tbuckley/cabot-search huggingface dataset:
Serum levels of a MMP-12 generated type IV collagen fragment is elevated in COPD and IPF patients
Authors: Jannie Marie Sand, Federica Genovese, Fernando Martinez, Meilan Han, Cory Hogaboam, Morten Asser Karsdal, Diana Julie Leeming
Journal: European Respiratory Journal (2013)

Introduction: Type IV collagen is a main component of the basement membrane (BM); the α3 chain is the most commonly expressed in lungs. Collagen type IV is degraded by the macrophage matrix metalloprotease MMP-12, which is elevated during inflammation leading to pathological structural changes in lungs.  Aims and objective: The aim was to investigate the relationship between serum assessed basement membrane degradation and chronic lung disease  Methods: Native human collagen type IV was in vitro cleaved by different proteases and peptides were identified by LC-MS/MS. A MMP-12 generated collagen type IV neoepitope cleaved at the amino acid position 438 (C4M12-a3) was chosen to generate a monoclonal antibody employed for ELISA development. C4M12-a3 was assessed in serum samples from a cohort of COPD (n=10), IPF (n=29) patients and healthy controls (n=11). Patients were stratified according to their forced vital capacity (FVC): mild COPD; mild, moderate and severe IPF.  Results: Levels of C4M12-a3 were significantly elevated in IPF and COPD patients compared to controls. The marker was not able to stratify IPF patients according to severity even if a trend showing elevated levels of the marker in mild and moderate IPF patients compared to severe IPF patients was observed. COPD patients were elevated the most.  Conclusions: This novel marker was able to separate IPF and COPD patients from healthy controls. Furthermore, C4M12-a3 was able to identify mild IPF patients, showing potential for early diagnosis. Even though these findings need to be validated in larger clinical settings, these preliminary results show a good potential for C4M12-a3 as marker of BM remodeling during lung diseases.
Irinotecan combined with infusional 5-fluorouracil and folinic acid (folfiri) in patients with metastatic gastric cancer resistant to cisplatin-containing chemotherapy
Authors: N. Fazio, G. Zampino, F. Nolè, K. Lorizzo, R. Ardito, S. Manzoni, A. Rocca, I. Minchella, F. De Braud
Journal: Journal of Clinical Oncology (2004)

4146 Background: irinotecan is an active drug for pretreated gastric cancer patients. It resulted particularly effective when combined with cisplatin, but no reference regimen exists for patients progressive after cisplatin. Activity and toxicity of FOLFIRI is well known in metastatic colorectal cancer patients. Therefore, we studied the tolerability and activity of this regimen in patients with metastatic gastric carcinoma progressive after chemotherapy containing cisplatin. Patients and methods: Patients with histologically proven gastric cancer, measurable or evaluable disease, age ≤ 75 years, PS 0–2 (ECOG), were enrolled. The regimen included irinotecan 180 mg/m2 i.v. over 90' + Folinic Acid 200 mg/m2 i.v. over two hours + 5-Fluorouracil (5-FU) 400 mg/m2 i.v. bolus + 5-FU 2400 mg/m2 i.v. continuous infusion over 46 hours, and was repeated every two weeks. Restaging was performed after 4 courses. Responsive patients could be treated until progression. Results: From June 2002 to August 2003 twenty-seven consecutive patients were treated. Informed consent was obtained from all patients. Progressive disease after a cisplatin-based first-line chemotherapy or within six months after a neo-/adjuvant chemotherapy was present in all patients. Previous treatments were: Epirubicin,Cisplatin,5-FU (ECF) in 15 patients, Taxotere,Cisplatin,5-FU (TCF) in five, Taxotere,Cisplatin (TC) in seven. Four out of the 27 patients were refractory to neo-/adjuvant chemotherapy. Eighty-eight courses were administered (median per patient 5; range 1–14). Grade (G) 4 neutropenia in two patients was the only G3–4 toxicity. Quality of life evaluation in over half of the patients is ongoing. Five objective responses and nine stable diseases were obtained (intent to treat). Four patients showed a stable disease for > four months. One patient is not evaluable because too early. Conclusion: FOLFIRI is a proposable second-line chemotherapy in metastatic gastric cancer patients resistant to cisplatin-containing chemotherapy. Phase II and III studies in chemotherapy-naive patients are warranted. No significant financial relationships to disclose.
Efficacy and Safety of Bevacizumab (Bv) and Irinotecan (I) in Elderly Patients with Recurrent Glioblastoma Multiform (Gbm): a Monocentric Retrospective Study
Authors: M. Robert, C. Leux, C. Gourmelon, M. Campone, J. Frenel
Journal: Annals of Oncology (2014)
Women should be given maternity care budget of £3000
Authors: Jacqui Wise
Journal: BMJ (2016)

Maternity services in England should offer more personalised care, with women given a personal care budget of £3000 (€3810; $4193), an independent review commissioned by NHS England has said.1

The National Maternity Review recommended trialling an NHS personal maternity care budget that would let women choose the provider of their antenatal, intrapartum, and postnatal care.

