tbuckley/cabot-search huggingface dataset:
Validation of a questionnaire on screening for frailty in elderly patients: The Barber test.
Authors: M. J. Molina-Garrido, C. Guillen-Ponce, M. Munoz Sanchez, J. A. Santiago Crespo, A. Olaverri Hernandez, C. Ortega Ruiperez, A. Carrato
Journal: Journal of Clinical Oncology (2011)

e19570 Background: The term ‘frailty’ is spreading in the field of Oncogeriatry. However, there is no unanimity about the methods to detect it. In assessing ambulatory elderly, the Barber test/BT) has traditionally been applied, but its use is not widespread in the elderly population with cancer. The aim of this study is to validate this last questionnaire in the elderly with cancer. Methods: In the General Hospital de Cuenca, the BT was applied prospectively to all elderly over 70 years of age and diagnosed with cancer in the period between June and December 2010. Descriptive data related to each patient and the tumor, were also collected. Using SPSS 15.0, we calculated the reliability of this questionnaire by calculating the internal consistency (Cronbach index, CR), and the temporal stability of the questionnaire (intraclass correlation coefficient, ICC). All patients gave their consent to participating in this study. Results: Data were collected from a total of 86 patients. The mean age was 78.66 years (70.23 minimum, and maximum 91.8). 62.4% of the sample were men (n = 53). 43.5% of patients had ECOG 1 (n = 37), and 34.1% had ECOG 0 (n = 29). 44.7% (n = 38) had been diagnosed with gastrointestinal tumors, 23.5% (n = 20) with breast and gynecological tumors and in 9 cases (10.6%) there was a urological or prostate tumor. The average score of the BT was 1.31 (minimum 0 and maximum 5). There were 61 patients (72.6%) at risk of frailty according to the BT (score ≥ 1). The CR and the index of absolute agreement were 0.782. The ICC was 0.275. Conclusions: The Barber test presents a heterogeneous variability in its items and leads to wrong conclusions (CR 0.782). In addition, this questionnaire lacks temporal stability (ICC 0.275). The BT as screening of frailty, lack of reliability in the field of Oncogeriatry, so that in this population, another frailty screening tools should be used.
Retrospective review of MRIs in lung cancer patients with brain metastases: An assessment of early response.
Authors: R. Zinner, M. Debnam, G. W. Gladish, B. Konda, J. M. Hanneken, D. J. Stewart, R. F. Munden, L. Chi
Journal: Journal of Clinical Oncology (2011)

7543 Background: Although chemotherapy (chemo) may be effective in treating brain metastases from both small cell (SCLC) and non-small cell (NSCLC) lung cancer, ability to detect non-response early has potential advantages. We report our experience in early assessment of brain metastases after one chemo course. Methods: This is a retrospective study of consecutive SCLC and NSCLC patients (pts) with asymptomatic brain metastases treated with chemo from 01/2005 to 11/2010 who underwent repeat MRI before the 2nd chemo course. Pts with no prior therapy or with progressive disease (PD) in brain after prior whole brain XRT or chemo were included. Serial 1.5 or 3.0T MRI scans done at baseline (scan #1), within 31-days of first round chemo (scan #2) and after the 2nd cycle of chemo (scan #3) were independently reviewed by 2 neuroradiologists. A maximum of 3 lesions were measured using RECIST criteria, in the axial plane, using electronic calipers on a PACs workstation (Philips iSite). Results: There were 37 pts (12 men, 25 women), median age 61 (range 29-76); 4 with SCLC and 33 with NSCLC. Twenty pts had received no prior therapy and 17 had received 1-7 prior regimens. bevacizumab was given in 17/37 (46%). No pts developed symptomatic brain metastases within 2 cycles. Nine pts had at least one lesion > 1cm and 28 pts had a largest lesion < 1cm. Scan #3 was performed in 32/37 patients. 6/37 (16%) pts had partial response (PR) at scan #2. At scan #3, 5 pts continued to have PR. The 6th pt died prior to scan #3. 24/37 (65%) pts had stable disease (SD) at scan #2. At scan #3, 9 pts continued to have SD, 12 converted to PR, 2 converted to progressive disease (PD), and one was lost to follow-up. 7/37 (19%) pts had PD at scan #2. At scan #3, 4 had further progression. 3 pts stopped chemo after 1 course without further imaging. Thus, 7/9 (78%) pts who had documented PD on either scans #2 or #3, had evidence of PD by scan #2 and no pts with PD at scan #2 had a better response on later evaluation. Of 3 pts with prior whole brain XRT (5-23 mos. previously), 2 had PD after 1 course, 1 had PR after 2 courses. Conclusions: Short-term follow-up MRI in SCLC or NSCLC pts receiving chemo for brain metastases can detect PD and permit early discontinuation of ineffective therapy.
Erratum: Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells
Authors: H Dolatshad, A Pellagatti, M Fernandez-Mercado, B H Yip, L Malcovati, M Attwood, B Przychodzen, N Sahgal, A A Kanapin, H Lockstone, L Scifo, P Vandenberghe, E Papaemmanuil, C W J Smith, P J Campbell, S Ogawa, J P Maciejewski, M Cazzola, K I Savage, J Boultwood
Journal: Leukemia (2015)
Long-term quality of life after conventional-dose versus high-dose radiation for prostate cancer: Results from a randomized trial (PROG 95–09)
Authors: J. A. Talcott, J. D. Slater, A. Zietman, C. Rossi, W. U. Shipley, J. A. Clark
Journal: Journal of Clinical Oncology (2008)

