bluuebunny/crossref_metadata_2025 huggingface dataset:
Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206
Authors: Rini B. I. , Halabi S. , Rosenberg J. , Stadler W. M. , Vaena D. A. , Atkins J. N. , Picus J. , Czaykowski P. , Dutcher J. , Small E. J.
Published: February 2017

LBA5019

Background: Bevacizumab (BEV) plus interferon alpha (IFN) demonstrated a superior objective response rate and progression-free survival (PFS) versus IFN monotherapy in renal cell carcinoma (RCC) patients in 2 phase III trials. The primary objective of CALGB 90206 was to compare overall survival (OS) for advanced RCC patients receiving BEV plus IFN or IFN alone. Methods: Patients with previously-untreated, metastatic RCC with a clear cell component and Karnofsky performance status of ≥ 70% were eligible. Patients were prospectively randomized to receive BEV (10 mg/kg intravenously every 2 weeks) plus IFN (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN as monotherapy. Randomization was stratified by nephrectomy status and number of MSKCC adverse features. The primary endpoint was OS, defined as the time from randomization to death due to any cause. The trial was designed with 86% power to detect a hazard ratio (HR) of 0.76, assuming a two-sided type I error of 0.05. The primary analysis was an intent-to-treat approach using the stratified log-rank statistic, and the present analysis was based on the target number of 588 deaths. Results: Between October 2003 and July 2005, 732 patients were enrolled; 369 pts to BEV plus IFN and 363 pts to IFN monotherapy. The median duration of follow up among censored patients was 46.2 months (IQR=45.2–48.2). The median OS was 18.3 months (95% CI; 16.5–22.5) for BEV plus IFN and 17.4 months (95% CI; 14.4–20.0, unstratified log rank p = 0.097) for IFN monotherapy. The stratified HR was 0.86 (95% CI; 0.73–1.01) for BEV plus IFN compared to IFN (stratified log-rank p = 0.069). The median OS for BEV plus IFN versus IFN was 32.5 vs. 33.5 months (p = 0.524) for MSKCC good risk, 17.7 vs. 16.1 months (p = 0.174) for intermediate risk and 6.6 vs. 5.7 months (p = 0.245) for poor risk patients. The median PFS was 8.4 months vs. 4.9 months (p<0.0001). Fifty-three percent of patients received subsequent systemic therapy. Conclusions: The addition of BEV to IFN significantly improves the objective response rate and PFS versus IFN monotherapy. Overall survival favored the BEV plus IFN arm, not meeting pre-defined criteria for significance.

[Table: see text]
Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): Results from NCCTG Intergroup Phase III Trial N0147.
Authors: Alberts S. R. , Sargent D. J. , Smyrk T. C. , Shields A. F. , Chan E. , Goldberg R. M. , Gill S. , Kahlenberg M. S. , Thibodeau S. N. , Nair S.
Published: February 2017

CRA3507

Background: FOLFOX is standard adjuvant therapy for stage III CC. Adding Cmab to FOLFOX benefits pts with metastatic CC WT KRAS tumors. N0147 assessed the potential benefit of Cmab added to FOLFOX.

Methods: 21-56 days following resection and informed consent, KRAS status was centrally determined. Pts with wtKRAS CC were randomized to 12 biweekly cycles of oxaliplatin 85 mg/m2 d1, with leucovorin 400 mg/m2, 5FU 400 mg/m2 bolus IV, then 46-hr IV 5FU 2,400 mg/m2 on d1-2 (mFOLFOX6), without (arm A) or with Cmab (arm D) 250 mg/m2 d1&8, with Cmab at 400 mg/m2, cycle 1, d1. Primary endpoint was 3-yr disease free survival (DFS). Secondary endpoints included overall survival (OS) and toxicity. Planned accrual of 2,070 wtKRAS pts provided 90% power to detect hazard ratio (HR) of 1.33 with 2-sided α=0.05; with interim analyses after 25%, 50%, and 75% of planned events.

Results: 1,760 wtKRAS pts (Arm A-858, Arm D-902) were enrolled at the time of closure; median follow-up on 1,624 pts is 15.9 months. Trial closed to accrual when preplanned interim analysis after 50% of planned events demonstrated no benefit to addition of Cmab. 3-yr DFS favored FOLFOX alone (HR 1.18, 95% CI 0.92-1.52; p=0.33). No benefit of Cmab was observed in any subgroups assessed. Any grade ≥ 3 AE, diarrhea, and failure to complete 12 cycles was significantly increased in arm D. Increased toxicity and greater differences in all outcomes were observed in pts aged ≥ 70 ( Table ).

Conclusions: In this randomized phase III trial the addition of Cmab to mFOLFOX6 was of no benefit for pts with resected stage III wtKRAS CC. Supported by NIH Grant CA25224, Bristol-Myers Squibb, ImClone, Sanofi-Aventis, and Pfizer.

[Table: see text]

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Sunitinib (SU) in combination with docetaxel (D) versus D alone for the first-line treatment of advanced breast cancer (ABC).
Authors: Bergh J. , Greil R. , Voytko N. , Makhson A. , Cortes J. , Lortholary A. , Huang X. , Giorgetti C. , Kern K. A. , Lichinitser M.
Published: February 2017

LBA1010

Background: Taxane-based chemotherapy (CT) improves progression-free survival (PFS) in patients (pts) with newly diagnosed HER2-negative metastatic BC (MBC). SU, an oral multitargeted tyrosine kinase inhibitor (MTKI), demonstrated antitumor activity in combination with D in a phase I/II study in pts with MBC. A randomized, open-label, multicenter phase III trial in pts with newly diagnosed ABC tested the hypothesis that addition of a MTKI to D improves PFS vs. D alone.

