tbuckley/cabot-search huggingface dataset:
A phase II study of oxaliplatin with ELF regimen in patients with advanced gastric cancer
Authors: H.-M. Pan, N. Zhu, F. Lou, Y. Guo, W. Jin, H.-Z. Lou, Y. Zheng
Journal: Journal of Clinical Oncology (2004)

4206 Background: ELF (Etoposide, Leucovorin, 5-FU) regimen is widely used in gastric cancer. Oxaliplatin (Eloxatin) is a third generation platinum compound with activity against gastric cancer. A phase II study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin and ELF regimen in the treatment of patients with advanced gastric cancer. Methods: Patients received Oxaliplatin 100mg/ m2 2hr on day 1, calcium folinate 200mg/m2 1/2 hr on day 1–3, 5-FU 500mg/ m2 2 hr on day 1–3 and etoposide 100mg/ m2 3 hr on day1–3. Cycles were repeated every 21 days. Efficacy and safety were evaluated every 3 cycles and responses were re-confirmed 4 weeks later. Forty-five patients were entered in the study: 46% male / 54% female, median age 44 years (range 28 – 72 yrs), 38 adenocarcinoma and 7 signet ring cell carcinoma, 64% newly diagnosed disease and 36% previously treated. Results: A total of 172 cycles were given, 39 patients were analyzed for response. There were 7 complete responses and 13 partial responses (response rate 51%), 11 stable disease (28%) and 8 progressive disease (21%). The median time to progression was 5.8 months and median overall survival was 8.2 months. All patients were analyzed for toxicity. The most common hematologic toxicity were anemia in 24.4% of patients (7/45 Gr1, 4/45 Gr2), leucopenia in 53.3% (16/45 Gr1, 4/45 Gr2, 4/45 Gr3) and thrombocytopenia in 22.2% ( 6/45 Gr1, 3/45 Gr2, 1/45 Gr3). No Gr4 anemia, leucopenia and thrombocytopenia were observed. The most common non-hematologic toxicity was nausea/vomiting: 48.9% of patients (15/45 Gr1, 4/45 Gr2, 3/45 Gr3). Peripheral neuropathy was noted in 44.4% of patients (12/45 Gr1, 5/45 Gr2, 3/45 Gr3; NCI scale). Grade 3 & 4 alopecia was noted in 13 cases (29%). Conclusions: This Oxaliplatin / ELF regimen shows good efficacy and an acceptable safety profile in advanced gastric cancer patients and may proved to be a suitable alternative regimen in this indication. No significant financial relationships to disclose.
WT1 Peptide Vaccine Is Able to Induce WT1-Specifc Immune Response with TCR Clonal Enrichment to Control Minimal Residual Disease in Patients with Myeloid Leukemia
Authors: Hongtao Liu, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Margaret Green, Jae-Hyun Park, Yusuke Nakamura, Richard A. Larson, Andres M Salazar, Olatoyosi Odenike, Thomas Gajewski, Wendy Stock
Journal: Blood (2016)
Three-year survival in stage IV non-small cell lung cancer (NSCLC): The importance of metastatic distribution.
Authors: Daniel D. Karp, Jan M Hanneken, Sarah H Taylor, Taoyan Men, Xifeng Wu, Xia Pu
Journal: Journal of Clinical Oncology (2012)

