tbuckley/cabot-search huggingface dataset:
UCBT with ATG in adult patients.
Authors: W. M. Linkesch, D. Strunk, W. Zinke-Cerwenka, H. Sill, P. Neumeister
Journal: Journal of Clinical Oncology (2011)

6583 Background: Unrelated donor umbilical cord blood transplantation (UCBT) has been increasingly used as an alternative haematopoietic stem cell source (HSCT) for adult patients lacking a suitable human leucocyte antigen (HLA) matched donor. Methods: Between 2001 und 2011 28 UCBT's in 22 adult patients have been performed at our department: 13 AML, 5 Ph+ALL, 2 blastic plasmozytoid dendritic B-cell neoplasms, 1 CML-blast crisis, 1 CML chronic phae (43 [21-60]) years, 14 male/8 female) 2 patients got a second UCBT due to primary non engraftment and 4 additional patients were retransplanted after preceding allo- or auto HSCT. Myeloablative conditioning (n=11) consisted of Cyclophosphamide 60 mg/kg x 2 days, fractionated total body irradiation (fTBI) 1.200 cGy or VP16 60 mg/kg x 1 d/fTBI 1.200 cGy, whereas non-myeloablative conditioning (n=11) consisted of Cyclophosphamide 50 mg/kg x 1 d, Fludarabine 30 mg/m² x 6 d/fTBI 400 cGy. All patients received a Graft versus Host Disease (GvHD) prophylaxis: Cyclosporin for a minimum of 180 days after UCBT, Antithymocyte Globlulin (ATG Fresenius) 5 mg/kg x 4 d and Methotrexate 10 mg/m² day +1 and +3. Results: Nucleated cell dose infused for single UCBT was 3,52 (2-5,72) x 107/kg and 3,23 (2,74-4,21) x 107/kg body weight for double UCBT. CD34+ cell dose infused was 1,44 (0,21-5,6) x 105/kg for single and 1,19 (0,86-1,85) x 105/kg for double UCBT. Concerning HLA match 75 % had a HLA mismatch 4/6, 25 % 5/6. In double UCBT no DRB1 mismatch, but A and/or B mismatch was allowed. Time to neutrophil and platelet recovery was not different between single and double–unit recipients. Recovery of platelets ≥ 20 x 109/L took place after 40 (0-56) days in single UCBT and after 40 (36-43) days in double UCBT. Neutrophil recovery > 0,5 x 109/L appeared after 28 (15-42) days in single and after 29 (20-35) days in double UCBT's. The incidence of grade III-IV acute GvHD was remarkable low with 5 % and grade I-II acute GvHD was 15 %. Until now we could not observe extensive chronic GvHD. Conclusions: After an observation period up to 122 months overall survival was 50 %. We conclude that low dose ATG seems to contribute to a remarkable low incidence of GvHD in mainly heavily pretreated patients.
Comparative prognostic value of myocardial strain derived from DENSE CMR: the British Heart Foundation MR-MI study
Authors: Kenneth Mangion, David Carrick, Jaclyn Carberry, Ahmed Mahrous, Christie McComb, Hao Gao, Xiayou Luo, Keith Oldroyd, Hany Eteiba, Margaret McEntegart, Mitchell Lindsay, Mark Petrie, Xiaodong Zhong, Caroline Haig, Colin Berry
Journal: The Lancet (2017)
Investigating racial disparities in use of NK1 receptor antagonists to prevent chemotherapy-induced nausea and vomiting among breast cancer patients.
Authors: Devon Check, Katherine Elizabeth Reeder-Hayes, Ethan M. Basch, Leah L. Zullig, Morris Weinberger, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2016)

