tbuckley/cabot-search huggingface dataset:
Randomized pilot study of a weight gain prevention intervention for breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Karen Basen-Engquist, James L. Murray, George Baum, Angelica M. Gutierrez-Barrera, Banu Arun
Journal: Journal of Clinical Oncology (2012)

e11090 Background: Weight gain is a common problem after breast cancer diagnosis and treatment, particularly for women who receive chemotherapy. The weight gain has negative effects on quality of life, increases risk for chronic disease, and may increase risk of breast cancer recurrence. This pilot study tested a behavioral weight gain prevention intervention on weight, IGF-I, and IGFBP-3. Methods: Thirty-nine breast cancer patients receiving neoadjuvant chemotherapy were randomized to the weight gain prevention intervention or usual care. The intervention focused on exercise (resistance training, aerobic) and eating a low energy dense diet. Participants received 20 sessions during chemotherapy (14 in person and 6 by telephone) and 9 sessions after surgery (3 in person, 6 by telephone). They completed weight and other assessments at baseline (t0), mid-chemotherapy (T1), post-chemotherapy (t2), post surgical recovery (T3), after the post-surgical intervention (T4) and long term follow-up 6-9 months post surgery (T5). Serum was collected at T0, T2, T3, and T5 and analyzed for IGF-I and IGFBP-3. Results: Controlling for baseline weight, the intervention group weighed less than the control group at T1-T4, a result which approached significance (p=.08) in the intent to treat analysis. There was also a significant obesity x treatment group interaction, indicating that the intervention was most effective for patients who were obese at baseline (p=0.03). The groups did not differ in weight at the post-intervention follow-up (p=0.839). There was no significant difference between the groups in IGF-I or IGFBP-3. Conclusions: A diet and exercise intervention delivered during and after chemotherapy can promote weight loss in breast cancer patients, but the results may not be sustained after the intervention ends. [caption]Participants’ weights in kilograms, adjusted for baseline weight (least squares means).[caption] [Table: see text]
Multicenter randomized phase II study of weekly docetaxel alone versus weekly docetaxel plus oxaliplatin as a second-line chemotherapy in patients with advanced gastric cancer: Preliminary response and safety results.
Authors: Jin Young Kim, Young Rok Do, Keon Uk Park, Hun-Mo Ryoo, Sung Hwa Bae, Yee Soo Chae, Min Kyoung Kim, Kyung Hee Lee, Sun Ah Lee, Jong Gwang Kim, Hong-Suk Song
Journal: Journal of Clinical Oncology (2012)

e14570 Background: Gastric cancer is a frequent malignancy with worldwide estimated incidence of 990,000 cases, representing 7.8% of all cancers in 2008. There are limited data suggesting a benefit for doublet second-line chemotherapy in advanced gastric cancer. Methods: The eligibility criteria were patients 1) with prior exposure to cisplatin based chemotherapy and advanced or recurrent stomach cancer 2) with pathologically proven gastric adenocarcinoma, 3) with an ECOG performance status 0 to 2, 4) with measurable lesions. Each treatment cycle was consisted of docetaxel 36 mg/m 2 in docetaxel mono therapy group and docetaxel 36 mg/m 2 , oxaliplatin 80 mg/m 2 in docetaxel/oxaliplatin doublet therapy group on days 1, 8. The primary end point of this study was response rate, and secondary end points included toxicity, progression free and overall survival. Results: Fifty two patients were enrolled; median age was 63 years; male (n=42) and female (n=10); docetaxel mono therapy (n=27) and docetaxel/oxalliplatin doublet therapy (n=25). The median number of cycles administered was 2.5 (range,1-9). Fourty eight patients were assessable for efficacy. Four partial responses, 7 stable diseases in mono therapy group (RR; 4/27, 14.8%) and 1 complete remission, 4 partial responses, 13 stable diseases in double therapy group (RR; 5/25, 20.0%) were confirmed (p=0.198). Median progression free survival was 1.97 months in the mono therapy group and 4.93 months in doublet therapy group (p=0.007). Median overall survival was 11.57 months in the mono therapy group and 8.13 months in doublet therapy group (p=0.650). Grade 3 or 4 adverse events were reported in 11 of 52 patients; G3 pain were in 2 patients and G3 pneumonia was in 1 patient in mono group, G3/4 neutropenia were 5 patients in the combination group, G3 nausea, vomiting, general weakness was 1 patient each group in combination group. Conclusions: Weekly docetaxel/oxaliplatin doublet therapy showed superior progression free survival to monotherapy group as second line therapy in cisplatin pretreated advanced gastric cancer patients.
Functional implications of Neandertal introgression in modern humans
Authors: Michael Dannemann, Kay Prüfer, Janet Kelso
Journal: Genome biology (2017)

