bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Adjuvant! Online to predict the effect of optimal endocrine therapy (ovarian function suppression plus tamoxifen) for premenopausal breast cancer patients with estrogen-receptor-positive breast cancer
Authors: Paridaens R. J. , Gelber S. , Cole B. F. , Gelber R. D. , Thürlimann B. , Price K. , Holmberg S. , Crivellari D. , Coates A. S. , Goldhirsch A. 
Published: August 2020

585 Background: Adjuvant! Online (AOL) is a user-friendly, web-based tool that provides estimates of adjuvant therapy outcomes for individual patients. While reliable evidence underpins estimates for most patient cohorts, there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer. Methods: International Breast Cancer Study Group (IBCSG) Trial 11–93 enrolled 174 premenopausal women with estrogen-receptor positive, node-positive breast cancer from 1993 to 1998. Fifty percent of patients had 1 positive axillary lymph node and 97% had between 1 and 3 positive nodes. Patients were randomized to receive ovarian function suppression plus five years of tamoxifen with or without chemotherapy. The estimated hazard rates and corresponding 10-year relapse-free survival percents obtained from Trial 11–93 data (Breast Cancer Res Treat. 2009;113:137–144) were compared with those predicted using AOL. Results: The 10-year relapse-free survival percents predicted from AOL were 64.4% (95% CI, 61.9% to 67.2%) for endocrine therapy alone and 74.9% (95% CI, 73.1% to 76.8%) for chemoendocrine therapy. By contrast, these estimates in Trial 11–93 were 76.4% (95% CI, 65.8% to 84.0%) for endocrine therapy alone and 74.9% (95% CI, 64.5% to 82.7%) for chemoendocrine therapy. The AOL estimate for the endocrine alone control group is lower than that observed in Trial 11–93 (p = 0.03), while the estimates for the two chemoendocrine therapy groups are similar. Conclusions: AOL appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer, thus overestimating the added benefit - if any - from chemotherapy for this patient population. Prospective clinical trials addressing the question are warranted. No significant financial relationships to disclose.
Neoadjuvant exemestane for 24 weeks in postmenopausal women with hormone receptor positive stage II or IIIA breast cancer (JFMC34–0601)
Authors: Sato N. , Masuda N. , Saji S. , Takei H. , Yamamoto Y. , Sasano H. , Toi M. 
Published: August 2020

591 Background: Exemestane (EXE) is a steroidal aromatase inhibitor and has shown efficacy for not only metastatic breast cancer but also for primary breast cancer situation. Recently it is reported that preoperative treatment with EXE for 24weeks (wks) is more effective than 8 or 16wks. This study aimed to evaluate 24wks treatment of EXE in the neoadjuvant setting for hormone receptor positive, stage II/IIIA, postmenopausal breast cancer. Methods: Stage II/IIIA pts were eligible with confirmed invasive breast cancer and ER/PgR status using needle biopsy. Primary endpoints were ORR and Safety. EXE 25mg/day was administered, and if pts were evaluated CR, PR, SD at 16wks, 8wks treatment was added. Additionally rates of breast conserving surgery (BCS), nodal status, biomarker changes and the relationship between response and survival are being investigated. Results: Between March 2006 and January 2008, 116 pts were enrolled (stage IIA:77%, IIB:20%, III:3%). All pts were ER +, and 80 (69%) were PgR+, and 29 (27.1%) were HER-2+, respectively. At 24 wks, 109pts were evaluable. OR rate was 53% (58/109) and SD rate was 39% (43/109) by investigator's evaluation. Two pts withdrew due to the adverse events. At diagnosis 14 pts would have required mastectomy and after treatment only 5 pts underwent mastectomy. Central pathological review exhibited that biomarker changes during the treatment correlated with tumor response. Conclusions: EXE has shown attractive response for hormone receptor positive breast cancer in neoadjuvant setting. Especially 24wks treatment seems effective with sufficient safety and tolerability. Additional investigations are conducted to explore predictive biomarkers for response and survival. [Table: see text]
Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)
Authors: Arce-Salinas C. H. , Lara F. U. , Leon E. 
Published: August 2020

