tbuckley/cabot-search huggingface dataset:
Phase II of oral vinorelbine (NVB oral) in combination with Cisplatin (P) followed by NVB oral single agent as consolidation therapy in advanced non small-cell lung cancer (NSCLC): A Patient's Benefit Analysis
Authors: M. De Lena, R. Ramlau, O. Hansen, L. Wagner, S. Barni, V. Alberola, R. Huber, M. Mitrovic, J. Gasmi, J.-C. Pouget
Journal: Journal of Clinical Oncology (2004)

7338 Background: The goals of chemotherapy in advanced NSCLC are to improve survival and to palliate symptoms.This multinational phase II trial was designed to evaluate a new schedule of NVB oral in combination with P followed by consolidation therapy with NVB oral as single agent in advanced NSCLC. Methods: Chemonaive stage III/IV NSCLC patients (pts) were eligible to receive 4 cycles of P: 80 mg/m2 on d1 with NVB oral: 60 mg/m2 on d1 & d8 for the first cycle with dose escalation of NVB oral at 80 mg/m2 on d1 & d8 for the following cycles in absence of grade 3–4 neutropenia. Pts with objective response (OR) or stable disease (SD) received consolidation therapy with weekly NVB oral. The Clinical Benefit was the secondary end point and was assessed for each pt through a visual analogic scale (VAS) on 6 symptoms (pain, dyspnea, cough, haemoptysis, asthenia and anorexia). Pts were classified as responders or non responders according to scores obtained on VAS and also according to change in PS and weight. Results: Fifty-six pts were included (M/F 40/16), median age was 60 years (40–70), median KPS 90 % (80%–100%), stage IV (70%), IIIB (22%). Fifty-five pts were evaluable for safety and 49 pts for efficacy. OR, MS, 1YS were respectively 26.5%, 10 months and 42%. The main grade 3–4 toxicities (NCI-CTC) were neutropenia 34,5% pts,, nausea 5.4% pts, vomiting 8.9% pts, fatigue 12.5% pts,one pt experienced grade 3 neuropathy while another one had grade 3 constipation and two pts developed neutropenic infection.36 pts have completed the combination therapy and 25 pts have received at least 2 cycles of consolidation therapy. For all pts an improvement has been noticed at least after the first cycle for all symptoms. This improvement was maintained during the whole combination therapy in 69% of pts. Haemoptysis and cough improvement were also maintained through consolidation therapy. Weight remained stable over cycles. Conclusions: This schedule of NVB oral + P is active, safe and beneficial for pt as most symptoms improved along the treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Institut de Recherche Pierre Fabre Pierre Fabre, Parigi
Phase I feasibility and dose escalation multicenter trial of stereotactic body radiation therapy for liver metastases
Authors: T. E. Schefter, B. D. Kavanagh, R. D. Timmerman, H. R. Cardenes, L. E. Gaspar
Journal: Journal of Clinical Oncology (2004)

4157 Background: Stereotactic body radiation therapy (SBRT) involves the application of high dose, stereotactically localized, and tightly focused irradiation to tumors in the lung, liver, and other extracranial sites.It is an attractively non-invasive method of eradicating discrete foci of metastatic disease, a clinically appropriate consideration for patients with good performance status and limited systemic disease burden. SBRT is currently being evaluated in a multi-center IRB approved phase I/II clinical trial coordinated by the University of Colorado. Methods: Eligible patients had image-based evidence of 1–3 liver metastases from any solid tumor excluding germ cell histology, and stable or absent extra-hepatic disease.The protocol required that at least 700 cc of uninvolved normal liver receive less than a total cumulative dose of 15 Gy.Dose escalation started at 36 Gy in 3 fractions (12 Gy per fraction) over 3 to 10 days and was escalated by 6 Gy per cohort using the standard phase I design, up to the maximum tolerated dose (MTD) or a designated limit of 60 Gy in 3 fractions.Gross tumor volume (GTV) was delineated on the contrast enhanced planning CT scan.GTV was expanded by 5 mm radially and 10 mm craniocaudally to define the planning target volume(PTV).Breathing control or gating was used in all cases.Dose limiting toxicity (DLT) was defined as grade 3 liver, gastric, small bowel or spinal cord toxicity and any grade 4 toxicity ascribed to radiotherapy. Results: Since November, 2002, 9 subjects were enrolled. Patient accrual is ongoing. All patients completed protocol treatment as planned. 7 of 9 subjects remain alive at the time of interim analysis. The two deaths were not attributable to protocol treatment.No DLTs have been observed. Conclusions: An MTD has not yet been reached, and observations thus far indicate that it is safe to administer 48 Gy in three 16 Gy fractions to 1–3 liver metastases, as long as at least 700 cc of uninvolved normal liver receives less than 15 Gy.Additional observations from the next planned dose escalation cohort(s) will be presented at the time of the meeting. Supported (in part) by a grant from the ACS. No significant financial relationships to disclose.
Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis
Authors: Christian Lunetta, Andrea Lizio, Eleonora Maestri, Valeria Ada Sansone, Gabriele Mora, Robert G. Miller, Stanley H. Appel, Adriano Chiò
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. <h3>Objective</h3> To examine the prognostic significance of CRP in ALS. <h3>Design, Setting, and Participants</h3> Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. <h3>Main Outcomes and Measures</h3> Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. <h3>Results</h3> A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (<i>r</i> = –0.14818;<i>P</i> = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234;<i>P</i> = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056;<i>P</i> ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs –7.31 [6.23];<i>P</i> = .04). <h3>Conclusions and Relevance</h3> These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001.
The radiosurgery fractionation quandary: single fraction or hypofractionation?
Authors: John P. Kirkpatrick, Scott G. Soltys, Simon S. Lo, Kathryn Beal, Dennis C. Shrieve, Paul D. Brown
Journal: Neuro-Oncology (2017)

Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities.
Ovarian function after high-dose chemotherapy in childhood: Risk factors for developing partial ovarian failure and how to identify them early
Authors: M. Frey, L. Brugières, P. Bougnères, C. Bouvattier, C. Thomas-Teinturier, S. Calmanti, G. Goma, O. Oberlin, O. Hartmann
Journal: Journal of Clinical Oncology (2009)

e20665 Background: During the last 30 years, polychemotherapies, surgery and radiotherapy have been established as standard therapies for treating pediatric cancers thus leading to a significant improvement in terms of 5-year-overall-survival which is now around 70% among children and adolescents. On the other hand, these treatments cause severe sequelae such as ovarian failure (OF) in young girls leading to a premature menopause and infertility. Methods: 29 patients treated at the Institute Gustave Roussy (Villejuif, France) have been investigated in an attempt to find biological and/or clinical markers, and imaging predictive of a partial ovarian insufficiency leading to an early menopause. Eligibility criteria: age &gt;12 years at time of analysis; peripheral stem cell graft between 2–20 years; high dose chemotherapy. Results: 23/29 were eligible for this analysis (6 withdrawn due to oral contraception). 13/23 patients (56.5%) show no clinical evidence of ovarian treatment-related toxicity with a 13 years median time to transplant. 10/23 (43.5%) have complete ovarian insufficiency, among whom the majority have already received substitution hormone therapy (SHT). Out of 75% of pre-pubescent patients at transplant, only 2 have OF. All patients grafted at puberty (15.3 years) have high-dose chemotherapy-related immediate or definitive OF. Thiotepa &gt;900mg/mq is castrating (odds ratio-10.1; p-0.04). Dosages of anti-müllerian hormone (AMH) collapses in patients with IO (p=0.002). Mensed patients have lower AMH dosages compared to normal population (p=2.10-e9) as for antral follicule count (&gt;2mm). Conclusions: 1) 13/23 patients show no evidence of OF. 2) Main risk factors of OF: age ≥ 12 years; post pubertal status; thiotepa &gt;900 mg/m 2 (OR=10.1 and p=0.04). 3) Despite normal menses, many women who underwent high dose chemotherapy exhibit low AMH and Inhibine B levels and low count of follicles at a young age. These are possible markers of ovarian depletion. Cryopreservation of the ovarian cortex should be proposed to patients grafted due to a cancer independently of the age at which they have undergone high-dose chemotherapy. No significant financial relationships to disclose.
Docetaxel, cisplatin, UFT and leucovorin combination chemotherapy in advanced gastric cancer
Authors: S. C. Oh, S. Sung, G. Park, I. Choi, J. H. Seo, C. Choi, B. Kim, S. Shin, Y. Kim, J. S. Kim
Journal: Journal of Clinical Oncology (2004)

4231 Background: The gastric cancer is one of the most common malignancies in Korea. Large number of patients had advanced disease or metastasis either at presentation or later. Chemotherapy is the main modalities for the management of the advanced gastric cancer. Both docetaxel (Taxotere) and cisplatin combination was reported synergistic effects against gastric cancer. The aim of this study was to evaluate the efficacy and toxicity of docetaxel, cisplatin, oral UFT and leucovorin combination chemotherapy in advanced gastric cancer. Methods: Without considering previous treatment, Seventy-two patients were enrolled in this study at Korea University Hospital from September 2001 to April 2003. Docetaxel 60 mg/m2 was given as intravenous infusion for 1 hour at day 1 and cisplatin 75 mg/m2 was intravenous infusion after docetaxel infusion at day 1. Oral UFT 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. Results: The seventy-two patients received 267 courses of chemotherapy and the median number of course per patient was four with a range of one to eight. Sixty-three patients were evaluated for response. Six patients achieved a complete response (9.5 %) and twenty-five patients a partial response (39.7 %), overall response rate was observed in 49.2 % (95% confidence interval, 36.9–61.5%). The major toxicity was neutropenia which reached grade 3–4 in 65.2 %. However, most of the patients except three patients who died due to sepsis, recovered from neutropenia without complication with support of granulocyte or granulocyte -macrophage colony stimulating factor. Non-hematologic toxicities were usually mild. Grad 3–4 nausea and vomiting were observed in 17.9 %. The median time to progression was 27 weeks (range, 1 to 88 weeks), Median response duration was 26 weeks (range, 2 to 72 weeks). Conclusions: These results suggests that the combination of docetaxel, cisplatin, oral UFT and leucovorin is effective and tolerable regimen for the treatment of advanced gastric cancer with supported of a granulocyte or granulocyte-macrophage colony stimulating factor. No significant financial relationships to disclose.
Paclitaxel (PAC) alters the metabolism of gemcitabine (GEM) to its active metabolite difluorodeoxycytidine triphosphate (dFdCTP)
Authors: S. S. Shord, J. R. Camp
Journal: Journal of Clinical Oncology (2004)

2089 Background: Our group previously reported PAC significantly decreased the systemic clearance and volume of distribution of a fixed dose of GEM administered after PAC. Therefore, this study was conducted to determine the effects of PAC on the disposition and metabolism of GEM to difluordeoxyuridine (dFdU) in human hepatocytes and dFdCTP in human peripheral blood mononuclear cells (PBMC). Methods: PBMC or hepatocytes were treated with GEM 5, 15 or 30μM x 80 min alone or after PAC 3μM x 3 h. Extracellular GEM and dFdU concentrations were measured at 0, 40, and 80 min after adding GEM and 40 and 80 min after removing GEM and the intracellular accumulation of GEM, dFdU and dFdCTP were measured ∼80 min after removing GEM using high performance liquid chromatography. Results: In hepatocytes, mean extracellular gemcitabine concentrations were higher (17 to 95%) and mean extracellular dFdU concentrations were lower (19 to 73%) for cells treated with PAC+GEM compared to GEM alone. GEM, dFdU, and dFdCTP were not measurable in hepatocytes. In PBMC, mean extracellular GEM concentrations were similar for cells treated with PAC+GEM and GEM alone; however, intracellular dFdCTP accumulation was lower (21 to 44%) in cells treated with PAC+GEM. GEM and dFdU were not measurable in PBMC. Additional studies indicated TAXOL (formulated) similarly altered GEM metabolism and disposition and PAC did not alter the metabolism or disposition in cells treated with PAC after GEM. Conclusions: PAC reduced the formation of dFdCTP and dFdU at clinically achievable concentrations. PAC most likely reduced the intracellular accumulation of GEM or its metabolites and thus, reduced the metabolism of GEM to its inactive or active metabolite, respectively. The sequence of administration, but not the PAC formulation influenced this interaction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American Cancer Society Institutional Research Grant Program
Performing complex cancer surgery in the ambulatory setting.
Authors: Vincent Paul Laudone, Robert Durany, Behfar Ehdaie, Mario M. Leitao, Marcia Levine, Babak Mehrara, Snehal G. Patel, Peter T. Scardino, Lisa M. Sclafani, Arjun Sivaraman, Daniel Stein, Beverly Tseng, Rebecca Twersky, Brett A Simon
Journal: Journal of Clinical Oncology (2017)

106 Background: The drive to move complex surgeries into the ambulatory setting will impact the cancer population. In anticipation, we developed an “ambulatory extended recovery” (AXR) program for pathway-based management of patients undergoing procedures with traditional 1-4 day hospital stays. Then in 2016 we opened the Josie Robertson Surgery Center (JR), a freestanding ambulatory surgical facility designed for complex cancer surgeries with one overnight stay. Methods: Using hospital databases we identified AXR cases eligible to be performed at JR and examined pathway completion (discharge home on POD 1), and 30-day institutional urgent care center (UCC) visits and readmissions. We compared AXR program results before and after opening JR in January 2016. Results: The most frequent AXR procedures were mastectomy ± immediate reconstruction, thyroidectomy, and minimally invasive prostatectomy, nephrectomy, and hysterectomy. 3307 and 2359 AXR procedures were done in 2015 and Jan-Sep 2016. In 2016 74% of AXR cases were performed at JR with the remainder at Memorial Hospital (MH), primarily for scheduling considerations or patient or surgical complexity. Pathway completion was 92% in 2015 and 95% in 2016 (p &lt; 0.001). 30-day UCC visits/readmission rates were 8.8%/3.7% in 2015 and 8.6%/3.1% in 2016 (ns). Comparing cases at JR vs MH in 2016, pathway completion rates were 98.3% at JR vs 86.4% at MH (p &lt; 0.001). Patient satisfaction was high for care provided at both facilities. Conclusions: Many complex cancer surgeries may be safely completed with a single overnight stay at a freestanding ambulatory facility. UCC visits and readmissions were not different between years, suggesting that quality of care was maintained in the ambulatory setting. The difference in pathway completion in 2016 at JR compared to MH may reflect successful triage of more medically complex patients and/or surgically complex procedures to MH.
RARbeta P2 promoter methylation: Potential biomarker for use with breast Random Periareolar Fine Needle Aspiration in breast cancer risk assessment
Authors: B. E. Ratliff, G. Bean, P. K. Marcom, J. V. Scott, L. Yee, B. F. Kimler, C. J. Fabian, C. M. Zalles, H. Shaw, V. L. Seewaldt
Journal: Journal of Clinical Oncology (2004)

1014 Background: Methylation of RARbeta P2 promoter is hypothesized to be an important early event in mammary carcinogenesis. Random Periareolar Breast Fine Needle Aspiration (RPFNA) is a research technique developed to repeatedly sample mammary cells from the whole breast of asymptomatic high-risk subjects to assess both 1) breast cancer risk, and 2) response to chemoprevention [Fabian et al. JNCI, 2000; Fabian et al. Clinical Cancer Res., 2002]. Coupling RARbeta P2 promoter methylation to RPFNA has the potential to enhance the sensitivity and specificity of RPFNA and to further delineate breast cancer risk. Methods: The frequency of RARbeta P2 methylation was tested through methylation-specific-PCR (MS-PCR) in 1) tissue biopsy specimens from 17 low-risk, primary breast cancers with a five year patient clinical follow-up and 2) RPFNA samples performed in 21 subjects at increased risk of developing breast cancer. Risk was defined as either 1) 5 year Gail risk calculation > 1.7%, 2) prior biopsy exhibiting atypical hyperplasia, LCIS, DCIS, or 3) known BRCA1/2 mutation carrier. The presence of methylation in RPFNA was compared to the degree of cytologic abnormality as assessed by the Masood semiquantitative index score. Results: RARbeta P2 promoter methylation was present in 12/17 (71%) of the primary breast cancers. RARbeta P2 promoter methylation was present in 9/21 (43%) RPFNA aspirates. The presence of RARbeta methylation correlated with the severity of the mammary epithelial cell atypia seen in the RPFNA cytology. Conclusions: We detect the presence of RARbeta P2 methylation early in mammary carcinogenesis and its presence positively correlates with worsening degrees of mammary epithelial cell atypia (Masood score). These observations provide further support that presence of RARbeta P2 promoter methylation in RPFNA can contribute to assessment of breast cancer risk. No significant financial relationships to disclose.
One‐stop‐shop with confocal microscopy imaging vs. standard care for surgical treatment of basal cell carcinoma: an open‐label, noninferiority, randomized controlled multicentre trial
Authors: D.J. Kadouch, Y.S. Elshot, B. Zupan‐Kajcovski, A.S.E. Haersma de With, A.C. Wal, M. Leeflang, K. Jóźwiak, A. Wolkerstorfer, M.W. Bekkenk, P.I. Spuls, M.A. Rie
Journal: British Journal of Dermatology (2017)

Routine punch biopsies are considered to be standard care for diagnosing and subtyping basal cell carcinoma (BCC) when clinically suspected.We assessed the efficacy of a one-stop-shop concept using in vivo reflectance confocal microscopy (RCM) imaging as a diagnostic tool vs. standard care for surgical treatment in patients with clinically suspected BCC.In this open-label, parallel-group, noninferiority, randomized controlled multicentre trial we enrolled patients with clinically suspected BCC at two tertiary referral centres in Amsterdam, the Netherlands. Patients were randomly assigned to the RCM one-stop-shop (diagnosing and subtyping using RCM followed by direct surgical excision) or standard care (planned excision based on the histological diagnosis and subtype of a punch biopsy). The primary outcome was the proportion of patients with tumour-free margins after surgical excision of BCC.Of the 95 patients included, 73 (77%) had a BCC histologically confirmed using a surgical excision specimen. All patients (40 of 40, 100%) in the one-stop-shop group had tumour-free margins. In the standard-care group tumour-free margins were found in all but two patients (31 of 33, 94%). The difference in the proportion of patients with tumour-free margins after BCC excision between the one-stop-shop group and the standard-care group was -0·06 (90% confidence interval -0·17-0·01), establishing noninferiority.The proposed new treatment strategy seems suitable in facilitating early diagnosis and direct treatment for patients with BCC, depending on factors such as availability of RCM, size and site of the lesion, patient preference and whether direct surgical excision is feasible.