tbuckley/cabot-search huggingface dataset:
Predictive factors for skeletal complications in prostate cancer patients with hormone refractory disease
Authors: M. Tucci, A. Berruti, A. Mosca, F. Vana, G. La Manna, L. Russo, M. Poggio, R. Bitossi, G. Gorzegno, M. Tampellini, A. Saini
Journal: Journal of Clinical Oncology (2005)

4681 Background: Adverse skeletal related events (SREs) are the major causes of quality of life impairment in bone metastatic prostate cancer patients. Methods: We evaluated the frequency of SREs in 200 hormone refractory patients consecutively observed in our Istitution between 1990 and 2003. Baseline parameters were evaluated as potential predictive factors of SREs. Results: SREs were observed in 84 patients (43.0%), namely vertebra collapse in 41 patients (20.5%), fractures in 25 patients (12.5%) and spinal cord compression in 20 patients (10.0%). In 10 patients (5.0%) SREs occurred before the onset of hormone refractory disease. At the last follow-up on August 15 2004, 180 patients (90.0%) had died (median survival 14.5 months). One hundred and five of them (58.3%) without undergoing SREs. In univariate analysis, disease extent in bone (p=.015), bone pain (p=.011), serum alkaline phosphatase (p=.014) and urinary N-telopeptide cross-link (p=.001) directly correlated with a greater chance to develop SREs in the hormone refractory phase of the disease, whereas patient performance status, Gleason score, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions did not correlate. SREs occurring before the onset of hormone refractoriness were significantly associated to the duration of androgen deprivation (p=0.004), whereas SREs occurring in the hormone refractory phase were not. Both disease extent in bone and bone pain were independent variables predicting for the onset of SREs in multivariate analysis. SREs in patients with heavy tumor load in bone and great bone pain were almost double (26% vs 52%, p = 0.016) and occurred significantly earlier [hazard ratio 1.63 (95% Confidence Interval 1.32 - 2.00) p=0.000] than SREs in patients with limited disease extent in bone and low pain. Conclusions: Bone pain and disease extent in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone refractory disease. These findings could help the physicians in tailoring to each patient the most appropriate skeletal follow-up, and may prove useful for stratifying patients enrolled in randomized clinical trials testing bone antiresorptive agents. No significant financial relationships to disclose.
Effect of venous involvement on survival in locally advanced pancreatic cancer.
Authors: Kelly C. Hewitt, Jesse L Madden, Joslin C Christensen, Sean J. Mulvihill, Courtney L. Scaife
Journal: Journal of Clinical Oncology (2013)

153 Background: Locally advanced pancreatic cancer is defined as tumor that extends beyond the pancreas into surrounding structures. Borderline resectable disease usually includes a description of superior mesenteric vein (SMV) or portal vein (PV) involvement, while the AJCC staging no longer includes venous involvement in the staging system. We reviewed our institutional cancer database to determine if venous involvement affects overall survival and should be included in pancreatic ductal adenocarcinoma (PDA) staging. Methods: A retrospective review was performed of all patients with stage II or III PDA identified through our institutional prospective Clinical Cancer Research Database, between 2007-2012. Patients with superior mesenteric artery (SMA) or celiac artery and/or venous (SMV or PV) involvement were compared to those without. Vascular involvement was defined as either vessel encasement or abutment on endoscopic ultrasound or CT imaging. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison of survival curves. Results: A total of 194 patients were identified as having stage II or stage III pancreatic adenocarcinoma, with 85 having evidence of vascular involvement. In our patient population we found that in patients with stage IIA and IIB disease PV or SMV involvement did not portend statistically worse survival (median survival 14 months v 15 months p=0.63). In stage III patients survival was actually longer in patients with PV or SMV involvement, but this was not statistically significant (median survival 13 months v 7.9 months p=.066). When comparing those with PV or SMV involvement versus those with celiac axis or superior mesenteric artery (SMA) involvement in all patients with locally advanced pancreatic cancer (stage II or III), those with celiac or SMA involvement did significantly worse (mean survival 14 months v. 7.9 months p&lt;0.001). Conclusions: Venous involvement does not portend a worse survival in patients with stage II and III pancreatic cancer. The addition of venous involvement to the current AJCC staging scheme would not provide additional survival information.
Randomized phase III trial of irinotecan plus cisplatin versus irinotecan alone after S-1 based chemotherapy failure for patients with advanced and recurrent gastric cancer (AGC) (TCOG GI-0801).
Authors: Ken Shimada, Katsuhiko Higuchi, Naoshi Hosaka, Eisaku Sasaki, Norisuke Nakayama, Kenji Amagai, Yuiti Takeda, Toshikazu Moriwaki, Takashi Sekikawa, Toshikazu Sakuyama, Kazuhito Yajima, Satoshi Tanabe, Yusuke Saito, Yoshiharu Maeda, Ken Nishimura, Tohru Sasaki, Kouji Kobayashi, Tatsu Shimoyama, Ichinosuke Hyodo, Wasaburo Koizumi
Journal: Journal of Clinical Oncology (2013)