5058 Background: Increased radiation dose may improve local control of cancer, but may also increase treatment-related toxicity. The Proton Radiation Oncology Group (PROG) of the American College of Radiology randomized 392 patients to receive either 70.2 GyE or 79.2 GyE of combined photon and proton radiation (PROG 95–09) between January 1996 and December 1999. At a median follow-up of 5.5 years, freedom from biochemical failure was greater for high dose (HD) vs. conventional-dose (CD) patients (P<0.001) (JAMA 2005, 294:1233–9). While the treatment groups did not differ in physician-reported morbidity, such assessments are known to be insensitive compared to patient- reported data. Therefore, we initiated a cross-sectional patient survey at a minimum of 7 years after treatment to assess their long-term morbidity. Methods: We attempted to survey all surviving patients using the validated Prostate Cancer Symptom Indexes (PCSI), which measures urinary, bowel and sexual dysfunction, expressed as both numerical scale scores and levels of function (normal, intermediate and poor). Follow-up is nearly complete. Results: As of January 4, 2008, of 353 eligible study participants sent questionnaires, 241 patients have returned questionnaires, 10 patients had died, 17 patients refused participation, and 85 patients (24.1%) have not responded, for 17 of whom we did not have valid contact information. We found no differences in mean scale scores for urinary incontinence and obstruction/irritation, bowel problems and sexual dysfunction (see Table) nor for the proportions of patients with normal, intermediate and poor function (data not shown). Conclusions: These patient-reported results, the most sensitive indicator of treatment-related toxicity, indicate that increased doses of highly conformal radiation therapy sufficient to improve the control of clinically localized prostate cancer do not cause significantly increased morbidity. Results of survey of surviving patient in PROG 9509 Variable Conventional Dose Patients High-Dose Patients All Patients P-value Patients (number) 111 129 240 Age (mean, years) 75.0 75.2 75.2 0.80 Urinary Incontinence 11.8 10.1 10.9 0.45 Urinary Obstruction/Irritation 23.2 24.9 24.1 0.35 Bowel Problems 7.5 7.8 7.6 0.81 Sexual Dysfunction 65.3 66.4 65.9 0.80 Symptom scales 0–100 No significant financial relationships to disclose.
Gemcitabine alone versus gemcitabine plus cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic adenocarcinoma: A retrospective analysis of multicenter study.
Authors: A. Inal, A. Isikdogan, T. Kos, E. Algin, M. Gumus, M. Dikilitas, E. T. Elkiran, K. Helvaci, C. Geredeli, F. Dane, O. Balakan, A. Gok Durnali, H. Harputluoglu, G. Goksel, N. Ozdemir, S. Buyukberber, R. Yildiz, M. A. Kaplan, M. Ozkan, D. Uncu
Journal: Journal of Clinical Oncology (2011)