292 Background: Chemotherapy-induced nausea and vomiting (CINV) is a major concern for cancer patients and, if uncontrolled, it can have serious implications for patients’ treatment outcomes, including quality of life. Guidelines recommend the use of an NK1 receptor antagonist to prevent CINV among patients beginning chemotherapy with a high risk of causing the side effect. However, barriers to use of oral NK1s (i.e., aprepitant) exist. In many cases, patients are required to fill a prescription for aprepitant at their home pharmacy. As well, the drug is expensive, costing over $500 under Medicare Part D, and patients may be responsible for a large portion of that cost. These barriers may contribute to racial disparities as they disproportionately affect minority patients. Methods: We used 2006-2012 SEER-Medicare data to evaluate the use of NK1s among black and white women initiating adjuvant chemotherapy with an anthracylcline and cyclophosphamide for early-stage breast cancer. NK1 use during the first chemotherapy cycle was measured using Medicare Part D and Part B claims. We used modified Poisson regression to assess the relationship between race and (1) any NK1 use, (2) oral NK1 (aprepitant) use, and (3) intravenous NK1 (fosaprepitant) use. We report adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results: Of 1,015 eligible women (911 white; 104 black), 38% of white and 28% of black women received any NK1 at the start of their chemotherapy regimen. In adjusted analyses, black women were 30% less likely than white women to receive any NK1 (aRR black vs. white: 0.70, 95% CI: 0.52-0.94). This disparity was driven by a 44% gap in orally administered NK1s (aprepitant) (aRR: 0.56 95% CI: 0.35-0.89). We did not observe disparities in intravenous fosaprepitant use (aRR: 0.77, 95% CI: 0.46-1.28, NS). After controlling for variables related to socioeconomic status, disparities in NK1 and aprepitant use were reduced but not eliminated. Conclusions: Our study found racial disparities in women’s use of oral NK1s for the prevention of CINV. These disparities may be partly explained by racial differences in women’s ability to afford the medication.
Toward proven and prioritized quality measures: Which ASCO QOPI and other supportive care measures associate with improved quality of life (QOL)?
Authors: Arif Kamal, Janet Bull, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2012)

165 Background: An expanding array of quality measures, including the Quality Oncology Practice Initiative (QOPI) metrics, is being developed for oncology. To date, evidence demonstrating the impact of each metric on outcomes, ultimately aiding in prioritization of individual measures, remains immature. We investigated the relationship between conformance with quality measures and higher patient QOL among cancer patients receiving palliative care. Methods: A comprehensive systematic review of PUBMED and the gray literature (1995-2012) identifed all described supportive care quality measures. Patients receiving palliative care in 4 community-based programs were entered into a longitudinal quality registry; analyses focused on cancer patients registered between 6/08-10/11. To find predictors of higher QOL, conformance cohorts were examined for demographic variables, performance status (measured by palliative performance scale, PPS) and provider estimation of prognosis and included in univariate and multivariate regression. Results: The systematic review yielded 303 quality measures. Of these, 18 measures, representing components of the ASCO QOPI, Hospice PEACE, and Cancer-ASSIST measure sets, were evaluable using registry data. 460 cancer patients were included. 60% of patients had weeks to 6 months expected prognosis. Among QOPI measures, conformance with two measures was significantly associated with better QOL: constipation assessment at time of narcotic prescription and emotional well-being assessment (both p&lt;0.05). Other significant findings were conformance with screening of symptoms at first visit (p=0.017), timely treatment for uncontrolled dyspnea (p=0.005), and assessment of fatigue (p=0.007). In a multivariate model predicting higher QOL, measures involving emotional well-being assessment (OR 1.60; p=0.026) and screening of symptoms (OR 1.74, p=0.008) remained significant. Conclusions: Clinical care that conforms to quality measures reflecting regular symptom and emotional assessment is significantly associated with better patient experiences (QOL) and should be prioritized in quality assessment efforts.
Preoperative chemoradiotherapy with capecitabine and oxaliplatin in patients with locally advanced rectal cancer.
Authors: I. Marrodan, E. Azkona, S. Carrera, U. Aresti, B. Calvo, A. Buque, A. Sancho, A. Ruiz de Lobera, A. Munoz Llarena, G. Lopez-Vivanco
Journal: Journal of Clinical Oncology (2011)