61 Background: S-1based chemotherapy is the standard first-line chemotherapy for AGC in Japan. Currently, there is no high level evidence established for second-line treatment. Irinotecan (CPT-11) plus cisplatin (CDDP) are active in AGC. The combination of these 2 agents is synergistic effect in preclinical and clinical studies. We conducted a phase III study of CPT-11 plus CDDP (CP) compared with CPT-11 alone (C) in patients with AGC refractory to S-1 based chemotherapy. Methods: Patients with previously treated with S-1-based chemotherapy for AGC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either CPT-11 60 mg/m 2 plus CDDP 30 mg/m 2 on day 1 every 2 weeks or CPT-11 150mg/m 2 on day 1 every 2 weeks. The primary endpoint is progression free survival (PFS). The statistical design is based on superiority hypothesis; PFS is 110days in CP, 65days in C; two-sided α=0.05, 1-β=0.8; and planed accrual is 130 pts. Secondary endpoints include Overall Survival (OS), Time to Treatment Failure (TTF), Response Rate (RR), and safety. Results: From April 2008 to July 2011, 130 patients from 21 sites in Japan were randomized to CP (n=64) or C (n=66). Patient demographics were well balanced between the two groups. At the final analysis, total of 117 PFS events were observed. The primary endpoint was met. PFS for CP was superiority to C (median PFS, 4.17(95%CI 3.03-4.80) vs. 3.03(95%CI 2.20-3.33) months, respectively; HR=1.490(1.029-2.155), p=0.0324,). There were no significant differences in the TTF and RR (TTF was 3.4(95%CI 2.7-4.2) vs. 2.9(95%CI 2.2-3.3) months, RR was 21.9(95%CI 12.5-34.0) % vs. 16.4(95%CI 7.9-27.3) % with CP and C. OS is analyzing now. The most common grade 3/4 toxicities in CP/C (%) were neutropenia, 40.6/38.7; diarrhea, 1.6/7.9; anorexia, 4.7/11.1. Related adverse events were comparable with CP and C.Conclusions: CP has promising efficacy for the second-line chemotherapy compared with C for AGC.CP suggested to be one of the standard second-line chemotherapy regimen for AGC. Clinical trial information: 000001028.
Serum 25(OH) vitamin D3 response to vitamin D3 supplementation in men with prostate cancer: Results of a randomized phase II trial.
Authors: M. H. AL-Hussaini, C. S. Johnson, J. Muindi, M. K. Chadha, C. Silliman, L. Tian, W. Tan, M. Nesline, A. Sandecki, M. R. Kuettel, J. Mohler, K. Guru, D. L. Trump
Journal: Journal of Clinical Oncology (2011)

