CT is 14 mSv whereas CTBS is 21 mSv. Conclusions: Approximately 37% of patients with clinical stage IIA-IIIC breast cancer who underwent PET/CT prior to PST showed more extensive disease, including 23% with more extensive regional nodal metastases and 14% with distant metastasis. Given the high detection rate, comparable cost, lower radiation dose and greater convenience, PET/CT should be considered as an alternative to CTBS rather than “optional” after CTBS, especially in patients who require an efficient and expeditious work up prior to initiating PST.
Artificial intelligence to accurately identify breast cancer patients with a pathologic complete response for omission of surgery after neoadjuvant systemic therapy: An international multicenter analysis.
Authors: Pfob André , Sidey-Gibbons Chris , Tasoulis Marios Konstantinos , Lee Han-Byoel , Koelbel Vivian , Kuerer Henry Mark , Heil Joerg 
Published: May 2020

565 Background: Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in up to 80% of women with breast cancer. In such cases, breast surgery, the gold standard for confirming pCR in the breast, may be considered overtreatment. So far, no approach alone – e.g. imaging, vacuum-assisted biopsy (VAB) – has accurately detected and excluded residual disease without surgery in multicenter prospective trials. We evaluated the ability of Artificial Intelligence algorithms to securely identify patients with residual tumor in the breast to safely select patients who might be spared from surgery. Methods: We collected multicenter, international data from 570 women who were included in prospective trials with initial stage I-III breast cancer of all biological subtypes and at least partial response on imaging, undergoing VAB before guideline-adherent surgery. We trained an ensemble of algorithms (including Regularized Regression, Support Vector Machines, and Neural Network) using 27 patient, tumor and VAB variables. Data were randomly partitioned into training and test sample with a 3:1 ratio and developed with 10-fold cross-validation. Primary endpoint was the sensitivity to diagnose residual disease by algorithm compared to surgery. Diagnostic performance of the algorithm was further evaluated on an external, independent dataset. Results: The algorithm was able to reliably identify women with residual disease before surgery (see table): Sensitivity for the internal test set was 96.9% (94 of 97; 95%CI 91.2-99.4%) and for the external, independent dataset 96.2% (26 of 27; 95%CI 80.4-99.9%). Most informative predictor of residual disease were tumor cells diagnosed in the VAB specimen, DCIS in the initial diagnostic biopsy, grading, and largest diameter on imaging after neoadjuvant treatment. Conclusions: Safely selected patients without residual disease as assessed by our algorithm may be spared by breast surgery in future trials. [Table: see text]
Impact of axillary lymph node dissection (ALND) on survival in patients with ypN1 breast cancer that receive regional nodal irradiation (RNI): A national cancer database (NCDB) analysis.
Authors: Kharouta Michael , Damico Nicholas , Harris Eleanor Elizabeth , Lyons Janice A. 
Published: May 2020

572 Background: The innovation of sentinel lymph node biopsy (SLNB) has allowed many patients with invasive breast cancer to forego ALND. However, the benefit of ALND is unclear in patients with pathologic N1 disease detected on SLNB following neoadjuvant chemotherapy, particularly in patients who receive adjuvant regional nodal irradiation. Methods: The National Cancer Database (NCDB) was queried for women ages 18-75 with cT1-3N1, and ypT0-T3N1M0 invasive breast cancer who underwent definitive surgical resection with axillary staging and also received adjuvant RNI. Patients treated from 2012 – 2015 were included to allow for appropriate coding of extent of axillary surgery. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received SLNB alone and ALND with or without SLNB utilizing log rank testing. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of overall survival. Results: A total of 1411 women were identified who met inclusion criteria. The median age was 52 (23-75) years. 206 (15%) women had SLNB alone and 1205 (85%) had ALND with or without SLNB. Five year OS was 73% in patients who underwent ALND compared to 76% in those who had SLNB alone (p =0.39). Following propensity matching by age, race, Charlson Deyo Comorbid Condition score, pT stage, grade, ER status, and HER2 status, 5 year OS was 79% in patients who underwent SLNB alone vs. 69% in patients who had ALND performed (p = 0.33). On Cox regression analysis, none of the variables predicted for 5 year OS. Conclusions: ALND in addition to RNI did not improve survival in patients with cT1-3N1M0 and ypT0-3N1M0 breast cancer compared to SLNB and RNI. We await results of the Alliance 011202 randomized trial for prospective validation of ALND omission in a similar subset of patients. [Table: see text]
Inhibiting fatty acid synthase in operable triple negative breast cancer.
