tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemoradiotherapy (NCRT) compared with chemotherapy (NCT) in locally advanced squamous-cell cancer of the esophagus.
Authors: Xue Li, Daxuan Hao, Yuanyuan Yang, Xinyu Cheng, Yougai Zhang, Xiaoyuan Wu, Chunyu He, Jinsong Liu, Jianhua Wang
Journal: Journal of Clinical Oncology (2017)

202 Background: Neoadjuvant chemotherapy with or without radiotherapy are the common treatments for locally advanced squamous-cell esophageal cancer(ESCC). There is no sufficient data to choose between these two effective therapies. The aim of our retrospective study was to compare the clinical efficacy between these two strategies of complete pathological response (pCR), postoperative morbidity, mortality, and overall and disease-free survival in patients with locally advanced ESCC. Methods: Patients with stage T2-4N0-1M0 squamous-cell esophageal cancer at our institution were recruited, including patients who underwent NCRT (1 cycle of cisplatin and 5-fluorouracil with concurrent radiotherapy) or NCT (2 cycles of cisplatin and 5-fluorouracil only ) before esophagectomy. Results: From January 2009 to October 2015, a total of 177 patients were analyzed, with 72 received NCRT and the remaining 105 received NCT. The pathological complete response (pCR) rate was 22.2% (n = 16) in NCRT group and 9.5% (n = 10) in NCT group ( P= 0.019). The postoperative mortality was 1.4% in NCRT group, versus 4.8% in NCT group. The postoperative morbidity was 20.8% in NCRT group, versus 27.6% in NCT group. There was no significant difference in recurrence between the two groups ( P= 0.397). 1-,2-,3-year overall survival rates in NCRT and NCT group were 87%, 74%, 51% and 81%, 64%, 51%, respectively ( P= 0.527), and 1-,2-,3-year DFS rates were 77%, 54%, 50% and 65%, 54%, 46%, respectively( P= 0.379). Conclusions: For patients with locally advanced squamous-cell esophageal cancer, the addition of radiotherapy to neoadjuvant chemotherapy may result in higher complete pathological response with acceptable postoperative mortality and morbidity, while the long-term survival benefit is not significant.
Does pathologic complete response predict for outcome in <i>BRCA</i> mutation carriers with triple-negative breast cancer?
Authors: Shani Paluch-Shimon, Eitan Friedman, Raanan Berger, Moshe Zvi Papa, Maya Dadiani, Neil Friedman, Moshe Shabtai, Douglas Zippel, Mordechai Gutman, Talia Golan, Raphael Catane, Ady Yosepovich, Tami Mekel Modiano, Bella Kaufman
Journal: Journal of Clinical Oncology (2014)