Methods: Eligible pts (female; ≥18 yrs) had an ECOG PS ≤1, and newly diagnosed HER2-negative MBC or ABC. If (neo)adjuvant therapy included a taxane, relapse must have occurred ≥12 mos after CT. Pts were randomized (1:1) to treatment (tx) with D 75 mg/m2 iv on day 1 and SU 37.5 mg/day po from day 2–15 q3w (Schedule 2/1; Arm A), or to D 100 mg/m2 iv 1-hr infusion q3w (Arm B) that could be given until progression. If D was discontinued in Arm A for reasons other than progressive disease (PD), single-agent SU 37.5 mg daily was permitted until PD. Median, independently assessed, PFS (primary endpoint) was compared between tx arms using stratified and unstratified log-rank tests. Overall objective response rate (ORR), overall survival (OS), pt-reported outcomes, and safety were secondary endpoints.

Results: As of the data cutoff (February 1, 2010), the ITT population comprised 593 pts (SU+D, n=296; D, n=297). The trial did not meet its primary endpoint of prolonging PFS based on the independent radiologic assessment or in prolonging OS. Baseline characteristics were well balanced. Median relative dose intensity (RDI) was 94.2% and 92.4% for SU+D, and 92.6% for D arms, respectively. Median PFS was 8.6 mos (95% CI 8.2–10.3) in the SU+D arm vs 8.3 mos (95% CI 7.7–9.6) for the D arm (HR 0.922). Median OS was 24.8 mos (95% CI 21.5–33.1) in SU+D arm vs 25.5 mos (95% CI 22.8–27.8) for D arm (HR 1.207). ORR was significantly better for SU+D (51%) vs. D (39%) (p=0.0018). Frequent all causality grade 3/4 adverse events (≥10%) were neutropenia (46%), hand–foot syndrome (17%), and fatigue (12%) in the SU+D arm and neutropenia (44%) in the D arm.

Conclusions: Based on these data, SU+D is not a recommended treatment option for patients with newly diagnosed ABC. Strategies using antiangiogenic TKIs that increase RR but not OS may need to be revisited.

[Table: see text]
Randomized phase II/III trial comparing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in patients (pts) with advanced urothelial cancer (UC) unfit for cisplatin-based chemotherapy (CHT): Phase III results of EORTC study 30986.
Authors: De Santis M. , Bellmunt J. , Mead G. , Kerst J. M. , Leahy M. G. , Daugaard G. , Gil T. , Maroto J. P. , Marreaud S. , Sylvester R.
Published: February 2017

LBA4519

Background: About 50% of pts with advanced UC are not eligible for cisplatin based CHT (“unfit”) due to impaired renal function, performance status (PS) or comorbidity. This is the first randomized phase II/III trial comparing two chemotherapy regimens in this pts group.

Methods: The primary objective of the phase III part of this study was to compare the overall survival (OS) of CHT naïve pts with measurable disease and an impaired renal function (GFR<60 but >30 ml/min) and/or PS 2 who were randomized to receive either GC (G 1000 mg/m2 d1 and 8 and C AUC 4.5) q21 days or M-CAVI (M 30 mg/m2 d1 and 15 and 22, C AUC 4.5 d1 and VI 3 mg/m2 d1 and 15 and 22) q28 days. In order to detect an increase of 50% in median survival on GC compared to M-CAVI (13.5 versus 9 months) based on a two sided logrank test at error rates alpha=0.05 and beta=0.20, 225 pts were required. Secondary endpoints were overall response rate (ORR) and progression free survival (PFS).

Results: 238 pts, 119 in each arm, were randomized between January 2001 and March 2008 by 29 institutions. The median follow-up is 4.5 years. Two pts were ineligible and two other pts never started treatment. Best ORRs (CR + PR) were 41.2% (36.1% confirmed response) on GC versus 30.3% (21.0% confirmed response) on M-CAVI (p = 0.08). Median OS was 9.3 months on GC and 8.1 months on M-CAVI (p = 0.64). There was no difference in PFS between the two arms (p = 0.78). OS, PFS and ORR were similar in each of the risk groups (reason unfit for cisplatin and Bajorin risk group). Severe acute toxicity (SAT) (death, grade 4 thrombocytopenia with bleeding, or grade 3/4 renal toxicity, neutropenic fever or mucositis) was observed in 9.3% of pts on GC (2 toxic deaths) and 21.2% on M-CAVI (4 toxic deaths). The most common grade 3/4 toxicities were leucopenia (44.9%, 46.6%), neutropenia (52.5%, 63.5%), febrile neutropenia (4.2%, 14.4%), thrombocytopenia (48.3%, 19.4%), and infection (11.8%, 12.7%) on GC and M-CAVI, respectively.

Conclusions: There were no significant differences in efficacy between the two treatment groups. The incidence of SATs was slightly higher on M-CAVI.

[Table: see text]
A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma.
Authors: Pingpank J. F. , Hughes M. S. , Alexander H. R. , Faries M. B. , Zager J. S. , Royal R. , Whitman E. D. , Nutting C. W. , Siskin G. P. , Agarwala S. S.
Published: February 2017

LBA8512

Background: Patients with hepatic metastases from primary melanoma have a median survival between 6 and 9 months. Few treatment strategies provide a meaningful impact on outcome. This report examines the efficacy of a minimally invasive regional therapy with melphalan (MEL) in patients with hepatic metastases from malignant melanoma.