7608 Background: Although long term survival (LTS) is an important goal of lung cancer treatment, those with metastatic disease at presentation have a median of only 8-9 months in most series with a small “tail” on the survival curve. We analyzed a large cohort of Stage IV pts by performance status (PS), smoking history, number and sites of disease to assess factors associated with 36 month survival. Methods: From 2004–2008, 526 newly diagnosed untreated pts with Stage IV NSCLC received initial treatment at our institution. Sites of disease were analyzed according to lung, brain, bone, liver, adrenal, skin, malignant effusion, lymphangitic, bulky pleural disease, and “other”. No patient had definitive surgery. Results: Overall, 58/526 pts (10.8%) survived 36 months or more. 453 pts died within 36 months. 15 pts alive with follow-up time less than 36 months were removed from further analysis. Of those, 38/58 (65.5%) had only 1 metastatic site (p&lt;0.001). 14 (24.1%) had 2 sites, only 6 (10.3%) had 3 or more sites. Those 19 pts with lung to lung spread were the most common (32.8%) with LTS – reflecting the M1 status in the new International Staging System. Only 1 LTS pt had liver mets at diagnosis – a solitary lesion treated with radiofrequency ablation. 20 pts had PS=0 (0.019) and 29 had PS=1 (NS). PS=2 pts made up 6. 2 pts had PS=3 initially. 1 unknown. Only 6/58 (10.3%) were current smokers, 23 (39.7%) were never-smokers (p&lt;0.001). Adenocarcinoma made up 65.5%. Conclusions: Progress in lung cancer survival has been slow. Very few LTS pts have more than 1 site of metastatic disease at presentation, virtually none with liver disease (p=0.02). Number of metastatic sites and presence of liver metastases appear to be important stratification variables for lung cancer clinical trials.
Retrospective analysis of neoadjuvant chemoradiotherapy with carboplatin/ paclitaxel versus FOLFOX in newly diagnosed esophageal or junctional cancers: A single instituition experience.
Authors: Ranjit Nair, Usman Shah, Hope Kincaid, Jennifer Macfarlan, Eliot Lawrence Friedman
Journal: Journal of Clinical Oncology (2017)

168 Background: The retrospective study aimed to evaluate carboplatin / paclitaxel (CP) versus FOLFOX in the neoadjuvant combined modality setting for newly diagnosed esophageal or junctional cancers. Methods: Patients with esophageal or junctional cancers treated in combined modality setting were included. During the study period, there were seventy three patients who had T2-4N0-1M0 esophageal and junctional carcinomas. Results: 49 (67%) patients received CP and 24 (33%) patients received FOLFOX. Concurrent radiation was delivered 5400-cGy in CP arm and 5040-cGy in FOLFOX arm. 38 (78%) patients in CP arm and 19 ( 79 %) in FOLFOX arm underwent curative resection. In CP arm, 11(12%) did not undergo curative resection due to disease progression (5/11), death secondary to infection (2/11) and poor functional status post chemotherapy (4/11). In FOLFOX arm, 5(21%) patients did not have surgery due to progressive disease (3/ 5), sepsis ( 1/ 5) and Tracheo–esophageal fistula ( 1 / 5). In patients who underwent curative resection, overall response rate (RR) was 92% in the CP arm with *CR–10(26%), PR–25 (66%), NR–3 (8%); in FOLFOX arm, RR was 100 % with *CR–6(32 %), PR–13(68 %), NR- 0 (p = 0.06). Median follow-up in all patients was 22 months, with median overall survival (OS) for the CP group 20-months and the FOLFOX group 30.5-months.With curative resection the median OS was 23-months in CP arm and 41-months in FOLFOX arm. Median relapse free survival (RFS) was 9.5-months in CP arm and 11 months in FOLFOX arm. 45% relapsed in the CP arm and 42% relapsed in the FOLFOX arm after curative resection. Conclusions: With CROSS trial in esophageal and juntional cancers, there has been a paradigm shift away from infusional 5-FU based regimens (5FU/cisplatin and FOLFOX). With this study, we demonstrated the activity of FOLFOX in comparison to CP in the neoadjuvant setting with concurrent radiotherapy in the treatment of localized esophageal cancers. There was a trend in clinical efficacy and response rate towards FOLFOX when combined with curative resection. To definitively assess this and compare the efficacy, long term prospective studies are needed.
A phase I-II and pharmacodynamic (PD) study of the combination of the proteasome inhibitor bortezomib (B) and paclitaxel (P) in patients with taxane-sensitive solid tumors
Authors: E. Gallerani, S. Cresta, D. Tosi, C. Sessa, G. Capri, C. V. Catapano, F. Bertoni, S. Marsoni, J. Tursi, L. Gianni
Journal: Journal of Clinical Oncology (2006)

