tbuckley/cabot-search huggingface dataset:
Multicenter, non-randomized phase II study with RPR109881 in taxane-exposed metastatic breast cancer (MBC) patients (pts): Final results
Authors: V. Dieras, V. Valero, S. Limentani, G. Romieu, M. Tubiana-Hulin, A. Lortholary, J.-M. Ferrero, P. Kaufman, A. Buchbinder, M. Besenval
Journal: Journal of Clinical Oncology (2005)

565 Background: RPR109881 is a semisynthetic taxane with demonstrated broad spectrum of activity in in vivo tumor models, particularly in taxane-resistant models. Methods: This Phase II study with RPR109881 administered as 1-hour IV infusion every 3 weeks at 90 mg/m2 evaluated its efficacy in MBC pts previously treated with chemotherapy (CT) including paclitaxel or docetaxel. Pts were stratified in 2 strata: 1) taxane non-resistant (NRS) if they had demonstrated objective response (OR) to prior taxane or 2) taxane-resistant (RS) if DFI ≤ 12 months following adjuvant taxane CT or no OR for metastatic disease. Results: 62 pts were enrolled in NRS and 68 in RS. Median age: 54 years (33–76). 693 cycles were administered: median 6 (1–12) and 3 (1–21) in NRS and RS respectively. The most common and severe toxicities were: Table 1. 2 toxic deaths were reported in the RS (septic shock and sudden death at cycle 1). Ten additional pts (3 consent withdrawns, 2 lost to follow up, 1 non-measurable lesion, 1 incomplete tumor assessment, 3 discontinuations for toxicities) were not evaluable for response. Efficacy assessed by external reviewers in treated population per stratum. There was 41.9% OR (CI: 29.5–55.2%) in NRS and 19.4% (CI: 10.8–30.9%) in RS. TTP and survival will be presented. Conclusion: RPR109881 demonstrates promising activity in taxane-exposed MBC. A phase III study comparing RPR109881 versus capecitabine is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Aventis
Prognostic factors for the breast cancer patients with bone metastasis
Authors: O. Yavas, Y. Ozışık, E. Baltalı, N. Guler, G. Tekuzman
Journal: Journal of Clinical Oncology (2005)

835 Background: Median survival for breast cancer patients with bone metastasis is 2 years. Factors affecting the prognosis after bone metastasis are not clear. Methods: In this study, 141 metastatic breast cancer patients who have disease in bone and were followed in Hacettepe University Faculty of Medicine, Department of Medical Oncology between 1990 and 2003 were evaluated for the prognostic factors. Results: The median overall survival (OS) was 68.4 months, the disease free survival (DFS) was 21.3 months, the bone metastasis free survival (BFS) was 23.3 months and overall survival after bone metastasis (BOS) was 28.4 months. In univariate analyses statistically significant predictors for OS and DFS were the size of the primary tumor, presence of lymphovascular invasion and the site of the first metastasis, for BFS were the size of the primary tumor, number of the metastatic lymph nodes and presence of lymphovascular invasion and finally for BOS were the size of the primary tumor, presence of lymphovascular invasion, nuclear and histological grade of tumor, receptor status and development of subsequent any visceral metastasis after first bone metastasis only. In multivariate analyses, the size of the primary tumor was the significant independent prognostic factor for all OS, DFS and BFS, Presence of LVI was the significant independent prognostic factor for OS and BOS. Conclusions: In the result of study, for patients with breast cancer, survival after bone metastasis is affected by primary prognostic factors. No significant financial relationships to disclose.
Survival time and its prognostic factors in advanced unresected cholangiocarcinoma without chemoradiation
Authors: J. Park, M. Kim, J. Kim, J. Lee
Journal: Journal of Clinical Oncology (2009)