e13060 Background: There is substantial evidence that low serum 25(OH) vitamin D3 [25D3] levels are associated with higher cancer incidence, mortality and other medical morbidities (e.g., heart disease, stroke, venous thrombosis, infection, and autoimmunity). Considerable data document that >60% of normal individuals and patients with prostate, colorectal and breast cancer have serum 25D3 levels below the lower limit of normal (32ng/ml). The relationship between these low levels and cancer outcome is controversial and the response of cancer patients to vitamin D3 (cholecalciferol) [VD3] supplementation has not been studied carefully. This study evaluated the response and safety of 4 different daily replacement doses of VD3 in men with prostate cancer. Methods: 137 patients with prostate cancer who had either localized or advanced disease, were randomized to assure that 120 patients completed 6 months of VD3 replacement at doses of either 4,000, 6,000, 8,000, or 10,000 IU daily. 117 patients have been completely analyzed. 25D3 plasma levels, serum and urine calcium levels, parathyroid hormone (PTH) plasma levels and signs of toxicity were assessed at 1, 3, and 6 montths. Results: Toxicity and adverse events were negligible and not clearly related to VD3; no clinically significant changes in serum or 24hr urine calcium occurred. 25D3 levels achieved were proportional to VD3 dose. There were no changes in PTH level related to VD3 dose, serum level of 25D3 or duration of supplementation. Conclusions: Each of the 4 doses of VD3 supplementation was well tolerated. At 3 months, >80% of patients achieved normal 25D3 serum concentrations. Further studies to explore factors associated with response to VD3 supplementation are being carried out. VD3 dose of 4,000 IU or 6,000 IU daily is very safe and appropriate for future study of the role of supplementation in men with prostate cancer. VD3 dose Baseline 25D3(median, ng/ml) 1 mo 3 mo 6 mo 4,000 IU 24.7 35.5 49.3 56.4 6,000 IU 27.8 51.9 63.7 68.3 8,000 IU 27.8 41.3 55.5 63.9 10,000 IU 25.4 52.2 72.8 84.1
Fluorine and Dental Caries
Authors: Vlado A. Getting
Journal: New England Journal of Medicine (1946)

Effect of Fluorine on Dental CariesTHE earliest references in the literature on the relation of fluorine to dental caries were made in 1916 by McKay and Black,56 , 57 who studied the so-called "Colorado brown stain." During the following decade mottled enamel and dental caries were extensively studied by McKay58 , 59 and Bunting et al.51 It was not until 1931, however, according to Dean60 that fluorine was discovered as the cause of mottled enamel. Four methods were used in studying the cause, prevalence and control of mottled enamel and the lowered prevalence of dental caries in certain areas. These consisted in refinements . . .
Comparison of pemetrexed plus cisplatin versus pemetrexed plus carboplatin in the initial treatment of locally advanced or metastatic non-small cell lung cancer.
Authors: A. A. R. Pereira, R. C. Lessa, C. E. P. Souza, F. A. I. Pinto, D. M. Gagliato, E. S. Santos, M. F. Fanelli, J. A. Rinck, A. A. Dettino, U. R. Nicolau, L. T. D. Chinen, V. C. C. de Lima, J. R. Pereira, M. R. D. S. Cruz
Journal: Journal of Clinical Oncology (2011)