The review, chaired by the Conservative peer Julia Cumberlege, said that every woman should develop a personalised care plan with her midwife and other health professionals. Women should be able to access information …
Autologous bone marrow transplantation for advanced stage adult lymphoblastic lymphoma in first complete remission
Authors: Gino Santini, P. Coser, T. Chisesi, A. Porcellini, R. Sertoli, A. Contu, O. Vinante, A. M. Congiu, A. M. Carella, T. D’Amico, D. Pierluigi, E. Rossi, D. Scarpati, V. Rizzoli
Journal: Annals of Oncology (1991)
Low Birth Weight in Relation to the Interval between Pregnancies
Authors: T J Sheehan, D I Gregorio
Journal: New England Journal of Medicine (1995)

Regarding the article by Rawlings et al. (Jan. 12 issue) we wonder whether a short interpregnancy interval might be confounded by factors that were not considered in the analysis. Although all the women studied were drawn from military families with access to high-quality health care no information was provided about the proportion of mothers who worked and what types of occupations they had. Since it has previously been shown that physical exertion associated with employment in the Army may increase the risk of preterm delivery might a racial difference in employment patterns account to some extent for the increased risk of preterm birth among the Black women in the sample?  The large racial difference in the prevalence of low birth weight or preterm delivery among women with interpregnancy intervals of 3 to 5.9 months also deserves comment. It is puzzling to find that this interpregnancy interval has such a disparate effect among Black women as compared with White women when no marked racial difference is apparent at shorter or longer intervals. Nonetheless the presence of a racial difference associated with even one interpregnancy interval suggests that short intervals themselves cannot wholly explain the racial disparity in pregnancy outcomes. Also noteworthy is the fact that interpregnancy intervals of less than nine months are associated with poor outcomes among Black women whereas only the shortest intervals (less than three months) are disadvantageous for White women. The authors report in addition that the adverse effect of a short interpregnancy interval was strongest when the preceding pregnancy resulted in a low-birth-weight or preterm infant. These findings are interesting and merit additional discussion. (full text)
The Mayo Lung Project (MLP) and non-small cell lung cancer (NSCLC): Does overdiagnosis (OD) explain improved survival?
Authors: G. M. Strauss, D. G. Babbitt
Journal: Journal of Clinical Oncology (2005)

7181 Background: Screening for lung cancer (LC) is not recommended. While randomized trials consistently demonstrate significant survival advantages in populations randomized to screening, survival advantages have been interpreted as indicating that CXR screening leads to the OD of LC. The objective of this analysis is to consider whether MLP data are consistent with OD. Methods: In MLP, all participants had a negative prevalence screen, consisting of chest x-ray (CXR) and sputum cytology (SC). Subsequently, 4,607 men were randomized to an experimental group (EG), which underwent CXR and SC every 4 months, and 4,585 to a control group (CG). CG participants were advised to undergo annual CXR and SC. EG was screened for 6 yrs, followed by 3 yrs of observation, while CG was followed for 9 yrs. Results: After 9 yrs, 158 NSCLC were detected in EG and 115 in CG (RR=1.37, 95% CI: 1.08–1.73). In EG, 107 cases (68%) were screen-detected compared to 40 (35%) in CG (p<0.001). CXR detected 88% of all screen-detected cases. Resection was performed in 88 (56%) EG and 48 (42%) CG cases (p=0.027). Six yr survival was 39% in EG vs 17% in CG (p=0.0095). However, there were 86 LC deaths in EG and 76 in CG. Accordingly LC mortality was slightly higher in EG (RR 1.13; 95% CI: 0.83–1.53). The survival/mortality discrepancy occurred because NSCLC incidence was 37% higher in EG. These findings led to the hypothesis that OD was responsible for a spurious survival advantage. However, if screening detects pseudodisease, some NSCLC patients should be long-term survivors despite conservative treatment, and this was not observed. Six yr survival was 58% in 136 resected NSCLC and 0% in 137 unresected NSCLC (p<0.0001). Among 117 resected patients with screen-detected NSCLC, 6-yr survival was 60%, compared to 0% among 28 unresected patients (p<0.0001). Multivariate analysis indicated that resection was the only significant predictor of survival. Screen-detection was only important insofar at it predicted resection. Among NSCLC patients, LC was responsible for 89% of all deaths. Conclusions: OD does not explain survival/mortality discrepancies in MLP. Survival advantages reflect a benefit for screening, and support that CXR screening is effective. No significant financial relationships to disclose.
Synergy Of Small-Molecule Inhibitors In Cutaneous T-Cell Lymphoma Cells: A Discovery Tool To Define New Therapeutic Targets In T-Cell Receptor (TCR) Signaling Pathways
Authors: Meghan Bliss-Moreau, Cristian Coarfa, Weimin Xiao, Preethi Gunaratne, Nancy L Krett, Steve T. Rosen
Journal: Blood (2013)
A phase Ib dose-escalation study of orally administered MP-470, a multi-kinase inhibitor and supressor of Rad51, in combination with carboplatin doublet containing regimens shows activity in highly refractory solid tumor patients
Authors: M. M. Mita, A. Tolcher, M. S. Gordon, L. Rosen, A. Mita, G. Fine, G. Choy, G. Berk
Journal: Journal of Clinical Oncology (2009)