Authors: Sardesai Sagar D. , Thomas Alexandra , Gallagher Christopher , Lynce Filipa , Ottaviano Yvonne Lynn , Ballinger Tarah Jean , Schneider Bryan P. , Storniolo Anna Maria , Bauchle Amber , Althouse Sandra K. , Perkins Susan , Zhang Jian-Ting , Miller Kathy 
Published: May 2020

584 Background: Fatty acid synthase (FASN) is overexpressed in 70% of newly diagnosed triple negative breast cancer (TNBC) and is associated with poor prognosis. In vitro, FASN overexpression induces drug resistance to DNA damaging agents. Proton pump inhibitors (PPI) selectively inhibit FASN activity and induce apoptosis in breast cancer cell lines with minimal effect on non-malignant cells. We report the results of a single arm phase II study of high dose omeprazole (OMP) in combination with anthracycline- taxane (AC-T) based neoadjuvant chemotherapy. Methods: Patients (pts) with operable TNBC independent of baseline FASN expression; and no prior PPI use within 12 months were enrolled. Pts began OMP 80 mg PO BID for 4-7 days prior to AC-T; carboplatin was allowed per physician discretion. OMP was continued until surgery. Paired biopsy samples were obtained before and after OMP monotherapy. The primary endpoint was pathologic complete response (pCR), defined as no residual invasive disease in breast or axilla, in pts with baseline FASN expression (FASN+) assessed using immunohistochemistry. Relevant secondary endpoints included pCR in the intent to treat population, change in FASN expression, enzyme activity and downstream target gene expression after OMP monotherapy; safety and limited OMP pharmacokinetics. We targeted a pCR rate of 60% in FASN+ pts (null pCR ~ 40%) with 80% power and alpha of 0.10. Results: A total of 42 pts were recruited from 5 US sites. Median age was 51y (28-72). Most pts had >cT2 (33, 79%) and ≥N1 (22, 52%) disease. 14 (33%) were African American. FASN expression prior to AC-T was identified in 28 (85%) samples available for analysis. The pCR rate was 71.4% (95% CI 51.3 to 86.8) in FASN+ pts and 71.8 %( 95% CI 55.1 to 85.0) in all enrolled pts. Fifteen pts (36%) received carboplatin with AC-T; pCR in this subset was 73%. Peak OMP concentration was significantly higher than IC50 observed during preclinical testing; FASN positivity significantly decreased with OMP monotherapy from 0.53(SD 0.25) at baseline to 0.38(SD 0.30; p = 0.02). OMP was well tolerated with no known grade (G) 3 or 4 toxicities. Chemotherapy toxicity was similar to prior studies using AC-T with G3 or 4 neutropenia (19%), febrile neutropenia (7%) and peripheral neuropathy (7%) being the most common. Conclusions: Consistent with previous studies, FASN is frequently expressed in early stage TNBC. OMP can be safely administered in doses that inhibit FASN. The addition of high dose OMP to neoadjuvant AC-T yields a promising pCR rate without adding toxicity. Funded by the Breast Cancer Research Foundation. Clinical trial information: NCT02595372 .
Efficacy of neoadjuvant chemotherapy (NAC) in male breast cancer (MaBC) compared with female breast cancer (FBC): A National Cancer Database (NCDB) study.
Authors: Leone Jose Pablo , Freedman Rachel A. , Hassett Michael J. , Leone Julieta , Tolaney Sara M. , Vallejo Carlos Teodoro , Leone Bernardo Amadeo , Winer Eric P. , Lin Nancy U. 