e18067 Background: The combination of pemetrexed plus cisplatin (PC) was recently approved in the initial treatment of advanced stage non-small cell lung cancer (NSCLC). Studies reported comparable efficacy of the combination pemetrexed plus carboplatin (PCar) in the same setting. Methods: We assessed 69 patients with locally advanced or metastatic NSCLC treated with pemetrexed combined to cisplatin or carboplatin from January 2004 to June 2010. Clinical data was collected and the following endpoints were analysed: overall survival (OS), progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and toxicity profile. We performed univariate analysis to identify the predictive factors of response to both combinations. Results: Twenty six (37.68%) patients were treated with pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 and 43 (62.32%) with pemetrexed 500 mg/m2 plus carboplatin AUC 5 every 21 days. The groups were well matched for age, sex, TNM stage, smoking status and histology. There were significantly more patients with ECOG 2 in the PCar group (46.5% vs. 15.6%, p=0.009). The efficacy of PCar and PC combinations were comparable in OS (11.64 x 9.96 months; p=0.96), PFS (5.69 x 7.04 months; p=0.60), ORR (37.21% x 42.31%; p=0.50) and DCR (86.05% x 80.70%; p=0.63). Both combinations were well tolerated and the rate of grade 3 or 4 neutropenia was significantly higher in the PCar group (25.5% x 3.8%; p=0.003). The group with stable disease (SD) had comparable OS to the group with objective response (OR) (10.33 x 15.60 months, respectively; p=0.27). Non-squamous cell histology had a significantly longer OS than squamous cell histology (13.1 x 8.2 months; p=0.033). In the univariate analysis, non-squamous was the only predictor of response. Conclusions: PCar presents efficacy and safety comparable to PC in the community setting. Patients with SD had OS comparable to patients with OR. Non-squamous cell histology is the only predictive factor for treatment response with PCar and PC.
Quality of life (QOL) analysis from E3805, chemohormonal androgen ablation randomized trial (CHAARTED) in prostate cancer (PrCa).
Authors: Linda J. Patrick-Miller, Yu-Hui Chen, Michael Anthony Carducci, David Cella, Robert S. DiPaola, Benjamin Adam Gartrell, David Frazier Jarrard, Glenn Liu, Alicia Katherine Morgans, Yu-Ning Wong, Christopher Sweeney
Journal: Journal of Clinical Oncology (2016)

286 Background: Docetaxel concurrent with androgen deprivation (ADT) for metastatic hormone sensitive prostate cancer (mHSPC) improves overall survival over ADT alone. However, docetaxel as a cytotoxic has an adverse event profile that can diminish QOL. Methods: Patients were randomized to ADT plus 6 cycles of docetaxel every 3 weeks (Arm A, N = 397) or ADT alone (Arm B, N = 393). Validated QOL instruments for PrCa and docetaxel including Functional Assessment of Cancer Therapy (FACT)–Prostate were administered at baseline and 3, 6, 9 and 12 months (mos.) after randomization. Paired t-tests were used to examine QOL changes over time. A mixed effect model compared QOL between arms at each time point (Table). Results: 790 patients were randomized and QOL completed for Arm A and B (91% and 88%, baseline; 87% and 80%, 3 mos.; and 70% and 67%, 12 mos.). Patients in Arm A (ADT + docetaxel) reported -2.7 [Standard Error (SE) 0.9] decline in FACT-P at 3 mos. (p = 0.003), but did not differ significantly from baseline at 12 mos. (-0.7, SE 1.1). In contrast, patients in Arm B (ADT alone), did not differ significantly at 3 mos. [-1.1 (SE: 1.0)], but reported a significant decline [-4.2 (SE: 1.1); p = 0.0001] from baseline to 12 mos. FACT-P scores differed significantly between Arm A and B at 3 mos. (p = 0.02) and 12 mos. (0.04), with Arm A lower at 3 mos. and higher at 12 mos. Conclusions: Docetaxel is associated with decreased QOL on treatment (at 3 mos.) not seen with ADT alone. However, 12 mos. QOL was better for the patients who had docetaxel versus ADT alone, returning to baseline. This suggests that docetaxel + ADT does not confer long-term negative impact on QOL for mHSPC. Clinical trial information: NCT00309985. [Table: see text]
Specification and validation of prostate cancer quality-of-care e-measures in the Veterans Health Administration (VHA).
Authors: Jeremy B. Shelton, Ted A. Skolarus, Joan Joonsun Ryoo, Jennifer Malin, Anna Liza M. Antonio, Ren He, Christopher Saigal
Journal: Journal of Clinical Oncology (2013)