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m2) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size > 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.
Utility of a multigene prognostic algorithm in combination with TP53 expression for prediction of benefit from adjuvant taxane-containing chemotherapy in node-positive breast cancer patients
Authors: Kronenwett R. , Stropp U. , Briasoulis E. , Gehrmann M. , Razis E. , Hennig G. , Bafaloukos D. , Wirtz R. M. , Economopoulos T. , Fountzilas G. 
Published: August 2020

593 Background: Recently, we have shown that the Siemens Prognostic Score (SPS) based on mRNA expression of nine informative genes predicted outcome in node-positive (N+) patients with breast cancer (SABCS 2008, abstract 6044). The aim of this retrospective biomarker study was to examine the utility of the SPS in combination with TP53 expression to predict benefit from adjuvant taxane therapy. Methods: The 211 N+ patients included in this study were treated in the context of a randomized two-arm phase III study (E-T-CMF vs. E-CMF) investigating adjuvant dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was isolated from formalin-fixed, paraffin-embedded tissue samples, using a Siemens proprietary method, followed by kinetic one-step RT-PCR for assessment of mRNA expression of the nine SPS genes, TP53 and two normalization genes. The continuous SPS was calculated using a linear combination of expression values of the SPS genes. Patients were separated into a high- and low-risk group using a cutoff at the median of the SPS. Optimal cutoff for low or high TP53 expression was defined on the basis of a ROC curve in SPS high-risk patients. Distant metastasis-free survival (MFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared using the log-rank test. Results: For patients with high SPS or high TP53 expression, we observed a trend for a better MFS in the E-T-CMF arm (SPS: p = 0.18; HR = 0.66; TP53: p = 0.23; HR = 0.67; n = 211). Combining both parameters, patients with high SPS and high TP53 expression (n = 44) had a significantly better MFS following E-T-CMF compared to E-CMF (5-year MFS 80% vs. 40%, p = 0.003, HR = 0.21; OS: p = 0.09; HR = 0.34). On the other hand, patients with high SPS and low TP53 expression (n = 32) showed a trend for a worse outcome with E-T-CMF (MFS: p = 0.09; HR = 3.54; OS: p = 0.35, HR = 1.90). Conclusions: Our prognostic algorithm combined with TP53 mRNA expression predicts the benefit from the addition of paclitaxel to E-CMF and might be used for identification of patients who should be considered for adjuvant taxane therapy. This hypothesis needs to be confirmed in an independent clinical study. [Table: see text]
Oral vinorelbine (NVBo) and anastrozole (A) as neoadjuvant treatment of locally advanced (LA) breast cancer (BC) in hormone receptor positive (HR+) postmenopausal patients: Results of an international phase II trial
Authors: Riggi M. , Moreno-Lopez E. M. , Rolski J. , Petruzelka P. , Ferrero J. M. , Tellez-Bernal E. , Vaissiere N. , Lucas C. 
Published: August 2020

600 Background: Two recent randomized studies with anastrozole, as single agent or with an unspecified cytotoxic, produced an objective response rate (RR) of 24 and 39.5% by ultra-sound (US) [baseline primary tumor diameters (PTD) of 2.6 cm (median) and 3.6 cm (mean), respectively] in LA BC. This trial assessed the effect of the combined NVBo-A therapy. Methods: 55 assessable HR+ patients (pts) with LA breast cancer (tumor size > 3 cm) were expected, including 10 with pharmacokinetics (PK). Pts received 3 (if progression or complete response) to 6 courses of NVBo at day 1(D1) and 8 every 3 weeks (60 mg/m2 escalated to 80 mg/ m2 at cycle 2) with 1 mg of A daily. Both US (primary criteria) and calliper assessments were performed at cycle 3 and 6, with surgery within 4 weeks of the last D1 NVBo. Anastrozole interaction on NVBo was studied by comparing NVBo PK between D1 and D8. NVBo interaction on A was assessed by comparing trough concentrations between D8 and D21. Results: Between July 2005 and June 2008, 60 women were enrolled. The first 58 pts were analyzed: at baseline, median age 64.9 years, median and mean PTD 3.7 and 4 cm, respectively; 59% N1–2(17% N2), with a feasible breast conservative surgery (BCS) in only 12%; 19% were inoperable. The RR was 59% (95% CI 45–71%) by US and 69% (55–80%) by calliper. Clinical nodal invasion on TNM (N+) regressed by 32%. 10/11 inoperable pts at baseline became operable. Among 51 resections (concurrent events 4 pts, unresectable 3 pts) 20% were BCS. The pCR was 3.9%. Grade (G) 3–4 toxicities: haematological toxicities (neutropenia) in 6 pts; hepatic enzymes G3 1 pt; gastrointestinal toxicities G3 5 pts and 1 G4 musculoskeletal pain. PK interim analysis showed an absence of interaction between the 2 drugs. Conclusions: NBVo plus A led to an increased RR compared with previous experiences with A alone or not (IMPACT, PROACT trials). The operability rate was notably improved from baseline in this population with unfavorable characteristics and BCS was slightly increased. This combination treatment was well tolerated and pts could benefit from an oral therapy allowing preservation of daily living activities. [Table: see text]
Mass spectrometry profile as a predictor of overall survival benefit after treatment with epidermal growth factor receptor inhibitors in head and neck squamous cell carcinoma
Authors: Chung C. H. , Seeley E. H. , Grigorieva J. , Yarbrough W. G. , Gilbert J. , Murphy B. A. , Argiris A. , Caprioli R. , Carbone D. P. , Cohen E. E. 
Published: August 2020

