tbuckley/cabot-search huggingface dataset:
Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta analysis of the literature
Authors: G. Dranitsaris, M. Johnston, S. Poirier, T. Trudi Schueller, T. Savage, D. Debbie Milliken, E. Green, W. Evans, B. Zanke
Journal: Journal of Clinical Oncology (2005)

6082 Background: It has been well documented in the literature that cancer patients receiving certain chemotherapy drugs are at an increased risk for developing secondary malignancies. This concern has also been extended to health care staff involved in the preparation and administration of cancer therapy. To evaluate this risk, a systematic review and meta analysis of the literature was conducted to test the hypothesis that health care providers involved in the preparation and administration of chemotherapy are at an increased risk of cancer, reproductive complications and acute toxic events. Methods: A structured literature search of Medline, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews and Healthstar was performed from 1966 to October 2004 for human epidemiological studies evaluating the risk of toxic events in health care workers exposed to cytotoxic drugs. Raw data and adjusted odds ratios (OR) reported in eligible studies were combined using a random effects model to calculate point estimates and 95% confidence intervals for each potential risk outcome. Results: The systematic review identified 14 studies evaluating the outcomes of interest, 7 of which were suitable for statistical pooling. Due to lack of evidence, we were unable to estimate a pooled odds ratio for the risk of cancer and acute toxic events. However, no statistically significant association was detected between exposure to cytotoxic drugs and; congenital malformations (OR=1.64; 95%CI: 0.91–2.94) and stillbirths (OR = 1.16; 95%CI: 0.73–1.82). In contrast, an association was identified between exposure to chemotherapy and spontaneous abortions (OR=1.46; 95%CI: 1.11–1.92). Conclusions: The results of this systematic review identified a small incremental risk for spontaneous abortions in female staff working with cytotoxic agents. Health policy decision makers should effectively communicate the magnitude of this risk to their staff and implement cost effective interventions for its reduction or elimination. No significant financial relationships to disclose.
Male breast cancer: Overall survival in a single institution.
Authors: Anke Bergmann, Marcelo Adeodato Bello, Celia Regina Andrade Costa, Paulo Francisco Mascarenhas Bender, Luiz Claudio Santos Thuler
Journal: Journal of Clinical Oncology (2012)

93 Background: Male breast cancer is an uncommon disease and the therapy is mainly based on what is know from female breast cancer. Objective: To investigate the clinicopathologic characteristics of male breast cancer and the overall survival in a single institution. Methods: The clinical data and survival status of 75 male breast cancer treated in a Brazilian public cancer hospital from 2000 to 2009 were collected. The association with clinicopathological characteristics and overall survival was analyzed using Kaplan-Meier curves and the Cox proportional hazards regression (enter method) was used to assess survival differences after adjusting for confounders. The study was approved by National Cancer Institute Research and Ethics Committee (number 128/11). Results: The median patient age was 64 years (range 33-86). Estrogen receptor (ER) was positive in 58 (77.3%) patients, while progesterone receptor (PR) were positive in 47 (62.7%). Histology type was ductal infiltrant carcinoma for 57 (76.0%) and 51 (68.0%) patients underwent surgery. The median follow-up period was 43,1 months (range 2.7-147.8). The median survival from the diagnosis of breast cancer was 97.0 months (95%CI 53.6 -140.4) with a 61.7% 5-year overall survival (OS). In the final Cox regression model, independent factors associated with increased risk of death were metastasis at diagnosis (HR = 18.1; 95%CI: 5.9-55.2), ≥ 65 years old (HR = 4.3; 95%CI: 1.7-10.5); tumor stages ≥ IIb (HR = 3.5; 95%CI: 1.3-9.7) and smoking (HR = 1.6; 95%CI: 1.04-2.6). Conclusions: Invasive ductal carcinoma is the main pathologic type. The median survival from the diagnosis of breast cancer was 97.0 months and metastasis at diagnosis, patient age, tumor stage and smoking are independent prognostic factors.
Nimotuzumab and vinorelbine concomitantly to radiation and as maintenance for diffuse pontine glioma in childhood: Results from a series of 12 patients.
Authors: M. Massimino, V. Biassoni, L. Gandola, E. Schiavello, E. Pecori, F. Bach
Journal: Journal of Clinical Oncology (2011)