178 Background: Quality measures based on chart abstraction are the “gold-standard,” but the costs of measurement limit widespread adoption. Electronically specified measures (e-measures) promise a way forward, however the fidelity of electronic abstraction compared to chart abstraction is unknown. We sought to validate e-measure versions of VHA-developed prostate cancer quality of care measures. Methods: Quality measures were chart abstracted on 11,263 men in the VHA with incident prostate cancer in 2008. We identified and linked VHA cancer registry and administrative data for the same cohort. E-measures were specified iteratively and validated by comparing accuracy of measure denominators and numerators, and the overall pass rates to chart abstracted results. Results: 3 of 6 quality measures were successfully validated (Table). Conclusions: The VHA’s information technology infrastructure is sufficiently advanced to support valid e-measurement that is equivalent to that performed by chart abstraction, however data availability at this time limits the breadth of e-measurement as compared to chart abstraction. [Table: see text]
Phase II trial of gemcitabine (G), carboplatin (C) and bexarotene (B) in patients (pts) with newly diagnosed, locally-advanced or metastatic non-small cell carcinoma of the lung (NSCLC)
Authors: F. F. Estephan, N. Hasham-Jiwa, F. Klementich, R. Logrono, M. Eltorky, M. Bhutani, E. Walser, J. Zwischenberger, I. Kessel, D. V. Jones
Journal: Journal of Clinical Oncology (2005)

7308 Background: The current standard of care for unresectable NSCLC is platinum-based chemotherapy. There is no benefit to adding together 3 or more cytotoxic agents, but adding a biologic agent may improve response rates and survival. B, a retinoic acid X-receptor agonist, is a differentiating agent with antineoplastic activity. Recent data suggests that the addition of B to platinum-based therapy may increase response rates and survival in NSCLC. Due to the poor outcome in this disease, we are studying a combination of G, C, and B as front-line therapy. Methods: Eligibility criteria includes histologically diagnosed NSCLC stage IIIB/IV; Karnofsky PS 70–100%; age ≥ 18, adequate bone marrow, renal and hepatic function, and written informed consent. Pts receive G, 1 g/m2 days 1 and 8 with C, AUC 5 (Calvert formula) on day 8. B, 400mg/m2 PO QD in divided doses is given days 1–28 of each treatment cycle. Pts may receive up to 6 cycles of chemotherapy or 2 cycles after CR achieved. Tumor restaging is performed every 2 cycles of therapy, in the absence of obvious rapid disease progression. Results: 19 pts have been enrolled; 10 males, 9 females; median age is 63.5 years (range 30–85 years). 2 pts had protocol violations (prior chemotherapy (1); small cell cancer on further pathologic evaluation (1)). A median of 2 cycles has been delivered (range 1–6). To date, the overall PR rate is 23.5% (4/17); 2 have had SD (1 progressed by cycle 4), for an overall clinical benefit rate of 35%. One is too early to evaluate. 18 pts to date are evaluable for toxicity. Thus far, the mean TTP is 68 days, and the mean OS is 142 days. The therapy has been well-tolerated with 7 pts experiencing Grade 2–3 myelosuppression (no febrile neutropenia), and 3 pts experiencing Grade 3–4 nausea and emesis. There have been no significant B-related adverse events. Conclusions: The addition of the differentiating agent B to a regimen of G and C is tolerable and active. In contrast to other studies, our early results suggest that the addition of B at this dose and schedule may add little to the clinical benefit observed with this regimen. Accrual continues in an effort to better define response rate and duration. No significant financial relationships to disclose.
A mechanistic radiographic and biologic phase 2 study of sunitinib in relapsed/refractory esophageal (E) and gastroesophageal (GE) cancers.
Authors: Christina Sing-Ying Wu, Sameh Mikhail, Lai Wei, Ludmila Katherine Martin, Xiaobai Li, Cynthia Dawn Timmers, James Lin Chen, Sanaa Tahiri, Alison Neal, Jon P Walker, Samer S El-Dika, Jonathan B Rock, Daniel Clark, Xiangyu Yang, Kevin Foy, James Jingyao Liu, Michael V. Knopp, Pravin Kaumaya, Tanios B. Bekaii-Saab
Journal: Journal of Clinical Oncology (2014)