e15681 Background: To evaluate survival time and its prognostic factors contributing to survival of advanced unresected cholangiocarcinoma. Methods: We reviewed the experience of 330 patients with histologically proven unresected advanced intrahepatic and hilar cholangiocarcinoma and evaluated their survival time and significant prognostic factors. They did not receive any surgery, chemotherapy and radiotherapy and they underwent only palliative nonsurgical biliary drainage if it was needed to relieve biliary obstructive symptom. Results: Survival time of overall cholangiocarcinoma (median±SD) was 3.9±7.8 months; 3±5.3 months for intrahepatic cholangiocarcinoma, 5.9±10.1 months for hilar cholangiocarcinoma. By Kaplan-Meier survival analysis, intrahepatic cholangiocarcinoma patients survived significantly shorter than hilar cholangiocarcinoma patients. By multivariate analysis for intrahepatic cholangiocarcinoma, distant metastasis was independently associated with shorter survival time. Multivariate analysis for hilar cholangiocarcinoma showed initial CEA &gt; 30 ng/dl were independent predictors of shorter survival. Conclusions: Patients with unresectable cholangiocarcinoma who do not undergo surgery, chemotherapy and/or radiotherapy have a dismal prognosis. We hope that the outcome of our study would help clinicians better predict the prognosis of cholangiocarcinoma patients not receiving such aggressive treatments. These data would be used as the comparable data for control groups of future studies to assess the outcome of newly designed or developed treatment method. No significant financial relationships to disclose.
Factors associated with fatigue in children with cancer at the end of life
Authors: C. K. Ullrich, J. M. Hilden, J. W. Sheaffer, C. L. Moore, C. B. Berde, J. C. Weeks, J. Wolfe
Journal: Journal of Clinical Oncology (2006)

8574 Background: Fatigue is prevalent in children with cancer but is poorly understood. Improved understanding of this symptom will inform development of interventions aimed at alleviating it. Methods: Cross-sectional survey conducted between 1997–2001 of 144 parents of children who died of cancer cared for at Dana-Farber Cancer Institute/Children’s Hospital Boston and Children’s Hospital and Clinics, St Paul and Minneapolis (response rate 65%). Parents reported the child’s experience of symptoms in the last month of life and associated suffering, and patient characteristics. Determinants of suffering from, and treatment of fatigue were explored with univariate analyses adjusting for physician and time since death. A logistic regression model was built to determine factors associated with suffering from fatigue, with a threshold for entry of P&lt;.05, and accounting for physician clustering. Results: Almost all children experienced fatigue and 50% suffered significantly from it (a great deal/a lot versus some/a little/none at all). Only 15% received treatment, and of them, 79% were not successfully treated. Univariate analyses revealed significant associations between suffering from fatigue and suffering from pain, dyspnea, anorexia, diarrhea, and nausea/vomiting, as well sadness, anemia and successful treatment of pain (P&lt;.05). Treatment of fatigue was associated with side effects from treatment of pain (OR 3.9, P=.008) and treatment of dyspnea (OR 3.9, P=.02). In the multivariate analysis of suffering from fatigue, successful treatment of pain remained significant (OR 4.2, P=.009). Conclusions: Suffering from fatigue is common in children with cancer at the end of life and efforts to palliate it are limited. Significant fatigue is highly associated with other symptoms and their treatments. Increased attention to treatment-related fatigue and evaluation of interventions such as stimulants may be effective in ameliorating fatigue in children with advanced cancer. No significant financial relationships to disclose.
Dose-finding study of NKTR-102 in combination with cetuximab
Authors: J. T. Hamm, D. Richards, R. K. Ramanathan, C. Becerra, G. Jameson, J. Walling, D. Gribben, S. Dhar, M. Eldon, D. Von Hoff
Journal: Journal of Clinical Oncology (2009)

e13503 Background: NKTR-102 is an advanced polymer conjugate of irinotecan with broad single agent activity and a unique pharmacokinetic (pk) profile. The apparent half-life of the active metabolite SN-38 in patients (pts) administered NKTR-102 is approximately 50 days. NKTR-102 in combination with cetuximab was evaluated in pts with refractory solid tumors to define the maximum tolerated dose (MTD). Methods: NKTR-102 was infused over 90 minutes every 3 weeks per cycle. Cetuximab was infused over 2 hours at 400mg/m2 on day 1 followed by a weekly 1 hour infusion at 250mg/m2. Cohorts of 3 -12 pts were treated with escalating doses of NKTR- 102. MTD was established based on the dose limiting toxicities observed in cycle 1 and safety data from subsequent cycles. Serial plasma samples were collected throughout the study for PK analysis. Results: Eighteen pts were enrolled: main tumor types include colon (5), pancreas (4), rectal (2), breast (2), gastric (1), other (4). Pts received 100 mg/m2 (12) or 125 mg/m2 (6) of NKTR-102 for a median of 2.5 cycles (range 1 to 11+). At 125 mg/m2, 3 pts had G3 diarrhea, 1 in cycle 1; 2 in cycle 2. At 100mg/m2, 1 pt had G3 diarrhea in cycle 1 and a further pt had G4 fatigue in cycle 2. Other G3 toxicities for all patients in both dose groups include nausea (3), vomiting (3) and neutropenia (2). No G3 rash was reported. Partial responses (PR) were observed in 3 pts at 100 mg/m2: confirmed (rectal, colorectal) and unconfirmed (gastric). Another pt with pancreatic cancer had a decrease in CA19–9 from 2000 at baseline to 157 U/ml with associated symptomatic benefit. NKTR-102 resulted in sustained exposure to SN-38 with no evidence of PK drug interactions between NKTR-102 and cetuximab. Conclusions: NKTR-102 shows evidence of clinical antitumor activity in combination with cetuximab. Toxicity is manageable; diarrhea and neutropenia are dose limiting. The recommended dose of NKTR-102 with cetuximab is 100mg/m2 every three weeks. Data support further evaluation of this combination in appropriate tumor types. [Table: see text]
Vasectomy and risk of lethal prostate cancer: A 24-year prospective study.
Authors: Lorelei A. Mucci, Mohummad Minhaj Siddiqui, Kathryn M Wilson, Mara Meyer Epstein, Jennifer R Rider, Neil E Martin, Philip W. Kantoff, Meir J. Stampfer, Edward L. Giovannucci
Journal: Journal of Clinical Oncology (2013)