9557 Background: Childhood MRI diagnosed diffuse pontine glioma have a universally known awful prognosis. After joining a previous trial with nimotuzumab and radiation, reported also at ASCO (2008), and continuing for a total of 37 patients from January 2006-June 2009 according to this new combination, we obtained median PFS 7 months, median OS 11 months, thus entirely consistent with best literature data and those previously reported by ourselves (Massimino 2008). All treatment was given on an outpatient basis, without any side effects correlated with the use of nimotuzumab. Two of 37 children were alive without tumor progression 17 and 27 months after diagnosis. Methods: In a subsequent mono-institutional experience, exploring add-on strategies, we began a pilot protocol on a compassionate case-by-case basis, using nimotuzumab together with vinorelbine, combined with radiation, adopting consolidation courses with the same timing as in the previous international radiation plus nimotuzumab protocol. Vinorelbine was at a dose of 20 mg/sqm/weekly together with nimotuzumab at the standard dose of 150 mg/sqm during the 6 weeks of radiotherapy, and 25 mg/sqm in any other week, with the same dose of nimotuzumab during the consolidation courses, planned until tumor progression or for a duration of two years. Results: We have so far treated 12 children, 7 males and 5 females, age range 3-13 years, enrolled according to the standard MRI inclusion criteria. After a mean follow-up of 10 months, 10/12 were alive, their PFS at 9 months was 69 ± 21% and their OS at 12 months was 81.5 ± 12 %. According to MRI evaluation, in 10/12 children evaluable for response, 7 had partial remission and 3 stable disease with 100% symptom amelioration. The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. As in the case of nimotuzumab alone, all children were treated on an outpatient basis. Conclusions: The observation time for this new series is long enough to give the impression that this combination has promise, with statistically significant differences with previous reported experiences.
Advanced stage serous papillary ovarian cancer: Impact of histological grade in clinical outcomes
Authors: J. P. Orezzoli, E. G. Munro, L. R. Duska
Journal: Journal of Clinical Oncology (2008)

16579 Background: Grade of tumor in early stage ovarian cancer has prognostic value and dictates post-operative adjuvant therapy. The purpose of this study is to determine if grade is of prognostic significance in serous cancer of the ovary in advanced stage disease. Methods: All grade 1 ovarian carcinomas stages III or IV seen at an academic university practice between 1993 and 2003 were identified. Patients with grade 1 advanced stage serous carcinoma were matched with grade 3 controls by age and stage using a ratio of 1 case to 3 controls. The data were analyzed using the chi-squared test, Fisher’s exact test, and the Kaplan-Meier survival method. Results: A total of 35 patients with grade 1 ovarian cancer were identified. Only 9 of these had serous tumors, and 7 of those 9 had advanced disease. The 7 cases were matched with 21 grade 3 controls. All patients received comprehensive surgical staging and platinum-based first line chemotherapy. Over 80% of women in each group were optimally cytoreduced. All 7 of those with grade 1 disease responded to their initial course of chemotherapy, while 2 of the 21 patients with grade 3 progressed during their initial treatment. Though progression free survival in months showed a trend toward longer for women with grade 1 tumors (median = 28 [95% C.I. 13–43]) compared to those with grade 3 tumors (median = 21 [95% C.I. 16–26]), this trend was not significant (p = 0.652). Overall survival in months for grade 1 tumors was significantly longer with a median of 104 (95% C.I. 31–177) versus 57 (95% C.I. 35–79) for grade 3 tumors (p = 0.013). When only the patients who had an optimal cytoreduction were considered, we could not find any statistically significant survival difference. Recurrence rate was similar in both groups. Conclusions: Women with advanced grade 1 ovarian cancer are equally likely to have disease recurrence when compared to those with grade 3 disease, suggesting that grade is not prognostically important in advanced stage disease. However, the overall survival of those with grade 1 disease is significantly longer when compared to those with grade 3 disease, even in this small study. This finding is worthy of further study with larger patient groups, perhaps through the Gynecology Oncology Group (GOG) database. No significant financial relationships to disclose.
Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy.
Authors: Elizabeth FitzSullivan, Henry Mark Kuerer, Roland L. Bassett, Elizabeth Ann Mittendorf, Min Yi, Kelly Hunt, Gildy Babiera, Abigail Suzanne Caudle, Dalliah M. Black, Isabelle Bedrosian, Funda Meric-Bernstam, Rosa F. Hwang
Journal: Journal of Clinical Oncology (2013)