e13511 Background: MP-470 (MP) is an oral multi-targeted tyrosine kinase inhibitor which inhibits a number of validated tumor targets including c-kit, flt3, and PDGFα. MP470 targets cancer cells by disrupting DNA repair, an important survival pathway in many human cancers. Results presented herein are from two arms of a phase-Ib five arm trial of MP combined with standard of care (SOC) anti- cancer therapies. Methods: MP is administered in combination with SOC in a 21-day cycle. Adults with ECOG PS of 0–2 and malignant disease appropriate for SOC regimens consisting of paclitaxel/carboplatin (PC), carboplatin/etoposide (CE), topotecan, docetaxel, and erlotinib were enrolled. Each arm follows a 3+3 design where MP is escalated based on the modified Fibonacci sequence until the MTD of MP in combination with SOC agents is reached. RECIST and CTCAE are utilized to assess response and safety, respectively. The primary objectives of the study are to determine the MTD, DLTs, and quantify the effects of MP on the PK of SOC agents. Results: Between Dec 2007 and Aug 2008, 26 subjects were enrolled in the PC and CE arms and received a total of 70 cycles (median 2; range, 0–8) of MP at 4 dose levels (100–500 mg/day). Median number of prior therapies was 2 (range, 0–19). Male/Female: 14/12. Median age, 56 years (range, 24–76). Subjects completing ≥ 6 and ≥ 4 cycles were 5 and 7, respectively. Six PRs (2 neuroendocrine, 2 SCLC, 1 NSCLC, 1 small cell of anal canal) and 3 SDs (≥ 4 cycles) was observed. The MTDs have not been reached and DLTs have not been identified. Adverse events occurring in ≥ 15% of patients were myelosuppression, diarrhea, constipation, nausea, reflux, fatigue, alopecia, rash, neuropathy, anorexia, hypokalemia, dyspnea, and myalgias. MP470 did not alter the kinetics of SOC agents. Dose escalation in the PC and CE arms is ongoing. Conclusions: MP470 combined with carboplatin-containing regimens may promote tumor regression and may also sensitize/resensitize tumors to the anticancer effects of such agents. An amendment will be issued to collect tumor tissue biopsy at baseline and during treatment to adequately evaluate DNA damage in tumor tissue. [Table: see text]
Axitinib with or without dose titration as first-line therapy for metastatic renal cell carcinoma (mRCC).
Authors: E. Jonasch, A. Bair, Y. Chen, B. I. Rini
Journal: Journal of Clinical Oncology (2010)