e14534 Background: The majority of patients with pancreatic cancer is advanced disease The aim of this retrospective multicenter study is to evaluated the efficiency of gemcitabine alone versus gemcitabine plus cisplatin in patients with locally advanced and/or metastatic pancreatic adenocarcinoma. Methods: A total of 372 patients, from referral center were evaluated retrospectively. All patients received gemcitabine (Gem) or gemcitabine plus cisplatin (GemCis) as first-line treatment between September 2005 to January 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. Results: Gemcitabine arm 130 (M: 86, F: 44), the combination arm 242 (M: 171, F: 71) were patients. Gemcitabine arm patients older than the combination arm (median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25% vs 9%, p=0.001) and dose delay (34% vs 17.2%, p=0.001). Among patients with the combination and gemcitabine alone arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the gemcitabine alone arm (69.1% vs 50.9, p=0.001). Progression-free survival (PFS) were more favorable in the GemCis arm than Gem arm, but the difference did not attain statistical significance (7.8 vs 5.0, p=0.07). Overall survival (OS) was not significantly superior in the GemCis arm (9.4 vs 8.0, p>0.05). Grade III-IV neutropenia (21% vs 8.3% p=0.006), and diarrhea (7.7% vs 2%, p=0.05), was higher in the combination arm. Other toxicities profile was similar in both groups (p>0.05). Conclusions: PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. Overall survival (OS) was not significantly superior in the GemCis arm.
Effect of race on cyclophosphamide (CP) metabolism.
Authors: M. D. Walsh, A. J. Combest, J. H. Hull III, A. Dvorak, J. M. Hoskins, E. C. Dees, H. L. McLeod, C. M. Walko
Journal: Journal of Clinical Oncology (2010)

e13127 Background: CP, an alkylating prodrug used to treat many cancers, undergoes metabolism via two pathways: conversion to active 4-hydroxy-CP (4-OH) by cytochrome P450 (CYP) 2B6 (major) and 3A4 (minor), and cleaved to inactive 2-dechloroethyl-CP (DCE) + chloroacetalaldehyde (CA) by CYP3A4/5. Neuro- and nephro-toxicity of CP is attributed to CA. Preliminary results of a drug interaction crossover study consisting of doxorubicin/CP and aprepitant or placebo indicated substantial inter-pt variability in the PK of CP (ASCO 2009, abstract 588). Accordingly, we sought to determine the effect of race and genetics on CP PK when CP was given alone. Methods: Breast cancer (n=18; 12 C, 6 AA) pts received CP 600 mg/m2 IV over 30 min. Serial blood samples were collected at baseline to 24 h. Plasma was analyzed by LC-MS/MS for CP, 4-OH and DCE. Noncompartmental PK was estimated using WinNonlin for area under the conc vs time curve to 24 h (AUCt). DNA from blood was extracted and pts were genotyped for CYP2B6*6, CYP3A4*1B and CYP3A5*3using pyrosequencing. Data analyses included descriptive statistics and regression with α=0.05. For analyses, AUCt values were loge-transformed (ln). Results: As all AAs had at least 2 variant alleles, genotype analysis was confounded by race. A significant direct correlation was shown between lnAUCt for CP and DCE (r=0.67, p<0.01) but not CP and 4- OH. The higher CP lnAUCt in AAs was not significant. Included in the same model, both CP lnAUCt (p<0.01) and race (p<0.02) were significant predictors of DCE lnAUCt. Neither variable was predictive of 4-OH lnAUCt. Conclusions: After adjusting for CP AUCt, AAs have significantly more DCE (but not 4-OH) than Cs. Greater DCE formation may be due to variant alleles as all AAs carried variant alleles in at least two genotypes. Higher DCE suggests a greater risk of CP toxicity by CA. Both findings should be interpreted with caution, since the current study was small and not designed to address these issues. A large, adequately powered, clinical study designed to address effects of race/genetics on CP PK is needed. Geometric mean (95% CI) AUCt Compound C (n=12) AA (n=6) CP 217 (177, 267) 256 (225, 291) 4-OH 7.5 (6.1, 9.1) 6.7 (4.6, 9.9) DCE 7.4 (5.2, 10.4) 15.1 (10.7, 21.3) No significant financial relationships to disclose.
Humoral Compensation after Bortezomib Treatment of Allosensitized Recipients
Authors: Jean Kwun, Christopher Burghuber, Miriam Manook, Neal Iwakoshi, Adriana Gibby, Jung Joo Hong, Stuart Knechtle
Journal: Journal of the American Society of Nephrology (2017)