53 Background: Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have a low rate of regional recurrence when treated with breast conserving surgery and radiation. Patients who fit criteria for the ACOSOG Z0011 trial are candidates to avoid completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment, including CLND and/or radiation therapy (XRT). Methods: We utilized an institutional database to identify patients who were treated with a TM for invasive breast cancer and had a positive SLN from 1994-2010. CLND was defined as removal of 10 or more lymph nodes. Clinicopathologic factors were analyzed and the rate of regional recurrence as well as overall and disease-free survival were determined. Results: A total of 730 patients with invasive breast cancer and a positive SLN were treated with TM including 71 patients who did not have CLND or XRT and 27 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The 10-year actuarial rate of regional recurrence was not significantly different for patients who received no further axillary treatment when compared to those who underwent CLND and XRT (4.9% vs 3.1%) or to those who underwent CLND without XRT (4.9% vs 1.4%). Survival was not significantly different between patients who did not receive further axillary treatment compared to those who underwent CLND without XRT or those who underwent both CLND and XRT. Using a nomogram previously developed by our group, the predicted probability of additional non-SLN involvement was significantly lower for patients who did not undergo CLND compared to those who did (10% vs. 23%, p&lt;0.0001). Conclusions: In select patients with early stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.
One-step optogenetics with multifunctional flexible polymer fibers
Authors: Seongjun Park, Yuanyuan Guo, Xiaoting Jia, Han Kyoung Choe, Benjamin Grena, Jeewoo Kang, Jiyeon Park, Chi Lu, Andres Canales, Ritchie Chen, Yeong Shin Yim, Gloria B Choi, Yoel Fink, Polina Anikeeva
Journal: Nature Neuroscience (2017)
A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer.
Authors: Takashi Sasaki, Hiroyuki Isayama, Yousuke Nakai, Naminatsu Takahara, Dai Akiyama, Hiroshi Yagioka, Hirofumi Kogure, Saburo Matsubara, Yukiko Ito, Natsuyo Yamamoto, Naoki Sasahira, Kenji Hirano, Nobuo Toda, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2013)

258 Background: The data of second-line treatment for advanced biliary tract cancer is still limited. We have previously reported feasibility study of gemcitabine and cisplatin combination therapy for refractory biliary tract cancer (Sasaki T et al, Invest New Drugs 2011). In this feasibility study, only 20 pts were enrolled, and both second-line and third-line treatments were involved. Therefore, we conducted a retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment to clarify the treatment outcome of this combination therapy. Methods: Pts with advanced biliary tract cancer who were refractory to gemcitabine containing regimen were enrolled in this study. Gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 were administered intravenously on days 1 and 8 repeated every 3 weeks. Results: Fifty-nine pts were enrolled in this study. Patient characteristics were: median age 68 (range 25-84); male/female 32/27; performance status 0/1/2 (15/38/6). The primary tumor site was; 24 pts in gallbladders, 18 pts in intrahepatic bile ducts, 15 pts in extrahepatic bile ducts, and 2 pts in ampulla of Vater. The numbers of the pts with locally advanced, metastatic, and recurrent cases were 8, 44, and 7, respectively. Four pts received gemcitabine monotherapy and 55 pts received gemcitabine and S-1 combination therapy as first-line treatment. Response rate and disease control rate were 1.7% and 56.0%, respectively. The median time-to-progression and median overall survival were 3.9 months (95%CI, 2.6 – 5.0 months) and 6.4 months (95%CI, 4.9 – 8.0 months), respectively. Conclusions: Gemcitabine and cisplatin combination therapy showed a moderate efficacy for the treatment of advanced biliary tract cancer as second-line treatment.
Docetaxel and cisplatin therapy and survival outcomes with patients with relapsed and refractory squamous cancer.
Authors: K. Suzuki
Journal: Journal of Clinical Oncology (2011)

e16005 Background: The standard salvage chemotherapy excluding certuximab for recurrent, unresectable or matastatic head and neck squamous cancer (SCCHN) is controversial. We investigated that docetaxel and cisptlatin therapy (DC) gave better prognosis than (S-1), docetaxel, cisplatin and fluorouracil therapy (DCF), paclitaxel and carboplatin therapy (PC) and docetaxel therapy (DOC) as salvage chemotherapy for SCCHN. Methods: We retrospectively reviewed 113 patients with the recurrent, unresectable or matastatic SCCHN treated with DC, S-1, DCF, PC and DOC from 2007 January to 2009 December in our institution. Primary endpoint is overall survival (OS) since salvage chemotherapy starts. Prognostic factors are analyzed. We define that original site A is nasopharynx, oropharynx and hypopharynx and original site B is tongue and the other sites. OS was analyzed by Cox’s stepwise proportional hazard regression method. Results: Median age is 60.1 year (range 21.4 - 81.6). Median follow-up time is 13.9 month (95%CI: 9.6 - 18.1). Original sites are 36 hypopharynx, 21 oropharynx, 10 nasolarynx, 24 tongue and 22 the others. Salvage chemotherapies are 30 DC, 31 S-1, 22 DCF, 22 PC and 8 DOC. OS of DC arm is 27.4 month, S-1 arm is 16.5 month, DCF arm is 11.7 month, PC arm is 9.2 month and DOC arm is 11.2 month, which is not significant (p= .217). Poor prognostic factors about OS are original site B (p= .015), Hb < unl (p= .049), interval between primary therapy and salvage therapy > 1 year (p= .035) and CRP > unl (p= .033). Among the patients with SCCHN of original site A, DC predicts good prognosis than the other 4 arms significantly (p= .035). Among the patients with SCCHN of original site B, DC does not predict good prognosis (p= .670). Among the patients with normal CRP level, DC does predict good prognosis significantly (p= .038). Salvage chemotherapy is not independent prognostic factor about OS significantly according to classification of anemia and interval between primary therapy and salvage therapy. Conclusions: DC therapy predicts better survival among the patients with relapsed and refractory squamous cancer of nasopharynx, oropharynx and hypopharynx significantly.
Identification of serum protein biomarkers for small cell lung cancer.
Authors: Y. Kim, P. Khatri, K. Park, J. Dudley, J. Sage, A. Butte
Journal: Journal of Clinical Oncology (2011)

e21005 Background: Lung cancer is the most common cause of cancer mortality in the world. Small cell lung cancer (SCLC) is characterized by rapid progression, extensive metastasis, and very high mortality (95%). The fact that SCLC prognosis improves when it is detected early underscores the urgent need for a non-invasive method such as serum protein quantification for timely diagnosis. Many researchers have tried to identify serum protein biomarkers for various diseases using a proteomics approach, but challenges such as low sensitivity of mass spectrometry, variable protein concentrations in serum, small sample sizes, and clinical confounding factors still exist. We hypothesized that integrative meta-analysis of a number of SCLC gene expression data sets would increase the sample size as well as address the issue of confounding factors, which in turn will allow us to identify serum protein biomarkers for SCLC. Methods: We performed meta-analysis on 9 SCLC gene expression data sets consisting of total 749 samples. We characterized the genes discovered from meta-analysis to identify candidate serum protein biomarkers and utilized ELISA to validate our in silico findings in human SCLC patient serum samples in vivo. Results: Meta-analysis of gene expression data revealed 100 genes (false discovery rate < 0.1) that are over-expressed in SCLC. These included not only ASCL1, a well-known neuroendocrine marker, but also possible drug targets such as HDAC1 and RXRG. We demonstrated that this meta-analysis approach is more successful at identifying over-expressed genes in SCLC compared to widely used Significant Analysis of Microarrays method. We selected a subset of genes from our initial genes based on their presence in serum, expression in SCLC mouse model, and potential involvement in SCLC pathogenesis. We are currently conducting ELISA of human SCLC patient serum samples to validate our predicted serum protein biomarkers. Conclusions: Candidate SCLC serum protein biomarkers were identified using meta-analysis of gene expression profiles. The methods that we described in this study will enable us to discover serum protein biomarkers for other diseases and potentially apply them clinically for their early detection and better diagnosis in the future.
Promoting palliative care access to persons with cancer: A model for mapping statewide services.
Authors: Constance Dahlin, Joshua Nyambose, Gail Merriam, Cherline Gene
Journal: Journal of Clinical Oncology (2015)

127 Background: The CDC comprehensive cancer initiatives value comprehensive quality care within its mission and program development. Currently, over 75% of hospitals in the United States have palliative care services for cancer patients (CAPC 2011). In order to promote access to quality palliative care in the community outside the hospital, an evaluation is essential. The CDC model of comprehensive cancer care and prevention control structure is an appropriate mechanism to perform such an evaluation. From 2014-2015, the Massachusetts Comprehensive Cancer and Prevention Control Network Palliative Care Workgroup performed a survey to hospitals, home health agencies, hospices, long term care facilities, and community providers to determine palliative care services available to cancer patients across the state. Methods: Using the National Consensus Project for Quality Palliative Care Clinical Practice Guidelines, a robust palliative survey tool was created by the Massachusetts Comprehensive Cancer and Prevention Control Palliative Care Workgroup. It was individualized to each of the following settings - hospitals, home health organizations, hospices, skilled nursing facilities, and community health agencies. Follow-up telephonic key informant interviews regarding palliative care services were conducted within the various settings, service organizations, and insurers. Results: The results of qualitative and quantitative data will be concluded in August. Initial results reveal significant disparities in access to palliative care across by geography and setting of care. Hospices and hospitals had the most access to palliative care services. Long term care settings and community health settings had the least access. Conclusions: Data reveals disparities in palliative care access within Massachusetts by geography, race, and setting of cancer care. This data will serve as the basis of regional networks to promote better access to palliative care for cancer patients across all settings. It is hoped this evaluation process will serve as a model for other states to perform a similar evaluation.
Comparison of PFS and safety for Asian compared to North American and European populations in the phase III trial of pazopanib versus sunitinib in patients with treatment-naive RCC (COMPARZ).
Authors: Jun Guo, Jie Jin, Yiran Huang, Jin-Wan Wang, Ho Yeong Lim, Hirotsugu Uemura, Sun Young Rha, Hsi Chin Wu, Rocco Crescenzo, Keith C. Deen, Lauren McCann, Robert John Motzer
Journal: Journal of Clinical Oncology (2013)

366 Background: Pazopanib (P) and sunitinib (S) are multi-kinase angiogenesis inhibitors that positively impact progression-free survival (PFS) in patients (pts) with metastatic renal cell carcinoma (mRCC) (NEJM 2007 356:115; JCO 2009 29:475). The safety profile of multi-kinase angiogenesis inhibitors has been shown to vary depending upon ethnic background (Oncology 2011 80:395). Methods: Treatment naïve pts with clear cell mRCC and measurable disease were randomized 1:1 to P, 800mg QD continuous dosing or S, 50 mg QD for 4 weeks followed by 2 weeks off treatment. Primary endpoint was PFS. A subgroup analysis compared PFS (Cox analysis with treatment as only covariate) and AEs between the Asian, North American (NA), and European (EU) populations. Of the 1,110 pts 367 were from Asia (188 P, 179 S). Results: PFS in the Asian subgroup was consistent with NA and EU. HR (95% CI): Asia 1.07 (0.81, 1.42); NA 1.18 (0.90, 1.53); EU 1.03 (0.79, 1.36). Median PFS mos (95% CI) P: Asia 8.4 (8.3,11.1); EU 8.5 (8.0, 11.0); NA 8.3 (6.6, 11.0); S: Asia 11.1 (8.2, 14.3); EU 9.0 (8.1, 12.9); NA 10.5 (8.2, 13.4). AEs in &gt;25% of pts in any arm in any region and a difference of 15% between any region within an arm are shown. Conclusions: In both arms, PFS in the Asian population was similar to NA and EU. In the Asian population increased incidences of hematotoxicity, hypertension, HFS, LFT increase, proteinuria, and decreased incidences of GI symptoms, headache were observed in both arms. Consistent with NA and EU, more frequent AEs in the Asian population (&gt;10% difference between arms): ALT increase (P); HFS, thrombocytopenia, neutropenia (S). [Table: see text]