TPS235 Background: Axitinib is a potent, selective inhibitor of VEGFRs 1, 2, 3 that demonstrated significant activity in 2 phase II trials of patients (pts) with refractory mRCC (objective response rate [ORR] 23 and 44%; median progression-free survival [PFS] 7.4 and 15.7 mo; median overall survival [OS] 13.6 and 29.9 mo, respectively). In these trials treatment-induced diastolic blood pressure (dBP) ≥90 mmHg correlated with significantly longer median OS and ORR vs dBP <90 mmHg (30 vs. 9.8 mo; 50.8 vs. 10.2%). Further, increases in dBP and higher AUC were independently associated with increased probability of partial response, larger reductions in tumor size, and longer OS. Axitinib dose escalation was permitted in these studies; similar safety profiles were observed with titrated and untitrated doses. We hypothesize that axitinib dose titration in mRCC pts who tolerate and do not experience dBP ≥90 mmHg at the standard starting dose may increase efficacy by optimizing AUC and pharmacodynamic effects without significantly increasing toxicity. Methods: A prospective randomized phase II trial is enrolling ∼200 treatment- naïve mRCC pts to evaluate axitinib ± dose titration and relationships among AUC, dBP, and efficacy. Following an initial 4-week cycle at the standard starting dose (5 mg BID), 70 pts who meet randomization criteria will be randomized 1:1 to receive axitinib+axitinib dose titration or axitinib+placebo dose titration using a prespecified dose titration scheme; the dose titration portion is blinded. Randomization criteria include: systolic BP ≤150 mmHg, dBP ≤90 mmHg, no grade 3/4 axitinib-related toxicities, no dose reduction in the first cycle, and ≤2 concurrent antihypertensive medications. Pts not meeting these criteria will continue axitinib without dose titration in a third arm. Crossover is not permitted. Treatment will continue until disease progression or unacceptable toxicity. The primary end point is ORR between the 2 dose titration arms; secondary end points are PFS, OS, response duration, safety, pharmacokinetics, BP, and biomarker correlations. This study has ≥80% power (1-sided type I error 10%) to detect a ≥25% absolute improvement in ORR in pts receiving axitinib titration vs. placebo titration. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Genentech, Novartis, Pfizer Pfizer Bayer, Novartis, Onyx, Wyeth Pfizer
Combination immunotherapy for high-risk and advanced melanoma patients.
Authors: A. I. Riker, N. N. Vahanian, C. J. Link, L. Tennant, W. J. Ramsey, G. R. Rossi, L. C. Alsfeld, E. Davila, M. Harrison
Journal: Journal of Clinical Oncology (2011)

8534 Background: Patients with metastatic melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment option for high risk, resected stage III, recurrent, refractory or stage IV melanoma. Methods: We completed a phase II clinical trial of HyperAcute Melanoma vaccine (NLG-12036, NewLink Genetics) combined with pegylated interferon (PEG-Intron). Trial design was a 12-week regimen with the initial 4 weekly treatments consisting of NLG-12036 alone (intradermally) followed by 8 additional treatments of NLG-12036 + PEG-Intron (subcutaneously, 6 µg/kg). Trial endpoints include clinical response, overall safety and correlative findings for observed anti-tumor effect. Results: N=25, median age 60, 68% male with 21 patients completing the trial, 4 stopped due to progressive disease (PD). NLG-12036 related common side effects include erythema and induration at the injection site, without significant grade 3 or 4 toxicities reported. By RECIST criteria, of 16 stage IV patients, there were 3/16 (18.7%) responders, 2 complete responders (CR) and 1 stable disease (SD). An additional 3/16 patients remain NED after resection and 10/16 patients developed PD with 4 deaths. For stage III patients, 5/9 remain NED and 4/9 died. Relapse-free interval ranges from 4 to 25 months. In correlative studies among evaluable patients, anti-αGal Ab increased in 23/24 by up to 100-fold (median 17, range 3-109). All evaluable patients (21/21) seroconverted to production of autoimmune antibodies. Anti-tyrosinase Ab’s developed in 4/23 correlating with 1 CR and vitiligo developed in 4/25 patients, correlating with 2 CR’s. While acknowledging that patient heterogeneity in this high-risk patient population can greatly affect survival analysis, 17/25 patients in this study remain alive with a median survival of 20 months. Conclusions: Combinatorial immunotherapy with NLG-12036 plus PEG-Intron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and addition of other potentially synergistic agents should be explored to further enhance the benefit of this immunotherapeutic approach.
A novel copay foundation assistance support program for patients receiving cancer therapy in cancer centers
Authors: S. P. Rajurkar, C. Presant, L. Bosserman, W. McNatt
Journal: Journal of Clinical Oncology (2009)