The efficacy of bortezomib monotherapy in desensitizing kidney transplant candidates with preformed donor-specific antibodies remains unclear. We evaluated the effect of bortezomib on preformed antibodies and upstream components of the B cell response in a primate model sensitized by fully mismatched allogeneic skin transplants to provide mechanistic insights regarding the use of bortezomib as a means of desensitization. Bortezomib treatment given intravenously twice weekly for 1 month (1.3 mg/m2 per dose) clearly reduced the numbers of antibody-producing cells and CD38+CD19+CD20- plasma cells in the bone marrow (P<0.05), but donor-specific alloantibody levels did not decrease. We observed a rapid but transient induction of circulating IgG+ B cells and an increased number of proliferating B cells in the lymph nodes after 1 month of treatment. Notably, bortezomib treatment induced germinal center B cell and follicular helper T cell expansion in the lymph nodes. These data suggest that bortezomib-induced plasma cell depletion triggers humoral compensation.
Tubular carcinoma of the breast: A single institution's experience of prognosis.
Authors: William P Boyan, Michael Farr, Brian Shea, Manpreet Kohli, Ernest Ginalis
Journal: Journal of Clinical Oncology (2015)

37 Background: Tubular carcinoma is a less aggressive form of breast cancer which emcompasses 1-4% of invasive breast cancer. Prior studies have shown a nearly 100% 15 year survival rate for tubular carcinoma compared to the 89.2% five year survival of all breast cancers. The question asked is if these two cancers should be treated the same. The goal of oncologic treatment is to maximize survival while limiting side effects. At the very least, care givers should be able to give prognostic encouragement to patients based on this less aggressive histological subtype. Methods: A retrospective study of charts for tubular carcinoma of the breast from 2000 to 2015 were analyzed. A total of 57 patients were captured. All relevant aspects of the patients history, as well as therapies rendered and outcomes were documented. The aim of our study was compare treatment outcomes in our group of tubular carcinomas to that of breast cancer as a whole. Results: A total of 57 patients were diagnosed and treated for tubular carcinoma of the breast between 2000 and 2015 from a single institution. Of the 57 patients, local recurrence was seen in two patients. The first patient underwent lumpectomy, endocrine and radiation therapy then recurred as an invasive ductal carcinoma 12 years later. A second patient underwent lumpectomy with endocrine treatment but refused radiation, recurring as a tubular carcinoma 10 months later. In our 16 year sample the recurrence rate was 3.5% or 1.75% recurring as tubular. This is lower than the rates of recurrence of all breast cancer. To this date there were no cancer related mortalities in our group. Conclusions: A look into our institution’s data supported the notion that tubular carcinoma of the breast is a less aggressive histological type. Of our 57 cases and mean follow up time of six years ranging from one year to fifteen, only two recurrences (3.5%) were noted and there was no cancer related mortalities. Interestingly only one (1.75%) recurred as tubular carcinoma. Without controlling for adjuvant therapy, recommendations cannot be made for a less aggressive treatment plan at this point. Based on this study and others like it physicians can give evidenced based favorable prognosis when the diagnosis of tubular carcinoma is made.
Breast cancer survivors perception of family physician (FP) or specialist as principal provider of routine follow-up care.
Authors: E. Grunfeld, M. N. Levine, J. Julian, A. Folkes, G. R. Pond, E. Maunsell
Journal: Journal of Clinical Oncology (2010)