548 Background: Locally advanced rectal carcinoma is associated with high rate of abdomino-perineal amputation. We analyzed a cohort of patients (pts) diagnosed of locally advanced rectal cancer, treated with neoadjuvant chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (XELOX) followed by four cycles of adjuvant XELOX after surgery. Methods: Patients with locally advanced rectal cancer (T3-T4 and/or N+) were treated with oxaliplatin (50mg/m 2 day 1, 8, 22 and 29) and capecitabine (1,650mg/m 2 on days 1 to 14 and 22 to 35) combined with pelvic radiotherapy (180 cGy/day; 45Gy in 25 fractions). Surgery was scheduled 4 to 6 weeks after completion QT-RT. Four cycles of adjuvant XELOX were administered (capecitabine 2,000mg/m 2 on days 1 to 14 and oxaliplatin 130mg/m 2 on day 1) every 3 weeks. Main end points assessed were: rate of sphincter preservation, pathologic complete response (pCR) rate and the feasibility of postoperative chemotherapy. Results: From March 2007 to April 2010, 98 pts with locally advanced rectal cancer were included. M/F: 66/32; ECOG 0/1: 19/79; median age: 64 (38-81); upper/mid/distal rectum: 13/50/35; clinical stage: cT3/N- 9, cT2-T3/N+ 72, cT4/N- 4, cT4/N+ 13. Full dose of preoperative QT-RT was administered in 93 pts (95%). Main toxicities were grade 1/2 neurotoxicity (56/4) and grade 2/3 diarrhea (23/10). After treatment 96 pts underwent surgery. Sphincter preservation, R0 resections and pCR were achieved in 57, 93 pts and 17 (18%) patients, respectively, and 65 pts (66%) received all 4 cycles of adjuvant XELOX. Grade 3/4 toxicities included diarrhea 3/0, vomiting 2/0, neurotoxicity 5/0, hand-foot syndrome 1/0, neutropenia 4/0 and thrombopenia 0/4. 3-year progression-free and overall survival were 66% and 72%, respectively. No toxic deaths were reported. Downstaging in T/N stage was achieved in 53/71 pts (55/74%) respectively. Conclusions: Combination preoperative QT-RT with capecitabine and oxaliplatin is a well tolerated regimen and achieves encouraging rates of pCR, R0 resection, sphincter preservation and tumor downstaging in patients with locally advanced rectal cancer. No significant financial relationships to disclose.
Are there benefits to long-term bisphosphonate treatment in multiple myeloma (MM)? Insights from temporal analyses of zoledronic acid (ZOL) versus clodronate (CLO) in the MRC Myeloma IX Trial.
Authors: F. Davies, G. Morgan, P. Wu, W. Gregory, S. E. Bell, A. Szubert, N. Navarro Coy, M. Drayson, R. G. Owen, S. Feyler, J. Ashcroft, F. Ross, J. Byrne, H. Roddie, C. Rudin, G. Cook, G. H. Jackson, K. Boyd, J. A. Child
Journal: Journal of Clinical Oncology (2011)

8011 Background: The MRC Myeloma IX Study (MMIX) showed significant benefits for zoledronic acid (ZOL) beyond those of clodronate (CLO) for overall survival (OS) in patients (pts) with newly diagnosed multiple myeloma (MM; Lancet 2010). Guidance is needed for the optimal initiation and duration of bisphosphonate therapy for MM. Treatment effects across the duration of MMIX could provide additional insight. Methods: Newly diagnosed MM pts were randomized to antimyeloma therapies plus ZOL (4 mg q 21-28 days) or CLO (1,600 mg q day) at least until disease progression; pts could participate in a subsequent randomization to either maintenance thalidomide (Thal) or no Thal. Exploratory analyses of OS and skeletal-related events (SREs) were performed for time periods within the study to evaluate potential temporal differences. Results: Among the intent-to-treat population (N=1,960; median follow-up, 3.7 yr), 917 died. Median OS was 5.5 mo longer with ZOL vs CLO (hazard ratio [HR]=0.84; 95% CI, 0.736, 0.963; P=.012). The OS benefit first achieved statistical significance during mo 2 and was especially profound during the first 4 mo, wherein ZOL significantly reduced the risk of death by 36% relative to CLO (HR=0.64; P=.004). ZOL consistently reduced the mean number of SREs/pt vs CLO by 26% at 1 yr (D0.11; 95%CI 0.04, 0.18), by 30% at 2 yr (D0.18; 95%CI 0.09, 0.26), by 33% at 3 yr (D0.23; 95%CI 0.12, 0.33), by 38% at 4 yr (D0.30; 95%CI 0.17, 0.44), and by 39% at 5 yr (D0.32; 95%CI 0.18, 0.46). Overall, ZOL reduced the cumulative incidence of SREs vs CLO (HR=0.74; 95%CI, 0.62, 0.87; P=.0004). ZOL continued to significantly reduce SRE risk vs CLO during the maintenance phase in both the Thal (P=.044) and no-Thal (P=.003) groups. Conclusions: In MMIX, the OS benefit from ZOL vs CLO became apparent during the first 4 mo of therapy, supporting early use of ZOL for potential anticancer effects in pts with newly diagnosed MM. ZOL produced significant reductions in SRE risk vs CLO with either Thal maintenance therapy or no Thal, and during each yr of the study, supporting ongoing use to prevent SREs.
A combination herbal supplement for biochemically recurrent prostate cancer.
Authors: Tanya B. Dorff, Debra Hawes, Denice D. Tsao-Wei, David I. Quinn, Amir Goldkorn, Gary Lieskovsky, Nicholas J. Vogelzang, Susan G. Groshen, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2012)