Published: May 2020

587 Background: NAC is frequently used in the treatment of FBC. The efficacy of NAC in MaBC is unclear. Few studies have compared outcomes for MaBC and FBC after similar treatment. The aim of this study was to compare proportions of pathologic complete response (pCR) between MaBC and FBC according to tumor subtype (TS). Secondary aims were clinical response and overall survival (OS). Methods: We evaluated men and women with breast cancer treated with NAC between 2010 and 2016 with known hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status at NCDB centers. The proportion with pCR (ypT0/Tis ypN0) was compared for MaBC and FBC for each TS by Fisher’s exact test. Logistic regression evaluated odds of pCR. OS was estimated by Kaplan-Meier and compared by log-rank test. Results: Of 7,721 MaBC and 859,096 FBC patients, 385 MaBC (5%) and 68,065 FBC (7.9%) underwent NAC and were included in this study. Median age for MaBC was 58 years (y) (range 23-88) and for FBC was 53 y (range 18-90). Within each TS, there were no significant differences in the distribution of tumor grade between MaBC and FBC. Clinical stage in MaBC and FBC were: Stage I: 8% v 11%, Stage II: 54% v 59%, Stage III: 38% v 30%; respectively. Median time from initiation of NAC to surgery was 143 days in MaBC and 148 days in FBC. Compared with FBC, MaBC had a lower proportion of complete clinical response (18% v 31%) and a higher proportion of no clinical response (14% v 7%); p < 0.001. Proportions and odds of pCR were numerically lower in MaBC compared with FBC for each TS and statistically significant for HR+/HER2- and HR+/HER2+ (table). pCR was associated with OS in both MaBC and FBC. Specifically, in MaBC who achieved pCR v not, 5 y OS was 90% v 64.7%; p = 0.02. In FBC who achieved pCR v not, 5 y OS was 91.9% v 75.3%; p < 0.01. Among pts receiving NAC, MaBC had worse OS at 5 y than FBC (67.1% v 79.0%; p = 0.02). Conclusions: Men receiving NAC achieved lower proportions of pCR than women and had significantly worse OS. However, pCR is prognostic in both MaBC and FBC. Limitations include small sample sizes for HR-/HER2+ and triple-negative TS and lack of detailed regimen information. Nevertheless, our results suggest that, compared with FBC, MaBC may be intrinsically more resistant to NAC. [Table: see text]
Impact of body composition on toxicity and pathological complete response in locally advanced breast cancer (BC).
Authors: Munoz-Arcos Laura Sofia , Mayer Jessica , Haken Orli , Goldman Jessica , Sparano Joseph A. , Anampa Mesias Jesus Del Santo 
Published: May 2020

593 Background: Obesity, defined as body mass index (BMI) > 30 kg/m2, has been associated with inferior outcomes in localized breast cancer (BC), including lower pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High BMI is usually associated with excess adipose tissue (AT), but also reflects skeletal muscle (SM) mass. Low SM mass (sarcopenia) has also been associated with inferior outcomes and more chemotherapy-associated toxicity. We aimed to evaluate the association of BMI, AT and SM tissue with pCR and toxicity after NAC for stage II-III breast cancer (BC). Methods: 191 patients with stage II-III BC received NAC, had information regarding baseline BMI, toxicity and pCR to NAC at surgery, and, had abdominal computerized tomography (CT) prior to NAC. Total AT (TAT), visceral AT (VAT), subcutaneous AT (SAT), SM area (SMA) and SM density (SMD) were measured by CT at the L3 level using the TOMOVISION software. SM index (SMI) was calculated (SMA/height) to assess for sarcopenia (SMI < 40). Association linking BMI, SAT, VAT, SMA and SMD to pCR and severe toxicity (ST ≥ grade 3) was evaluated using logistic regression models. Results: Patients were predominantly black (51%) with a median age of 54 years (interquartile range = 45-63). pCR was achieved in 31% (60/191) of patients. Of those, 47% (n = 28/60), 40% (n = 24/60) and 13% (n = 8/60) corresponded to HER2(+), triple negative, and hormone receptor-HR(+)/HER2(-) tumors, respectively. ST occurred in 38% (n = 73/191) of patients. Obesity and sarcopenia were present in 52% (n = 100/191) and 14% (n = 27/191) of patients, respectively. There was a statistically significant association between VAT and pCR (median VAT 95.3 cm2 vs. 121.8 cm2 in the pCR vs. no-pCR groups, respectively, p = 0.03). This association remained after adjusting for age, race, tumor grade, stage, BMI, SMD, HR and HER2 status (p = 0.04). There was a statistically significant association between SMA and ST (mean SMA 123 cm2 vs. 130 cm2 in the ST vs. no-ST groups, respectively, p = 0.03). This association disappeared after adjusting for age, race, BMI, VAT, SAT, and SMD (p = 0.21). Conclusions: This study provides evidence that in patients with stage II-III BC receiving NAC, excess VAT is associated with significantly lower pCR rates, and low SMA is associated with ST. Additional research is needed to elucidate the pathophysiologic mechanisms contributing to these associations.