9090 Background: Clinical practice guidelines recommend clear assignment of which provider will be responsible for routine follow-up care. However, studies have shown confusion amongst patients and providers as to who is principally responsible. Methods: 408 early stage breast cancer survivors under active routine follow-up at tertiary cancer centers in Canada were enrolled in a randomized controlled trial to evaluate a survivorship care plan. Patients had completed adjuvant chemo- or radiotherapy at least 3 months previously and were without recurrent or new primary cancer. The trial is ongoing and patients are still being followed for the primary outcome. At baseline, patients were asked to identify the physician “primarily responsible for your breast cancer follow-up care.” Results: Thirty-three percent (135/408) identified their family physician (FP) as primarily responsible (of which, 26% identified their FP as solely responsible while 7% identified their FP plus a cancer specialist). Patients who received adjuvant systemic therapy (n=124/350; 35%) and were within two years of diagnosis (n=98/183; 54%) were significantly more likely to identify their FP as primarily responsible (p=0.01 and p<0.001, respectively). Conclusions: It is surprising that one-third of breast cancer survivors under active routine follow-up at tertiary cancer centres consider their FP as primarily responsible for their breast cancer follow-up care, since these patients were at the time all considered to be under specialist follow-up care. In the context of the growing prevalence of breast cancer survivors on routine follow-up and the challenge of rising health care costs, our results suggest that there is a need for clear allocation of responsibility for routine follow-up care. This may help to optimize the use of health care resources and avoid duplication of care. No significant financial relationships to disclose.
The impact of therapeutic modalities on the outcome of advanced epithelial ovarian cancer patients treated in Japan. A JMTO study
Authors: K. Ochiai, H. Kuramoto, K. Yamashita, K.-I. Tanaka, T. Saito, M. Hiura, K. Mizutani, H. Hoshiai, S. Teramukai, H. Tada
Journal: Journal of Clinical Oncology (2004)

5097 Background: The basic treatment strategy of advanced epitherial ovarian cancer (EOC) patients is the combination of maximal surgical debulking and platinum-based adjuvant chemotherapy. The purpose of this study was to assess the impact of treatment modalities on the outcome of stage III and IV EOC patients treated in Japan between 1994 and 2000. Methods: Clinical records of 18 institutions in which the study protocol was approved by their IRB were reviewed. The logrank test was performed to test associations between prognostic facrtors and outcomes. Statistical analyses were done using SAS version 8. Results: Six hundred and ninety four patients were enrolled and their median age was 55 year old. The FIGO stage and number of patients were IIIa 24, IIIb 64, IIIc 471 and IV 135, respectively. The histopathology and number of patients were serous 433, mucinous 55, endometrioid 89, clear cell 60, mixed 16, others 35 and unknown 7, respectively. Median follow-up period was 4.16 years and range was 0.14–8.95 years. In 694 patients, 358 patients had recurred and 346 patients died with the disease. Among prognostic factors we studied, performance status (p=0.0001), FIGO stage (p=0.0001), nodal status (p=0.043), distant metastasis (p=0.0001) did, but overall histopathology (p=0.116) and histological grade (p=0.37) did not affect overall survival (OS) and progression free survival (PFS). Clear cell and mucinous types were significantly worse than other histological cell types on OS (p=0.006) but not on PFS (p=0.192). Residual tumor size after primary surgery was also a strong prognostic factor for OS (p=0.0001) and PFS (p=0.0001). These results were consistent regardless of the lymphadenectomy. Five year survival rates (5YSR) according to the first-line chemotherapy were as follows: CAP (cyclophosphamide + doxorubicin + cisplatin) (n=190): 50.1%, CP or CJ(C + carboplatin) (n=71): 43.7%, TP or TJ (taxol + P or J) (N=193): 44.4%, and there were no significant impact on OS and PFS. Conclusions: Surgical debulking of intra-abdominal tumor mass is the most important procedure to improve the prognosis of advanced EOC patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb