bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant radiotherapy use in a population-based sample of breast cancer patients
Authors: Jagsi R. , Abrahamse P. , Griggs J. J. , Katz S. J. 
Published: August 2020

617 Background: Previous studies have suggested underutilization and socioeconomic disparities in use of adjuvant radiotherapy (RT) among patients with breast cancer. However, these studies used registry data which may be incomplete. Methods: We evaluated data from 2260 survey respondents with nonmetastatic breast cancer, aged 20–79 years, diagnosed from June 2005-February 2007 in Detroit and Los Angeles and reported to SEER registries (72% response rate). Survey responses regarding treatment and sociodemographic factors were merged to SEER data. Rates of RT receipt were based on patient report. Patients were divided into 3 populations: DCIS pts undergoing breast conservation (BCS), invasive pts undergoing BCS, and invasive pts undergoing mastectomy. These were then stratified based on recurrence risk in the absence of RT (3 groups based on tumor size and grade for DCIS pts, 2 groups separating pts over 70 with Stage I, ER+ tumors from others undergoing BCS for invasive disease, and 3 groups based on tumor size and nodal status for those undergoing mastectomy for invasive disease). Results: Among 306 pts undergoing BCS for DCIS, 85.6% received RT (77.9% of pts at low recurrence risk, 84.8% at intermediate risk, and 95.8% at high risk). Among 1018 pts undergoing BCS for invasive disease, 93.6% received RT (83.6% of low-risk patients and 94.9% of others). Among 661 pts undergoing mastectomy for invasive disease, 39.3% received RT (81.5% of pts at high-risk, 44.5% at intermediate-risk, and 12.1% at low risk). In separate multivariate logistic regression models including risk grouping and sociodemographic variables for each population, there were no significant associations between RT receipt and race, education, or income. Among pts receiving RT, delay was reported by 15.9% of the DCIS group, 19.5% of those treated for invasive disease after BCS, and 27.4% of those treated for invasive disease after mastectomy. Conclusions: RT use is high after BCS with little evidence of socioeconomic disparities. But lower than optimal rates after mastectomy even among patients with high expected benefit suggest lingering barriers to effective treatment in these patients. Less RT use in patients with lower expected benefit suggests that legitimate clinical uncertainty influences decision-making. No significant financial relationships to disclose.
Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel
Authors: Inhorn R. C. , Daniel B. , Daniel D. , Naot Y. , Zubkus J. , Lane C. , Trieu V. , Knauer D. , Desai N. , Yardley D. A. 
Published: August 2020

618 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated substantial activity with pCR rates of 20–25%. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin binding activity and is a poor prognostic factor for survival. This study was designed to evaluate the feasibility and safety of a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with G and epirubicin (E) with SPARC tumor assessments performed in consenting patients (pts). Methods: Eligibility: Clinical T1c-T4d and/or N0–3, M0 breast cancer (T1N0M0 excluded), normal LVEF. ER/PR/HER-2 obtained for all pts. Treatment: neoadjuvant G 2,000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days x 6 cycles followed by surgery. Post operative therapy: G 2,000 mg/m2 and nab-P 220 mg/m2 q14 days x 4 cycles. Myeloid growth factors were mandated with all cycles. Two different antibody reagents were used to probe for SPARC expression of tumoral SPARC and stromal SPARC; level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts enrolled. Pathologic responses are available for 112 pts with 11 unevaluable. 82 pts consented to SPARC tumor testing. Median age 51 (29–72). Median tumor size 4.5 cm. 42% ER-/PR -. 55% clinical T3/T4 and 66% node positive. Pathologic complete responses (pCR) were noted in 22 pts (18%) with PRs in 84 pts (68%), and 6 SD (5%). SPARC IHC staining was available in 77 tumor samples; SPARC positivity was noted in 89% of evaluated tumors achieving pCR. Triple negative, ER negative or PR negative tumors were associated with worse PFS. SPARC + tumors showed a trend to improved PFS that was strongly associated with tumoral SPARC but not stromal SPARC. Conclusions: Dose dense neoadjuvant G, E, and nab-P is active and well tolerated with a favorable pCR rate of 20%. ER neg, PR neg, and triple negative tumors were associated with worse PFS. Despite literature reports of SPARC positivity associated with poor prognosis, SPARC+ tumors in this study showed a high concordance with tumor response and a trend to improved PFS with tumoral SPARC. [Table: see text]
Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients
Authors: Leone J. P. , Guardiola V. , Venkatraman A. , Pegram M. D. , Welsh C. , Silva O. , Larrieux R. , Franchesci D. , Gomez C. , Hurley J. 
Published: August 2020

625 Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15–20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28–86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26–43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28–51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16–45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC. No significant financial relationships to disclose.
Intraoperative radiotherapy (IORT) as a boost during breast conserving surgery (BCS) using low kV X-rays: The first 5 years of experience with a novel approach
Authors: Wenz F. K. , Welzel G. , Blank E. , Hermann B. , Steil V. , Suetterlin M. , Kraus-Tiefenbacher U. 
Published: August 2020

626 Background: Recently, the concept of IORT during BCS has been introduced using linear accelerators, brachytherapy or dedicated mobile IORT devices generating fast electrons or low energy X-rays. Here, we report the first 5 years of a single center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. Methods: 155 breast cancers in 154 women (median age 63 yrs, range 30 - 83 yrs, T1/T2 = 110/45, N0/N+ = 104/51) were treated between February 2002 and December 2007 at the University Medical Center Mannheim/University of Heidelberg, in whom IORT as tumor bed boost was applied using 50 kV X rays (20 Gy, INTRABEAM, Carl Zeiss Oberkochen, additional OR time about 45 - 60 min) followed by 46 - 50 Gy external beam whole breast radiotherapy (EBRT). Chemotherapy was given before EBRT. The median interval between BCS+IORT and EBRT was 10 wks. Median follow-up was 34 mon (max 79.6 mon, 1 pt lost to f/u). Overall survival (OS), local relapse free survival (LRFS) and disease free survival (DFS) were calculated at 5 yrs using the Kaplan Meier method. 81 patients were evaluated at 3 yr f/u for normal tissue effects using the LENT SOMA scoring system. Results: Ten patients have died, 2 pts suffered from in breast relapse and 8 pts developed distant metastases yielding a 5yr OS of 87.0%, a 5yr LRFS of 98.4% and a 5 yr DFS of 73.9%. Grade 3 fibroses of the tumor bed were detected in 6% of the patients after 3 yrs. Skin toxicity was mild (teleangiectases and hyperpigmentations in 6% each). Conclusions: IORT as a tumor bed boost using the INTRABEAM system yields low recurrence and toxicity rates when followed by external beam whole breast radiotherapy. [Table: see text]
The final results of the United Kingdom sentinel node training program: New Start
Authors: Mansel R. E. , McNeill F. 
Published: August 2020

629 Background: Formal introduction of new surgicaltechniques is rare, but the rate of technological advances in cancer surgery mandates that surgeons in current practice will need to learn new techniques in an enviroment less rigorous than residency programs. The rapid introduction of sentinel node biopsy in breast cancer is a classic exemplar of the problematic issues around quality assurance and patient safety in new technology. In the UK this technique was introduced in a unique formal program –The New Start training program –which utilised educational methods with a mandatory quality assurance system for each individual surgical team prior to routine introduction of the technique in practice. Methods: Every hospital had to submit the breast team to a formal program consisting of a theory training day followed by in house supervised training for the first 5 cases in the operating room in their instituition.Surgical teams performed 5 directly supervised procedures followed by 25 further audited cases with data being submitted centrally. All sentinel procedures were combination isotope/blue dye, (Nanocoll 99 Tm and a blue dye (Patent Blue V- laboratoires Guerbert Paris, France). In order to be approved each team had to achieve a localisation rate of at least 90% and a false negative rate of less than 10%. Results: The program has now trained 242 surgeons performing a total of 6341 audited sentinel node validation procedures. The localisation rate was 99% and the false negative rate was <8%. The median number of sentinel nodes was 2 and in 54% of the node positive patients, the sentinel node was the only positive node. Preoperative scintigraphy showed hotspots in 83% of patients. Blue dye reactions in this large dataset were lower than quoted in the literature, (<1% of patients), suggesting over-reporting in smaller trials. There was short learning curve for false negativity falling to <4% after 40 audited cases. Failure to find a sentinel node correlated strongly with a higher rate of histological node positivity. Conclusions: This major national training program with in house practical training has shown a high localisation rate and a shortened learning curve for false negative cases, and has demonstrated the value of a formal training program, which can form the template for the introduction of new surgical techniques. No significant financial relationships to disclose.
Survival advantage by neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer
Authors: Roth S. L. 
Published: August 2020

638 Background: The impact of timing of radiochemotherapy (RCT) relative to surgery has been assessed in terms of ten year survival rate for locally advanced or surgically in terms of breast conserving surgery or simple mastectomy unfavourable, noninflammatory breast cancers (LABC). Methods: A total of 644 women were included in the retrospective study from 1991–1998. Chemotherapy was applied in 166 as neoadjuvant, in 236 simultaneously and in 113 as adjuvant. 119 patients received no chemotherapy. 40% of the patients received four courses of epirubicin/ cyclophosphamide, 26% concurrent mitoxantrone, 5% three cycles of CMF, 3% six cycles of CMF and 15% had no chemotherapy. 315 patients with locally advanced breast cancer (LABC) received neoadjuvant and 329 adjuvant RCT. Preoperative radiotherapy consisted of 50 Gy to the breast and the supra/infraclavicular lymph nodes with a 10 Gy electron or interstitial boost. The mean time interval between the end of radiotherapy and the surgery was 27 weeks (6–89 weeks). Results: Breast conservation was possible in 48% in the preoperative arm and in 52% in the postoperative arm. The rate of pT0 after neoadjuvant RCT was 38% (120/315) and the pCR in breast and axilla 30% (95/315). The ten year survival in the neoadjuvant group (n = 315) compared favourably 68.6% vs. 65% in case of the adjuvant group (n = 329; p = 0.21) in spite of more advanced disease. Patients with cT1- (n = 3) and cT2- (n = 97) categories had a significantly 13.6% better ten year survival rate after neoadjuvant RCT (85.76% vs. 72.19%) compared to cT1- (n = 1) and cT2- (n = 180) after adjuvant RCT (p = 0.0026). Conclusions: This study compares, retrospectively, neoadjuvant RCT vs. adjuvant RCT in LABC. Preoperative RCT achieved a pT0-rate of 38% and a prolonged ten year survival to a degree of 13.6% statistically significant in patients with cT2- category breast cancer compared to adjuvant RCT. No significant financial relationships to disclose.
Quality of breast cancer care in NCCN centers as assessed by the ASCO/NCCN quality measures: Overall performance and reasons for nonconcordance
Authors: Hughes M. E. , Ottesen R. , Niland J. C. , Edge S. B. , Theriault R. L. , Wilson J. , Blayney D. W. , Wong Y. , Weeks J. C. 
Published: August 2020

6506 Background: To assess the quality of breast cancer care in the National Comprehensive Cancer Network (NCCN), we compared practice against the ASCO/NCCN quality measures (QM). Methods: Using the NCCN Outcomes Database, we studied the care of women with newly diagnosed stage I-III breast cancer treated at 8 NCCN centers in 2003–6 to determine the proportion whose care was consistent with the 3 QMs (tamoxifen or anastrozole within 1 year of diagnosis for HR+ >1 cm tumors [HT]; post- lumpectomy radiation within 1 year of diagnosis for women <70 yo [RT]; and chemotherapy within 120 days of diagnosis of HR- >1 cm tumors for women <70 yo). Based on chart review, reasons for non-concordant care were classified as: 1) treatment recommended, but declined; 2) MD recommended against treatment; 3) non-recommended treatment administered; or 4) system problem (referral to the relevant specialist not documented or specialist not seen, delayed treatment initiation, or no relevant documentation in the chart). Results: 5,175 women were analyzable on at least one QM. Overall, treatment was consistent with the QM for 6,628/7,265 (91%) of the unique patient-recommendation pairs. Non-concordant care was received by 11% of patients eligible for the HT QM, 5% for the RT QM, and 13% for the chemotherapy QM. The reasons for non-concordance are shown in the table. Conclusions: Overall, breast cancer care in the NCCN is highly concordant with the ASCO/NCCN quality measures. System problems rather than patient refusal or physician recommendations account for the majority of care that deviates from the QM recommendations. This suggests that quality improvement targeting systems rather than physicians would be especially efficient and effective. [Table: see text] No significant financial relationships to disclose.
Absolute benefits of experimental medical therapies in phase III randomized clinical trials (RCTs) in breast and colorectal cancer
Authors: Seruga B. , Hertz P. C. , Wang L. , Booth C. M. , Krzyzanowska M. , Cescon D. W. , Tannock I. F. 
Published: August 2020

6513 Background: New treatments are approved based on results of RCTs, which have become larger and powered to detect smaller absolute benefits (Booth et al, J Clin Oncol 26, 2008).The purpose of this study was to evaluate temporal trends in absolute benefits of experimental medical therapies in RCTs. Methods: RCTs with 200 or more participants evaluating medical therapies for breast and colorectal cancer were identified by searching Medline from 1975 to 2007. For each trial, absolute benefits were determined as: (i) the difference in either 3-year event-free survival (EFS) or 5-year overall survival (OS) for adjuvant trials, or in median survival for metastatic trials, as per usual practice; and (ii) the area between time-to-event curves for the treatment arms relative to total area, up to a given time. Monthly incremental cost of new therapies approved by the FDA between 1995 and 2007 were determined for treatments for metastatic disease. Results: We identified 236 eligible RCTs, with 57% evaluating adjuvant treatments for breast (N=102) and colorectal cancer (N=33). Median absolute benefits of experimental treatments decreased substantially in the last decade (Table) and were in the range of only 1.3 to 2.7% when analyzed as the relative area between time-to-event curves. Among RCTs evaluating treatment for metastatic cancer there was no change in absolute benefits with time, but incremental monthly cost of new approved treatments increased with time (1995: median $U.S. 65; 2007: median $U.S. 6560, p<0.0001). Conclusions: Evaluating absolute benefit as the relative area between time-to-event curves does not depend on the shape of the curves and is preferred. Over time, RCTs evaluating adjuvant treatment for breast and colorectal cancer show decreasing absolute benefit. New costly treatments may not assure meaningful clinical benefits. [Table: see text] No significant financial relationships to disclose.
Pharmacoeconomic study in head and neck cancer patients: Impact of prospective DPD deficiency screening with 5-fluorouracil (5-FU) dose tailoring on toxicities-related costs
Authors: Mercier C. , Brunet C. , Yang C. , Dupuis C. , Bagarry-Liegey D. , Duflo S. , Giovanni A. , Zanaret M. , Lacarelle B. , Duffaud F. , Ciccolini J. 
Published: August 2020

6515 Background: Dihydropyrimidine dehydrogenase (DPD) plays a pivotal role in the detoxification of 5-FU. We studied the impact of screening DPD impairment in head and neck cancer (HNC) patients, both on reduction of drug-related toxicities and as a pharmacoeconomic endpoint. Methods: A total of 148 consecutive patients with HNC treated with 5-FU+platinum were monitored. Seventy-four patients (Arm A - before 2006) were treated with standard dosage, whereas 74 other patients (Arm B - after 2006) had their DPD status phenotypically evaluated prior to receiving 5-FU, with subsequent dose reduction if DPD deficiency were suspected. Severe toxicities and response were compared. Additionally, direct and indirect costs required to manage the treatment-related toxicities and to establish DPD status were calculated. Results: Sepsis was observed in 16.2% of patients treated with standard dosage. In Arm B, DPD deficiency was suspected in 35% of the patients and 5-FU dosage was subsequently reduced. Consequently, only 1.8% of them experienced sepsis. Of note, response rates were comparable between Arm A and B (62 vs 61%, p>0.05), thus demonstrating that 5-FU dose tailoring did not negatively impact on treatment efficacy, while reducing the occurrence of severe toxicities. Managing toxicities required an average 23-days of extra-hospitalization (4–96 days), including an average 1.6-day stay in ICU. No patients from Arm B had to stay in ICU. Drugs required for managing toxicities cost an average of $339 per patient (Arm A) and was reduced down to $38 per patient (Arm B). Similarly, mean extra-hospitalization cost was $5,940/patient in Arm A and $245/patient in Arm B. Testing DPD cost $49/patient in Arm B. Conclusions: Developing an adaptative dosing strategy based upon DPD status evaluation led to a dramatic reduction of the incidence of 5-FU-related severe toxicities, while maintaining optimal efficacy. Subsequently, extra-cost (medication + hospitalization costs) required to manage the toxicities fell down from $6,279 to $294/patient. Overall, this study advocates that systematic screening for DPD deficiency could be cost-efficient in the setting of 5-FU-based chemotherapies, with a reduction of 95% of the extra-costs. No significant financial relationships to disclose.
The impact of obesity on adherence to the National Comprehensive Cancer Network (NCCN) guidelines recommending chemotherapy for patients with operable breast cancer
Authors: Brewster A. M. , Etzel C. , Zhou R. , Wong Y. , Edge S. B. , Blayney D. W. , Wilson J. , Hudis C. , Weeks J. C. , Theriault R. L. 
Published: August 2020

6517 Background: Obesity (measured using body mass index [BMI]) is regarded as a prognostic factor for worse breast cancer survival. We hypothesized that obesity may influence adherence to NCCN guidelines recommending chemotherapy for patients with operable breast cancer at NCCN centers. Methods: We identified women < 70 years diagnosed with stage I, II, or III breast cancer from 1997 to 2006 at 8 NCCN centers for whom guidelines recommended chemotherapy. Body mass index was assessed in categories (<25 kg/m2 [normal], 25 to <30 kg/m2 [overweight], 30 to 39kg/m2 [obese], ≥40 kg/m2 [morbidly obese]) and in 5 kg/m2 increments. Multivariable logistic regression analysis adjusting for center, age at diagnosis, ethnicity, comorbidity score, and guideline was used to examine the association between BMI at diagnosis and non-receipt of chemotherapy. Results: 9,389 women were eligible for the study: 38% normal weight; 30% overweight; 23% obese; 5% morbidly obese; and 4% unknown. In multivariable analysis with BMI as a categorical variable, there was no association between weight status and non-receipt of chemotherapy (p = 0.35). When BMI was assessed in 5kg/m2 increments, weight status was a statistically significant predictor of non-receipt of chemotherapy (p = 0.02), but the odd ratios exceeded 1.0 only for BMIs ≥42.6kg/m2. Other patient-related factors associated with non-receipt of chemotherapy included older age at diagnosis (p < 0.01), presence of comorbidities (p < 0.01) and center (p < 0.01). Conclusions: Overall, the quality of breast cancer care as measured by adherence to NCCN guidelines recommending chemotherapy was not affected by patient overweight or obese status. Chemotherapy use was lower among patients with extreme morbid obesity, which may represent appropriate clinical decision-making. Evaluating factors that may contribute to worse prognosis among obese patients is essential for individualizing care and improving breast cancer outcome. No significant financial relationships to disclose.