Methods: Between February 2006 and October 2009, 93 patients (M:F; 45:48) were accrued to a phase III, random-assignment trial comparing percutaneous hepatic perfusion (PHP-mel) (n=44) to standard of care (BAC) (n=49). This represents 100% of a planned 92 patient accrual. The primary endpoint was hepatic progression-free survival (H-PFS). Crossover to PHP-mel therapy was permitted at hepatic progression. Secondary endpoints included assessment of response rate (RR), duration of response (RES), and overall survival (OS) after PHP. A planned PHP treatment regimen included 4 to 6 PHP procedures at 28 to 35 day intervals. MEL (3.0 mg/kg) was delivered via the hepatic artery in a 30-minute hepatic artery infusion via a percutaneously placed catheter with hepatic venous hemofiltration using a retrohepatic, double balloon catheter (Delcath Systems, Inc.) and paired hemofiltration cartridges. Patients randomized to BAC were offered treatment considered to be the best alternative regimen by the treating physician. Staging evaluations were performed at baseline and then at 6 to 8 week intervals post baseline. All responses represent investigator-based results and were evaluated via standard RECIST criteria. Intent to treat based survival analysis was via the Kaplan-Meier method, with a 2-sided p< 0.05 defining significance.

Results: Median H-PFS was 245 days (CI:136, 267) for PHP-mel vs. 49 days (CI:43, 68) for BAC (p<0.001). Overall response rate was 34.1 % (15/44) (CI: 20.5, 49.9) for PHP (15/44) vs. 2.0 % (1/49) (CI: 0.1, 10.9) for BAC (p<0.001). Upon hepatic progression, crossover to PHP occurred in 27 patients (55%) randomized to BAC.

Conclusions: For patients with metastatic melanoma to the liver, H-PFS is significantly improved with PHP-mel versus best available care.

[Table: see text]
Adjuvant capecitabine and oxaliplatin for gastric cancer: Results of the phase III CLASSIC trial.
Authors: Bang Y. , Kim Y. W. , Yang H. , Chung H. C. , Park Y. , Lee K. , Lee K. H. , Kim Y. H. , Noh S. , Ji J. , Johnston M. , Sirzen F. , Noh S. H.
Published: February 2017

LBA4002

Background: Surgical resection is a recommended treatment for operable gastric cancer (GC) in general, despite high recurrence rates (40%–80%). Adjuvant chemotherapy aims to reduce recurrences; however, there is currently no universally accepted adjuvant regimen for GC. Methods: CLASSIC is a randomized, open-label, multicenter, international (South Korea, China, and Taiwan) study of XELOX (capecitabine 1000mg/m2 bid, d1–14, q3w and oxaliplatin 130mg/m2, d1, q3w x 8 cycles) vs observation, following D2 gastrectomy. Eligible patients were chemotherapy- and radiotherapy-naive, with stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), or IIIb (T3N2) GC resected within 6 weeks prior to randomization. The primary endpoint is 3-year disease-free survival (DFS). A sample size of 512 patients per arm was planned to observe the 385 DFS events required to provide 80% power at a 5% significance level for the hypothesized treatment effect (hazard ratio [HR] 0.75). The Independent Data Monitoring Committee recommended full evaluation and reporting of results following a positive pre-planned interim analysis at 266 events. Results: The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. The median duration of follow-up was 34.4 (16–51) months. XELOX-related grade 3/4 adverse events (AEs) occurred in 244/496 patients (49%) of the safety population. Neutropenia was the only AE observed in >10% of patients (21%, n=106/496). Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of XELOX and observation arms, respectively, mostly due to disease progression. Efficacy results in the ITT population are summarized below. Conclusions: This study demonstrates the superior efficacy of adjuvant XELOX vs observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. These data support the use of adjuvant XELOX for GC.

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Phase III trial of low-level laser therapy to prevent induced oral mucositis in head and neck cancer patients submitted to concurrent chemoradiation.
Authors: Antunes H. S. , Herchenhorn D. , Araujo C. M. , Cabral E. , Ferreira E. M. d. S. , Small I. A. , Rampini M. P. , Teich N. , Rodrigues P. C. , Silva T. G. P. d. , Dias L. F. , Ferreira C. G. M.
Published: February 2017

LBA5524

Background: Oral mucositis (OM) remains a limiting factor in in head and neck squamous cell carcinomas (HNSCC) patients (pts) treated with chemoradiation (CRT) leading to pain, dysphagia, and weight loss. Low-level laser therapy (LLLT) emerges as a promising, preventive therapy of CRT-induced OM. Yet, a definitive randomized trial supporting its use is lacking. This study was designed to assess the efficacy of LLLT in reducing the incidence and/or severity of OM. Methods: Assuming OM grade (G3) for placebo 0.4 (P0); LLLT 0.15 (P1) ; β=0.2; α=0.05, sample size was 94 pts. From Jun 2007 to Dec 2010, 47 LLLT and 47 placebo pts bearer of HNSCC of nasopharynx, oropharynx and hipopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional RT 70.2 Gy (1.8Gy/d, 5 times/wk) + concurrent cisplatin 100 mg/m2 every 3 wks. Main endpoints were OM incidence and severity, RT interruptions due to OM and pain intensity. The LLLT used daily was a diode InGaAlP (660nm-100mW-4J/cm²). OM evaluation was done by WHO and OMAS scale. Results: Mean age was 54.6 and 87.2% of pts were male. Primary site: oropharynx (74 pts), nasopharynx (9 pts), hypopharynx (11 pts). In the LLLT arm the incidence of OM G 3/4 was only 6.4% versus 48% in the placebo arm; HR of 0.13 (IC 95%, p<0.001). Besides in the LLLT arm 51% of pts did not have ulcers versus 17% in placebo arm (p<0.001). LLLT pts had less severe pain (p=0.012), used less narcotic analgesic, HR 0.33 (IC 95%, p<0.001) and required less gastrostomia, HR 0.037 (IC 95%, p= 0.005). No LLLT pts had RT interrupted due to OM. EORTC QLQ-C30 and its specific head and neck module QLQ-H&N35 were applied. Results clearly favored the LLLT arm. In QLQ-C30 benefit was seen in both physical and emotional functioning (p=0.037), fatigue (p=0.011), pain (p=0.043); and in QLQ-H&N35, pain (p=0.007), swallowing (p=0.001) and trouble with social eating (p=0.026). Conclusions: Our results indicate that upfront LLLT in HNSCC pts submitted to CRT is an effective tool in reducing G 3/4 OM, oral pain, use of narcotic and gastrostomia. QoL data supports the efficacy findings. Thereby LLLT should be the new standard of care in this setting.
Efficacy, tolerability, and biomarker analyses from a phase III, randomized, placebo-controlled, parallel group study of gefitinib as maintenance therapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC; INFORM; C-TONG 0804).
Authors: Zhang L. , Shenglin M. , Song X. , Han B. , Cheng Y. , Huang C. , Yang S. , Liu X. , Yun-Peng L. , Wang M. , Zhang X.
Published: February 2017