Prediction of response to neoadjuvant hormonal therapy (NAHT) using upfront oncotype Dx recurrence score (RS): Results from the SAFIA phase III trial.
Authors: Al-Saleh Khalid A , Bounedjar Adda , Oukkal Mohammed , Mahfouf Hasen , Bouzid Kamel , Bensalem Assia , Fillali Prof Taha , Larbaoui Blaha , Kandil Alaa , Alfoheidi Meteb , Errihani Hassan , Ghosn Marwan , Abdulaziz Nashwa A , Dabouz Farida , Bahadoor Mohun Ranvir K. , El Zawahry Heba Mohamed , Kullab Sherif A , Nabholtz Jean-Marc A. 
Published: May 2020

594 Background: While hormonal therapy (HT) is a fundamental treatment in breast cancer therapy, neoadjuvant NAHT is not considered standard. The SAFIA trial is a prospective international neoadjuvant Phase III investigating the potential role of the addition of palbociclib (P) in patients (pts) sensitive to HT. We report the results of induction Faslodex (+/- zoladex) in pts initially selected by RS < 31, in order to assess their individual HT sensitivity before double-blind randomization HT vs HT + P followed by surgery. Materials and Methods: A total of 308 pts (stages II and IIIA Luminal A/B HER2 negative) in 24 centers and 6 countries (Middle-East/Maghreb) underwent upfront RS to select pts for induction HT. Pts with RS < 31 received induction neoadjuvant fulvestrant (500 mg i.m Day 1, 14, 28 then q.4 weeks) + goseriline (3.6 mg s.c q.4 w for pre and peri-menopausal pts) for 4 months, followed by clinical and radiological assessment of the disease response before randomization. Response was defined as no progression: Complete Response-CR/ Partial Response-PR: > 50% and Minor Response-MR: < 50% to > 0%/ No Response-NR: progression > 0%. Results: A total of 70 pts (22%) with RS > 31 were excluded, leaving 238 eligible pts for NAHT, age (25-84); pre-peri/ post menopause: 135 (57%)/103 (43%); Luminal A/B: 112 (49%)/114 (51%); Stage II/IIIA: 196 (87%) / 29 (13%). One hundred and seventy-seven pts (177) have validated responses to induction NAHT: CR: 9 pts (5%) / MR: 105 pts (59%) for major response rate: 64% / MR: 56 pts (32%) / NR: 7 pts (4%); available RS 0-10: 23 pts (16%) / RS 11-18: 67 pts (47%) / RS 19-25: 34 pts (24%) / RS 26-30: 18 pts (13%). Correlations between Response to NAHT and RS are shown in the table below (not statistically significant). Conclusions: In our population, upfront Oncotype DX RS < 31 allowed to select pts for induction NAHT without loss of chances with a no-progression rate (CR+PR = MR) of 96%. No significant correlation was found between RS and response to NAHT. Upfront RS > 31 (22%) is selecting pts candidates for neoadjuvant chemotherapy with a potential high risk of endocrine resistance. Clinical trial information: ICRG1201 .