Admixture between early modern humans and Neandertals approximately 50,000–60,000 years ago has resulted in 1.5–4% Neandertal ancestry in the genomes of present-day non-Africans. Evidence is accumulating that some of these archaic alleles are advantageous for modern humans, while others are deleterious; however, the major mechanism by which these archaic alleles act has not been fully explored. Here we assess the contributions of introgressed non-synonymous and regulatory variants to modern human protein and gene expression variation. We show that gene expression changes are more often associated with Neandertal ancestry than expected, and that the introgressed non-synonymous variants tend to have less predicted functional effect on modern human proteins than mutations that arose on the human lineage. Conversely, introgressed alleles contribute proportionally more to expression variation than non-introgressed alleles. Our results suggest that the major influence of Neandertal introgressed alleles is through their effects on gene regulation.
Phase II study of vinorelbine (NVB) and UFT in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes
Authors: A. Anton, T. Puertolas, M. Ramos, A. Barnadas, J. Florian, R. Grande, N. Ribelles, M. Lomas
Journal: Journal of Clinical Oncology (2004)

751 Background: To assess the efficacy and safety of the combination of NVB and UFT as first or second line treatment in patients with MBC previously treated with anthracyclines and taxanes. Methods: Patients with histologically confirmed breast cancer, measurable disease, no more of one prior regimen of chemotherapy for metastatic disease, ECOG PS<2, and adequate bone marrow, renal and liver function were eligible. Patients received NVB 30 mgrs/m2 on day 1 and UFT 250 mgrs/m2 daily, q2w, until progression or unacceptable toxicity. Toxicity was evaluated every cycle and objective response every six cycles. Results: Between 2/2001 and 8/2003, 37 patients have been included, all evaluables for toxicity, and 36 for response: median age 62 years (range 37–80; median PS 1. Twenty eight patients (76%) received neo/adjuvant therapy, and twenty nine patients (78%) received one prior chemotherapy regimen for metastasic disease. Patients had metastasis in bone (18 pts), liver (18 pts), lung (13 pts), nodes (7 pts), other sites (8 pts) and 23 (62%) had two or more metastatic sites. A total of 301 cycles were administered (median 7 cycles, range 1–19). Toxicity was generally mild; grade 3–4 toxicity consisted of neutropenia in 14 pts (10% cycles), thrombocytopenia in 1 pts (0,4% cycles), asthenia 3 pts (2% cycles), mucositis in 1 pt (0,4% cycles), neuropathy in 1 pt (0,4% cycles), and constipation in 1 pt (0,4% cycles). Efficacy: To date, 13 pts (36%) achieved partial response, 7 patients (19%) had stable disease, 12 patients (33%) had progressive disease, and 4 patients (11%) were no evaluables. Median time to progression was 18 weeks range (5–47.2). Conclusions: The combination of NVB and UFT in patients with MBC previously treated is a well-tolerated an effective regimen, and achieved disease control in 55% in this group of patients. No significant financial relationships to disclose.
A phase 1b trial of mFOLFOX6 and everolimus (NSC-733504) in patients with metastatic gastroesophageal adenocarcinoma (NCT01231399).
Authors: Vincent M. Chung, Paul Henry Frankel, Dean Lim, Joseph Chao, Christina Haeyoung Yeon, Lucille A. Leong, Joseph Kim, Eloise Luevanos, Carol Rose, Marwan Fakih
Journal: Journal of Clinical Oncology (2014)

