tbuckley/cabot-search huggingface dataset:
The effect of chemotherapy (CT) and external beam radiotherapy (RT) on bone marrow (BM) toxicity of radionuclides in the treatment of bone metastases secondary to breast cancer
Authors: D. E. Heron, K. Gerszten, A. M. Brufsky, M. Kurman
Journal: Journal of Clinical Oncology (2004)

796 Background: Bone metastases are commonly seen in patients with metastatic breast cancer. Radionuclide therapy has been shown to alleviate the pain of bone metastases but may be associated with BM toxicity, particularly thrombocytopenia. Because many patients with breast cancer and bone metastases also receive CT and RT, we examined the effects of these other treatments on the BM of samarium (Sm)-153-EDTMP (Quadramet®). Methods: A retrospective review of patients (pts) with breast cancer and bone metastases who had received Sm-153-EDTMP was undertaken. Dates of CT and RT, as well as CT regimens were noted. Pre-and post-radionuclide platelet (PLT) and WBC counts were compared, as were the percent decreases in these parameters. Results: Forty-eight pts received 79 courses of Sm-153-EDTMP. Twenty-eight pts received 29 different chemotherapy regimens prior to treatment with Sm-153-EDTMP. Pre- and post-treatment data were available for 21 courses of Sm-153-EDTMP in 20 patients who received CT and RT and for 6 courses of Sm-153-EDTMP in 5 patients who received CT alone. For the entire cohort, the mean ± SEM baseline PLT count was 268 ± 12 x 103/μL, the mean nadir PLT count was 160 ± 10 x 103/μL and the mean percent (%) decrease in PLT count was 42%. The mean baseline WBC was 5.8 ± 0.23 x 103/μL, the mean nadir WBC was 3.7 ± 0.18 x 103/μL and the mean % decrease was 33%. The mean % decrease in PLT and WBC counts in patients receiving CT and RT was 45% and 41% respectively and the mean % decrease in PLT and WBC counts in patients receiving CT alone was 27% and 35%, respectively. The lowest nadir PLT count was 29 x 103/μL and the lowest nadir WBC was 1.3 x 103/μL. Median time to nadir was 28 days. Conclusions: Sm-153-EDTMP is well tolerated in patients with breast cancer who also receive CT and RT. BM toxicity is minimal with relatively small changes observed from pre-radionuclide levels of PLTs and WBCs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytogen Corp.
PH-METRÍA TELEMÉTRICA ENDOSCÓPICA (SISTEMA BRAVO®). ASPECTOS CLÍNICOS Y ENDOSCÓPICOS. RESULTADOS INICIALES
Authors: E Espinet Coll, C Hernández Ballesteros, JA Gómez Valero, C Vila Lolo, A Juan-Creix Comamala, D Maluenda Colomer, S Bacchiddu, J Nebreda
Journal: Endoscopy (2015)

La pH-metría esofágica ambulatoria de 24h es el método estándar para cuantificar el reflujo gastro-esofágico. Sin embargo, las molestias de la sonda, cierta incomodidad física y social y el registro limitado a 24h pueden subestimar el reflujo real. La pH-metría telemétrica consistente en la inserción endoscópica de un pequeño chip esofágico que mide el pH y trasmite los datos por radiotelemetría a un receptor externo, sin sonda nasal y permitiendo registros superiores a 24h.
The predictive value of [<sup>18</sup>F]-FDG PET in neoadjuvant chemotherapy for breast cancer.
Authors: Lingzhu Wen, Guochun Zhang, Shengli An, Chongyang Ren, Haitong Lv, Ning Liao
Journal: Journal of Clinical Oncology (2015)

