bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine plus erlotinib (GE) followed by capecitabine (C) versus capecitabine plus erlotinib (CE) followed by gemcitabine (G) in advanced pancreatic cancer (APC): A randomized, cross-over phase III trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Authors: Boeck S. H. , Vehling-Kaiser U. , Waldschmidt D. , Kettner E. , Märten A. , Winkelmann C. , Klein S. , Kojouharoff G. , Jung A. , Heinemann V. 
Published: February 2017

LBA4011 Background: Gemcitabine plus erlotinib (GE) is regarded as one standard of care for patients (pts) with APC and CE as an all-oral regimen could be a feasible option in this population. To date, the value of a prospectively defined second-line treatment is unclear in APC. Methods: Within a prospective multicenter phase III trial, 281 pts with histologically confirmed APC and adequate organ function were randomly assigned to first-line treatment with either C (2,000 mg/m2/d, d1-14 q3w) plus E (150 mg/d, arm A) or G (1,000 mg/m2 over 30 min weekly x 7, then d1, 8, 15 q4w) plus E (150 mg/d, arm B). In case of treatment-failure (e.g. disease progression or toxicity, TTF1), pts were "crossed-over" to second-line treatment with the comparator cytostatic drug without E. The primary study endpoint was time to treatment failure of second-line therapy (TTF2); secondary endpoints included TTF1, objective response, overall survival (OS) and toxicity. Results: Of 279 eligible pts, 60% were male and median age was 64 years; 47 pts had locally advanced and 232 metastatic disease, 141 pts (51%) received second-line chemotherapy. Objective response rate (CR+PR, ITT) to first-line treatment was 5% (A) vs. 13% (B). Currently, TTF2 is estimated with 4.4 months (mo) in arm A and 4.2 mo in arm B (HR 0.98, p=0.43), median OS is 6.9 mo (A) and 6.6 mo (B), respectively (HR 0.96, p=0.78). TTF1 was significantly prolonged in arm B (2.4 mo vs 3.4 mo; HR 0.69, p=0.0036). Hematological toxicity was more frequent with G-containing regimens, skin rash > grade 1 during E treatment occurred in 31% pts in arm A and in 43% pts in arm B. Tissue tumor samples are available from 204 pts; 123 tumors (70%) harboured a somatic KRAS mutation (mut). Pts with KRAS wildtype (wt, n=53) had an improved OS (wt: 8.0 mo vs. mut: 6.6 mo; HR 1.62, p=0.011). Conclusions: TTF2 and OS were comparable in both arms; GE was superior compared to CE with regard to TTF1. Wt KRAS status was associated with an imprved OS in pts with APC. [Table: see text]
A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer.
Authors: Fizazi K. , Carducci M. A. , Smith M. R. , Damião R. , Brown J. E. , Karsh L. , Milecki P. , Wang H. , Dansey R. D. , Goessl C. D. 
Published: February 2017

LBA4507 Background: Bone metastases from hormone-refractory (castration-resistant) prostate cancer (CRPC) are associated with RANKL-mediated osteoclast activation resulting in bone destruction and skeletal-related events (SRE). Denosumab is a fully human monoclonal antibody against RANKL. This phase III, randomized, double-blind, active-controlled trial compared the efficacy and safety of denosumab vs. zoledronic acid (ZA) in patients with metastatic CRPC. Methods: Patients (n = 1,901) with CRPC and at least 1 bone metastasis, but no prior IV bisphosphonate use, received either SC denosumab 120 mg and IV placebo (n = 950), or SC placebo and IV ZA 4 mg (n = 951) adjusted for creatinine clearance every 4 weeks. All patients were instructed to take supplemental calcium and vitamin D. The primary endpoint was time to first on-study SRE, defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression. Results: Denosumab significantly delayed the time to first on-study SRE compared with ZA, (HR 0.82 ; 95% CI: 0.71, 0.95 ; p = 0.008.) The median time to first on-study SRE was 20.7 mo denosumab vs. 17.1 mo ZA, a difference of 3.6 months. Denosumab also significantly delayed the time to first and subsequent on-study SRE (multiple event analysis) (HR 0.82 ; 95% CI: 0.71, 0.94 ; p = 0.004). Greater suppression of the bone turnover markers uNTx and BSAP occurred in denosumab patients compared with ZA (p < 0.0001 for both). Overall, adverse event (AE) rates (97% each) and serious AEs (63% denosumab, 60% ZA) were similar, irrespective of potential relationship to study drugs. AEs of hypocalcemia were reported in 13% and 6% of denosumab and ZA patients. Osteonecrosis of the jaw occurred in 22 (2.3%) denosumab compared with 12 (1.3%) ZA patients (p = 0.09). Overall survival (HR 1.03 ; 95% CI: 0.91, 1.17 ; p = 0.65) and time to cancer progression (HR 1.06; 95% CI: 0.95, 1.18; p = 0.30) were similar between treatment arms. Conclusions: Denosumab demonstrated superiority over ZA in delaying or preventing SREs in patients with bone metastases from CRPC. Adverse events were consistent in both treatment groups with those previously reported in advanced cancer populations. [Table: see text]
Safety and efficacy of targeted intraoperative radiotherapy (TARGIT) for early breast cancer: First report of a randomized controlled trial at 10-years maximum follow-up.
Authors: Baum M. , Joseph D. J. , Tobias J. S. , Wenz F. K. , Keshtgar M. R. , Alvarado M. , Bulsara M. , Eiermann W. , Williams N. R. , Vaidya J. S. ,   on behalf of the TARGIT Trialists’ Group
Published: February 2017