1023 Background: Pathological complete response (pCR) has been demonstrated to serve as a surrogate for outcome in patients receiving neo-adjuvant systemic therapy (NAT) for triple negative (TN) breast cancer (BC). To date no data has been published to establish if this is also true for BRCA1/BRCA2mutation carriers with TNBC. Methods: From a prospective NAT database of 588 BC cases, 80 TN cases who had undergone BRCA genotyping were identified. All received dose-dense chemotherapy with an anthracycline and a taxane. pCR was defined as absence of invasive disease in breast and lymph nodes. A logistic regression model was fitted to examine association between BRCA1/2 status and pCR. Survival outcomes were evaluated using Kaplan-Meier method, differences between study groups calculated by log-rank test. Results: 37 BRCA1/2 carriers and 43 non-carriers were identified. The BRCA1/2 carriers had superior pCR compare with non-carriers (61% vs. 39% , p=0.007). Despite the higher pCR, there was no difference in Relapse Free Survival (RFS) between the BRCA1/2 carriers and non-carriers. Amongst those that achieved pCR there was superior RFS for non-carriers compared with BRCA1/2 carriers (Log-rank p=0.043). Conversely, amongst those that did not achieve a pCR, the RFS was superior amongst BRCA1/2 carriers (Log-rank p=0.024). No difference in RFS were noted amongst BRCA1/2 carriers with or without pCR (Log-rank p=0.712), while in the non-carrier group RFS was superior for those achieving pCR compared with those not displaying a pCR (Log-rank p<0.0001). Preliminary translational data demonstrate ALDH1 over-expression in the BRCA1/2 carriers pre-treatment biopsies but not in the non-carriers. Conclusions: BRCA1/2 associated TN BC differs to non-BRCA TN in chemo-sensitivity as demonstrated by superior pCR, We demonstrate here for the first time that pCR in BRCA1/2 carriers, is not a surrogate for RFS as opposed to pCR in non-BRCA TN BC. The chemo-sensitivity in BRCA associated TNBC may increase the mutational spectrum in these tumors due to predisposition to DNA breaks, resulting in selection of more aggressive, metastases prone clones, in addition, BRCA1/2 tumors may be enriched for breast cancer stem cells.
Development of skin rash within the 1st week is a potential surrogate marker of therapeutic effect in afatinib monotherapy in patients with EGFR-mt non-small-cell lung cancer (NSCLC): Okayama Lung Cancer Study Group Experience.
Authors: Kenichiro Kudo, Katsuyuki Hotta, Akihiro Bessho, Naoyuki Nogami, Toshiyuki Kozuki, Shoichi Kuyama, Koji Inoue, Shingo Harita, Toshiaki Okada, Kenichi Genba, Masanori Fujii, Naohiro Oda, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2015)

e19051 Background: EGFR-TKI, gefitinib or erlotinib, is a key drug in pts with EGFR-mt NSCLC. Its efficacy would be predicted by development of skin rash [J Clin Oncol 2006].). However, although afatinib, 2nd generation EGFR-TKI, has proved to be effective [Lancet Oncol 2015], it has not been fully evaluated if the occurrence of any toxicity is a potential surrogate for its efficacy. Now, we investigated a potential association between development of toxicity and efficacy of afatinib. Methods: We retrospectively studied 49 pts with EGFR-mt NSCLC who received afatinib therapy between 2014 and 2015. Relationship with several toxicities and tumor response was examined by chi-square test. To avoid the potential bias of early treatment failure, we excluded pts who failed to continue afatinib for more than 1week. Results: Pt demographics were as follows: men, 17; median age, 69 yrs; PS 0-1, 40; stage IV, 41; Ad, 49; prior TKI use, 26; exon19, 28. The ≥ G2 adverse events (AEs) were hepatitis in 2 pts (4%), skin rash in 17 pts (35%), diarrhea in 19 pts (39%), paronychia in 17 pts (35%), and mucositis in 15 pts (31%). Of these, 1 pt (2%; hepatitis), 5 pts (10%; skin rash), 12 pts (25%; diarrhea) and 4 pts (8%; mucositis) developed ≥ G2 AEs within the first week. As for overall response, 21 (43%) of 49 pts had partial response. In association with AEs and antitumor effect, pts who had ≥ G2 skin rash within the first week tended to have better tumor response as compared with those who did not have (80% v 39%; p = 0.077). Conclusions: We demonstrated that early development of skin rash would predict the response to afatinib monotherapy.
Effect of postoperative chemotherapy (CT) on survival in patients (pts) with resected rectal cancer who received neoadjuvant therapy.
Authors: Christina Sing-Ying Wu, Lai Wei, Katherine Glass, John Wilson, Sherif Abdel-Misih, Terence Marques Williams, Ludmila Katherine Martin, Sigurdis Haraldsdottir, Alan Harzman, Syed Husain, Carl Richard Schmidt, Mark Arnold, Richard M. Goldberg, Tanios B. Bekaii-Saab
Journal: Journal of Clinical Oncology (2013)

e14535 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August, 2005 to July, 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19% N1 or N2, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]
Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer.
Authors: Andrea Cercek, Cara Siegel, Diane Lauren Reidy, Leonard Saltz
Journal: Journal of Clinical Oncology (2012)

