tbuckley/cabot-search huggingface dataset:
Case-control study of long-term survivors of glioblastoma
Authors: E. C. Quant, M. Silver, S. Yip, P. Ryg, K. Provencher, K. McCormack, D. N. Louis, R. Betensky, C. Nutt, T. T. Batchelor
Journal: Journal of Clinical Oncology (2009)

e13021 Background: Survival of patients with glioblastoma (GBM) remains poor. However, a small percentage of GBM patients live ≥ 3 years. Relatively little is known about the patterns of care and outcomes of these long term survivors relative to GBM patients with standard or short-term survival. Methods: Nested case-control study of long term survivors (≥ 36 months), short term survivors (≤ 6 months) and standard survivors (&gt; 6 months but &lt; 36 months). Pathology was confirmed in all study subjects by a single neuropathologist. Each long term survivor (LTS) was matched to a short term survivor (STS) and 3 standard survivors (SS) by the well-established prognostic factors, age and postoperative Karnofsky Performance Status. Clinical characteristics, treatment regimens and outcomes were reviewed. Conditional logistic regression models were used to assess potential associations between baseline factors and the probability of long or short term survival. Results: Matching yielded 23 LTS with 23 STS and 69 SS. Patient characteristics are summarized in the table below. Conclusions: Controlling for the well-established prognostic factors of age and performance status, long-term GBM survivors differed significantly from short-term GBM survivors based on tumor location and extent of resection. However, there were no significant differences in baseline factors between long-term survivors versus standard survivors in this analysis. Short-term GBM survivors differed from standard survivors by tumor location and extent of resection. Molecular factors are being assessed in these groups as potential contributors to these survival differences. [Table: see text] [Table: see text]
Etoposide (VP-16) and cisplatin in previously treated small-cell lung cancer: clinical trial and in vitro correlates.
Authors: G Batist, D N Carney, K H Cowan, S R Veach, M Gilliom, P A Bunn, D C Ihde
Journal: Journal of Clinical Oncology (1986)

Treatment of patients with relapsed small-cell lung cancer (SCLC) has been uniformly unsuccessful. Recently, the combination of etoposide (VP-16) and cisplatin in this setting has been reported to result in up to 50% response rates. We treated 29 patients with relapsed SCLC with this combination and found only a 12% response rate. The discrepancy between our results and those of others is most likely due to differences in prior treatment of the patients, although the effect of dose and schedule modifications are considered. Our patients had received a six-drug regimen over a median of 7 months and had a median drug-free interval before this treatment of only 3 weeks. Evidence is presented that suggests that this aggressive initial therapy affected both host tolerance to further treatment and the development of tumor resistance at the cellular level.
Characterization of cancer pain syndromes (PS) seen at a Comprehensive Cancer Center (CCC) and pain response (PR) to palliative care consultation (PCC)
Authors: D. S. Zhukovsky, J. Palmer, E. Bruera, B. Pei, T. Zhang, C. Nekolaichuk, R. Fainsinger
Journal: Journal of Clinical Oncology (2006)

8551 Background: Comparison of cancer PS across settings is challenging due to differences in prognostic features. Data from 1 CCC participating in a multi-site international study of a pain classification system is presented to characterize cancer PS &amp; response to PCC. Methods: The Edmonton Classification System for Cancer Pain was completed by prospective chart review to characterize PS of 100 consecutive hospitalized patients (pts) seen in PCC. Pts were followed until major PR, hospital discharge or death. Major PR was defined as &lt;2 p.r.n. opioid doses/d &amp; pain intensity (PI) &lt;3/10 for 3 consecutive days (d). Results: 85% of pts had pain (n=85), with age 62.9+13.3, 47.1% male &amp; KPS 44.5+23.1. The most common tumor diagnoses were lung (24.7%) &amp; GU (21.2%). Pts were followed for a median of 4 d (0–27). 39% achieved a major PR. Except for steroids (49.4%) &amp; anticonvulsants (29.4%), other adjuvant analgesic use was all &lt;10%. Pain-associated features: * Numeric Rating Scale 0–10, 10=worst suggestivie of alcoholism + Mean morphine equivalent daily dose On univariate analysis, older age (p=.006), lower initial PI (p=.003), lower final PI (p=.001) &amp; lower final MEDD (p=.002) were significantly associated with achieving major PR. On multivariate analysis, lower initial PI (p=.03) &amp; lower final MEDD (p=.02) retained significance for achieving major PR. Conclusions: Only 39%of pts with cancer pain seen in PCC achieve a major PR by discharge or death. Despite aggressive opioid titration, 61% do not achieve a major PR &amp; require better pain management. Potential strategies for achieving improved PR include earlier PCC, identification of more sensitive prognostic variables &amp;critical evaluation of targeted therapies. [Table: see text] No significant financial relationships to disclose.
Adjuvant combination chemotherapy and radiotherapy versus radiotherapy alone in the treatment of early stage cervical cancer after radical hysterectomy
Authors: M. F. Benoit, S. Hatch, E. V. Hannigan, C. D. Arrastia, T. A. Dinh
Journal: Journal of Clinical Oncology (2005)