LBA517 Background: After breast conserving surgery, 90% of local recurrences (LR) occur within the index quadrant. Hence, restricting the radiation therapy to the immediate area around the tumour bed after removal of the primary tumour may be adequate (Vaidya JS, et al. Br Cancer.1996;74:820-4) Methods: Having safely piloted a new technique of partial breast irradiation (Vaidya JS, Baum M, Tobias JS et al Ann Oncol 2001;12:1075-80) we launched the TARGIT-A trial in March 2000 comparing TARGIT vs. standard whole breast external beam radiotherapy (EBRT) after breast conserving surgery in patients ≥45 years with invasive duct carcinoma. LR was the primary outcome measure (core protocol: www.thelancet.com/protocol-reviews/99PRT-47 ). Trial accrual from 31 international centers is complete (n=2232), with 80% power to detect a difference in relapse rate of 2.5% - the non-inferiority margin. Results: Median age was 63 (IQR 57-69), median tumor size 13mm (IQR 9-18mm), lymph nodes 17%+ve. Median follow-up is 24.6 months (max 10 years). Wound breakdown or delayed healing were reported in 28 of the TARGIT group and 20 in the EBRT group (p=0.24). RTOG grade 3 toxicity (nil grade 4) was seen in 6 vs. 21 (p=0.004) respectively. Overall local toxicity was equivalent (34/1092 TARGIT v. 41/1096 EBRT, p=0.42). The Kaplan-Meier estimate of LR in the breast, was 0.31% (CI 0.08-1.26) for TARGIT versus 0.29% for EBRT (CI 0.07-1.16) at 24 months. Conclusions: In the TARGIT group, the radiotherapy toxicity was significantly lower than in the EBRT group, while the increase in wound complications was not statistically significant. This analysis suggests that at a median follow-up of 24 months the local control with TARGIT is comparable to EBRT. Longer term follow-up is essential and accrual in similar studies is encouraged. [Table: see text]
Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC).
Authors: Socinski M. A. , Bondarenko I. N. , Karaseva N. A. , Makhson A. , Vynnichenko I. , Okamoto I. , Hon J. K. , Hirsh V. , Bhar P. , Iglesias J. 
Published: February 2017