5086 Background: In the United States, 10 to 15 percent of adult men have undergone a vasectomy. There is conflicting evidence whether vasectomy is associated with increased prostate cancer risk. Methods: We undertook a prospective study among 49,432 men in the US Health Professionals Follow-up Study. The men were age 40 to 75 years at baseline in 1986 and were followed prospectively for cancer incidence and mortality through 2010; 6,398 incident cases of prostate cancer were diagnosed, including 734 with high grade (Gleason 8 – 10) and 813 with cancer causing death or bony metastasis (lethal). We used cox regression models to calculate hazard ratios (HR, 95% confidence intervals) of the association between vasectomy and incidence of high grade and lethal prostate cancer, adjusting for potential confounders. We examined associations in the total cohort, and in a subset of 12,371 men highly screened by PSA in order to disentangle potential diagnostic bias. Results: At baseline, 22 percent of men reported having had a vasectomy. Men who had undergone vasectomy were at increased risk of high-grade (HR 1.23, 95% CI: 1.04-1.47) and lethal (HR 1.20, 95% CI: 1.01-1.43) prostate cancer. In the highly screened cohort, the association was similar for high-grade cancer, and even stronger for lethal disease (HR 1.56, 1.03-2.36). The risk of lethal prostate cancer was higher among men who had a vasectomy before age 38 years compared to at older ages. The increased risks with vasectomy could not be explained by differences in hormone levels, prevalence of sexually transmitted infections, or cancer treatments. Conclusions: Data from this study support the hypothesis that vasectomy is associated with a small increased incidence of aggressive prostate cancer defined as high grade cancer and disease causing death or bony metastasis. Differences in diagnostic intensity or confounding bias do not explain this elevated risk.
Androgen deprivation therapy does not impact cause-specific or overall survival in high-risk prostate cancer treated with brachytherapy and supplemental external beam
Authors: Z. Allen, G. S. Merrick, W. Butler, K. Wallner, R. Galbreath, E. Adamovich, J. Lief
Journal: Journal of Clinical Oncology (2007)

15578 Background: To determine cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) in high risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods: From April 1995 through July 2002, 204 patients with high risk prostate cancer (Gleason score = 8 and/or PSA &gt; 20 ng/mL and/or clinical stage = T2c) underwent brachytherapy with or without supplemental therapies. Of the 204 patients, 193 (94.6%) received supplemental XRT and 119 (58.3%) received ADT (ADT = 6 months n=40 and ADT &gt; 6 months n = 79). Median follow-up was 7.0 years. All patients were implanted at least 4 years prior to analysis. BPFS was defined by a PSA = 0.40 ng/mL after nadir. Multiple clinical, treatment and dosimetric parameters were evaluated for the impact on survival. Results: The ten-year CSS, bPFS and OS were 88.9%, 86.6% and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naïve, ADT = 6 months and ADT &gt; 6 month cohorts (79.7% vs. 95.0% vs. 89.9%, p= 0.032). ADT did not impact CSS (94.0% vs. 87.1%, p=0.983 ) or OS (65.2% vs. 70.3%, p = 0.713). For bPFS patients, the median post-treatment PSA was &lt; 0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent positive biopsies and duration of ADT best predicted for bPFS. OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died with 26 of the deaths due to cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: Androgen deprivation therapy improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact overall survival. No significant financial relationships to disclose.
Long-term outcomes of high-dose therapy using busulfan, etoposide, and cyclophosphamide followed by allogeneic hematopoietic cell transplantation for patients with high-risk or advanced stages of myeloid malignancies
Authors: S. G. Naik, R. Negrin, G. Laport, D. Miklos, J. Shizuru, S. Arai, K. Blume, R. Wong, R. Lowsky, L. Johnston
Journal: Journal of Clinical Oncology (2009)