e15007 Background: Gastric cancer remains a significant problem worldwide with approximately 870,000 new cases and 650,000 deaths per year. Although the Granite trial did not show any benefit of everolimus over best supportive care in patients with advanced gastric cancer, preclinical combinations of platinum chemotherapy and mTOR inhibition have shown a synergistic effect. We conducted a phase 1 trial combining mFOLFOX6 with everolimus. Methods: Patients with metastatic gastric, gastroesophageal and esophageal adenocarcinoma were eligible. A standard 3+3 design was employed and patients received standard dose mFOLFOX6 and escalating doses of everolimus ranging from 2.5 to10 mg/day. Patients were evaluated for dose limiting toxicities during the first 4 weeks of treatment. Tumor tissue was collected for next generation sequencing. Results: Six patients were accrued to the first dose level of everolimus at 2.5 mg daily, four with metastatic gastric cancer and 2 with metastatic esophageal cancer. Two dose limiting toxicities (DLT’s) were observed at the first dose level with one patient being hospitalized for fever secondary to a possible infection. The second patient developed grade 2 neutropenia that resulted in a treatment delay greater than 7 days. Toxicities were manageable with mucositis, nausea, neutropenia, fatigue and rash being the most common. Five patients required everolimus dose reduction during their course of treatment. The median time to treatment failure was 8.9 months. Next generation sequencing revealed mutations in APC, EGFR, FGFR3, FLT3, KDR, KIT, PDGFRA, PIK3CA, RET, STK11 and TP53. Conclusions: The immunosuppressive effect of chemotherapy in combination with everolimus resulted in two DLT’s at the first dose level. One patient that required dose reductions due to mucositis had a FLT3 mutation which more commonly occurs in acute myelogenous leukemia. A FLT3 genotype variant associated with the development of pneumonitis in renal cell carcinoma patients treated with mTOR inhibitors was previously reported (Y. Urun, et al, ASCO 2013). Further research is needed to identify biomarkers of treatment response and toxicity. Clinical trial information: NCT01231399.
Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer.
Authors: Maria Jiang, Soundouss Raissouni, Jamison Mercer, Aalok Kumar, Rachel Anne Goodwin, Daniel Yick Chin Heng, Patricia A. Tang, Corinne M. Doll, Anthony MacLean, Erin Diana Powell, Julie A. Price Hiller, Jose Gerard Monzon, Michael M. Vickers, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2014)

6516 Background: There are limited studies assessing the outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer. Our aim was to assess the impact of age on clinical outcomes in a large multi-institutional database. Methods: Data from patients across Canada with locally advanced rectal cancer who received nCRT and had curative intent surgery from 2005 to 2012 were collected from Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and Dr. H. Bliss Murphy Cancer Centre. Age was analyzed as both a continuous and a dichotomous variable (<70 v ≥ 70 yrs) and correlated with time free of recurrence (TFR where death without recurrence is censored), disease free survival (DFS), and overall survival (OS). Multivariable analyses (MVA) controlled for sex, ECOG, circumferential resection margins, radiation dose, distance from anal verge, pre-treatment anemia, clinical stage, pathologic stage and completion of neoadjuvant chemotherapy. Results: A total of 1,172 patients were included with a mean age of 62 years (SE±0.33) and a mean follow-up of 3.8 yrs (SE±0.05). Among them, 295 (25%) patients were ≥ 70 years. Elderly patients were less likely to receive adjuvant chemotherapy (ACT) (57% v 77%, p<0.0001), oxaliplatin-based ACT (12% v 31%, p<0.0001). They were also less likely to complete neoadjuvant chemotherapy (76% v 86%, p<0.001) but more likely to be anemic at initiation of nCRT (42% v 31%, p=0.0004). In the MVA, elderly patients had improved TFR (HR 0.65, 95% CI 0.45 – 0.95, p = 0.02), similar DFS (HR 0.928, 95% CI 0.68 – 1.26, p = 0.63) and similar OS (HR 1.28, 95% CI 0.88 – 1.86, p =0.2) compared to younger patients. As a continuous variable, age was not significantly associated with TFR (HR 0.99, 95% CI 0.98 – 1.01, p = 0.47) or DFS (HR 1.00 95% CI 0.99 – 1.02, p =0.49). However, it was significantly associated with inferior OS (HR 1.02, 95% CI 1.00 – 1.03, p =0.04) in the MVA. Conclusions: Elderly patients (≥ 70 yrs) who receive nCRT followed by surgery appear to have similar cancer related outcomes compared to younger patients. Decisions regarding eligibility for nCRT and surgery should not be based on age alone.
Treatment strategies after failure to reversible tyrosine kinase inhibitors (rTKI) in <i>EGFR</i> mutant (mut) non-small cell lung cancer (NSCLC) patients (p): A retrospective analysis of 41 Spanish p.
Authors: Jordi Remon, Teresa Moran, Diego Alcaraz, Laia Capdevila, Rut Porta, Noemi Reguart, Pilar Lianes, Enric Carcereny Costa, Joaquim Bosch-Barrera, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

e19089 Background: Different therapeutic approaches have been used in the clinical setting in NSCLC p harbouring EGFR mutations progressing to rTKI, although the standard of care in this situation is still not well established. Methods: A multi-institutional database from four different centers in Spain was review to identify EGFR mut p with acquired resistance to rTKI in order to evaluate the therapeutic strategies after rTKI failure and the effect on the post-progression survival (PPS) of these treatments. Results: 41 p with acquired resistance to rTKI were identified: 63% female; median (m) age 62 ±11 yrs; 95% Caucasian; del19 76%, never or light former smokers 100%; 90.2% adenocarcinomas; 51 % received TKI as first line therapy; 85% were initial stage IV .mPFS for the rTKI was 8.4 months (mo) and mOS was 29.7 mo for the entire population. P were treated with a median of 2 therapeutic strategies after the rTKI failure. 6 therapeutic strategies have been identified. As immediate approach, 16 p were switched to chemotherapy (CT) with a mPPS of 3 mo. 9 p were switched to an irreversible TKI obtaining a mPPS of 3.9 mo. rTKI plus other drug was maintained in 11 p: rTKI plus CT in 9 p with a mPPS of 4 mo and rTKI plus other drug different to CT in 2 with a mPPS of 2 mo. Despite the progression, rTKI was maintained in 2 p considered slow progressors and local therapy, in addition to the rTKI, was administered in 3 p with oligoM1progressive disease obtaining a mPPS of 1.4 and 36 mo, respectively. 8 p were treated sequentially with ≥5 strategies. These p attained a mOS of 27.7 mo. Conclusions: The combination of different strategies when treating EGFR mut p after rTKI failure may impact the survival especially when p are candidates to receive some of this treatments sequentially. These strategies may reflect different subsets of EGFR mut disease.
Stereotactic body radiotherapy for pancreatic cancer: Analysis of toxicity.
Authors: Subha Perni, Pan Kim, Theodore Yanagihara, Ashish Jani, Christine Chin, Ping Yan, Brian Wolthius, Carl Elliston, Daniela Gidea-Addeo, David Paul Horowitz
Journal: Journal of Clinical Oncology (2017)

436 Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis, with significant morbidity and mortality from local progression. Radiotherapy can be administered for local control, with stereotactic body radiotherapy (SBRT) increasingly being utilized. We aim to compare the toxicity of SBRT with intensity-modulated radiotherapy (IMRT) in this setting. Methods: A retrospective analysis of patients with PDAC receiving IMRT or SBRT at our institution between April 2011 and November 2015 was performed. 81 patients were identified. Clinical notes were reviewed for treatment details and acute and late toxicities. Late toxicity data was available for 62 patients. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Radiology reports were reviewed to assess for the presence of recurrence and/or progression. Results: Median follow-up from RT was 29 months (95% CI 22-36 months), and median survival from RT was 25 months (95% CI 22-34 months). IMRT patients received 37.5-54 Gy in 15-30 fractions. SRBT patients received 19.8-39.6 Gy in 3-6 fractions. 45% of IMRT and 29% of SBRT patients had local failure (p = 0.1329). IMRT patients were significantly more likely to have Grade ≥2 acute gastrointestinal (GI) toxicity than SBRT patients (RR 1.70; 95% CI 0.98-2.96, p = 0.0489), although one SBRT patient had to have treatment stopped due to extrahepatic stricture. There were no significant differences in late GI toxicity (67% Grade 2 or higher vs. 57%, respectively, p = 0.4244), although one IMRT patient died due to late GI bleeding.IMRT patients were more likely to lose weight during RT(Median -0.03% vs. -0.004%, p = 0.0001) and have moreEmergency Department (ED) visits after RT (Range 0-8 vs. 0-3, p = 0.0019). There were no significant differences in dermatitis, fatigue, or hematologic toxicity. Conclusions: Patients with locally advanced PDAC treated with IMRT versus SBRT had significantly more acute gastrointestinal toxicity, median weight loss, and ED visits after RT, but no significant differences in late gastrointestinal toxicity, dermatitis, fatigue, or hematologic toxicity. SBRT is a relatively tolerable and more convenient alternative for patients with pancreatic cancer.
Retrospective analysis of second malignancies in patients with multiple myeloma.
Authors: Giampaolo Talamo, W. Christopher Ehmann, Nathan G Dolloff, Jozef Malysz, Joseph J. Drabick, Witold B. Rybka
Journal: Journal of Clinical Oncology (2012)

8090 Background: Recent data from patients with multiple myeloma (MM) enrolled in randomized clinical trials have shown an increased incidence of second malignancies after treatment with lenalidomide, but the prevalence of second malignancies in the overall MM population is uncertain. Methods: We retrospectively analyzed the medical records of 320 consecutive MM patients followed at the Penn State Hershey Cancer Institute between 2006 and 2010. We excluded from the analysis basocellular and squamocellular carcinomas of the skin. Results: Forty-three patients (13%) were found to have second malignancies, and 5 of them had a third cancer. One pt had 4 cancers. They included cancers of the prostate (8 pts), breast (8), MDS/leukemia (6), colon/rectum (5), melanoma (5), lung (4), uterus (4), bladder (3), kidneys (2), pancreas (2), testicle (1), myeloproliferative disorders (1), and sarcoma (1). Of 50 cancers, 36 (72%) developed before the diagnosis of MM, at a median of 65 months (range, 1-372), and 14 after that, at a median of 37 months (range, 3-104). Lenalidomide was used in 239 (75%) patients, and in 9 of 14 cases of post-MM second malignancies. Conclusions: Second malignancies usually develop before the diagnosis of MM, i.e., MM is the second malignancy for the majority of patients. The use of lenalidomide could not be indicated as a possible carcinogenic factor for the majority of MM patients with second malignancies.
Clinical prognostic characteristics in predicting brain metastasis in patients with colorectal cancer: A single institution analysis.
Authors: Katherine Wei-Lin Chang, Brian Hernandez, Joel Michalek, Richard L. Crownover, John Floyd, Devalingam Mahalingam
Journal: Journal of Clinical Oncology (2015)

e14640 Background: Colorectal cancer (CRC) rarely metastasizes to the brain. With improved survival of patients (pts) with metastatic CRC following the advent of targeted agents such as bevacizumab (Bev) and anti-EGFR therapy, the incidence of brain metastases (BM) secondary to CRC is rising. We aimed to evaluate the clinical characteristics of who developed BM secondary to CRC. Methods: A historical cohort analysis of CRC pts with BM treated at our institution from 01/2005-01/2015 was performed. Data collected included primary tumor location (colon/rectum), lymph node (LN) involvement, location of extra-cranial metastases (lung/non-lung), number of BM, KRAS status, CEA levels, Bev or cetuximab (Cet) therapy prior to and after BM, and recursive partitioning analysis (RPA) prognostic class I-III (determined by age, Karnofsky performance status (KPS) and presence of extra-cranial metastases). Overall survival (OS) was estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. Results: A total of 39 pts were included. Median age was 56 (range 34–78), 69% males, and 28% KRAS mutated. 69% had both oxaliplatin and irinotecan chemo backbone. 64% had Bev and 26% Cet. Median OS from time of primary tumor diagnosis was 1093 days, any metastatic disease was 949 days, and BM diagnosis was 97 days. Pts with KRAS wild type tumors had longer OS compared to pts with KRAS mutated tumors (1103 vs. 679 days, p = 0.0263, HR 0.36). Pts with lung metastases were more likely to develop BM compared to non-lung metastases (30 vs. 9 patients), but pts with lung metastases had longer OS than pts with non-lung metastases (1042 vs. 569, p = 0.0002, HR 0.23). RPA class I had longest OS (897 days), followed by class II (97 days), and class III the shortest OS (43 days). There was no OS difference with regard to tumor location, LN involvement, number of BM, CEA levels and use of Bev or Cet prior to or after BM. Conclusions: KRAS mutation status, location of extra-cranial metastases, and RPA class are prognostic factors in pts with CRC with BM. Further studies with larger number of pts are needed to confirm and analyze if other clinical and histologic characteristics have impact on prognosis of these pts.
Development of a T-cell Receptor Mimic Antibody against Wild-Type p53 for Cancer Immunotherapy
Authors: Demin Li, Carol Bentley, Amanda Anderson, Sarah Wiblin, Kirstie L.S. Cleary, Sofia Koustoulidou, Tasneem Hassanali, Jenna Yates, Jenny Greig, Marloes Olde Nordkamp, Iva Trenevska, Nicola Ternette, Benedikt M. Kessler, Bart Cornelissen, Mark S. Cragg, Alison H. Banham
Journal: Cancer Research (2017)

Abstract The tumor suppressor p53 is widely dysregulated in cancer and represents an attractive target for immunotherapy. Because of its intracellular localization, p53 is inaccessible to classical therapeutic monoclonal antibodies, an increasingly successful class of anticancer drugs. However, peptides derived from intracellular antigens are presented on the cell surface in the context of MHC I and can be bound by T-cell receptors (TCR). Here, we report the development of a novel antibody, T1-116C, that acts as a TCR mimic to recognize an HLA-A*0201–presented wild-type p53 T-cell epitope, p5365–73(RMPEAAPPV). The antibody recognizes a wide range of cancers, does not bind normal peripheral blood mononuclear cells, and can activate immune effector functions to kill cancer cells in vitro. In vivo, the antibody targets p5365–73 peptide–expressing breast cancer xenografts, significantly inhibiting tumor growth. This represents a promising new agent for future cancer immunotherapy. Cancer Res; 77(10); 2699–711. ©2017 AACR.