5156 Background: This study was conducted to retrospectively evaluate the benefits and risks of adjuvant pelvic radiotherapy (RT) versus combination pelvic radiotherapy and chemotherapy (RCT) in the treatment of early stage cervical cancer patients with adverse prognostic factors following radical hysterectomy and pelvic lymphadenectomy. Methods: Fifty patients were eligible for inclusion. Adverse prognostic factors were identified as: stromal invasion greater than half the cervical length, lymphovascular space involvement, lower uterine segment involvement, positive resection margins, positive margins with 5mm of resection, positive parametrial margins, clinical tumor diameter greater than half the cervical size, and positive pelvic lymph nodes. All patients were diagnosed and treated at a single institution from 1992–2002. Results: Twenty-nine patients were treated with adjuvant RT and 21 patients were treated with adjuvant RCT. Progression free interval was 62.9 months in the adjuvant RT group compared to 30.4 months in the RCT group. The 2-year survival in the RT group was 96.6% versus 81% in the RCT group. Overall survival was 69 months in the adjuvant RT group versus 35 months in those treated with RCT. Eight (27.5%) patients recurred in the RT group and 10 (47.6%) recurred in the RCT group: 8 (27.5%) patients had pelvic recurrence in the RT group; 7 (33.3%) patients recurred locally in the RCT group. Five patients died in the RT group, 4 (13.8%) of disease; 6 (28.6%) patients died of disease in the RCT group; none died of treatment related complications. Grade 3 toxicity was experienced in 24.1% of the patients who received adjuvant RT compared to 28.6% in the RCT group. Conclusions: There was no increase in overall survival and progression free interval by the addition of adjuvant chemotherapy to irradiation. Consideration should be given to limiting chemotherapy administration due to its adverse side effects and cost without a decrease in cancer recurrence or mortality. Further information for treatment with adjuvant chemotherapy in addition to adjuvant irradiation should be obtained from randomized controlled trials. No significant financial relationships to disclose.
Is sorafenib (S) safe and effective in patients (pts) with hepatocellular carcinoma (HCC) and Child-Pugh B (CPB) cirrhosis?
Authors: G. K. Abou-Alfa, D. Amadori, A. Santoro, A. Figer, J. De Greve, C. Lathia, D. Voliotis, S. Anderson, M. Moscovici, S. Ricci
Journal: Journal of Clinical Oncology (2008)