LBA7511 Background: Platinum-based doublet therapy in NSCLC, regardless of the combination used, reached a therapeutic plateau. PC produced 15-25% overall response (ORR, Kelly 2001; Sandler 2006; Schiller 2002). Albumin-bound paclitaxel, nab-P, utilizes the albumin receptor (gp60)/caveolin-1 (CAV1) pathway achieving high intratumoral paclitaxel accumulation (Desai 2006), which may have contributed to a 48% ORR observed with nab-PC in NSCLC (Stroyakovsky, 2009). This phase III trial studied the efficacy of nab-PC vs. PC in advanced NSCLC of all histologic types. Methods: First-line stage IIIB or IV NSCLC pts (ECOG 0/1) were randomized to C AUC6 q3w and either nab-P 100 mg/m2 qw w/o premed (n = 521) or P 200 mg/m2 q3w with premed (n = 531). Primary endpoint: ORR by independent radiologic review (IRR). Results: Baseline and histologic characteristics were well balanced. Dose intensity of paclitaxel was higher in nab-PC vs. PC (82 vs. 65 mg/m2/wk). nab-PC was superior to PC both by IRR (33 vs. 25%, p=0.005), a 31% improvement (1.31 response ratio [RR], 95% CI: 1.08, 1.59), and by investigator review (37 vs. 30%, p=0.008), a 26% improvement (1.26 RR, CI: 1.06, 1.50). Histologic analysis showed significantly improved ORR for nab-PC (n = 228) vs. PC (n = 221) in squamous cell carcinoma (SQC) pts (41 vs. 24%, p<0.001, IRR), a 67% improvement (1.67 RR, CI: 1.26, 2.21). nab-PC was as effective as PC in nonSQC pts (ORR 26 vs. 25%). nab-PC was well tolerated, with significantly improved safety profile vs. PC despite higher paclitaxel dose delivered (1,338 vs. 1,100 mg/m2). Conclusions: The primary endpoint was met, with significantly improved ORR and safety profile of nab-PC vs. PC as first-line therapy for advanced NSCLC. nab-PC was highly active in the SQC subset, which may in part be attributed to the aberrant CAV1 overexpression in SQC (Yoo 2003) and the high intratumoral accumulation of nab-P via the gp60-CAV1 pathway. [Table: see text] [Table: see text]
Comparison of high-dose methotrexate (HD-MTX) with Capizzi methotrexate plus asparaginase (C-MTX/ASNase) in children and young adults with high-risk acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group Study AALL0232.
Authors: Larsen E. C. , Salzer W. L. , Devidas M. , Nachman J. B. , Raetz E. A. , Loh M. L. , Heerema N. A. , Carroll A. J. , Gastier-Foster J. M. , Borowitz M. J. , Wood B. L. , Willman C. L. , Winick N. J. , Hunger S. , Carroll W. L. 
Published: February 2017

3 Background: Although EFS continues to improve for children and young adults with HR-ALL, central nervous system (CNS) disease has become an increasing site of treatment failure. AALL0232 was designed to test the safety and efficacy of interventions targeted to enhance CNS control including comparisons of HD-MTX versus Capizzi escalating methotrexate plus PEG asparaginase (C-MTX/ASNase) during interim maintenance-1 (IM-1) and dexamethasone (DEX) versus prednisone (PRED) during Induction. Methods: AALL0232 was a Phase III, randomized trial for patients 1-30 years old with newly diagnosed NCI high risk B-precursor ALL that utilized a 2 x 2 factorial design with an augmented intensity Berlin-Frankfurt-Münster (BFM) backbone. Patients were randomized to receive DEX versus PRED during induction and HD-MTX (5gm/m2 biweekly x 4) versus C-MTX/ASNase during IM-1. To date 2104/3156 AALL0232 patients have completed IM-1. Results: Planned interim monitoring showed 5-year EFS for patients randomized to receive HD-MTX (N=1,209) was 82 + 3.4% versus 75.4 + 3.6% for the C-MTX/ASNase (N=1,217) regimen, p=0.006. Because this difference crossed a pre-defined boundary, enrollment was halted and patients were crossed over from C-MTX/ASNase to HD MTX when feasible. There were fewer marrow and CNS relapses in the HD-MTX versus C-MTX/ASNase arms (42 and 22 versus 68 and 32). The incidence of febrile neutropenia was lower with HD-MTX compared to the C-MTX; 5.2% vs 8.2%, respectively, p=0.005. There were no statistically significant differences in acute neurotoxicity, osteonecrosis, or other clinically relevant toxicities between the two regimens. Conclusions: HD-MTX administered in place of C-MTX, during the IM-1 phase of augmented BFM therapy is associated with superior EFS, with no increase in acute toxicity, in children and young adults with HR-ALL.
Randomized double-blind placebo-controlled international trial of abago-vomab maintenance therapy in patients with advanced ovarian cancer after complete response to first-line chemotherapy: The Monoclonal Antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abago-vomab (MIMOSA) trial.
Authors: Pfisterer J. , Berek J. S. , Casado A. , Cwiertka K. , Pinter T. , Pluzanska A. , Pujade-Lauraine E. , Scambia G. , Vermorken J. B. , Simonelli C. , Bertolotti M. , Capriati A. , Sabbatini P. ,   AGO-OVAR, COGI, GEICO, GINECO
Published: February 2017

