tbuckley/cabot-search huggingface dataset:
Second-line chemotherapy for advanced biliary tract cancer after failure of gemcitabine plus platinum: Results of an AGEO multicenter retrospective study.
Authors: Bertrand Brieau, Laetitia Dahan, Yann De Rycke, Tarek Boussaha, Philippe Vasseur, David Tougeron, Thierry Lecomte, Romain Coriat, Jean Baptiste Bachet, Pierre Claudez, Aziz Zaanan, Pauline Soibinet, Jérôme Desramé, Anne Thirot-Bidault, Isabelle Trouilloud, Florence Mary, Christophe Locher, Lysiane Marthey, Wulfran Cacheux, Astrid Lievre
Journal: Journal of Clinical Oncology (2014)

4093 Background: First-line chemotherapy (CT1) with the combination of gemcitabine (gem) + platinum has become a new standard in advanced biliary tract cancer (ABTC) but data on second-line CT (CT2) are lacking. The aim of this study was to evaluate the efficacy and tolerability of CT2 in patients (pts) with ABTC who received gem-platinum in CT1. Methods: We retrospectively reviewed data of consecutive patients who received CT2 for ABTC after failure to gem-platinum in 17 French institutions from November 2002 to December 2013. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of L2 CT using Kaplan Meier method. Cox models were applied for multivariate analyses. Results: Among 603 pts who were treated by gem-platinum in CT1, 196 pts (median age, 63 years, range: 28-82; male, 51.5 %) received a CT2. CT1 included gem + cisplatin (7%) or oxaliplatin (ox) (93%), with a median PFS of 9.7 months (mo) and an ORR of 31%. Characteristics at the beginning of CT2 were: metastatic disease, 94% ; 1-2 metastatic sites, 68%; ECOG PS 0-1, 68%. CT2 CT was 5FU-irinotecan (iri) (n=62), 5FU-ox (n=17), 5FU-cisplatin (n=37), 5FU/capecitabine (CAP) (n=39) or other various regimens (n=41). Among the 186 evaluable pts, there were 22 PR (12%) and 70 SD (38%). After a median follow-up of 26.4 months, median PFS and OS were 3.2 and 6.7 mo respectively. There was no significant difference between CT regimens in terms of PFS (5FU-iri, 2.6 mo; 5FU-ox/5FU-cisplatine, 4.0 mo; 5FU/CAP, 3.2 mo and others, 3.7 mo; p=0,27) and OS (6.0 mo, 6.3 mo, 5.6 mo and 9.7 mo respectively; p=0.27) In multivariate analysis, PS 2-3, bilirubine > 17 µmol/L and CA19.9 > 400 UI/mL were significantly associated with a shorter PFS while PS 2-3, CA19.9 > 400 UI/mL and non-response to CT1 with a shorter OS. A grade 3-4 toxicity was observed in 32% of pts (neutropenia, 33%; diarrhea, 17%) and a toxic death occurred in 1.4% of pts. Conclusions: CT2 is associated with a disease control in a half of pts with ABTC who received gem-platinum in CT1. Nevertheless, the short median PFS observed in this study should encourage the evaluation of new treatments in pts with good clinical conditions and an adequate biliary drainage.
Association of the fibroblast growth factor receptor-4 (FGFR4) Gly388Arg polymorphism with clinical and pathological response to primary systemic therapy (PST) for early breast cancer (EBC)
Authors: F. Marme, C. Sohn, B. Burwinkel, P. Sinn, M. Hahn, P. Lichter, A. Benner, A. Schneeweiss
Journal: Journal of Clinical Oncology (2009)

525 Background: The FGFR4 Arg388 genotype has recently been shown to be associated with decreased disease free survival after adjuvant systemic therapy for EBC and thus therapy resistance (Harbeck et al, J Clin Oncol. 2006). Primary systemic therapy (PST) for EBC allows in-vivo chemosensitivity testing. Pathological complete response (pCR) in the breast following PST is associated with improved survival. We evaluated the FGFR4 Gly388Arg polymorphism as a predictive factor for response to PST for EBC in the setting of a prospective, randomized phase 2 trial. Methods: Patients (pts, n = 257) with T2–4/N0–2/M0 EBC were randomized to 4 cycles (cy) A 60 mg/m2 + C 600 mg/m2 day (d) 1 every three weeks (q3w) followed by 4 cy D 100 mg/m2 d1 q3w, or 4 cy A 60 mg/m2 + P 500 mg/m2 on d1 q3w followed by 4 cy D 100 mg/m2 d1 q3w, stratified by hormone receptor (HR) status. Surgery was performed after last chemotherapy. Genotyping was performed using a Taqman Genotyping assay. The genotype was confirmed by RFLP-PCR for 50% of samples with 100% congruence. Results: Genotype was available for 252 of 257 pts enrolled into this study. Using Fisher´s Exact Test there was no correlation between genotype and clinical tumour size (cT), HR status, HER2neu status, grading, menopausal status or triple negative phenotype. The G/G genotype correlates significantly with clinically positive axillary lymph nodes before chemotherapy (p = 0.03). Considering all pts the G/G genotype (vs G/A + A/A) is associated with a significantly lower overall response rate (ORR)(OR 0,47; 65% vs 80%; p = 0.03). Separate analysis of treatment arms showed a significant correlation between the G/G genotype (vs other genotypes) and a lower pCR rate (OR 0.33; 12.5% vs 30.4%; p = 0.04), clinical complete response (p = 0.02) and ORR (OR 0.25; p = 0.01) in the AC-D arm, whereas there was no correlation for pts treated with AP-D. Conclusions: This study provides important evidence that the FGFR4 genotype might serve as a valuable predicitve marker for response to PST with AC-D for EBC. No significant financial relationships to disclose.
Correlation between epidermal growth factor receptor gene status and clinical outcome of gefitinib in Japanese patients with non-small cell lung cancer
Authors: K. Kasahara, T. Sone, H. Kimura, K. Nishio, T. Tamura, K. Shibata, M. Mizuguchi, A. Yoshimoto, M. Fujimura, S. Nakao
Journal: Journal of Clinical Oncology (2006)

7192 Background: Epidermal growth factor receptor (EGFR) gene amplification and mutation have been reported to be predictors of response to EGFR inhibitors. We evaluated EGFR gene copy number and mutations in biopsy samples of non-small cell lung cancer (NSCLC) treated with gefitinib (G) and analyzed the correlation between gene status and clinical outcome. Methods: EGFR gene copy numbers in biopsy samples were evaluated using FISH and categorized as described by Cappuzzo et al. We also performed mutational analysesof exons 18, 19 and 21 of EGFR by PCR and direct sequencing. Response was judged using the RECIST guidelines. Time to progression (TTP) and overall survival (OS) were calculated and evaluated by the Kaplan-Meier method. Groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. Results: Of 59 patients (pts) enrolled in this investigation, 24 pts (41%) were female and 21 pts (35%) had never smoked. The most common histological subtype was adenocarcinoma (73%) and 36 pts (61%) had good PS 0–1. Gene copy numbers could be analyzed in 54 pts. Gene amplification was observed in 21 pts, high polysomy in 5 pts, low polysomy in 18 pts, low trisomy in 5 pts and disomy in 5 pts. FISH positivity was observed in 26 pts (48%). EGFR mutations were detected in 18 pts (31%); point mutations in exon 21 were observed in 5 pts, in-frame deletions in exon 19 in 12 pts, a point mutation in exon 18 in 1 pt. Response rate in pts with EGFR mutations was significantly higher than in pts without mutations (56% vs. 15%, p = .0011). Response rate in FISH-positive pts was 31% and that in FISH-negative pts was 21%, the association with response was not significant. EGFR mutations were also correlated with improved TTP (median 8.3 m vs. 1.8 m, p = .0014) and OS (median 18.8 m vs. 6.4 m, p = .0059). There were no significant differences in TTP and OS based on FISH positivity. On multivariable analysis, EGFR mutations remained significantly associated with improved TTP and OS. Conclusions: Our results suggest that EGFR mutations are a better predictor of clinical benfit of G when compared with gene copy number in Japanese NSCLC pts. [Table: see text]
Metronomic chemotherapy with cyclophosphamide and celecoxib in breast cancer patients progressing after standard chemotherapy: Phase I/II trial.
Authors: V. R. Rozados, A. Rossa, C. M. Alasino, H. A. Perroud, F. N. Queralt, S. M. Pezzotto, O. G. Scharovsky
Journal: Journal of Clinical Oncology (2010)

TPS126 Background: Cancer is a chronic illness and should be treated chronically. Metronomic chemotherapy (MCT), the chronic administration, with regular intervals, of low doses of chemotherapeutic drugs, without extended rest periods, allows chronic treatment with therapeutic efficacy and low toxicity. It could be a therapeutic window for multidrug resistant breast cancer with MCT, which molecular target is mainly the endothelial cell, that has high genetic stability and, hence, it is less prone to develop drug resistance. Our previous experimental results suggest that the combined MCT with cyclophosphamide (CY) and celecoxib (CEL), could have an antitumor action in breast cancer treatment and that the combined treatment would be more effective than those with each drug. We aim to: determine the toxicity, safety and efficacy of the oral chronic administration of low doses of CY and CEL, in breast cancer patients progressing after anthracyclines, taxanes and capecitabine treatments; identify early markers of therapeutic response; study the mechanism/s of action of the treatment administered. Methods: Patient eligibility criteria: 21-80 years old, more than 3 month of life expectancy, patient with advanced breast cancer in progression after, at least, anthracyclines, taxanes and capecitabine treatments, no more than 4 chemotherapy schemes, at least one lesion according to RECIST criteria, ECOG scale 0, 1 or 2, appropriate renal function and number of white blood cells and platelets, normal calcemia, signed informed consent. Treatment: oral CY, 50 mg/day + oral CEL, 400 mg/day (200 mg 2 times/day). Study design: The trial will have two stages: the first integrated by 15 patients and the second by 10, looking for a 25% general response rate (β error = 0.10; α error = 0.05). Primary endpoint: relapse or illness progression. Toxicity: all the serious adverse events will be registered by CTCAE criteria and followed until their resolution. Angiogenesis parameters: the serum level of vascular endothelial growth factor and thrombospondin 1 will be determined by ELISA, and the circulating endothelial cells and circulating endothelial progenitor cells numbers by flow cytometry. No significant financial relationships to disclose.
Community cancer control task forces in Rhode Island
Authors: A. S. Glicksman, L. Tisch, P. Calabresi
Journal: Journal of Clinical Oncology (2004)

1038 Background: Despite Rhode Island (RI) being a small State geographically, its population is strongly community centric. Recognizing this problem, cancer education and resources must address each community's needs. Methods: The State Legislature in 2000 recommended that Community Cancer Control Task Forces (CCCTF) be developed in each of the 39 cities and towns in RI and asked the Rhode Island Cancer Council (RICAN) to undertake this development. RICAN has been joined by the Department of Health and the American Cancer Society in this endeavor. Results: Today 14 CCCTF are in varying stages of development. Working with local government, RICAN has brought medical leadership and community hospitals into partnership with school committee members, senior housing, nursing organizations and voluntary agencies. The most developed CCCTF is in the city of Pawtucket, which has undertaken anti-tobacco programs and a colorectal cancer screening initiative. Conclusions: Each community's population differs by ethnic mix and has a different profile of cancer incidence and death rates. Therefore, programs are designed to meet specific local needs. Working with the task forces RICAN has presented educational programs at the local YMCA's, churches, health fairs, senior centers and schools. Outcome measures are in place so that the impact of community programs will be accessible. No significant financial relationships to disclose.
The impact of the duration of adjuvant hormonal therapy in patients with unfavorable prognosis prostate cancer treated with radiotherapy: Secondary analysis of RTOG 85–31
Authors: L. Souhami, K. Bae, M. V. Pilepich, H. Sandler
Journal: Journal of Clinical Oncology (2007)

5062 Background: RTOG 85–31 was a Phase III trial of androgen suppression for life as an adjuvant to radiotherapy. However not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrent disease. This analysis correlates duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued long-term hormonal therapy. Methods: The protocol mandated pelvic radiotherapy (60–66 Gy) followed by goserelin 3.6 mg monthly given indefinitely or until disease progression. To avoid potential bias due to early progression/death, only patients who were alive with no evidence of disease at the time of cessation of hormonal therapy were included. There were 377 analyzable patients. Patients were divided in groups based on the hormonal therapy duration (HTD), as follows: = 1 year (27.3%), 1&lt; and =2 years (11.4%), 2&lt; and =4 years (13.3%), 4&lt; and =6 years (10.6%) and &gt; 6 years (37.4%). End-points were overall survival, disease-free survival, disease-free survival with PSA &lt;1.5 ng/mL, disease-specific survival, local failure and distant failure. Cox-proportional hazards regression model was used to test the outcomes among the 5 groups. Results: The median follow-up time of surviving patients is 11.27 years. Pretreatment characteristics by hormone duration groups were well balanced except for age. The median duration of adjuvant hormonal therapy was 3.59 years. For each outcome, there are statistically significant differences among the 5 HTD groups in all outcomes without adjusting for other covariates. Pairwise comparisons show that HTD &gt; 6 year group is significantly associated with having an improved survival and fewer failure events than all other HTD groups (HR &lt; 1, p-value &lt;0.0001). Adjusted for age and stratification variables, the HTD&gt;6 year group remains the only group significantly associated with having fewer failure events in all outcomes. Conclusions: Prolonged HTD of &gt; 6 years is significantly associated with improvements in all end-points studied. Based on these data, decreasing HTD to &lt; 6 years may have a detrimental effect in patients with unfavorable prostate cancer. No significant financial relationships to disclose.
The efficacy, tolerability, and speed of onset of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain (BTCP): A multicenter, placebo-controlled, double-blind, two-phase crossover study
Authors: N. Y. Gabrail, A. W. Burton, E. Reyes, A. Nguyen, D. R. Taylor
Journal: Journal of Clinical Oncology (2009)

9535 Background: Breakthrough cancer pain (BTCP) affects up to 95% of patients with cancer pain but oral fentanyl formulations do not consistently match the typical time course of BTCP, which is rapid in onset and lasts for 30–60 min. To tailor fentanyl delivery for the treatment of BTCP, a new nasal formulation of fentanyl (fentanyl pectin nasal spray [FPNS]) has been developed to provide both rapid and controlled nasal delivery of fentanyl. Methods: A randomised, placebo-controlled, double-blind (DB) study assessing the efficacy and tolerability of FPNS was conducted in 114 cancer patients experiencing 1–4 BTCP episodes/day while taking ≥60 mg/day of oral morphine (or equivalent) for cancer pain. Patients who completed a titration phase (N=83) continued to a DB phase where 10 episodes of BTCP were treated with the effective dose identified during titration (7) or placebo (3). Pain intensity (PI) was measured using an 11-point categorical scale and pain relief (PR) using a 5-point scale, both PI and PR were measured at 5, 10, 15, 45 and 60 min post-dose. The primary endpoint was the Summed Pain Intensity Difference at 30 min (SPID 30min ). Secondary efficacy endpoints included Pain Intensity Difference (PID) from baseline, PI and PR. Safety was assessed by adverse events (AEs) and both objective and subjective nasal assessments. Results: Compared with placebo, FPNS significantly improved mean SPID 30min scores (P&lt;0.0001) and significantly improved SPID scores as early as 10 min (P&lt;0.05) and up to 60 min (P&lt;0.0001). Significant differences in favour of FPNS were found in PI as early as 5 min (P&lt;0.05). Similar benefits were also seen with PID, with a trend at 5 min (P=0.07) that was significant from 10 min onward (P&lt;0.01). PR was significant from 10 min (P&lt;0.001) and at all time points to 60 min (P&lt;0.001). Only 5.3% of patients withdrew from titration due to AEs; no significant nasal effects were reported. Conclusions: FPNS provided rapid and effective analgesia in BTCP and was generally safe and well tolerated. [Table: see text]
Sentinel lymph node mapping for T1 esophageal cancer.
Authors: Hiroya Takeuchi, Hirofumi Kawakubo, Yoshiro Saikawa, Tadaki Nakahara, Tai Omori, Makio Mukai, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2012)

7 Background: Extended radical esophagectomy with three-field lymph node dissection has been recognized as the standard procedure for thoracic esophageal cancer in Japan, even for clinically T1N0 cases. However, to eliminate the uniform application of the highly invasive surgery, we hypothesized that sentinel lymph node (SLN) mapping would play a key role to obtain individual information and allows modification of the surgical procedure for early esophageal cancer. Methods: We have established radio-guided method to detect SLNs in patient with early esophageal cancer using endoscopic injection of technetium-99m tin colloid. Preoperative lymphoscintigraphy and intra-operative use of hand held gamma probe were reliable to locate the radioactive SLNs. Intra-operative gamma probing was also feasible in thoracoscopic or laparoscopic surgery using a special gamma detector which is introducible from trocar ports. Results: SLN mapping has been performed for 70 patients with clinically N0 and early (pT1) esophageal cancer in our institute since 1999. Detection rate of hot node using our procedure was 94% (66/70). The mean number of sentinel nodes per case was 4.6. Twenty-one of 23 cases (91%) with lymph node metastasis showed positive SLNs. Accuracy of metastatic status based on SLN was 97% (64/66). SLNs widely spread from cervical to abdominal areas. In more than 80% of the cases, at least one SLN was located in the 2 nd or 3 rd compartment of regional lymph nodes. However, 56 (85%) of 66 patients had no lymph node metastasis or metastasis (+) only in SLNs. Conclusions: Our results suggest that SLN concept for clinically N0 and T1 esophageal cancer could be validated. Theoretically more than 80% of patients with pT1b esophageal cancer may be controlled by local treatments such as surgery and chemoradiotherapy targeting primary tumors plus their SLNs. Individualized selective and modified lymphadenectomy targeted on SLN basins for clinically N0 early esophageal cancer should become feasible and clinically useful as less invasive surgical procedures.
Superior survival after sequential high-dose chemotherapy (HDCT) as compared to single HDCT in patients with relapsed or refractory germ cell tumors (GCT): Six-year long-term follow-up of a prospective, randomized phase II trial.
Authors: A. Lorch, A. Kleinhans, A. Kramar, J. T. Hartmann, C. Bokemeyer, O. Rick, J. Beyer
Journal: Journal of Clinical Oncology (2011)

4507 Background: Sequential and single high-dose chemotherapy (HDCT) can both be curative in patients (pts) with relapsed or refractory germ-cell tumors (GCT). The long-term efficacy of either modality is unknown. Methods: Between 11/99 and 11/04, 211 pts with relapsed or refractory GTC were prospectively randomized to treatment with either one cycle of cisplatin 100 mg/m², etoposide 375 mg/m² and ifosfamide 6 g/m² (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m² and etoposide 1,500 mg/m² (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m², etoposide 1,800 mg/m² and cyclophosphamide 6,400 mg/m² (CEC, arm B) followed by stem cell reinfusion (JCO 2007,25:2778). Five pts were excluded from further analysis due to non-GCT histologies at review. We evaluated long-term progression-free (PFS) and overall survival (OS) six years after randomization of the last patient. Survival probabilities were compared using the logrank test. Results: Overall, 108 and 103 pts were randomized to arms A and B respectively. The study was stopped prematurely due to excess treatment-related mortality in am B (14%) compared to arm A (4%) (p=0.01). As of December 2010, 9/211 (4%) pts were lost-to-follow at 31, 32+, 36+, 47+, 47+, 51+, 55, 61+, 71+ months. Median follow-up was 7.5 years (range 2.5 to 10.5 years). Alive are 94/211 (45%) and 88/94 pts are progression-free. All but 6 relapsed patients died from progressive disease, 4 pts became disease-free with third-line treatment and two were alive with disease at last follow-up. Five year PFS is 47% (95%CI: 37-56%) in arm A and 45% (95%CI: 35-55%) in arm B (HR=1.16 (95%CI: 0.79-1.70, p=0.454). Five year OS is 49% (95%CI: 40-59%) in arm A and 39% (95%CI: 30-49%) in arm B (HR=1.42 (95%CI: 0.99-2.05, p=0.057). Relapses more than two years after randomization occurred in 5/211 (2.4%) pts. One patient developed secondary acute myeloid leukemia. Conclusions: In this prospective, randomized trial in pts with relapsed or refractory GCT, sequential HDCT was superior to single HDCT with respect to long-term OS.
Time to adjuvant chemotherapy (TTAC) after open or laparoscopic resection surgeries in colorectal cancers (CRC).
Authors: Selene A. Miller, Laura Sevick, Sergio Acuna, Marck Mercado, Nancy N. Baxter, Marcus J. Burnstein, Sandra De Montbrun, Ori D. Rotstein, Grace Tang, Winthya Varatheswaran, Christine Brezden-Masley
Journal: Journal of Clinical Oncology (2015)

768 Background: This single institution retrospective study evaluates the reason for delay in Time To Adjuvant Chemotherapy (TTAC) from curative resection surgery to start of adjuvant therapy in CRC. The reason for this study was to determine if type of surgery (laparoscopic versus open) increased TTAC of which evidence indicates poorer disease free survival and overall survival (Biagi J, Raphael M, Mackillop W, Kong W, King W, Booth C. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA, 305(22):2335-42. doi: 10.1001/jama.2011.749.) Methods: CRC patients treated at St. Michael’s Hospital in Toronto, Canada were included if diagnosed with stage II or III disease, underwent curative resection surgery between January 1, 2006, and December 31, 2012, and either received systemic adjuvant chemotherapy or surveillance protocol. Results: Among 259 patients, 92 patients (35.7%) underwent curative laparoscopic resection and 166 open resection (64.3%). Intraoperative and/or postoperative complications were experienced in 73 patients. Complications were less prevalent among patients who underwent laparoscopic surgery versus open resection (11.9% vs. 36.8%; p&lt;0.0001). Of these 73 complications, wound infection (39.7%), intraoperative procedural complication (14.3%), and postoperative gastrointestinal complications (6.4%) were most prevalent. After adjusting for complication and clustering within the operating surgeon, there were no statistical differences in TTAC between open (51.310 ± 1.7 days) and laparoscopic (49.2 ± 1.6 days) resection surgeries (p=0.1996). However, presence of a complication was associated with delay in TTAC (HR 0.501; 95% CI, 0.43-0.58; p&lt;0.001). Conclusions: TTAC in CRC patients does not differ statically for each type of resection surgery. However, presence of a complication is associated with delays in TTAC and is over three-fold more prevalent in open than laparoscopic resections. Therefore, there is an increased risk of delay in TTAC for open resection surgeries than laparoscopic resections due to a higher prevalence of surgical complications.