e11529 Background: This study aimed to assess the value of [18F]-FDG PET in predicting pathological complete response (pCR) of breast cancer patients who underwent neoajuvant chemotherapy (NAC). Methods: Breast cancer patients diagnosed by core needle biopsy, who underwent NAC subsequently, with [18F]-FDG PET scanning both before starting after the completing of NAC, were retrospectively enrolled. Definitive surgery was performed for all patients with pCR status evaluated. Relative changes in maximum standardized uptake value (ΔSUVmax%) of breast tumor and axillary lymph node (ALN, if any) were calculated. Receiver operating characteristic (ROC) curves were used to assess the pCR predicting ability of ΔSUVmax%. Results: In total, 87 patients were enrolled with the mean age of 46 years. pCR was noted in 30 (34.5%) patients by postoperative pathological examination. Thirty-six (41.4%）patients was categorized as CR by PET scanning before definitive surgery. The area under the ROC curve (AUC) of ΔSUVmax% were 0.802 (95%CI 0.680-0.893, P < 0.0001), with the sensitivity of 61.90%, speciﬁcity of 87.50%. For the Luminal B（HER2-）subtype, the AUC was 0.907(P＝0.037，95％CI:0.750-1.000). We further found that, in the 41 patients diagnosed to have positive axillary lymph node (ALN) metastasis by pre-therapy PET/CT scanning, ΔSUVmax% also did very well in predicting the clearance of ALN metastasis, which AUC was 0.782(P = 0.0001, 95％CI 0.625-0.895) with the sensitivity of 83.33%(95% CI 51.6 - 97.9) and the speciﬁcity of 68.97%(95% CI 49.2 – 84.7). However, the predicting value of SUV changes was insignificant in other subtypes and in those with initially negative ALN. Conclusions: Relative SUV changes between pre-NAC and post-NAC [18F]-FDG PET scanning is able to predict pCR in luminal B (HER2-) subtype breast cancer, as well as clearance of ALN metastasis in patients with initially positive ALN.
Management of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in community services: Retrospective study of 130 patients from a single institution.
Authors: Ali Al-Ameri, Neema Patel, Zeyad Kanaan, Nairmeen Awad Haller
Journal: Journal of Clinical Oncology (2012)

e17004 Background: Acute myeloid leukemia (AML) is a heterogeneous disease resulting from accumulation of blast cells in the marrow Age greater than 75 years and cytogenetics are the most important factors in the prognosis, whereby increased age and monosomal karyotypes carry the worst prognosis The most favorable cytogenetics are patients with normal karyotypes and can receive standard therapy Aim Study the over survival (OS) of AML/High risk MDS treated according to standard of care at a community Service Methods: An IRB-approved retrospective study of AML &amp;High risk MDS patients treated at an Akron General Medical Center during 2002-2010 reviewed patient demographics diagnosis types/subtypes, treatment, and cytogenetics. Patients were classified as low-intermediate risk or high risk according to cytogenetics background using WHO criteria. Overall survival (OS) rates were determined by Kaplan-Meier Survival Analysis. Prognostic factors were evaluated by Log Rank analysis Results: Charts of 130 pts, we are able to classify 98 (75%) pts 52 (53%) as high risk and low-intermediate risk. 46(47%) low risk the latter include intermediate risk. Median age was 55 years (range: 19-90), 43 (45%) pts were older than 75 years. AML pts made up 71%, 45 patients (35%) in total had complex cytogenetics, and 15% had AML arise from MDS. Median survival overall was 22.4 weeks, 14.4 weeks for high risk and 53.8 weeks for low risk (p&lt;0.01). Median survival for pts greater than 75 years was 11.5 weeks compared to 35.8 weeks for those younger than 75 years (p&lt;0.05) Conclusions: Overall survival was low in the study population, with survival in high risk patients and those greater than 75 years being significantly lower than low risk and younger than 75 years respectively These results may support early referral to a specialized center, possible clinical trials
Klotho expression in osteocytes regulates bone metabolism and controls bone formation
Authors: Hirotaka Komaba, Jovana Kaludjerovic, Dorothy Z. Hu, Kenichi Nagano, Katsuhiko Amano, Noriko Ide, Tadatoshi Sato, Michael J. Densmore, Jun-ichi Hanai, Hannes Olauson, Teresita Bellido, Tobias E. Larsson, Roland Baron, Beate Lanske
Journal: Kidney International (2017)

Osteocytes within the mineralized bone matrix control bone remodeling by regulating osteoblast and osteoclast activity. Osteocytes express the aging suppressor Klotho, but the functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression in osteocytes as a potent regulator of bone formation and bone mass. Targeted deletion of Klotho from osteocytes led to a striking increase in bone formation and bone volume coupled with enhanced osteoblast activity, in sharp contrast to what is observed in Klotho hypomorphic (kl/kl) mice. Conversely, overexpression of Klotho in cultured osteoblastic cells inhibited mineralization and osteogenic activity during osteocyte differentiation. Further, the induction of chronic kidney disease with high-turnover renal osteodystrophy led to downregulation of Klotho in bone cells. This appeared to offset the skeletal impact of osteocyte-targeted Klotho deletion. Thus, our findings establish a key role of osteocyte-expressed Klotho in regulating bone metabolism and indicate a new mechanism by which osteocytes control bone formation.
Use of Expansion Cohorts in Phase I Trials and Probability of Success in Phase II for 381 Anticancer Drugs
Authors: Diogo D.G. Bugano, Kenneth Hess, Denis L.F. Jardim, Alona Zer, Funda Meric-Bernstam, Lillian L. Siu, Albiruni R.A. Razak, David S. Hong
Journal: Clinical Cancer Research (2017)