6630 Background: With advent of newer CT (biotherapy, chemotherapy, and supportive care) treatment is becoming increasingly expensive for cancer pts. Pts enrolled with Medicare and commercial insurance plans often have large copay requirements with each treatment cycle. Often, these pts undergo significant financial hardship and some pts decline treatment. We have developed a novel support program to coordinate all copay assistance foundations (FDNs) in order to secure financial assistance to facilitate appropriate CT. Methods: In September, 2008 in our multi-site cancer center (11 oncologists, 6 CT sites), we developed a dedicated support program to coordinate pt applications to copay assistance FDNs including Healthwell, Cancer Care, Patient Access, Chronic Disease Fund, Beckstarnd Cancer, Lilly Cares, and Leukemia and Lymphoma Society. Pts requesting assistance with CT copay were enrolled in this program. A dedicated staff individual obtained information about diagnosis, insurance, income level, CT plan and associated co-pay requirements. Data was given to FDNs who determined the amount of monetary assistance. Responses of FNDs and administrative costs were analyzed. Results: Of 264 pts started initiating CT between September 2008 and December 2008, 25 (9.3%) requested assistance for either IV or PO treatments. The average interval between the submission of FDN application and date of determination of assistance was 10 days. Out of 83 applications (3.32 applications/pt), 50 (60%) were approved. Ultimately 22/25 pts received FDN support of $113,475. The most common reasons for denial were if the pt's income exceeded a certain level, exclusion of coverage of certain medications and the FDN being out of funds. The administrative costs associated with this program were $18,000/yr ($720/pt, or $217/application). Administrative costs were 1.64% of approved support. More difficulties were encountered with applications for oral CT than IV CT. Conclusions: Copay for CT drugs is a financial hardship for a significant number of pts. Coordinated resources must be provided and reimbursed to facilitate appropriate and sustainable cancer care. This program is a successful model for other centers. No significant financial relationships to disclose.
Repeated immune cell transfer therapy combined with non myeloablative chemotherapy in patients with refractory recurrent gastrointestinal and lung cancer
Authors: U. Toh, H. Yamana, T. Fujii, T. Sasatomi, S. Takamori, Y. Araki, E. Ogo, K. Shirozou
Journal: Journal of Clinical Oncology (2004)

2541 Background: Autologous tumor cells stimulated T lymphocytes (AuTL) were generated ex vivo from peripheral blood lymphocytes (PBL) over a two week co-culturing process and they may have potential for efficacy as a cellular immunotherapy (IT) in refractory gastrointestinal and lung cancer patients (pts). We investigated the feasibility of a combination of AuTL transfer and chemotherapy (ChT) with S1or ZD1839 (Iressa) conditioning regimen in order to take advantage by both the anticancer and lymphodepleted effects for reconstruction of antitumor immune followed by AuTL transfer as well as an adoptive IT. Method: 13 patients were enrolled in a pilot clinical trial. The two administrations of AuTL were given prior to one ChT for one treatment cycle. The treatment was repeated at least three cycles with a one-week interval. The nonmyeloablative ChT regimen was based on standard dose of S-1 for pts with gastric (4 pts), colon (4 pts) or esophageal (3 pts) cancer and of ZD1839 for 2 pts with lung adenocarcin...
21-gene Recurrence Score testing and subsequent treatment decisions in patients (pts) with estrogen-receptor-positive (ER+) early-stage breast cancer (ESBC).
Authors: Jennifer B. Manders, Joan Burkhart, Debra Campbell, James J. Devitt, Judith Vacchino, Amy Pratt Sing
Journal: Journal of Clinical Oncology (2013)

30 Background: The utilization of the 21-gene Recurrence Score (Oncotype DX) in community settings is now well established for ER+, node negative (N-) pts with ESBC. The utility of the Recurrence Score result is to guide treatment decisions and spare exposure to chemotherapy (CT) in pts that have little likelihood of benefitting. To better understand physician behavior as it relates to OncotypeDX testing, we examined the characteristics of pts tested versus not tested, the Recurrence Score distribution and treatment patterns in approximately 160 pts with ESBC seen in 2010. In addition, provider utilization and treatment patterns were also assessed. Methods: Using data from 2010, the number of pts who were eligible to undergo OncotypeDX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, ER+, HER2-negative ESBC. We determined the number of pts with a Recurrence Score value in the low (RS &lt;18), intermediate (int; RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of the 233 pts identified with ESBC, 158 were eligible for OncotypeDX testing and 107 (67.7%) underwent testing. Fifty-five percent of pts were low, 37% int, and 7.7% high-risk, respectively. Nineteen percent of low, 56% of int, and 100% of high-risk pts received CT. In the 11 pts with a low Recurrence Score result that received CT, the reason cited was pt decision in 4 and young age in 3. Conclusions: Oncotype DX use in the community is well established. Recurrence Score-guided use of CT in the low- and int-risk groups was as expected based on adjuvant chemotherapy guidelines; however, there were still some physicians treating low Recurrence Score pts with CT-mostly based on younger age or larger tumors. Data from 2011 and 2012 will be included in the final presentation allowing greater insight into pt groups less represented in the single year experience.