13029 Background: Proteasome inhibition blocks the chemotherapy-induced activation of NF-кB increasing chemosensitivity to anticancer agents due to increased apoptosis. NF-кB is frequently aberrantly activated in primary human carcinomas and over-expressed in aggressive breast cancer lines 1 supporting the rationale for combining B with P. We designed a phase I-II and PD trial to determine the recommended dose (RD) of the B&amp;P combination, to screen for antitumor activity in patients with potentially taxane-sensitive tumors, to search for drug-induced changes and to identify potential surrogate markers of drug activity and toxicity in peripheral blood mononuclear cells (PBMC). Methods: Eligibility included ECOG performance status &lt; 2, neurotoxicity &lt; 2 and adequate organ functions. Treatment was given Q21 days: B on days 1,4, 8 and 11 and P on days 1 and 8. PBMC for gene expression profiling have been collected on day 1 and 4 before and after therapy. RECIST for response was applied. Results: Twenty-nine patients (20 female, median age 60 yrs) were accrued and 25 are evaluable (breast cancer: 13, ovarian cancer: 7, prostate cancer 1, other 4) ; 16 pts were treated in 4 escalation levels and the RD defined respectively at 1.3 mg/m 2 /dose &amp; 100 mg/m 2 /dose for B&amp;P. Neurotoxicity was the main toxicity (G1 36%, G2 20% and 1 case G3) requiring treatment discontinuation in 2 pts at cy 6 &amp; 7. Other toxicities (all grades) were nausea and vomiting (68%), diarrhea (56%, G3 12%), alopecia (52%), asthenia (36%, G2 4%), and myalgia (32%, G2 8%). Antitumor activity consisted of 3 PR in pts with ovarian cancer lasting respectively 14, 8+ and 16 wks; 2 PRs in pts with breast cancer (12+ wks,14+ wks) and 1 PR in a pt with prostate cancer. Conclusions: Thus far the regimen has acceptable toxicity with evidence of antitumor activity. The trial will continue until accrual of four additional patients as planned. Footnotes 1 Adams J Current Opin Oncol 2002, 14:628–634. [Table: see text]
Spontaneous and cyclophosphamide-enhanced metastasis inhibited by traditional Chinese medicine (TCM) herbal mixture LQ.
Authors: Lei Zhang, Chengyu Wu, Yong Zhang, Robert M. Hoffman
Journal: Journal of Clinical Oncology (2013)

e22209 Background: Cyclophosphamide pretreatment of mice enhances metastatsis of HT1080 human fibrosarsoma cells (Cancer Res. 68, 516-520, 2008). Methods: HT1080 human fibrosarsoma cells were injected into the footpad or were injected into the epigastric cranialis vein of mice pre-treated with cyclophosphamide (CYC) or a combination of CYC and the herbal mixture LQ. The efficacy was monitored through dynamic subcellular imaging of trafficking of cancer cells in lymph nodes and blood vessels in live mice. Results: LQ significantly inhibited HT1080 spontaneous metastases to local lymph nodes in the foot-pad-injection model. In the control group, 100% of mice had lymph node metastasis, compared to 12.5% of the mice in the LQ treatment group. LQ also significantly inhibited CYC-enhanced experimental metastasis in the epigastric cranialis vein injection model. LQ prolonged the overall survival of mice in the spontaneous-lymph-node metastatic footpad-injection model. Conclusions: The TCM herbal mixture LQ shows promis to inhibit metastasis and will be further tested in other metastatic models.
Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: Results of the international collaboration on primary urethral carcinoma.
Authors: Georgios Gakis, Todd Matthew Morgan, Siamak Daneshmand, Kirk A. Keegan, Harras B Zaid, Jan Hrbacek, Bedeir Ali-El-Dein, Rebecca Helen Clayman, Lars Weissbach, Tilman Todenhoefer, Sigolene Galland, Hans-Martin Fristche, Michael Rink, Maximilian Burger, Sam Chang, Marek Babjuk, George N. Thalmann, Arnulf Stenzl, Jason Alexander Efstathiou
Journal: Journal of Clinical Oncology (2014)

4587 Background: The present analysis aims to investigate the prognostic benefit of perioperative chemotherapy in patients undergoing surgery for primary urethral carcinoma. Methods: A total of 124 patients (86 men, 38 women) who were diagnosed with primary urethral carcinoma in ten tertiary international academic centers between 1993 and 2012, underwent surgery for primary treatment. Platinum-based neoadjuvant and adjuvant chemotherapy was administered in 18 (15%) and 21 (17%) patients, respectively. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemotherapy on progression-free (PFS) and overall survival (OS). The median follow-up was 20 months (mean: 32 months; IQR: 4-48). Results: Median age at surgery was 67 years (IQR: 53-74). Receipt of neoadjuvant chemotherapy was associated with clinically node-positive tumor stage (cN+; p=0.009). Conversely, delivery of adjuvant chemotherapy was associated with locally advanced primary tumors (≥cT3; p=0.003). No further significant associations were found between perioperative chemotherapy and age, gender, tumor location (proximal vs. distal), underlying histology, tumor grade and use of palliative therapy. The 3-year PFS/3-year OS for patients with cN+-stage disease who underwent neoadjuvant chemotherapy was 40%/100%, compared to 0%/29% for no neoadjuvant chemotherapy (p=0.043 and p=0.034, respectively). By contrast, the 3-year PFS/3-year OS for patients with ≥cT3-stage disease who received adjuvant chemotherapy was 23%/46%, versus 20%/53% for no adjuvant chemotherapy (p=0.44 and p=0.20, respectively). The 3-year OS for patients with ≥cT3 and/or cN+ stage disease who received neoadjuvant chemotherapy was 100%, compared to 20% for adjuvant chemotherapy (p=0.031). Conclusions: In this series, patients who received neoadjuvant platinum-based chemotherapy for locally advanced primary urethral carcinoma exhibited improved survival compared to those who underwent immediate surgery and adjuvant chemotherapy.
Changes in the biologic markers between primary tumor and ipsilateral breast tumor recurrence after breast conserving surgery: Discordance and prognosis.
Authors: Yasuhiro Okumura, Reiki Nishimura, Katsuhiko Nakatsukasa, Atsushi Yoshida, Norikazu Masuda, Masahiko Tanabe, Tadahiko Shien, Nobuyuki Arima, Yoshifumi Komoike, Tetsuya Taguchi, Hideo Inaji, Makoto Ishitobi
Journal: Journal of Clinical Oncology (2013)

1116 Background: Changes in biological markers due to recurrence are clinically experienced in breast cancer. However, the clinical significance is still uncertain, especially after breast conserving surgery. The changes in biological markers between primary tumor and ipsilateral breast tumor recurrence (IBTR) and their correlations with prognosis were investigated, retrospectively. Methods: A total of 117 consecutive patients with IBTR without distant metastases were enrolled in this study. All patients were examined for ER, PgR, HER2 and Ki-67 in both the primary and recurrent tumors. The cases were categorized into 3 groups: patients with Ki-67 values &lt;20%, &lt;50% and ≥50%, and divided into 2 groups according to the IBTR site, same quadrant(SQ)and different quadrant(DQ) from the initial sites. The distant disease-free survival (DDFS) was calculated using the Kaplan-Meier method and evaluated by the log-rank test and multivariate analyses using Cox proportional hazards model. The median follow-up period was 4.8 years after IBTR. Results: The PgR positive rate from the primary tumor to IBTR decreased from 57% to 39% and the Ki-67 values increased significantly from a mean of 17% to 23%. The concordance rate of the subtype was 62%. In the SQ group, the PgR positive rate significantly decreased and the mean Ki-67 values significantly increased, whereas there was no significant difference in the DQ group. In terms of changes by category due to relapse, the discordance rate in Ki-67 was high in the SQ group, and HER2 was high in the DQ group. Regarding DDFS by a change in the categorization, the cases with discordance in Ki-67 values had significantly lower DDFS in the SQ group(5-year DDFS: 75% vs 52%, p=0.04). However, a clear difference was not found in the DQ group. Conclusions: The PgR positive rate decreased while the mean Ki-67 values increased due to IBTR in the SQ group. The categorical discordance in the Ki-67 values was significantly associated with lower DDFS, especially in the SQ group. These findings suggest that the recurrent site and change in the biological markers were clinical significant in the evaluation of the characteristics and treatment in cases with IBTR.
Impact of t (11;14) on the outcome of autologous hematopoietic cell transplantation (Auto-HCT) in multiple myeloma.
Authors: Koji Sasaki, Gary Lu, Chitra Hosing, Uday R. Popat, Sairah Ahmed, Nina Shah, Qaiser Bashir, Yvonne Dinh, Robert Z. Orlowski, Richard E. Champlin, Muzaffar Qazilbash
Journal: Journal of Clinical Oncology (2012)