7033 Patients (pts) with high risk (HR) or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single institution long-term follow-up of 96 pts, median age 50 (20–60) yrs, who received HLA matched related HCT between 1992 and 2007. All pts were treated with a uniform preparatory regimen: busulfan 16.0 mg/kg (d-8 to-5), etoposide 60mg/kg (d-4), cyclophosphamide 60mg/kg (d-2), and graft-versus-host-disease (GVHD) prophylaxis of cyclosporine and prednisone. Disease status at transplantation was induction failure (IF) acute myeloid leukemia (AML) (n = 10), HR AML in 1st complete remission (CR1) n = 11, in CR2 (n = 5), in CR3 (n = 2), relapsed refractory (RR) AML (n = 14), chronic myeloid leukemia (CML) in second chronic phase (n = 6), blast crisis (n = 2), myelofibrosis (n = 6), myeloproliferative disorders (n = 2), and MDS (n = 38). Thirty-six % (n = 35) of pts received bone marrow while 64 % (n = 61) received G-CSF mobilized peripheral blood mononuclear cells (PBMC). With a median follow up of 5.6 yrs (1.6–14.6 yrs) actuarial 5-year overall survival (OS) was 32% (95% CI 22–42%) and 5-year probability for freedom from progression (FFP) was 64% (95% CI 52%-76%). Relapse rate was 32% at 1 year and remained at 36% (95%CI 24%-48%) at 2 and 5 years with no further increase in relapse beyond two years. Non-relapse mortality (NRM) was 29 % (95% CI 20%5–38%) at day 100 and 39% (95% CI 29%-49%) at one yr. Cumulative incidence of acute (grade 3–4) and chronic GVHD was 28% (95% CI 19%-37%) and 38% (95% CI 24%-52%), respectively. There was no statistically significant difference in OS; 31% versus 32% (p = 0.89) or FFP 71% versus 60% (p = 0.29) for recipients of BM versus PBMC with similar results in IF and RR AML. These results confirm that pts with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning. Relapse and acute GVHD remain significant causes of mortality. Strategies to augment graft-versus-tumor reactions and reduce GVHD remain essential for improving long-term outcomes. No significant financial relationships to disclose.
Surgical resection of gastric cancer in New York City 2000
Authors: D. Graham, D. G. Coit
Journal: Journal of Clinical Oncology (2004)

4046 Background: A New York City National Cancer Institute supported Comprehensive Cancer Center (CCC) has a high hospital volume providing surgical resection of gastric cancer. The demographic differences between the CCC and other Community University (C/U) hospitals in NYC are not known. The objective of this study was to examine the potential impact of demographic differences between referral centers (CCC) and C/U hospitals in regards to outcomes after gastric cancer resection. Methods: Using the Statewide Planning and Research Cooperative System (SPARCS) database for NYC 2000, descriptive statistic(s) on the prevalence of gastric cancer and surgical procedures was observed. Chi square test of significance was performed to measure the relationships between race/ethnicity, insurance status, types of surgical resection and access to C/U versus CCC care. Results: There were 1153 admissions in 51 NYC hospitals for gastric cancer and a total of 420 patients were resected, 312 resections were done in 50 C/U hospitals, the highest C/U doing 25 cases, while 108 cases were performed by 5 surgeons in one CCC. The median length of stay was 10 days in the CCC and 11 in the C/U. The in-hospital death rate was 1.9 % for the CCC compared with 5.4% in the C/U. There were differences between the two populations when considering the areas listed in the table below: Conclusions: The CCC had a lower mortality, shorter length of stay, more Medicare, more proximal lesions and less Medicaid and black patients. These improved outcomes for the CCC may be related to high volume, quality of care, location of tumors or demographic differences. No significant financial relationships to disclose.
Effect of the quality of the methodology on the relationship between progression-free survival (PFS) and overall survival (OS) in advanced colorectal cancer clinical trials.
Authors: X. Garcia-Albeniz, G. Carrera, J. Feliu, J. Aparicio, F. Torres, J. Maurel
Journal: Journal of Clinical Oncology (2010)