Purpose: Evaluate the association between the use of phase I expansion cohorts (ECs) and drug performance in phase II as well as time to approval by the FDA.Experimental Design: We performed a systematic search of MEDLINE for single-agent dose-finding adult oncology phase I trials published in 2006 to 2011 and subsequent phase II trials. Successful phase II trials were those that met their primary endpoints. Dates of approval were obtained from the Drugs@FDA website in April 2014. A logistic regression model was used to determine the associations between variables and success in phase II.Results: We identified 533 phase I trials evaluating 381 drugs; 112 drugs had at least one phase I trial with an expansion cohort. Phase I trials with expansion cohorts of two to 20 patients were associated with a higher rate of successful phase II trials than those with no expansion cohort [48% vs. 27%; OR, 2.1; 95% confidence interval (CI), 1.1-4.0; P = 0.037]. Phase II success rates were the same for expansion cohort with two to 20 and more than 20 patients (48% vs. 52%). Other positive associations were disease-specific trials (OR, 1.7; 95% CI, 1.0-2.9; P = 0.037), industry sponsorship (OR, 2.9; 95% CI, 1.5-5.7; P = 0.0024), and response rate of 6% to 20% (OR, 2.89; 95% CI, 1.6-5.2; P = 0.0007). Drugs tested in phase I trials with expansion cohorts had a higher rate of 5-year approval (19% vs. 5%; HR, 4.4; 95% CI, 2.2-8.8; P < 0.001).Conclusions: The use of expansion cohorts in phase I trials was associated with success of subsequent phase II trials. However, confounders may play a role in this association. Clin Cancer Res; 23(15); 4020-6. ©2017 AACR.
Time interval between final protocol approval (FPA) and inclusion of the first patient into randomized clinical trials (RCTs) performed by the Central European Cooperative Oncology Group (CECOG): A 10-year experience
Authors: T. Brodowicz, I. Steiner, S. Beslija, T. E. Ciuleanu, M. Inbar, M. Krzakowski, Z. Kahan, V. Tzekova, D. Vrbanec, C. C. Zielinski
Journal: Journal of Clinical Oncology (2009)

6546 Background: CECOG has been formed in 1999 to unite centers of clinical oncology from Central and Southeastern Europe and Israel in order to conduct and coordinate multicenter oncology RCTs. Based on the European legislation passed in 2001 (Directive 2001/20/EC), clinical trials must get ethical approval and approval from the competent authorities (CA). However, the duration of these regulatory procedures to initiate a clinical trial is a factor determining the competitive position in clinical research. Methods: Within the last 10 years, CECOG conducted trials in breast, colorectal, esophago-gastric, NSCLC, pancreatic, prostate cancer and GIST. We analyzed the dates of FPA, the approvals by Ethics Review Boards (ERB) and CAs, the letters of agreement between sponsor and site (LoA), the site initiation and the inclusion of the first patient in a total of 6 multicenter trials in 25 CECOG study centers in Austria, Bosnia, Bulgaria, Croatia, the Czech Republic, Hungary, Israel, Poland, Romania, Serbia, and Slovakia. Results: The average time interval from FPA to the inclusion of the first patient was 18.4 ± 9.4 months. Most of this time has been spent for regulatory procedures, i.e. the approval by ERBs (9.6 ± 7.2 months) and CAs (10.0 ± 6.6 months). The LoA were signed 11.5 ± 9.4 months after FPA. The time interval from approval by the CAs to site initiation was 3.3 ± 3.7 months and the interval between site initiation and the inclusion of the first patient was 4.2 ± 4.5 months. Conclusions: The ‘paper to patient process‘ - the time interval between the approval of the final study protocol and the inclusion of the first patient - required 18.4 months on average in 6 multicenter trials conducted by CECOG. As the regulatory procedures used up more than 50% of duration of the whole process, optimization is necessary and realistic in order to make novel therapies available to patients more quickly. No significant financial relationships to disclose.
Association of positive peritoneal cytology in early endometrial cancer with some prognostic factors: A systematic review and meta-analysis.
Authors: Banghyun Lee, Kidong Kim, Dong-Hoon Suh, Jae Hong No, Hee Seung Kim, Yong Beom Kim
Journal: Journal of Clinical Oncology (2015)