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (&gt;PR1: 82 vs. 76%, &lt;PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.
Frontline treatment of localized osteosarcoma without methotrexate: Results of the St. Jude Children's Research Hospital OS99 trial
Authors: N. C. Daw, M. D. Neel, B. N. Rao, C. A. Billups, J. Wu, J. J. Jenkins, M. Villarroel, L. Luchtman-Jones, J. Quintana, V. M. Santana
Journal: Journal of Clinical Oncology (2009)

10036 Background: Standard treatment of osteosarcoma includes cisplatin and high-dose methotrexate (HD-MTX), but both agents are associated with significant toxicity and MTX administration requires complex pharmacokinetic monitoring. In our previous OS91 trial, the combination of carboplatin and ifosfamide with doxorubicin and HD-MTX yielded outcomes comparable to those of cisplatin-based regimens with less long-term toxicity in localized osteosarcoma. Methods: Between 1999 and 2006, we conducted a multi-institutional trial (OS99) to evaluate the activity of carboplatin, ifosfamide, and doxorubicin without HD-MTX in newly-diagnosed patients with localized osteosarcoma. Treatment comprised 12 cycles of chemotherapy given every 3 weeks: 3 consecutive cycles of carboplatin (dose targeted to AUC 8 mg/ml×min on day 1) and ifosfamide (2.65 g/m 2 daily for 3 days) and one cycle of doxorubicin (25 mg/m 2 daily for 3 days) followed by definitive surgery (week 12) and 2 additional cycles of carboplatin/ifosfamide and 3 cycles each of ifosfamide/doxorubicin and carboplatin/doxorubicin for a total of 35 weeks. The log rank test was used to compare survival and event-free survival (EFS) distributions. Results: A total of 72 eligible patients were enrolled. The median age was 13.4 years and 41 (57%) were male. The most common tumor site was the femur (n = 46; 64%). The median follow-up for survivors was 4.4 years. Forty of the 66 (60.6%) evaluable patients had good histologic response (tumor necrosis &gt; 90%) to preoperative chemotherapy. There was no difference in EFS or survival distributions between OS99 and OS91. Four-year estimates of EFS were 68.1 ± 6.7% for OS99 compared to 70.2 ± 6.6% for OS91 (p = 0.89). The 4-year OS was 82.4% ± 5.7% for OS99 compared to 74.5% ± 6.3 for OS91 (p = 0.25). Conclusions: OS99 produced outcomes similar to cisplatin or HD-MTX containing regimens and offers an alternative treatment regimen especially for patients with renal compromise and institutions where pharmacokinetic monitoring of MTX is not available. No significant financial relationships to disclose.
Current patterns of care for patients with stage I testicular seminoma: Survey of U.S. radiation oncologists on treatment recommendations.
Authors: Timur Mitin, Aditya Jain, Catherine Degnin, Yiyi Chen, Arthur Hung, Jerry Jeff Jaboin, Charles R. Thomas
Journal: Journal of Clinical Oncology (2017)

418 Background: Most men with Stage I testicular seminoma are cured with surgery alone, now a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (RO) is unknown. Methods: We have surveyed practicing US RO via a short online questionnaire. Respondents’ characteristics, self-rated knowledge, perceived patient (pt) compliance rates with observation protocols and expected rate of infertility with and without adjuvant treatments were analyzed for association with treatment recommendations. Results: We received 353 responses from practicing US RO, of whom 23% consider themselves experts. Recommendations are summarized in the table. 34% believe that survival is jeopardized in case of recurrence on observation, but this belief does not impact the recommendation. Over 70% of respondents rate non-compliance with observation at &gt; = 30%. Responders with a higher perceived non-compliance rate are more likely to recommend adjuvant therapy (Fisher’s exact p &lt; 0.01). 52% routinely advise fertility assessment and/or sperm banking for pts who elect observation or chemotherapy, and 74% advise for pts undergoing RT. Respondents are more likely to recommend fertility assessment if they perceive a higher rate of infertility (Mantel-Haenszel Chi-square p &lt; 0.01). 45% administer adjuvant RT in pts with elevated pre-orchiectomy alpha-fetoprotein levels. Conclusions: There is a dramatic uptake of observation as the recommended approach to pts with Stage I seminoma in US RO practices, despite a significant concern among practitioners about pt compliance. Further clinical work must establish best practices to minimize the effect on fertility, as well as guidelines for pts with Stage IS testicular seminoma. [Table: see text]