e14009 Background: Our aim was to create a quality-index assuming that high-quality trials would have a proportional relationship between PFS and OS. Methods: Randomized clinical trials (RCT) with new compounds (oxaliplatin, irinotecan, cetuximab, panitumumab and bevacizumab) in at least one of the arms of the RCT in first-line therapy for advanced colorectal cancer were analyzed by two independent researchers. A quality score ranging from 0 to 7 based on the following variables was built: 3 aspects affecting PFS or/and OS; final planned-sub-analysis (1 point), multivariate validation of stratification factors (2 points), double blinding (1 point) or in the quality of the primary end-point (PFS) radiological central review (1 point), clear definition of events and censoring patients (1 point) and statement of protocol deviations in events and censored patients (1 point). The relationship between OS and PFS was investigated by means of meta-regression models following a random-effects approach using the ln(RR) as the dependent variable and weighting by the inverse of each study variance. RCT quality (indicator variable) and median PFS effect (ln of the median ratio) were the main factors assessed in this study. The analysis was performed using SAS version 9.1.3 software. Results: Forty-four RCT in advanced colorectal cancer published between 2000 and 2009 were included in the study. Five RCT were excluded because full data has not been published. Thirty-one RCT were classified as "low-quality" trials (LQT, score < 3) and eight RCT fell in the "high-quality" category (HQTscore > = 3). Taking the 39 RCT selected together, the association of OS and PFS was moderate and significant: the increment in ln(RR) for the relative change in median PFS was 0.21 (p = 0.0008; R = 0.45). The increment was higher in HQT (B = 0.44, p = 0.033; R = 0.62) than in LQT (B = 0.13, p = 0.013; R = 0.32). Conclusions: PFS explains a 27.8% more of variability of OS in those studies classified as "high-quality" RCT by the proposed score than those classified as "low-quality
Surgical treatment in extremely aged patients with gastric cancer.
Authors: Masanori Sudo, Atsushi Nashimoto, Atsushi Matsuki, Hiroshi Yabusaki, Masaki Aizawa
Journal: Journal of Clinical Oncology (2015)

163 Background: Average life expectancy is increased to 82.6-year-old nowadays in Japan, and there is the increase of the number of elderly patients diagnosed with gastric cancer. Methods: From 1991 to 2011, 5330 operations have been performed for patients diagnosed with gastric cancer in our hospital, and 78 patients (1.5%) were over 85-year-old (elder group). To analyze the problems of surgical treatment for the extremely aged patients, the clinic-pathological findings were investigated retrospectively and compared with those in 4494 patients under 75 years old (control group). Results: Median age of elderly group was 86 (85-95) and control group was 63 (19-75). Preoperative morbidity was higher in the elderly group than in control group (73.1% vs 23.2%,p&lt;0.001). The operative prosedures such as local/proximal/distal/total were 9/0/49/20 in elderly group and 216/172/2983/1123 in control group. The ratio of D2/D3 nodal dissection was lower in elderly group than in control group (30.8/0% vs 48.1/5.4%). Operation-time/blood-loss was less invasive in elderly group (135min/70ml vs 165min/100ml,p&lt;0.001), but the postoperative morbidity rate was higher in elderly group (24.4% vs 15.3%,p=0.029). Although the frequency of postoperative complications was similar in surgical field, (14.1% vs 13.1%), other morbidity such as pneumonia, cerebral infarction and renal impairment were more common in elderly group. There was no difference in postoperative hospital stay in two groups (15 days). The ratio of postoperative adjuvant chemotherapy was lower in elderly group (Stage II/III; 10.0/13.3% vs 54.2/67.9%). The best supportive care is highly selected in elderly group in case of recurrence (66.7% vs 11.9%). The overall 5-year survival rate of Stage I/II/III/IV was 70.6/70.0/30.3/0% in elderly group and 92.0/80.0/60.5/13.3% in control group. The ratio of non-cancer death was higher in elderly group (41% vs 14%,p&lt;0.001). Conclusions: The postoperative morbidity and non-cancer death is higher in elderly group. With the restriction for treatment failure, appropriate surgical procedures such as minimally invasive surgery and attentive care for the morbidity would need for the extremely aged patients for their better quality of life.