24 Background: After curative local therapy, thousands of men will have rising PSA as an early indicator of recurrent prostate cancer. For them, no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D &amp; E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods: Eligible men had rising PSA with doubling time (DT) 3-36 months, with no evidence of metastases on CT and bone scans. After IRB approval, 28 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after the first cycle, then every 2 cycles with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: The median age was 67 (range 54-84) and baseline PSA was 2.9 ng/mL (1.1-53.2); the median number of cycles was 6 (1-13). Stable PSA was the best response for 23/28 men (83%) and 8/27 men (29.6%) had a PSA decline (1.1%-29.4% maximum decrease). 47% stopped therapy for progression with median time to progression=9.2 months. There was no association between Gleason score or baseline PSA, vitamin D or selenium level and PSA decline. CTCs were detected in 5 of the first 23 subjects. The median PSA for these men was 2.77 ng/mL (range 1.63-16.8). There was no significant change in testosterone or DHT during treatment. Median PSA DT at baseline was 7.8 months (range 3-36). One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise toxicities were limited to grade 1 or 2 hypercalcemia(1), hyperkalemia(2), hyperglycemia(4), flatulence(4), other GI(5), and rash(1). Conclusions: PHC demonstrated activity in men with biochemically recurrent prostate cancer, resulting in PSA declines in nearly a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology.
Methylthioadenosine phosphorylase (MTAP) gene deletions are frequent in chondrosarcomas
Authors: W. A. Chow, M. Slovak, V. Bedell, D. Hicks, J. Goldblum, E. Borden
Journal: Journal of Clinical Oncology (2005)

9019 Background: Chondrosarcomas are the second most common primary malignant tumor of bone after osteogenic sarcomas. Conventional chemotherapy for non-low-grade chondrosarcomas is generally ineffective. MTAP is a ubiquitous enzyme that catalyzes the phosphorolysis of the nucleoside methylthioadenosine (MTA), which is generated during the synthesis of the polymines, spermidine and spermine. MTAP is an essential enzyme in the salvage pathway of adenine and in methionine synthesis. Cells lacking the MTAP gene are unable to salvage adenine from MTA, and therefore are more dependent upon the de novo synthesis of purines. Accordingly, the absence of MTAP function makes MTAP deficient cells more susceptible than wild-type cells to pharmacologic inhibitors of de novo purine synthesis. The MTAP gene locus has been mapped to chromosome locus 9p21. Homozygous deletions of MTAP have been reported in several hematologic and solid tumor malignancies. Based upon these observations, we investigated the frequency of MTAP deletions in non-low-grade chondrosarcomas by fluorescence in-situ hybridization (FISH) analysis. Methods: 23 grade 2 (intermediate-grade) chondrosarcoma patient samples from the Cleveland Clinic Foundation were analyzed for MTAP deletions. Results: Nuclei were successfully extracted from 14/23 samples (61% evaluable) for FISH analysis. 7/14 samples (50%) demonstrated a deletion of the MTAP gene, 6/14 (43%) failed to demonstrate a deletion, and 1/14 (7%) was inconclusive. Conclusions: These findings suggest that approximately one-half of grade 2 chondrosarcomas may be preferentially sensitive to pharmacologic inhibitors of de novo purine synthesis. This study has resulted in the development by the Intergroup Coalition Against Sarcomas of a phase II trial of pemetrexed, a multi-targeted anti-folate, for advanced chondrosarcomas. No significant financial relationships to disclose.
Concentration-depth profiles of mitomycin-C in the human bladder wall after passive diffusion, thermochemotherapy, and electromotive drug administration.
Authors: G. Leprini, R. Massoud, S. Dolci, P. Navarra, C. Verri, F. Torelli, F. Angelini, S. M. Di Stasi
Journal: Journal of Clinical Oncology (2010)