LBA7511

Background: INFORM (a phase III, randomized, multicenter, parallel group study; NCT00770588 ) investigated the efficacy, safety and tolerability of gefitinib (G) vs. placebo (P) as maintenance therapy in pts with locally advanced/metastatic NSCLC following standard first-line platinum based chemotherapy. Methods: Pts (≥18 years, with stage IIIB/IV NSCLC and WHO performance status 0-2) had completed 4 cycles of first-line platinum based doublet chemotherapy without progression/unacceptable toxicity. Pts were randomized 1:1 to G 250mg/day or P on discontinuation of first-line therapy. Progression-free survival (PFS; primary endpoint) was assessed in the intent to treat population (Cox proportional hazards adjusted for histology [adenocarcinoma vs. non-adenocarcinoma], smoking status [never-smoker vs. smoker], EGFR mutation status [positive vs. negative vs. unknown] and best response to first-line chemotherapy [complete response/partial response vs. stable disease]). PFS was considered superior with gefitinib if the G:P hazard ratio (HR) upper confidence interval (CI) was <1.00. Secondary endpoints included overall survival (OS), objective response rate, disease control rate, symptom improvement and tolerability. Results: 296 pts (n=148 G, n=148 P) were randomized (27 centers in china; 26 September 2008-10 August 2009). PFS data cutoff on 24 January 2011. Median duration of follow-up was 16.8 months: 91% pts progressed; 59% deaths. Demography was balanced between treatments; overall, 54.1% pts were never-smokers, 70.6% had adenocarcinoma, and 40.9% were female. For G vs. P, PFS HR=0.42; 95% CI 0.32-0.54; p<0.0001; median PFS 4.8 vs. 2.6 months. Most common AEs (any grade) with G were rash (49.7%), diarrhea (25.2%), and ALT increase (21.1%) which were generally mild/moderate. Overall incidence of serious AEs: G (6.8%); P (3.4%). Other secondary endpoint data (including OS and biomarkers) will be presented. Conclusions: PFS was significantly longer with G compared with P as maintenance therapy in Chinese patients with locally advanced NSCLC.
Multilumen breast brachytherapy in patients with 5 mm or less balloon surface-skin distance using the Contura brachytherapy catheter.
Authors: Reed D. R.
Published: February 2017

108

Background: To evaluate the toxicity of multilumen breast brachytherapy in patients with 5 mm or less balloon surface-skin distance (BSD) treated with the Contura catheter.

Methods: From September 2008 through February 2010 a total of 411 patients with early-stage breast cancer (stages 0, I, IIA) were treated with multilumen HDR brachytherapy for definitive APBI using the Contura brachytherapy catheter. Of those patients 92 had a balloon surface-skin distance (BSD) of 5 mm or less, with 6 months clinical follow-up. All patients received 34 Gy in 10 fractions bid over 5 days. The PTV_EVAL (cc) defined as a 1 cm expansion from the anterior surface of the device; BSD (mm) defined as the distance from the closest point on the balloon to the closet point on the skin surface; maximum skin dose (% and cGy); the volume of breast tissue (cc) receiving 150% and 200% of the prescription dose (V150, V200). Patient toxicity was evaluated at 1 week, 1 month, and 6 months following brachytherapy including; skin reaction (RTOG Acute Radiation Morbidity Scoring Criteria), pigmentation, telangiectasia, pain, fat necrosis, symptomatic seroma.

Results: The mean BSD was 3.7 mm, with a range of 1-5 mm. The mean maximum skin dose was 4508 cGy (132.5%). The mean V150 was 21 cc and the V200 was 4.7 cc. The mean PTV_EVAL V90 was 93.7%. 49% of patients had skin reaction, including at 1 week; 47% Grade 1, 0% Grade 2 or 3. At 1 month; 31% Grade 1, 14% Grade 2 and 0% Grade 3. At 6 months; 2% Grade 1, 2% Grade 2 and 0% Grade 3. 6.5 % developed pigmentation changes (hypo or hyper). 5.4% developed telangiectasias, 9.7% reported pain. No patients had fat necrosis, and 15.2 % had a symptomatic seroma. 1 patient had wound dehiscence (maxium skin dose 4195 cGy, 123.4% of prescribed dose). Patients that experienced toxicity had no difference in BSD (3.6 vs 3.9 mm) or in the maximum skin dose (132.6% vs. 132.6%) compared to those that did not experience toxicity.