LBA5002 Background: Abagovomab, a murine monoclonal anti-idiotypic antibody directed against CA125, has been shown to induce an active immune response against CA125 tumor-associated antigen in advanced ovarian cancer patients. Methods: Abagovomab (A) has been tested in a randomized (2:1) double-blind, placebo (P) controlled, multicenter phase II/III trial in patients with FIGO stage III/IV ovarian cancer after complete response to platinum-taxane first-line chemotherapy. A (2 mg/1 ml) or P was given subcutaneously every 2 weeks for 6 weeks (induction phase); then every 4 weeks (maintenance phase) until recurrence, or up to 21 months after the last patient had been randomized. Primary endpoint is progression-free survival (PFS); secondary endpoints are OS and immunological response. An estimated 870 patients, with a mean follow-up of 18 months, were needed to observe at least 535 recurrences, which provides a power >90% in rejecting the null hypothesis of equality between A and P on PFS according to a hazard ratio (HR) of 1.33, in which median P PFS time is 18 months, significance level (a) 5% (two-sided), and the overall dropout rate 10%. Primary analysis was run on PFS in the ITT population. The design included a prospective stratification in randomization for the following prognostic factors: FIGO stage (III-IV); tumor size after debulking (residual tumor <1 cm, >1 cm); and CA125 serum level after the third cycle (<35 U/ml, >35 U/ml). The Cox proportional hazards model was used for adjusting the primary analysis. Results: 888 patients were enrolled by December 2008, 593 in A arm and 295 in P arm. The median follow-up was 28.1 months and the mean number treatment administrations was 18. Baseline characteristics were balanced between arms. Overall tolerability profile was consistent with previous A studies. Median (95% CI) PFS was 13.24 (10.612-13.602) months for A arm and 13.21 (10.612-16.000) months for P arm; HR=1.099 (0.919-1.315); p=0.301. Conclusions: Treatment with A did not translate into a prolonged PFS.
Surgical and oncologic outcomes in patients with breast cancer undergoing tattooing prior to neoadjuvant chemotherapy.
Authors: Lannin D. R. , Grube B. J. , Killelea B. K. , Horowitz N. , Harris L. 
Published: February 2017

100 Background: Neoadjuvant chemotherapy for breast cancer increases the breast preservation rate, but also increases the rate of local recurrence, probably because there is no standard technique to determine the amount of breast tissue to be removed. In 2007 we described a technique where the surgeon maps the extent of a breast tumor, plans a surgical incision, and tattoos the breast prior to the patient receiving neoadjuvant chemotherapy. After the chemotherapy, digital photographs are retrieved that allow the surgeon to precisely reconstruct where the margins of the original tumor were in the breast, and to proceed with a planned operation to remove the entire tumor bed but minimal surrounding breast tissue. The purpose of this study is to describe a series of patients treated with this technique and to evaluate the surgical and oncologic outcomes obtained. Methods: Data were collected from a prospective breast cancer database and from chart review on all patients treated with this technique at a single institution. Most patients receiving neoadjuvant chemotherapy underwent the tattooing, unless they knew beforehand that they were going to undergo a mastectomy. Results: Between June 2005 and January 2011, 87 patients underwent breast tattooing followed by chemotherapy. Of patients who have completed subsequent definitive therapy, the initial surgery was mastectomy in 31 and lumpectomy in 53. Most patients’ tumors became nonpalpable following the therapy, and the pathologic complete and partial response rates were 22% and 64% respectively. Of patients who underwent an initial lumpectomy, 5/53 (9%) had positive margins and underwent further surgery (2 mastectomy and 3 wider lumpectomy). With a median follow-up of 36 months, only 1 patient has had an in-breast local recurrence. Conclusions: These early results clearly show a lower rate of re-excision and a lower rate of local recurrence than commonly reported in the literature for breast preservation following neoadjuvant chemotherapy. The technique warrants wider application and further study.
Study of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer.
Authors: Kinoshita T. , Hojo T. , Asaga S. , Suzuki J. , Jimbo K. , Tamura N. 
Published: February 2017