e16519 Background: The prognostic significance of isolated positive peritoneal cytology (PPC) in patients with endometrial cancer confined to the uterus is controversial, depending on the presence of some prognostic factors. However, the relationship of other prognostic factors with peritoneal cytology remains still unclear. Therefore, this study aimed to investigate the association of prognostic factors with peritoneal cytology in patients with early endometrial cancer (EEC, stage I and stage II). Methods: In January 2015 a PubMed search identified 315 articles. A combination of the following key words was used in the search: (endometrial/endometrium cancer/neoplasm/carcinoma or PPC) and (endometrial/endometrium cancer/neoplasm/carcinoma or positive peritoneal washing). When filtered for studies comparing PPC with negative peritoneal cytology (NPC) for EEC 12 case-control studies including 25,688 patients (1093 PPC, 24,595 NPC) met the selection criteria. Meta-analyses (random effects and fixed effects analyses) were performed to evaluate the risk of other prognostic factors in patients with PPC using Review Manager 5.2. Results: In patients with stage I, and stage I/II EEC, incidence of grade 3 and positive pelvic lymph node (LN) involvement were significantly higher in PPC compared with NPC, whereas incidence of grade 1, myometrial invasion < 50% and negative pelvic LN involvement were significantly lower in PPC compared with NPC. However, incidence of grade 2, myometrial invasion ≥ 50%, and para-aortic LN involvement showed no difference in both groups. In patients with stage I/II EEC, incidence of lymphovascular space invasion were significantly higher in PPC compared with NPC. A large scale study (812 PPC, 22,135 NPC) was included for analysis of grade. The results with or without it were not different (grade 3 stage I/II: OR = 2.37; 95% CI 2.07 to 2.71, p < 0.00001 vs OR = 2.27; 95% CI 2.84 to 4.03, p < 0.00001) Conclusions: This study demonstrate that PPC in patients with EEC has significant associations with some prognostic factors of endometrial cancer suggesting its possibility as a prognostic factor. Therefore, peritoneal fluid in EEC needs to be collected.
Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children’s Oncology Group AAML0431 trial
Authors: Jeffrey W. Taub, Jason N. Berman, Johann K. Hitzler, April D. Sorrell, Norman J. Lacayo, Kelley Mast, David Head, Susana Raimondi, Betsy Hirsch, Yubin Ge, Robert B. Gerbing, Yi-Cheng Wang, Todd A. Alonzo, Dario Campana, Elaine Coustan-Smith, Prasad Mathew, Alan S. Gamis
Journal: Blood (2017)
Masitinib in comparison to imatinib as first-line therapy of patients with advanced gastrointestinal stromal tumor (GIST): A randomized phase III trial.
Authors: Antoine Adenis, Loic Chaigneau, Pierre Michel, Nicolas Isambert, François Bertucci, Binh Bui Nguyen, Olivier Bouche, Laurent Mineur, Tanios S. Bekaii-Saab, Nicolas Penel, Yolene Acin, Alain Moussy, Olivier Hermine
Journal: Journal of Clinical Oncology (2012)

TPS10102^ Background: Masitinib is an oral tyrosine kinase inhibitor (TKI) that has greater in vitro kinase activity and/or selectivity than imatinib against KIT and PDGFRA/B. A phase 2 study has previously reported that masitinib treatment produced clinically relevant activity in imatinib-naïve patients with advanced GIST. Considering the promising long term response observed in overall survival (OS) (see Table) there is compelling evidence to compare masitinib against imatinib (the current standard of care) in the first-line setting. Methods: A multicenter, randomized, open label, phase 3, 1:1 study to compare efficacy and safety of masitinib (7.5 mg/kg/day) to the active control of imatinib (400 or 600 mg/day) in first-line treatment of patients with advanced GIST. Primary endpoint is progression-free survival (PFS), with secondary endpoints including OS, time to progression (TTP), and clinical response rates (RECIST). Based on a planned sample size of 222 patients (111/arm) this 15% non-inferiority study was designed to have an 85% power using a 95% two-sided CI of the hazard ratio. Patient eligibility criteria include: histologically proven, metastatic or locally advanced nonresectable, or recurrent post-surgery GIST; TKI naïve patient or patient previously receiving imatinib only as a neoadjuvant or adjuvant therapy; and confirmed KIT-positive or PDGFRA-positive tumors. Recruitment is ongoing. On 09/2011, the DMC recommended continuation of this study. Clinicaltrial.gov: NCT00812240. [Table: see text]
Order of hierarchy for the identification of breast cancer patients' (BCP) fears: A pilot study
Authors: E. Gil Deza, M. García Díaz, B. Rolnik, D. Gercovich, A. Obeid, S. Ares, C. García Gerardi, E. Morgenfeld, E. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2004)

8246 Background: The aim of this study was to explore and rank the most important fears that BCP experience during treatment. Methods: We studied pt's fear through 18 printed cards that had a given fear on it. Particular fears often encountered in clinical practice were selected according to the subjective perception of the participating doctors. After signing informed consent, patients were offered the cards. All patients were asked to rank in decremental order the mentioned cards. The Mann -Whitney test was used for subgroup comparison. Results: Twenty eight BCP were included in this pilot study. Mean age 59.5 y.o. (range 30–85). Breast conservation Y/N: 17/11. Mean time from diagnosis was 62 months (range 4–336). Chemotherapy Y/N 17/11. Patients selected a mean of 12 (range 1–21) fears. Fear from suffering physical pain was the most commonly identified one, median rank (M) = 3.5 followed by fear of damage of self image (M 4.5), fear to experience psychiatric disorders associated to treatment (M 4.5), fear to the unknown (M 6) and fear of death (own and beloved ones) (M7 and 8). There were significant differences in the distribution of fears between patients who received chemotherapy and those who did not. The former experienced more frequently fear to lose social prestige (p=0.031) and damage of self image (p=0.07), mainly because alopecia. Conclusions: After this preliminary data, this tool should be refined and therefore we have selected fewer number of cards. Fears related to physical suffering are the most prevalent in this population. Patients who receive chemotherapy are more prone to develop fears associated to self image that need to be identified and prevented. A larger study in order to validate these results and to potentially identify significant subgroups in BCP is ongoing. Specific psychological support could be designed accordingly. No significant financial relationships to disclose.
Response after treatment with pembrolizumab in a patient with myelophthisis due to melanoma: the role of checkpoint inhibition in the bone
Authors: Samuel Rosner, Filiz Sen, Michael Postow
Journal: Journal for ImmunoTherapy of Cancer (2017)

Myelophthisis due to melanoma is a rare phenomenon. Treatment strategies for patients with this serious complication of malignancy have not been well documented, and none have previously reported efficacy of immune checkpoint inhibition. Since bone metastases are not measurable lesions per standard response criteria, the efficacy of immune checkpoint inhibition in the bones is also not well described.We describe a patient with widespread melanoma metastases involving the bone marrow causing myelophthisis and pancytopenia who responded to immune checkpoint inhibition with the anti-programmed cell death-1 (PD-1) inhibitor pembrolizumab.This is the first report to our knowledge of disease response to immune checkpoint inhibition in a patient with myelophthisis. Clinical trials have recently emerged describing the efficacy of PD-1 inhibition for disorders regularly involving the bone marrow, such as hematologic malignancies, suggesting the importance of better understanding the bone marrow as an immunologically active compartment. Clinicians should be aware that immune checkpoint inhibition alone may be effective in treating malignancy involving the bone marrow, even in cases of extensive involvement resulting in pancytopenia due to myelophthisis from a solid tumor as our case suggests.
Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxen-based chemotherapy.
Authors: Jiayu Wang, Binghe Xu, Qing Li, Peng Yuan, Fei Ma, Yang Luo, Ying Fan, Pin Zhang, Ruigang Cai
Journal: Journal of Clinical Oncology (2012)

e11025 Background: To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxane-based chemotherapy. Methods: We studied the incidence and duration of amenorrhea induced by adjuvant chemotherapy(regimens: 6EC(Epirubicin and cyclophosphamide) or 4EC follow by 4Taxen) in 68 premenopausal patients with different age group. Reversible amenorrhea was defined as recovery of regular menses or premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy. Results: The incidence of chemotherapy-induced amenorrhea(CIA) at the end of chemotherapy was similar in the two groups: 81.3% in the 6EC arm and 86.3% in the 4EC/4T arm. The incidence of CIA was not significance higher in the middle age arm(older than 40 years old) than in the younger arm(40 or younger than 40 years old): 97.4% versus 86.7% (P=0.114). However, more reversible amenorrhea was observed in younger arm than in middle age arm (76.7% vs. 34.2%, P=0.001). The median duration of regular menses recovering was 9 months in the younger arm and 11 months in the median age arm. More persistent amenorrhea had been detected in the middle age arm than in younger arm: 63.2% vs.10%, P&lt;0.001). Multivariate analysis showed that age (&gt;40years) was independently associated with the incidences of CIA (P=0.048). Conclusions: Age was the strongest predictor of the incidence of amenorrhea during adjuvant chemotherapy. Our study suggests that most of CIA in younger patients induced by adjuvant chemotherapy were reversible amenorrhea. Therefore adjuvant aromatase inhibitors for early breast cancer patients with CIA should be cautiously administered.