4518 Background: S prolongs overall survival (OS) and time to progression (TTP) in pts with HCC and Child-Pugh A (CPA) (Llovet et al., ASCO 2007). A Phase II study (Ph II) evaluating S in advanced HCC included pts with CPA and CPB pts (Abou-Alfa et al. JCO 2006). Here, we assessed the safety and efficacy of S in subsets of HCC pts with CPA and CPB from the Ph II. Methods: Ph II accrued a total of 137 pts: 98 CPA and 38 CPB, 1 CP unknown. Pts received S standard dose of 400 mg PO bid continuously. Blood samples were collected for pharmacokinetics from 28 pts (21 CPA and 7 CPB) on day 1 of cycle 2 at 0.5, 1, 2, 4, 8 and 12 hours. 12th hour data was missing on few pts. We analyzed toxicity and clinical outcome data. Results: AUC (0–8) (mg.h/L) was comparable between CPA (25.4) and CPB (30.3) pts. Cmax (mg/L) were also comparable: 4.9 (CPA) and 6 (CPB). Incidence rates for all adverse events (AE) were similar in CPA (97%) and CPB (97%), and serious AE (52% vs 68%). Common sorafenib AE, as defined by NCI CTC v 2.0, included fatigue (CPA 41% vs CPB 37%), diarrhea (59 % vs 47%), hand foot skin reaction (30% vs 13%), and elevated bilirubin (18% vs 40%). Notably, the elevation of bilirubin was not associated with worsening of AST, ALT, or alkaline phosphatase. However, CPB pts had an increased rate of encephalopathy (CPA 2% vs CPB 11%) and worsening ascites (CPA 11% vs CPB 18%). Despite a shorter course of therapy for CPB (12.9 weeks) compared to CPA (24.9), S discontinuation rates (CPA 31% vs CPB 21%) and dose reduction (CPA 31% vs CPB 21%) were similar. Stable disease for ≥ 4 months was noted in 49% of CPA and 26% of CPB pts. Median TTP for CPA was 21 wks (95% CI: 16, 25 wks) and CPB 13 wks (95% CI: 9, 18 wks). OS for CPA was 41 wks (95% CI: 36.6, 63.6 wks) and CPB 14 wks (95% CI: 11.6, 25.7 wks). Conclusions: The data suggest a similar PK and toxicity profiles for CPA and CPB pts with advanced HCC from this phase II study. The elevated bilirubin on study may be related to the S inhibition of UGT1A1 activity. CPB pts, as would be expected, did worse than CPA, and had more frequent worsening of their liver cirrhosis (unclear if drug related versus disease progression). More data will be needed to confirm the safety and efficacy of S in HCC pts with CPB. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer
Effect of adjuvant radiation therapy on mortality according to primary tumor location in women with node-positive breast cancer: Is there a need to irradiate the internal mammary nodes?
Authors: V. Vinh-Hung, P. Truong, W. J. Janni, N. P. Nguyen, G. Vlastos, G. Cserni, M. E. Royce, W. A. Woodward, D. Promish, G. Storme, C. Bouchardy
Journal: Journal of Clinical Oncology (2008)

545 Background: This analysis evaluates the prognostic significance of primary tumor location and examines the question of whether the effect of adjuvant radiation therapy (RT) on survival varies according to tumor location in women with node-positive breast cancer. Methods: Data were abstracted from the Surveillance, Epidemiology, and End Results database for 24,410 women aged 25- 95 years, diagnosed between 1988–1997 with nonmetastatic T1-T2 axillary node-positive primary breast carcinoma. Subgroup analyses were performed using interactions within proportional hazards models in which the event was defined as death from any cause. Prognostic variables were selected using the Akaike Information Criteria. The joint significances of subgroups were evaluated with the Wald test. Results: The median follow-up time was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and RT use. A factorial presentation of these interactions showed a consistent 13% proportional reduction of mortality in all subgroups (Table). The sole exception was in women with medial tumors with ≥4 positive nodes treated with mastectomy. In this subgroup, the use of RT was associated with a 16% proportional increase in mortality. Conclusions: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision making for women with node-positive breast cancer. Improved survival was observed with RT use in all subgroups, except in women with medial tumors and ≥4 positive nodes treated with postmastectomy RT. These findings generate the hypothesis that the favorable effect of RT may have been offset by excess toxicities in the latter subgroup with the use of large fields to encompass the internal mammary nodes. Overall Mortality Hazard Ratio (HR) with or without Radiation (RT), by Number of Nodes, Surgery, Tumor Location No. of positive nodes Surgery Tumor quadrant RT=no HR (95% CI) RT=yes HR (95% CI) Relative mortality reduction with RT 1–3 BCS Outer 1 (=reference) 0.87 (0.82–0.92) 13% 1-3 BCS Inner 1.35 (1.20–1.52) 1.18 (1.12–1.23) 13% 1–3 Mastectomy Outer 1.09 (1.03–1.16) 0.95 (0.94–0.96) 13% 1–3 Mastectomy Inner 1.26 (1.16–1.37) 1.10 (1.07–1.12) 13% 4+ BCS Outer 1.13 (1.07–1.20) 0.99 (0.98–0.99) 13% 4+ BCS Inner 1.53 (1.34–1.75) 1.33 (1.24–1.43) 13% 4+ Mastectomy Outer 1.24 (1.14–1.34) 1.08 (1.06–1.09) 13% 4+ Mastectomy Inner 1.25 (1.17–1.34) 1.45 (1.34–1.56) -16% HRs adjusted by registry, year, race, marital, histo, grade, receptors, age, tumor size, nodal ratio No significant financial relationships to disclose.
The impact of cancer on geriatric syndromes in older Medicare beneficiaries
Authors: L. Fan, E. Reeve, S. Mohile
Journal: Journal of Clinical Oncology (2009)