104 Background: Despite the increasing use of both sentinel lymph node biopsy (SLNB) and preoperative chemotherapy (PST) in patients with operable breast cancer, there is still limited information on the feasibility and accuracy of SLNB following PST. In this study, the feasibility and accuracy of SLNB for breast cancer patients with clinically negative lymph nodes after PST were investigated. In addition, conditions that may affect SLN biopsy detection and false-negative rates with respect to clinical tumor response and clinical tumor/nodal status before PST were analyzed. Methods: Between 2003 and 2008, 200 patients with stage II and III breast cancer previously treated with PST were enrolled in this study. The eligible criteria for PST were (a) primary tumor > 3cm or (b) positive axillary lymph node status on initial examination. FNA biopsy was performed for clinically or ultrasonographically suspicious axillary lymph nodes. The patients then underwent SLNB, which involved a combination of intradermal injection over the tumor of radiocolloid and subareolar injection of blue dye. This was followed by Level I/II axillary lymph node dissection (ALND). Results: The median patient age was 49 years, and the median primary tumor size was 4.9 cm. The overall SLN identification rate was 94.5% (189 of 200). In 178/189 patients (94%) the SLN accurately predicted the axillary status. Eleven patients had a false-negative SLN biopsies, yielding a false-negative rate of 12.9%. There were no significant differences in the SLN identification rate according to tumor classifications before PST, the clinical nodal status before PST, the clinical tumor response after PST, or pathological response of the tumor after PST, although the SLN identification rate tended to be lower in patients with a T4 primary tumor. Conclusions: Our data and some reports suggested that SLNB was feasible method for axillary staging in breast cancer patients who received PST even in patients who initially with lymph node positive disease. However, false-negative rate of SLNB in patients with clinical and pathological complete tumor response tended to be higher than other group.
Locoregional recurrence risk factor and indications for postmastectomy radiotherapy in Japanese patients with tumors 5 cm or larger.
Authors: Nagao T. , Kinoshita T. , Tamura N. , Hojo T. , Morota M. , Kagami Y. 
Published: February 2017

127 Background: Locoregional recurrence (LRR) after mastectomy reduces the patient’s quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT has been the subject of substantial controversy. This study investigated what are risk factors for LRR and the efficacy of PMRT in this Japanese patient population. Methods: This study examined 589 cases of invasive breast carcinoma with tumors 5 cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1-3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined and the relationship between LRR and PMRT was estimated. Results: During the median follow-up was 44.2 months, 38 (6.5%) patients experienced LRR. In the multivariate analysis, independent predictors of LRR include pectoral invasion in patients with 1-3 positive nodes, and severity lymphatic invasion, estrogen receptor-negative status, and nodal ratio of positive/excised nodes ≥ 0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. PMRT did not improve the outcome of the patients at highest risk who had these variables. Conclusions: The efficacy of PMRT in patients with large tumors was not shown. In the context of systemic therapy and adequate lymph node dissection, PMRT by itself had a limited role in providing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. The indication for PMRT in patients with metastatic nodes remains controversial.
Toxicity of hypofractionated adjuvant radiation after breast-conserving surgery for DCIS.
Authors: Blakaj D. , Fox J. L. , Manzerova J. , Hannan R. , Hong L. , Mehta K. J. , Kalnicki S. 
Published: February 2017

128 Background: Traditional fractionation for whole breast radiation therapy after breast-conserving surgery has been 50Gy in 25 fractions over a 5-week period, with or without a 10 Gy boost. Hypofractionation has recently been adapted for early-stage invasive breast cancer, typically treating with 42.5 Gy in 16 daily fractions. This approach has been shown to have equivalent efficacy as the more traditional schedule. Its application to patients with DCIS has been an extrapolation of these data, and warrants further examination. This retrospective analysis reviews toxicity outcomes in women with DCIS treated with hypofractionation at our institution. Methods: 59 women with DCIS treated with lumpectomy and hypofractionated radiotherapy with or without boost between 2006 and 2010 at the Einstein-Montefiore Cancer Center were identified. Median age was 65 (39-85). Median follow-up was 13.7 months (2–37.6). Surgical margin status was negative in 55, positive in 1, and unknown in 3. Thirteen patients had high-grade DCIS, 17 intermediate-grade, and 13 low-grade nuclear features, and 16 did not have grade delineation. 68% of patients (40 women) had disease that was positive both for ER and PR receptors, 2 women were simultaneously positive for ER and PR, 5 women had ER-only positive disease, 2 women had HER2-neu-only positive disease, 1 woman was positive for both ER and HER2-neu receptors, 1 woman was positive only for PR receptors, and 6 women were negative for all receptors; receptor status of specimens from 2 patients is not known. All women were treated with whole-breast hypofractionated therapy (42.4 Gy, in 16 fractions of 2.65 Gy each). 49 women received a boost to the lumpectomy cavity consisting of 10Gy in 5 fractions or 9.6 Gy in 4 fractions at the physician’s discretion. Results: With this regimen, no patient experienced acute RTOG grade 3 or higher skin, or other toxicity. No treatment breaks were required due to toxicity. The most common side effects were grade 1 dermatitis, followed by grade 2 dermatitis with mild edema of the treated breast. Conclusions: Our results suggest that postoperative hypofractionated radiation to the breast is well tolerated by women with DCIS and does not result in untoward acute toxicity.