4568 Background: Device-assisted intravesical mitomycin-C (MMC), including electromotive administration (EMDA) and thermochemotherapy (TC), shows promise and offers the prospect of greater efficacy than passive diffusion (PD). Integration of drug delivery with tissue pharmacodynamic data provides a means to rational design of intravesical treatments. We compared concentration-depth profiles of MMC in the bladder wall after PD, TC and EMDA. Methods: During each experiment, 3 full thickness sections of viable human bladder wall were placed between the two chambers of individual diffusion cells, with urothelium exposed to donor compartments containing 40 mg of MMC in 100 ml water and with serosa-facing receptor compartments containing 100 ml of 0.9% NaCl solutions. Fifteen paired experiments were conducted over a 30-min period. In TC experiments, the two chamber cells were placed in a 37°C incubator with the donor compartments filled with heated MMC solutions at 44°C. In EMDA experiments an anode was placed in the donor compartment and a cathode in the receptor compartment. The electrodes were connected to the current generator and experiments were performed with pulsed direct current of 23 mA. No electric current or TC were applied in PD control experiments. Bladder wall sections were cut serially into 40-mm slices parallel to the urothelium, the tissues were homogenized and analyzed by high-performance liquid chromatography for MMC concentration. Results: Concentration-depth profiles of MMC in bladder wall tissues following PD, TC or EMDA are reported below (Table). Data are expressed as μ g of MMC/mg of wet tissue, the means ± standard error of the mean (SEM) of 15 replicates per experimental group. Conclusions: EMDA significantly enhances MMC transport into all of the layers of the bladder wall, compared to both PD and TC. The latter had no effect whatsoever on MMC transport into bladder wall tissues compared to PD. PD TC EMDA p value Urothelium (80-200 μ m) 53.057 ± 8.240 58.270 ± 8.820 207.991 ± 23.440 <0.001 Lamina propria(200-1,200 μ m) 18.095 ± 2.139 20.935 ± 3.205 85.339 ± 5.882 <0.001 Muscle layer(1,200-4,000 μ m) 2.120 ± 0.326 2.424 ± 0.297 24.888 ± 3.645 <0.001 No significant financial relationships to disclose.
Combination or irinotecan (I) and 5-fluorouracil, leucovorin (5 FU/LV) in first and second line treatment in elderly patients with metastatic colo-rectal cancer (MCRC)
Authors: H. G. Botto, M. E. Botto
Journal: Journal of Clinical Oncology (2005)

3743 Background: In a previous trial (ASCO 2004, 3717) we reported the efficacy and tolerability of patients (pts) > 70 years with MCRC, treated with OXA-5 FU/LV bi-weekly combination. The purpose of the present trail was to evaluate the feasibility, response, toxicity and survival with the Irinotecan, 5 Fluorouracil, leucovorin, (I-5 FU/LV) combination in first line treatment (1st L) and in second line treatment (2nd L), in elderly pts over 69 years with MCRC. Methods: Eighteen pts, with good cardiac, hematological and renal function, median age 75 years (range 70–84 y), M/F 10/8, PS, 0:9; 1:7; 2:2, predominant sites of disease, liver:10, locoregional:5, lung:3; 8 patients were previously untreated and 10 pts relapsed or had progressive disease after OXA-5-FU/LV combination. Treatment: I, 100 mg/m2, IV; 5 FU, 500mg/m2, IV; LV, 20 mg/m2, were given on days 1, 8 and 15; cycles have been repeated every 28 days. The total number of cycles was 84, and the median number of cycles was 4 (range 2–8). Response was examined every 8 weeks. All pts were evaluated for response, toxicity and survival. Results: CR 1/18 (5,55%); PR 6/18 (33,33%); SD 6/18 (33,33%); PR 5/18 (27,79%). OR: 7/18 (38,89%), (4/8, 50% in 1st L and 3/10, 30% in 2nd L). Toxicity: Gr 2/3: neutropenia 50%, thrombocitopenia 22%, anemia 33%, diarrea 33%, nausea 44%, astenia 39%. The median time to progression (TTP) was 6.5 months in all pts; 4,5 months in the 2nd L pts and 8.5 months in the 1st L pts. The median survival time (MST) was 16 months in all pts, 12 months in 2nd L pts and 23 months in 1st L pts. Conclusion: Eldest pts over 69 years, with MCRC, treated with the I-5 FU/LV combination following this schedule, proved antitumoral response, with OR: 50% in 1st L and 30% in 2nd L after OXA/FU/LV, acceptable tolerability and good survival time as well. No significant financial relationships to disclose.