9506 Background: Geriatric syndromes are highly prevalent in the elderly population and are associated with increased morbidity and mortality. The impact of a history of cancer on the presence of geriatric syndromes has not been well described. Methods: Using the 2003 Medicare Current Beneficiary Survey (MCBS), we analyzed a national sample of 12,480 community-based elders. Differences in prevalence of geriatric syndromes between those with and without cancer were estimated. Multivariate logistic regressions were used to identify independent predictors of geriatric syndromes, including the specific type of cancer. Results: 2349 (18%) reported current or history of cancer. Among cancer subjects, 63% had a prevalence ≥ 1 geriatric syndrome as compared to 57% of the non-cancer subjects (p&lt;0.0001). Cancer subjects overall had a significantly higher prevalence of hearing trouble, incontinence, falls, depression, and osteoporosis than those without cancer (all p values &lt;0.001). Adjusting for possible confounders including age and comorbidity, subjects with any diagnosis of cancer were more likely to have hearing trouble (OR 1.31, 95% CI: 1.10–1.56), incontinence (OR 1.35, 95% CI: 1.16–1.57), falls (OR 1.18, 95% CI: 1.05–1.31), depression (OR 1.19, 95% CI: 1.03–1.39), and osteoporosis (OR 1.20, 95% CI: 1.06–1.35). A cancer history was not significantly associated with dementia and poor eyesight. Analysis of specific cancer subtypes showed the following: lung cancer predicted vision and hearing trouble and depression; prostate cancer predicted incontinence and falls; and cervical/uterine cancer predicted incontinence, falls, and osteoporosis. Conclusions: Elderly cancer patients have a higher prevalence of geriatric syndromes than those without cancer. We advocate the use of geriatric assessment tools to detect geriatric syndromes in older cancer survivors as these may greatly reduce quality of life. More research is needed to evaluate whether cancer and/or its treatment leads to higher prevalences of geriatric syndromes in older cancer survivors and whether in older cancer survivors, geriatric syndromes are linked to higher morbidity or mortality. No significant financial relationships to disclose.
A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results
Authors: S. Sym, S. Park, J. Park, K. Kwon, I. Jung, E. Cho, W. Lee, M. Chung, D. Shin, J. Lee
Journal: Journal of Clinical Oncology (2009)

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.
Practice implications of the high false negative rate of sentinel lymph node biopsy reported in NSABP-32
Authors: L. Esserman, K. Sepucha
Journal: Journal of Clinical Oncology (2005)