6000 Background: Our previous study has shown that a matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) profile in serum or plasma can predict lung cancer patient survival after treatment with epidermal growth factor receptor inhibitors (EGFRI). We examined the ability of this same MALDI-MS profile in plasma or sera to predict for survival benefit of EGFRIs in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Spectra were obtained in triplicate using MALDI-MS from 314 samples obtained from five HNSCC cohorts treated with 1) gefitinib (G, n = 100); 2) erlotinib and bevacizumab (E/B, n = 81); 3) cetuximab (C, n = 21); 4) surgery (S, n = 78); and 5) palliative chemotherapy (PC, n = 34). Each sample was classified into “good” or “poor” outcome groups and overall survival was examined using this MALDI-MS classifier (VeriStrat, Biodesix, Steamboat Springs, CO). Results: Successful classification could be achieved in 311/314 (98%) of the samples. In all EGFRI-treated cohorts, the classifier predicted survival benefit while the cohorts without EGFRI-treatment showed no survival difference by log-rank testing (G: p = 0.007, HR 0.41, 95%-CI 0.22–0.79; E/B: p = 0.02, HR 0.20, 95%-CI 0.05–0.78; C: p=0.06, HR 0.26, 95%-CI 0.06–1.06; and PC: p = 0.76, HR 0.88, 95%-CI 0.4–1.97), independent of performance status, age, gender and smoking history. Conclusions: This study suggests that the same predictive algorithm for MALDI-MS generated from patients with lung cancer treated with EGFRIs is also predictive of survival outcome in HNSCC patients treated with both TKIs and cetuximab, and may allow rational selection of patients most likely to benefit from an EGFRI monotherapy. [Table: see text]
Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129
Authors: Gillison M. L. , Harris J. , Westra W. , Chung C. , Jordan R. , Rosenthal D. , Nguyen-Tan P. , Spanos W. J. , Redmond K. P. , Ang K. ,   Radiation Therapy Oncology Group
Published: August 2020