149 Background: Patients (pts) with relapsed or treatment-refractory E and GE cancers carry a poor prognosis. Inhibition of the vascular endothelial growth factor (VEGF) pathway may be a potential treatment approach. We conducted a phase II trial to assess the efficacy of sunitinib, a tyrosine kinase inhibitor that inhibits VEGFR 1 and 2. Methods: Pts received sunitinib 37.5 mg orally, daily. Primary endpoint was progression free survival (PFS) at 24 weeks. Secondary endpoints included overall response rate (ORR), overall survival (OS), PFS, and toxicity. Pts underwent serial functional imaging with DCE-MRI and measurements of serum VEGF, PIGF, VEGFR 2 and 3. Gene expression profiling and somatic mutational analysis using next-generation sequencing were also performed on tumor specimens (results to be presented at the symposium). Results: Clinical results are in the table. The PFS in the group that had clinical benefit [partial response (PR) + stable disease (SD)] with sunitinib was 99 days (95% CI: 74-161) vs. 39 days (95% CI: 26-42; Log-rank test p-value is &lt;0.0001) in pts who had progressive disease (PD). By RECIST criteria, sunitinib non-responders demonstrated an initial reduction in tumor size but then subsequent rapid tumor size increase by week 6 as compared to baseline values. In contrast, sunitinib responders demonstrated at least stable disease through weeks 2-6. Changes in serum VEGF-A and VEGF-C levels from baseline to 2 weeks were associated with PFS (p=0.04 and p=0.03, respectively). Furthermore, baseline VEGF-C was also associated with PFS (p=0.03) and RECIST response (p=0.04). Conclusions: Although the primary endpoint was not met, these results suggest that there is a subgroup of patients with clinical response to sunitinib. Our correlative analysis indicated that circulating biomarkers, such as VEGF-C, are worthy of further research to help us identify this subgroup. Clinical trial information: NCT00702884. [Table: see text]
Comparison of concurrent chemoradiotherapy and chemotherapy alone for locally advanced pancreatic cancer.
Authors: Younak Choi, Tae-Yong Kim, Do-Youn Oh, Kyubo Kim, Eui Kyu Chie, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Sung W. Ha, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2014)

351 Background: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), especially the role of chemoradiotherapy (CCRT), is still in debate. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with LAPC. Methods: We consecutively enrolled LAPC patients treated between 2003 and 2010. AJCC 7 th edition was followed for the diagnostic criteria of LAPC. We retrospectively evaluated the clinical outcomes according to treatment groups (CCRT vs CA). Results: A total of 86 patients were enrolled. Median age was 60 years. ECOG PS was 0-1 in 77 (89.5%) and 2 in 9 (10.5%). Forty five patients (52.3%) were treated with CCRT and 41 patients (47.7%) with CA. Baseline characteristics were not significantly different between CCRT and CA group. In the CCRT group, gemcitabine (n=7, 15.6%), 5-FU (n=10, 22.2%), and capecitabine (n=28, 62.2%) were concurrently used with radiation. Radiation was delivered with 55.8Gy/ 31fraction. All of the CA group patients were treated with gemcitabine-based chemotherapy. Median progression free survival (PFS) and overall survival (OS) of whole patients were 6.9 months [95%CI 4.8-9.0] and 12.7 months [95%CI 11.6-14.3]. PFS and OS of CCRT versus CA was 8.9 months [95%CI 6.8-11.0] vs 3.7 months [95%CI 2.9-4.5] (p&lt;0.001) and 15.8 months [95%CI 13.5-18.1] vs 11.3 months [95%CI 9.3-13.3] (p=0.017). In multivariate analysis, tumor size (≥3cm), positive lymph node, elevated CA 19-9, decreased serum albumin and CCRT was significant for PFS and OS (adjusted hazard ratio of CCRT was 0.424 (p=0.002) in PFS and 0.472 (p=0.014) in OS). Grade 3-4 hematologic toxicity was less frequent during CCRT period (p=0.002). Conclusions: In LAPC, patients who received CCRT show better OS and PFS compared with patients who were treated with palliative chemotherapy alone. It’s worthy to further study the role of CCRT in LAPC.