812 Background: Data from NSABP B-32 reports a false negative rate of 9.7% for sentinel lymph node biopsy (SLNB) with a negative predictive value (NPV) of 96.1%. Interpreting statistical information about tests is often difficult and counterintuitive. We were interested in learning whether clinicians would interpret the data correctly and how they would use it to guide decisions about the use of SLNB. Methods: We performed sensitivity analysis to determine what impact the prior probability of lymph node positivity would have on the negative predictive rate of sentinel node biopsy. We conducted a pilot survey of clinicians attending 2004 San Antonio Breast Cancer Conference. We asked them three questions about a 50-year old patient with a 5mm ER positive invasive tumor with an estimated 5% chance of lymph node involvement. The questions were: (1) Is the NPV for SLNB for this patient higher, lower or the same as reported in study? (2) Would you perform a SLNB on this patient? (3) Why or why not? Results: With a prior probability of node involvement of 5%, and the false positive rate of 9.7%, the negative predictive value is 99.2%. The negative predictive value, or confidence that the negative result is accurate, increases as the a priori risk of a positive node decreases, and decreases as the risk of having positive nodes goes up. Of the 22 physicians that we surveyed: 5/22 (22%) answered correctly that the NPV would be higher, 6/22 (27%) answered same, and 11/22 (50%) answered lower. The majority 17/22 (77%) would perform a SLNB for this patient and 23% would omit all lymph node surgery. Some reasons given for performing the SLNB included: positive result has potential to alter treatment plan, no harm with SLNB and more to lose in under treatment. The most common reason given for not performing the SLNB was because the false negative rate exceeded the chance for true positive. Conclusions: The majority of clinicians were not able to apply the information from the NSABP report correctly for this specific clinical situation. It is important to use examples to show how positive and negative predictive values can be translated accurately into different clinical situations. No significant financial relationships to disclose.
Safety and pharmacokinetics (PK) of AMG 706 with panitumumab plus FOLFIRI or FOLFOX for the treatment of patients (pts) with metastatic colorectal cancer (mCRC)
Authors: L. S. Schwartzberg, H. Hurwitz, J. Stephenson, D. Kotasek, D. Goldstein, N. Tebbutt, J. McGreivy, Y. Sun, L. Yang, H. Burris
Journal: Journal of Clinical Oncology (2007)

4081 Background: AMG 706 is an oral, investigational multikinase (MKI) inhibitor with antiangiogenic and direct antitumor activity, selectively targeting VEGF, PDGF and Kit receptors. Methods: This is an ongoing phase 1b, open-label, dose-finding study of AMG 706 with panitumumab plus FOLFIRI or FOLFOX in pts with mCRC. Objectives are to establish safety, PK, and the maximum tolerated dose of AMG 706 with this regimen. Pts =18 yrs with mCRC, ECOG 0–1, =1 prior chemotherapy for advanced disease and no prior oral VEGFr MKIs or anti-EGFR therapy, received either FOLFIRI or FOLFOX (based on prior therapy) plus panitumumab (6mg/kg IV day 1 of each 2-wk cycle), and escalating doses of AMG 706 (50, 75, 125mg QD; 75mg BID) given continuously from day 3 of cycle 1. Assessments included dose-limiting toxicities (DLT) during the first 2 cycles and tumor response (every 6–8 wks from wk 6). Results: As of Nov 2006, 45 pts were enrolled and received at least 1 dose of AMG 706 (FOLFIRI/FOLFOX n=33/12); 64% had prior chemotherapy. There were 6 DLTs: FOLFIRI n=4, all grade 3 (diarrhea n=2: 50mg QD, 75mg BID; deep vein thrombosis n=1: 75mg QD; high GI output n=1: 75mg BID); FOLFOX n=2 (all fatigue, grade 3: 50mg QD). Treatment-related adverse events (AE) occurring in =10% of pts included: any AE, FOLFIRI/FOLFOX 88/92% of pts (grade 3, 21/58%); fatigue 55/58% (12/33%), anorexia 24/50% (0/0%), diarrhea 24/33% (0/8%), epistaxis 27/0% (0/0%) and hypertension 15/8% (0/0%). There were no grade 4/5 AEs. 2 cases of cholecystitis (grade 3, n=1) occurred. Preliminary data showed that AMG 706 PK at 50mg QD (FOLFOX) and 50–125mg QD (FOLFIRI) was comparable to data from monotherapy studies at the same dose levels. AMG 706 did not markedly alter the PK profiles of irinotecan or its metabolites. Objective tumor response per RECIST is shown in the table . Conclusions: In this study of pts with mCRC, AMG 706 was tolerable when combined with panitumumab and FOLFIRI or FOLFOX, with little effect on AMG 706 PK. [Table: see text] No significant financial relationships to disclose.