Conclusions: Breast brachytherapy in patients with 5 mm or less BSD has acceptable toxicity with proper planning using the Contura multilumen catheter. Careful attention to maximum skin dose must be used, and we recommend not exceeding 145 % (4,930 cGy) of the prescribed dose.
Efficacy analysis of high-risk breast cancer patients treated with accelerated partial breast irradiation from a single institution.
Authors: Chen P. Y. , Vicini F. A. , Mitchell C. , Wallace M. , Benitez P. , Dekhne N. , Shah C. , Wilkinson J. B. , Martinez A.
Published: February 2017

111

Background: We present the results of an analysis of high-risk breast cancer patients as defined by the NSABP B-39/RTOG 0413 phase III trial, all treated with accelerated partial breast irradiation (APBI) from a single institution.

Methods: Between July 1993 and August 2010, 130 patients with any combination of at least one of the high-risk features of estrogen receptor (ER) negativity, age < 50, and/or axillary nodal positivity were treated with 1 of 3 forms of APBI. Sixty-seven patients were treated with interstitial needle-catheter brachytherapy, 44 balloon-based brachytherapy and 19 with 3D conformal external beam radiation therapy. Aside from the high-risk features, general eligibility criteria included infiltrating ductal carcinoma, with inclusion of invasive lobular and DCIS since 2003, margins > 2 mm, and surgically staged axilla. One-hundred eighteen patients had one high-risk factor, 11 had two, and 1 had all three factors. The median tumor size was 12.0 mm with margins > 2 mm in 80% of patients. Greater than 75% had T1 tumors and 50% were ER negative. Thirty-one percent of patients were node positive. Based upon the ASTRO Consensus Guidelines for use of APBI (2009) none of these patients were suitable, 38% cautionary and 62% were unsuitable.

Results: Median age was 56.5 yrs (range 40-90). With a median follow-up of 5.3 yrs (0.02-16.9) the 5-yr actuarial local recurrence rate (LR) was 4.2%; regional recurrence (RR) was 2.1%. Median time to LR and RR were 1.2 and 2.8 yrs, respectively. On univariate analysis, the only factor significant for LR was a close/positive margin (p=0.031), as ER/PR, age, nodal status, tumor size, histology, grade, hormonal or chemotherapy were all NS. The 5-yr actuarial cause specific, disease-free, and overall survivals as well as distant metastasis were 94%, 91%, 90%, and 6.4%, respectively.

Conclusions: This cohort of NSABP B-39/RTOG 0413 identified high-risk patients who have undergone APBI has yielded local-regional control rates and survival outcomes comparable to standard risk patients undergoing partial breast irradiation. Continued follow-up will be needed to assess the long-term efficacy of such high-risk breast cancer patients treated with APBI.
An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events.
Authors: Keene K. S. , Klepczyk L. C. , Meredith R. , Forero-Torres A. , Carpenter J. T. , Krontiras H. , Hyatt M. , Li Y. , De Los Santos J. F.
Published: February 2017

121

Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose.

Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT.

Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease.

Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.
Predictive factors for oligometastatic versus non-oligometastatic involvement of the central nervous system by brain metastases from breast cancer.
Authors: Garg S. , Marsh J. C. , Rao R. D. , Griem K. L.
Published: February 2017

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Background: To assess rates of oligometastatic (1-3 metastases) versus non-oligometastatic (4 or more) involvement of the central nervous system (CNS) from breast cancer and determine whether rates vary for different breast cancer subtypes.

Methods: We reviewed records of 65 patients with brain metastases from breast cancer. Fisher’s Exact Test compared incidence of oligometastatic versus nonoligometastatic CNS involvement and presence of visceral metastatic disease between groups. Paired Student's t test compared mean age and interval from initial diagnosis to development of brain metastases.

Results: 25 patients (38.5%) developed oligometastatic and 40 (61.5%) developed non-oligometastatic CNS disease. Subtypes predictive of oligometastatic disease included ER+ (p .04) and PR+ (p .008). Subtypes predictive of non-oligometastatic disease included HER2+ (p .05). HER2+ patients trended toward a lower incidence of visceral metastases compared to ER+ or PR+ patients (p .07). Non-oligometastatic and HER2+ patients developed brain metastases sooner after initial diagnosis (p .046 and .03, respectively).

Conclusions: ER+ breast cancer patients are more likely to develop oligometastatic CNS involvement and may be excellent candidates for stereotactic radiosurgery (SRS) alone. HER+ patients are likely to develop non-oligometastatic CNS involvement and may be better treated initially with whole brain radiotherapy (WBRT) even with apparent initial oligometastatic CNS involvement.
Use of intraoperative digital specimen mammography to improve operative efficiency.
Authors: Valero M. , Dominici L. S. , Golshan M.
Published: February 2017

138

Background: The traditional method of confirming excision of a targeted lesion during wire localized breast biopsy has been with standard specimen mammograms (SSM). More recently, intraoperative digital specimen mammograms (IDSM) have been used to provide immediate specimen evaluation for the surgeon in the operating room. We sought to evaluate operative time with the use of IDSM versus SSM.

Methods: A retrospective chart and electronic operating room record review of consecutive patients of a single breast surgical oncologist at a quaternary care academic center. Three hundred and forty-four (344) consecutive patients from 2003 to 2010 who underwent wire localized excisional biopsy or wire localized lumpectomy without lymph node evaluation, with specimen evaluation by IDSM or SSM. Operative time, defined as documented time of incision to documented time of closure, was recorded for SSM versus IDSM.

Results: We compared demographics of the two groups transitioning from SSM to IDSM (Table). During the study period, median operative time decreased from 50 minutes in the SSM group to 37 minutes in the IDSM group (p<0.001).

Conclusions: Operative times with the use of IDSM are significantly shorter than with SSM. Downstream effects include decreases in anesthetic time, anesthetic use, operating room charges, and increasing surgeon productivity.

[Table: see text]
Outpatient mastectomy clinical pathway.
Authors: Boughey J. C. , Jakub J. W. , Degnim A. C. , Osborn J. B. , Brodt J. K. , Vanderlei L. K. , Case J. K. , Dilger J. A. , Duncan C. M. , Hebl J. R.
Published: February 2017

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Background: Many patients require hospitalization after mastectomy, predominantly for pain management and treatment of postoperative nausea and vomiting (PONV). In order to improve a woman's perioperative experience after mastectomy and facilitate mastectomy on an outpatient basis, we initiated a clinical pathway for perioperative management of unilateral mastectomy patients at Mayo Clinic Rochester.

Methods: The clinical pathway consists of preoperative oral medications (celecoxib and gabapentin), preoperative ultrasound guided paravertebral block using bupivacaine, intraoperative anesthesia management with total intravenous anesthetic, and minimal use of long-acting opioids and postoperative acetaminophen and oxycodone. All patients are evaluated by the surgical team on the afternoon after surgery and if patients are recovering well are discharged on the day of surgery. The following morning, the surgical team telephones the patient to follow up on management of pain, nausea or vomiting, and drain output.

Results: Eighteen patients have been treated on this clinical pathway. Mean age of patients was 66 (range 51-81). Majority of patients (n=16, 89%) underwent unilateral mastectomy with sentinel lymph node biopsy, with 1 patient undergoing bilateral mastectomy and 1 patient undergoing mastectomy and axillary dissection. All patients are evaluated by the surgical team on the afternoon of surgery. Fourteen patients (78%) were without evidence of hematoma or PONV, pain was well-controlled on oral medications and they were discharged on the day of surgery. On morning after telephone calls, pain scale ratings ranged from 1 to 3 and no patients verbalized complaints of nausea. Four patients (22%) treated on this clinical pathway required overnight observation in the hospital, one for urinary retention, two for pain control, and one for high sanguineous drain output.

Conclusions: The clinical pathway presented provides preemptive analgesia and regional anesthesia for patients undergoing mastectomy, enabling the majority of patients to be discharged on the day of surgery. The clinical pathway is a safe and effective way to improve the perioperative experience of breast surgery patients and decrease hospital admission.
Surgical resection of the primary tumor in patients with distant metastatic breast cancer at diagnosis: Results of a retrospective series.
Authors: Arifi S. , Hijri f. Z. , Benbrahim Z. , Bendahou K. , Akasbi Y. , Nejjari C. , El Mesbahi O.
Published: February 2017

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Background: Among women with de novo stage IV breast cancer, the primary tumor is treated only when it causes symptoms. Recent data suggest that resection of in-breast tumors may avoid uncontrolled chest wall disease and may improve long-term survival. The authors evaluated the effect of surgery on chest wall status, and time to first progression (TTP) in such patients.

Methods: We reviewed the records of all stage IV breast cancer patients, treated at our institution between 2007 and 2010, who underwent a surgery for their primary tumor. Information collected included demographics, tumor characteristics, treatments, disease progression. Prognostic factors affecting loco regional relapse and TTP were assessed.

Results: Of 36 patients identified, 14 (38.9%) had postoperative diagnosis of distant metastases, and 22 (68.75%) were presented with intact primary tumor. The mean patient age was 50.22 (range 22–75) years. 52.8 were pre-menopausal women. 88.9% of tumors were hormone receptors (HR) positive while 11.1% were HR negative. HER2 was assessed in 18 cases and was positive in 16.7%. 77.7% women presented with locally advanced breast cancer, 61% were T4 with 25% T4d, and 16.7% were T3. Node status was N0 (16.6%), N1 (38.8%), N2 (16.6%), and N3 (13.8%). 86.1% patients had bone metastasis, 39% liver, 25.1% lung metastasis and 2.8% brain metastasis. All patients underwent mastectomy. Excision margins were positive in 2 cases. 55.6% had axillary lymph node dissection. All women received systemic therapy. Preoperative systemic therapy was given in 68.75%. First-line therapy consisted of anthracycline-based regimen (n=36) and/or taxane (n=9) and/or endocrine therapy (n= 30). None of the HER2-positive patients received trastuzumab. pCR occurred in 5 patients. Loco regional radiotherapy (RT) was given to 4 women (11.1%). Local recurrence (LR) occurred in 6 patients (16.7%). Median time to first progression was 17 months. LR was related to axillary lymph node dissection (p=0.027).

Conclusions: Most of our patients had locally advanced breast cancer and the mastectomy improved local symptoms in this group of patients, with acceptable rate of LR and TTP.
Needs and preferences of breast cancer survivors: A cross-sectional survey.
Authors: Stan D. L. , Pruthi S. , Jenkins S. , Lackore K. , Thompson C. A.
Published: February 2017

147

Background: The Institute of Medicine recommends development of cancer survivorship care models that are patient centered. We designed a cross-sectional survey to determine the medical and psychosocial needs and preferences of breast cancer survivors.

Methods: We identified a random sample, stratified by age and chemotherapy usage, of 600 women from MN, WI, and IA, ages 18-99, within 1-5 years of diagnosis of stage 0-3 breast cancer and seen at our institution.

Results: We received 329 surveys (response rate 55%). Respondents were a mean age of 58 years (range 26-89) and a mean of 3.3 years from cancer diagnosis (range 1.2-5.4). 96% were white and stage distribution was: 15% stage 0, 35% stage 1, 32% stage 2, 15% stage 3, and 3% missing. Treatment included mastectomy (60%), lumpectomy (40%), radiation (61%), chemotherapy (55%) and hormonal therapy (50%). Most common treatment-related sequelae were neuropathy (38%), chest wall or arm pain (27%), and lymphedema (26%). Over half (52%) report worry and 45% report fatigue as a problem in the past week. 74% stated that their medical needs were met, whereas 49% said their psychological and spiritual needs were met (p<0.01). 68% understood the follow-up plan after treatment was complete. Perceived barriers to follow up care were anxiety (30%) and lack of coordination (10%). When queried about post-treatment care, the following aspects were considered important (% of patients ranking ≥7 on scale 0-10: 0=not important, 10=very important): breast/chest wall exam (88%); screening for osteoporosis (71%), colorectal cancer (69%), and heart disease (65%); educational materials (64%); mammography (63%); physical therapy (61%); diet and exercise counseling (60%); and complementary/alternative medicine information (53%). Less important were psychology (44%), gynecology (43%), chaplain services (35%), support groups (32%), social work (20%), and infertility experts (4%). 60% expressed interest in attending a survivorship clinic.

Conclusions: This survey provides unique data on breast cancer survivors, and efforts should be made to optimize medical and psychosocial care in line with their needs and preferences. These results will be imperative in designing a wellness and survivorship clinic.
Sentinel lymph node biopsy following neoadjuvant chemotherapy in clinically node-negative breast cancer patients.
Authors: Enokido K. , Nakamura S. , Tsugawa K. , Kojima Y. , Iwata H. , Ohno S. , Akiyama F. , Motomura K.
Published: February 2017

15

Background: Sentinel lymph node biopsy (SLNB) is a widely accepted staging method for patients with early breast cancer. But SLNB following neoadjuvant chemotherapy (NAC) is also controversial because of insufficient evidence to recommend as a standard procedure. The aim of our study was to demonstrate the feasibility of SNLB following NAC.

Methods: The clinical study of SLNB for clinically node-negative breast cancer patient was conducted as a large cohort study to confirm the identification rate and safety of this procedure. It was investigated by The Japanese Breast Cancer Society and was accomplished between the years March 2008 and October 2009. In this study 11,228 cases are registered before SLNB from 64 institutions. Of the 11,228 eligible cases, analysis was conducted among 489 cases that were introduced neoadjuvant chemotherapy.

Results: SLNB was performed in 110 cases before NAC, 379 cases after NAC. The sentinel node identification rate before NAC was 106/110 cases (96.4%), after NAC was 373/379 cases (98.4%). Intraoperative frozen section analysis was performed in 280 cases, 71 cases were positive. The remaining 219 patients displayed no metastasis in the intraoperative examination, and 6 of these 219 (2.7%) were positive in the final pathological analysis.

Conclusions: The identification rate of SLNB following NAC is not inferior to the result of major clinical studies previously reported in the world. There is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis is necessary to identify whether SLNB following NAC is feasible or not (planned study). The primary end point for Group A is local relapse rate, Group B is not only the accuracy and false negative rate also the utility of One-step Nucleic Acid Amplification (OSNA).
Treatment patterns and costs following metastatic breast cancer diagnosis in U.S. women: A SEER-Medicare analysis.
Authors: Taylor D. C. A. , Sanon M. , Clements K. , Balu S. , Faria C. , Teitelbaum A.
Published: February 2017

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Background: To use SEER-Medicare data to evaluate treatment (tx) patterns and health care costs in U.S. women with metastatic breast cancer (MBC).

Methods: Key inclusion criteria included women diagnosed (dx) with breast cancer in 2001-2005 with 1) enrollment in Medicare 12 mo prior to dx through follow-up (2008) or death; 2) initial dx of “distant” disease or 2 indications of secondary malignancy >2 mo after initial dx; and 3) indication of tx with injectable hormonal, chemotherapy (chemo) or targeted/biologic therapies. Lines of tx were designated as: 1st-line if 1st agent (or agents, if on same day) after dx of MBC; new agents administered > 42 d after the previous agent are a new line, as well as an agent administered > 60 d after last dose of the same agent. Oral medication data were not available. Kaplan-Meier techniques estimated lifetime total health costs by partitioning data into 30-d intervals starting with MBC dx date and then summing the product of mean cost in each interval by the probability of survival to the start of the interval. Bootstrapping methods were used to generate 95% confidence intervals (CI).

Results: The table lists the top 5 injectable tx for first, second, and third line, with associated mean lifetime costs.

Conclusions: In this population, the injectable fulvestrant was the most commonly used first-line tx, with vinorelbine most frequently used in second- and third-line settings for MBC. Mean lifetime cost of MBC was $110,000.

[Table: see text]
Physician experience and challenges obtaining unfunded oral chemotherapy across Canada.
Authors: Han D. , Hogeveen S. , Trinkaus M. , Mamdani M. , Berry S. R. , Jang R. W. , Hoch J. , Simmons C. E.
Published: February 2017

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Background: Previous studies have shown hematologists and medical oncologists may not accept the financial limits set by governing agencies on access to oral chemotherapy for their patients. This requires increased time and effort on the clinician’s part to obtain funding. We captured physicians’ perceptions of barriers to obtaining unfunded chemotherapies and methods used to overcome these barriers.

Methods: A total of 640 medical oncologists and hematologists were surveyed using a web-based survey tool. A thirteen-item survey was designed to assess the practice type along with time spent and methods used on obtaining unfunded oral chemotherapy.

Results: Of the 640 invitees, 568 were delivered and 168 responded (response rate 30%). 91 respondents were medical oncologists, 44 were hematologists and 33 treated both solid and non-solid malignancies. 65% of physicians spent an average of 1-4 hours obtaining funding for oral drugs for patients per week. 62% indicated their institution has a drug access coordinator (DAC). Having a DAC did not impact the proportion of physicians spending >4 hrs/ week accessing oral drugs (38% vs 29%, p=NS). To overcome barriers to funding, physicians’ enrolled patients on clinical trials (91%), used compassionate access programs (96%) or special request forms to government (92%). Other methods included writing false claims on forms to fit funding criteria for a drug (36%) or use of leftover drug supplies (36%). The majority of physicians felt that their inability to obtain unfunded medications for their patients has negatively impacted patients’ clinical outcomes (56%) and psychosocial quality of life (74%). Of all respondents, only 28% of physicians contacted their governing body with concerns of funding for oral chemotherapy.

Conclusions: Practicing hematologists and medical oncologists in Canada use numerous methods to obtain unfunded oral chemotherapies, including lying on access forms. Overall, the majority of physicians spend 1-4 hours a week on obtaining funding; this did not differ for physicians with or without a DAC at their practice. Despite the challenges in accessing oral chemotherapies, most physicians have not contacted governing bodies for legislative change.
A clinical trial with culturally appropriate video to increase participation of African Americans in cancer clinical trials.
Authors: Banda D. R. , Mete M. , Swain S. M.
Published: February 2017

159

Background: There is a need to develop patient-level interventions to change attitudes and increase African American (AA) participation in breast cancer clinical trials (CT). This pilot study tested the efficacy of a 15 minute narrative-based video which we created in the first such intervention in AA patients.

Methods: This single group study enrolled 88 breast cancer patients in active treatment at a large urban cancer institute. Eligible patients were self-identified AA, ≥ 21 years, and never participated in a CT. The primary outcome was self-reported likelihood to enroll in a therapeutic CT. Participants were interviewed at baseline using an instrument developed specifically to assess attitudes on six trial barriers. An immediate post-test was administered following the video. McNemar’s test for matched pairs was used to assess the change in likelihood to enroll in a CT. Stuart-Maxwell marginal homogeneity test for matched pairs with multi-category outcomes was used to evaluate which attitudes were impacted by the intervention.

Results: Patients enrolled October 2010- February 2011 (n =108), 75% female. Age from 31-87 years, mean 61 (SD=12). Patients' likelihood of enrolling in a CT significantly increased post video [OR 19.5, 95% CI: 5.05 – 166.7, McNemar’s χ2 = 33.39, P <0.001]. Stuart-Maxwell tests showed significant changes in 28 of 30 attitudinal questions post video. Specifically, the video impacted attitudes associated with a concern about the ethical conduct of investigators; the fear of loss of autonomy after signing an informed consent form; worry about being treated poorly as a poor or minority patient; loss of privacy; and the lack of knowledge and awareness of clinical trials.

Conclusions: These data demonstrate the overall efficacy of our video and can be extrapolated to a single disease focus. This should have particular benefit for large cooperative group studies including breast cancer trials.
Identifying genomic rearrangements in BRCA1 and BRCA2 in high-risk individuals for hereditary breast and ovarian cancer.
Authors: Jackson M. , Mattair D. , Lin H. , Gutierrez-Barrera A. M. , Elsayegh N. , Litton J. K. , Hortobagyi G. N. , Arun B.
Published: February 2017

163

Background: Germline mutations in the BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancer (HBOC). Comprehensive gene sequencing detects ~87% of BRCA mutations, and large genomic rearrangement testing (BART) accounts for ~3%. Criteria have been established to capture individuals who most likely have a BART mutation, however, recent data shows that some individuals have BART mutations and do not meet the criteria. We conducted a single-institution study to evaluate the sufficiency of BART criteria to determine if new criteria are warranted.

Methods: During 2006-2008, 172 individuals underwent BRCA sequencing and BART at M. D. Anderson Cancer Center. A retrospective, IRB-approved chart review of a prospectively maintained database was conducted to determine BART criteria eligibility, personal/family history of breast and ovarian cancer and tumor characteristics. Univariate and multivariate analysis was performed to test the significance of each variable in relation to BRCA1/BRCA2 positivity.

Results: Of 172 individuals, 12/34 (35%) had BRCA1 BART mutations, and 7/11 (64%) had BRCA2 BART mutations. Of the 19 individuals who tested positive for BART mutations, only 8 (42%) met BART criteria and 11 (58%) did not and proceeded with BART for various reasons (family history, insurance covered, and patient request). Individuals who were BRCA1 positive (sequencing or BART) were more likely to have ER/PR negative breast cancer (p<0.0001) and a personal (p=0.0215)/family history of ovarian cancer (p=0.0001) compared to non-carriers and individuals who had no family history Individuals who were BRCA1 sequencing positive were more likely to meet BART criteria than BRCA1 BART positive (p=0.0151) individuals.

Conclusions: Given that no significant differences in family history/tumor characteristics between individuals who have sequencing and BART mutations were identified, and a majority of individuals who were BART positive do not meet BART criteria, it appears that these criteria may be insufficient. BART testing should be considered for all individuals who undergo BRCA sequencing; however, large scale collaboration studies should be conducted.