6003 Background: The favorable prognosis for HPV-positive (pos) OPC requires confirmation in a clinical trial of sufficient size to account for confounding variables including smoking. Methods: A correlative study was performed to evaluate the association of tumor HPV status (THS) and survival in a randomized phase 3 trial comparing standard fractionation (FX) radiotherapy (RT) and cisplatin (cis) (100 mg/m2, days 1, 22, 43) to accelerated FX-RT and cis (100 mg/m2, days 1, 22). THS for OPC cases was determined by HPV16 in situ hybridization (ISH). Two-year overall (OS, death) and progression-free survival (PFS, progression, salvage surgery, death) for patients with HPV-pos and HPV-negative [neg] OPC were estimated along with 95% confidence intervals (CIs) by Kaplan-Meier method and compared by log-rank test. Hazard ratios (HR) for OS/PFS comparing HPV-pos to HPV-neg OPC after adjustment for treatment assignment, age, race, T and N stage, and smoking (< or ≥ 20 pack-years [p-y]) were estimated by use of Cox models along with 95% CIs with multiple imputation for cases with undetermined THS and/or missing p-y. Results: THS was evaluable for 73% (317/433) of OPC cases and 60.6% (55.2–65.9) were HPV16-positive. OS/PFS outcomes were similar for cases with and without HPV determination. After median follow-up of 4.4 years, cases with HPV-pos OPC had better OS (p < 0.0001; 2-year 87.5% [82.8–92.2] vs 67.2% [58.9–75.4]) and PFS (p < 0.0001; 2-year 71.9% [65.5–78.2] vs 51.2% [42.4–59.9]). Patients with HPV-pos OPC had a 59% reduction in risk of death (HR 0.41 [0.27–0.64]) and a 46% reduction in risk of progression or death (HR 0.54 [0.37–0.78]). Results with and without imputation were consistent. The hazard of death was elevated for HPV-neg OPC with ≥ 20 p-y (HR 4.33), HPV-neg OPC with < 20 p-y (HR 2.41), and HPV-pos OPC with ≥ 20 p-y (HR 1.79), relative to HPV-pos OPC with <20 p-y. Second primary tumors were less common among HPV-pos cases and patterns of first failure were similar. Conclusions: Tumor HPV status is strongly associated with OS/PFS among OPC patients receiving standard of care chemo-radiation, and should now be a stratification factor for all clinical trials including OPC cases, and separate trials based on THS should be considered. No significant financial relationships to disclose.
Phase II study of bevacizumab (B) plus cisplatin (C) plus intensity-modulated radiation therapy (IMRT) for locoregionally advanced head and neck squamous cell cancer (HNSCC): Preliminary results
Authors: Pfister D. G. , Lee N. Y. , Sherman E. , Lisa D. , Carlson D. , Stambuk H. , Shen R. , Kraus D. , Shah J. , Fury M. G. 
Published: August 2020

6013 Background: For patients with locoregionally advanced HNSCC, concurrent high-dose cisplatin + radiation therapy is a historical standard of care. HNSCC tumors expressing high levels of VEGF have been associated with worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation. Methods: Percutaneous gastrostomy (PEG) tube was placed pre-treatment for all patients. Planned treatment consisted of definitive IMRT (total, 70 Gy) with concurrent C (50 mg/m2 days 1, 2, 22, 23, 43, 44) and B (15 mg/kg days 1, 15, and 43). The initial version of the protocol called for an additional 6 months of maintenance B, but this was discontinued in an amendment after a G4 pulmonary hemorrhage event in subject 1 during maintenance treatment. 1o endpoint was 2-year PFS. Results: 42 previously untreated patients (34 M, 8 F), median age 55 (27–75), with stage III/IV, M0 HNSCC (oropharynx 39, larynx 3) enrolled. HPV status by ISH: 16 pos, 14 neg, 12 unknown). All patients have completed treatment. CTCAE v3.0 toxicities (% patients) have included: functional mucositis G3 (76 %); nausea G3 (24%); vomiting G3 (17%); neutropenia G3 (31%), G4 (10%); hemoglobin G3 (17%); hyponatremia G3 (14%). Median weight loss during treatment was 8.9 kg (2.1–26 kg). There were two deaths within 90 days of last treatment: 1 aspiration pneumonia, 1 sudden death. Median follow up is approximately 9 months (range, <3 to 24 months). Locoregional control rate is 100%. Three patients have developed distant metastasis. Estimated one-year PFS is 83% (± 10%) and estimated 1 year OS is 88% (± 6%). At a median of 8 months after completion of radiation therapy, PSS-HN scores were 100 for eating, speech, and diet in respectively 88%, 76%, and 53% of surveyed patients (n = 17). Conclusions: The addition of B to C + IMRT did not appear to increase toxicity to unacceptable levels, and preliminary efficacy results are encouraging. [Table: see text]
Phase II trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and intensity moduled radiation therapy (IMRT) for locally advanced head and neck cancer
Authors: Kao J. , Policarpio L. , Teng M. , Burri R. , Genden E. , Packer S. 
Published: August 2020

6014 Background: This phase II study was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity modulated radiation (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Endpoints included overall survival (OS), locoregional (LRC) and (DC), quality of life and toxicity. Methods: Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled on a phase II trial. Prior organ-conserving surgical therapy or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low (43.2 to 48 Gy) and intermediate (54 to 63 Gy) risk volumes. A separate IMRT conedown plan was targeted to gross disease (72 Gy). The median radiation dose was 72 Gy (range 60 to 72 Gy) administered in 1.5 Gy fractions BID on weeks 1, 3, 5, 7 ± 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). Results: From January 2007 to April 2008, 33 subjects enrolled. Characteristics included 24 males; median age 59; ECOG performance status was 0 in 12. Disease was stage IVa-b disease in 31 (94%), T3–4 in 16 (48%), N2–3 in 23 (70%), and oropharynx primary in 15 (45%). Median follow-up in surviving patients is 15 months (range 6 to 22 months). The 1 year LRC, DC and OS is 91%, 82%, and 92%, respectively. Grade 3 toxicity consisted of mucositis (33%), radiation dermatitis (15%), anemia (15%), and leukopenia (15%), and neutropenia (9%). There were no grade 4–5 events. The majority of patients (64%) were able to tolerate treatment without a feeding tube. Median patient reported University of Washington QOL-R scores before, immediately after, 3 months and 8 months after chemoradiation were 85.5 (±14), 65 (±13), 76.5 (±15), and 84.5 (±9), respectively. Conclusions: Concurrent 5-FU, HU, cetuximab, and SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy in the curative therapy of locally advanced head and neck cancer. [Table: see text]
A single-arm phase II trial to evaluate the combination of cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (TPF) as induction chemotherapy (IC) in patients (pts) with unresectable SCCHN
Authors: Mesia R. , Vázquez S. , Grau J. J. , García-Sáenz J. A. , Bayona C. , Galceran J. C. , Irigoyen A. , Lozano A. , Mañós M. , Cruz J. J. ,   on behalf of the Spanish Head and Neck Cancer Research Group
Published: August 2020

6015 Background: TPF combination is the new standard IC. Adding cetuximab to PF chemotherapy is superior to PF alone in metastatic disease. We incorporated cetuximab into IC with TPF and subsequent radiotherapy (RT) in unresectable SCCHN. Methods: Phase II trial conducted in 7 Spanish hospitals. Previously untreated pts aged 18–70 yrs, ECOG PS 0–1 with unresectable SCCHN were eligible. Induction comprised T 75mg/m2 day 1, P 75mg/m2 day 1, F 750mg/m2 days 1–5, and cetuximab 250mg/m2 days 1, 8, and 15 (initial dose 400mg/m2 on cycle (C) 1, day 1), repeated every 21 days x 4 C, with prophylactic antibiotics and G-CSF support. Subsequently, pts received accelerated RT with a concomitant boost (69.9Gy) and cetuximab 250mg/m2 weekly. The primary endpoint was the objective response rate (RR) to cetuximab TPF as neoadjuvant therapy. Simon's optimal two-stage design was used to calculate the sample size of 49 evaluable pts. Results: 50 pts were enrolled: median age 54 yrs (33–68); 44 male; all stage IV (T4=31, N2–3=40). Primary sites were: oropharynx, 23; hypopharynx, 16; oral cavity, 5; larynx, 4.41(82%) pts received all 4 cycles of cetuximab TPF; 47 pts received ≥2 C and were evaluable for response using RECIST. 3 pts received <2 C (2 deaths from intercurrent disease and febrile neutropenia, 1 secondary neoplasm diagnosed). The table shows RR. Serious grade 3/4 adverse events (AEs) were: neutropenia 24%; neutropenic fever 20%; infection 6%; thrombocytopenia 4%; diarrhea 12%; hepatotoxicity 4%; hypomagnesemia 2%. Grade 3 AEs were: nausea/vomiting 2%; mucositis 6%; renal failure 4%; asthenia 4%; rash 4%; hypotension 4%. There were 2 AE-related deaths (febrile neutropenia and hepatic insufficiency). Conclusions: The addition of cetuximab to TPF IC in pts with unresectable SCCHN yields a high RR, mainly CR, potentially prolonging survival. Cetuximab TPF combination should be given to pts with good PS with specialized support provided. [Table: see text] [Table: see text]