e14112 Background: The gonadotoxicity of oxaliplatin-based chemotherapy is largely unknown. Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer (crc) survivors of premenopausal and child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of FOLFOX induced amenorrhea in women age 50 or younger treated with adjuvant therapy for colorectal cancer. Methods: A search of computerized pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011 . Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. Results: Seventy three patients returned the questionnaire. Twenty four patients were excluded from analysis; 19 were treated with radiotherapy, 1 patient had undergone bilateral oophorectomy, 1 had a hysterectomy and 3 stopped menstruating prior to diagnosis. Forty nine patients were analyzed. In total, 41% experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea approximately one year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients age 40 or older than in patients under 40 (59% vs 31% (p=.17) and 24% vs 13% (p=.33), respectively). Conclusions: In this retrospective study, it appears that the incidence of FOLFOX chemotherapy induced amenorrhea is increased with age. Due to the small sample size the study may be underpowered to detect a statistical difference. Prospective studies are planned to more accurately characterize the impact of FOLFOX on early menopause and fertility.
Predictive value of integrative epigenetic profiling in metastatic melanoma (MM) patients (p) treated with BRAF/MEK inhibitors (BMI) and chemotherapy (CT).
Authors: Jose Luis Manzano, Anna Martinez Cardús, Maria Teresa Fernandez-Figueras, Aram Boada, Jose Luis Cuadra-Urteaga, SebastiÃÂ¡n MorÃÂ¡n, Cristina Buges, Maria de los Llanos Gil, Laura Layos, Alberto Indacochea, Laia VilÃ Martinez, Max Hardy, Iris Teruel, Eva Martinez-Balibrea, Manel Esteller
Journal: Journal of Clinical Oncology (2015)

e20059 Background: The treatment of MM has evolved over the last four years to include novel treatments in addition to CT, requiring predictive markers of response. Treatment with BMI provides benefit in overall survival, although with early resistance development. The value of CT in these p is limited. Hence, the aim of this work is to perform an integrative epigenetic profiling as predictive tool of resistance to treatment in MM p treated, in one hand with BRAF/MEK inhibitors, and in the other hand, CT-based treatment. The final goal is obtain epigenetic biomarkers to optimize treatment selection and p's outcome. Additionally, we pretend to identify epigenetic biomarkers related to metastatic process. Methods: It was analyzed 35 paraffin-embebbed primary tumor tissue samples from 35 MM p, 20 of them had been treated with BMI and 15 with CT. Additionally, it was analyzed the paired metastasis tissue for a half of them to study the effect of epigenetics in metastatic process. Epigenetic screening was performed using DNA methylation array technology Infinium 450K from Illumina, following the manufacturer's instructions. Data analysis was performed using R statistics software. Results: Comparing responders and non-responders p, we obtained an epigenetic profile associated with drug resistance prediction for each treatment strategy (target therapy and CT). Regarding metastatic process, we compared primary tumor with paired metastasis identifying a set of epigenetic biomarkers candidates. In all cases, it was considered as significant those methylation changes with beta-values differences over 10% and ANOVA with p-value under 0.01. Conclusions: According our high-throughput epigenetic screening, we have been capable to discriminate in a cohort of MM p between responders and refractory tumors focusing in DNA methylation changes. Moreover, epigenetic changes are also presented as a strategy to understand better the metastasis process in this neoplasia. Hence, integrated epigenetic screening could be a useful tool to optimize treatment selection. Nevertheless, further studies are warranted to elucidate their potential role in the clinical setting.
Trends in hepatitis B virus screening in a large U.S. cancer center.
Authors: Jessica Hwang, Michael Fisch, Anna Lok, Hong Zhang, John Vierling, Maria Suarez-Almazor
Journal: Journal of Clinical Oncology (2012)

e19631 Background: In the past 5 years, national hepatitis B virus (HBV) screening recommendations differed with respect to populations that should be screened to prevent reactivation, which may occur in patients with hematologic or solid malignancies. Previous studies showed that up to 60% of oncologists are not screening. We sought to compare the HBV screening patterns over time in a large US cancer center in relationship to the 2010 ASCO Provisional Clinical Opinion (PCO) which includes recommendations to screen patients with hematologic malignancies prior to receipt of certain cancer therapies. Methods: Retrospective cohort study of patients with newly diagnosed cancer registered at MD Anderson (1/04 - 4/11) who received chemotherapy. Screening was defined as testing for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) before chemotherapy. We compared screening rates among patients with hematologic malignancies vs. solid tumors. Using Chi-square tests, we compared screening rates before and after the PCO. A generalized linear regression model was used to detect changes in the rates of HBV screening over time for patients based on cancer type. Results: During our study period, 141,877 patients were registered, and 13% (n=18,877) received chemotherapy. Of these, 18% (n=3475) had HBV screening: 1% (n=42) were HBsAg+/anti-HBc+, while 7% (n=242) were HBsAg-/anti-HBc+. The overall screening rate significantly increased from 18% before the PCO to 23% after the PCO (p&lt;0.01). After the PCO, the screening rate among patients with hematologic malignancies increased from 69% to 79% (p&lt;0.01), and among patients with solid tumors from 3.8% to 5% (p=0.05). Overall, the rate of increase of HBV screening among patients with hematologic malignancies was higher than for patients with solid tumors (p&lt;0.01). Conclusions: Rates of HBV screening increased after the PCO, although the rate of increase was greater among patients with hematologic malignancies than solid tumors. Because reactivation is an important and preventable cause of morbidity and mortality in patients with either hematologic or solid malignancies, further efforts are needed to screen patients at risk by identifying predictors of reactivation of HBV infection.
Mesothelin expression and survival outcomes in triple-receptor negative breast cancer.
Authors: Napa Parinyanitikul, George R. Blumenschein, Yun Wu, Xiudong Lei, Mariana Chavez-Mac Gregor, Melody L. Smart, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2013)

e12002 Background: Mesothelin is an ideal tumor-associated marker for the development of targeted therapy due to its limited expression in normal tissues. Identify the frequency of mesothelin expression in triple negative breast cancer may lead the path to customize the drug development in this lack of effective targeted subgroup. The aim of this study was to evaluate mesothelin expression in triple-negative breast cancer (TNBC) and its correlation with survival outcomes. Methods: Mesothelin expression was completed using immunohistochemistry on formalin fixed paraffin tumor sections, and quantified by H-score. An H-score &gt;10 was considered positive. Patient’s characteristics were compared by mesothelin expression. Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results: Median age was 52 years. Of the 109 TNBC, 37 (34%) were positive for mesothelin expression. There were no differences on patient/tumor characteristics by mesothelin expression with the exception of high frequency of lymphovascular space invasion in mesothelin-negative tumors (P=0.03). At a median follow up of 75.8 months 20 (18.3%) had experienced a recurrence and 22 (20.2%) had died. Five-year progression-free survival was 87% and 92% in patients with mesothelin-positive and mesothelin-negative tumors (P=0.43), and 5-year overall survival was 85% and 91% patients with mesothelin-positive and mesothelin-negative tumors (P=0.57), respectively. Mesothelin expression was not independently associated with PFS or OS in TNBC after adjustment for other patient and disease characteristics including grade, pathologic stage, lymphovascular invasion, and adjuvant chemotherapy survival outcomes. Conclusions: There was mesothelin expression in 34% of TNBC. No significant differences in the clinical characteristics by mesothelin expression with the exception of high lymphovascular invasion in mesothelin-negative tumors. Mesothelin expression did not correlate with survival outcomes in TNBC.
MM-005: Phase 1 trial of pomalidomide (POM), bortezomib (BORT), and low-dose dexamethasone (LoDEX [PVD]) in lenalidomide (LEN)-refractory and proteasome inhibitor (PI)-exposed myeloma.
Authors: Paul G. Richardson, Craig Hofmeister, Noopur S. Raje, David Samuel DiCapua Siegel, Sagar Lonial, Jacob Laubach, Yvonne Adeduni Efebera, David H. Vesole, Ajay K. Nooka, Jacalyn Rosenblatt, Mohamed H. Zaki, Ye Hua, Yan Li, Sheetal Shah, Jianming Wang, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2014)

8589 Background: Combination treatment (Tx) with IMiDs immunomodulatory agents and PIs demonstrated substantial efficacy in myeloma patients (pts) (Richardson, Blood, 2010). MM-005 was designed to identify the optimal PVD dose for a phase 3 trial (MM-007) comparing PVD vs. BORT + LoDEX in RRMM pts. A secondary objective examined subcutaneous (SC) BORT as part of PVD Tx. Methods: Eligible pts had 1-4 prior Tx lines, including ≥2 consecutive cycles (C) of LEN and a PI. Pts must have been LEN-refractory and PI-exposed but not BORT refractory. MTD was determined using a 3+3 design; an SC BORT cohort was added at the MTD. Tx continued until PD or unacceptable AE. MTD was the primary endpoint; additional endpoints included safety, overall response rate (ORR; ≥ partial response [PR]), time to response (TTR), duration of response (DoR), and pharmacokinetics. Results: The trial is fully enrolled (N=28): 22 pts in intravenous (IV) BORT and 6 pts in SC BORT cohorts. Median prior Tx was 2 (1-4). No dose-limiting toxicities (DLTs) were observed. Recommended PVD dose (21-day C) is POM 4 mg D1-14, BORT 1.3 mg/m2 on D1, 4, 8, 11 for C1-8; D1, 8 for C9+, and LoDEX 20 mg (10 mg for pts > 75 y) on D1-2, 4-5, 8-9, 11-12 for C1-8; D1-2, 8-9 for C9+. Most common grade (Gr) 3-4 AEs included (IV cohorts): neutropenia (36%) and thrombocytopenia (27%); (SC cohort): 7 Gr 3 AEs occurred in one pt each; no Gr 4 AEs were observed. Peripheral neuropathy (PN) in IV cohorts was 0% (Gr 3-4), 14% (Gr 2), and 32% (Gr 1); 1 pt reported Gr 2 PN (SC cohort). No pt discontinued due to Tx-related AEs. ORR (IV cohorts) was 71% (38% ≥ very good PR [VGPR]), median TTR was 1 C, and median DoR was 11 C. Preliminary (median 5 C) ORR for SC pts was 67% (1 PR, 2 VGPRs, 1 complete response). 4 of 6 pts receiving BORT SC still remain on Tx; 1 of 4 pts has not yet responded. BORT administration route (IV/SC) did not impact POM exposure, which was within the range previously observed. Long-term follow-up will be presented. Conclusions: PVD was effective and well tolerated across all cohorts in LEN-refractory/BORT-exposed pts with no DLTs or discontinuations due to Tx-related AEs to date. PVD is now under evaluation in the MM-007 phase 3 trial. Clinical trial information: NCT01497093.
The impact of oral Polypodium leucotomos extract on ultraviolet B response: A human clinical study
Authors: Indermeet Kohli, Rubina Shafi, Prescilia Isedeh, James L. Griffith, Mohammed S. Al-Jamal, Narumol Silpa-archa, Bradford Jackson, Mohammed Athar, Nikiforos Kollias, Craig A. Elmets, Henry W. Lim, Iltefat H. Hamzavi
Journal: Journal of the American Academy of Dermatology (2017)
Aberrant Regulation of the LEF-1 Locus in Monoclonal B Cell Lymphocytosis (MBL) and Chronic Lymphocytic Leukemia (CLL): A Possible Role for Epigenetic Regulation.
Authors: Albert Gutierrez, Renee Tschumper, Tait D. Shanafelt, Jeanette Eckel-Passow, Neil E. Kay, Diane F. Jelinek
Journal: Blood (2009)