tbuckley/cabot-search huggingface dataset:
Long-term survival in unfavorable-risk mRCC patients after intratumoral administration of a cell-based allogeneic vaccine adjuvant.
Authors: Anders Magnusson, AnnaCarin Wallgren, Einar Brekkan, Maria Lonnemark, Alex Karlsson-Parra, Anna Laurell
Journal: Journal of Clinical Oncology (2015)

e14006 Background: Initial data from a Phase I/II study in patients with recently diagnosed metastatic RCC demonstrated that intratumoral administration of a cell based allogeneic vaccine adjuvant before nephrectomy was associated with a prominent intratumoral infiltration of CD8+ T cells in a majority of patients and a trend towards prolonged survival was noted. Methods: Long-term survival as well as data on tumor response after subsequent TKI treatment has been studied. Results: Median overall survival (mOS) for MSKCC intermediate risk patients (n = 5) or high risk patients (n = 6) is still not reached but is currently (03FEB2015) 25.8 and 21.4 months, respectively. Three out of 6 patients who to date have received subsequent treatment with TKIs have experienced an objective tumor response. One responding patient (high risk), exhibited an extensive sarcomatoid transformation of the resected primary tumor. Another patient (high risk) who developed 4 brain metastases 3 months after nephrectomy responded with a complete disappearance of all 4 brain lesions and is still free from CNS-lesions 16 months after initiation of Sunitinib. Both patients exhibited a strong/massive intratumoral infiltration of CD8+ T cells in their removed kidney tumor. Conclusions: The current mOS (21.4 months) in high-risk patients has by far surpassed reported mOS of 9 months in comparable high-risk patients with recently diagnosed mRCC receiving upfront mono-therapy with sunitinib before nephrectomy. The objective tumor responses seen in two high risk patients after addition of sunitinib is surprising since historical data indicate that brain metastases as well as extensive sarcomatoid transformation are higly resistant to sunitinib treatment. Our findings indicate that intratumoral administration of an off-the-shelf vaccine adjuvant consisting of activated allogeneic DCs induces a CTL-mediated anti-tumor response that may prolong survival in mRCC-patients. Data on patients who have received additional treatment with TKIs indicate a synergistic anti-tumoral effect. A fully financed phase II study is currently in the final phase of planning. Clinical trial information: NCT01525017.
Utilizing Predictions of Early Prostate-Specific Antigen Failure to Optimize Patient Selection for Adjuvant Systemic Therapy Trials
Authors: Anthony V. D’Amico, Richard Whittington, S. Bruce Malkowicz, Yue Hui Wu, Ming-Hui Chen, Mark Hurwitz, Philip W. Kantoff, John E. Tomaszewski, Andrew A. Renshaw, Alan Wein, Jerome P. Richie
Journal: Journal of Clinical Oncology (2000)

Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed.A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome.The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P: < or =.009), PSA level greater than 10 ng/mL (P: < or =.01), seminal vesicle invasion (P: =. 02), prostatectomy Gleason score of 8 to 10 (P: =.04), and positive surgical margins (P: =.0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome.Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.
Incidence and risk factors for central nervous system (CNS) metastases in HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts)
Authors: S. Gori, V. De Angelis, S. Rimondini, A. M. Mosconi, G. Moretti, G. Bisagni, A. Sidoni, C. Aristei, E. Franceschi, M. Colozza, L. Crino
Journal: Journal of Clinical Oncology (2006)

10516 Background: Recently, an increased incidence of CNS metastases in HER2+ MBC has been reported. Aims of the observational study were to evaluate the incidence and risk for CNS metastases in HER2+ MBC pts. Methods: We reviewed the occurrence of CNS metastases in 122 consecutive HER2+ MBC pts treated with chemotherapy (CT) and trastuzumab (T)between April 1999 and June 2005. Patient characteristics included: median age 48 yrs (28–79); G3 in 58.1%;ER- in 53.2%; DFS &lt;24 mos in 48.3% and ≥24 mos in 51.7%. Visceral metastatic disease was dominant site of relapse in 67.2% of the pts. T+CT represented the 1st line of treatment in 54% of pts, 2nd line in 28.6% and ≥3th line in 17.2%. Results: At median follow up of 28 mos (2–167) from the occurrence of metastatic disease, 43 pts (35.2%) developed CNS metastases, confirmed by CT or MRI scanning. In 42 pts were present one or more parenchymal brain metastases and in 1 pt leptomeningeal carcinomatosis. Neurological symptoms were present in 90% of pts. Out of the 43 pts developing CNS metastases, 37.2% were in response in other metastastic sites and CNS represented the only site of progression. Median time of occurrence of CNS metastases (from diagnosis of metastatic disease) was 12 mos (0–78).Using the presence/absence of CNS metastases as dependent variable in logistic regression analysis, we obtained that age (p = 0.020) and visceral metastases (p = 0.024) were significantly associated with increased risk of CNS metastases. Panencephalic RT was given in 31 out of 43 pts; 16 pts (37.2%) received T ± further CT and 18 pts (41.8%) only cytotoxic CT. Median OS was 51.2 mos (1.9+-167.4) in the all population. Median OS was 35 mos (4–105) in pts with CNS metastases; at the present analysis median OS has not been reached in pts without CNS metastases (p = 0.002). Conclusions: CNS metastases is common, late event in the natural history of HER2-positive MBC. Age and visceral metastases were significantly associated with increased risk for CNS metastases. Clinical trials are indicated to evaluate:1) any clinical, pathological and molecular risk factors for CNS metastases; 2) if there is indication to specific treatment in a population at high risk of CNS metastases. No significant financial relationships to disclose.
Impact of the amount of tumor cells in tissue samples for detection of <i>KRAS</i> mutations in colorectal cancer.
Authors: J. Selves, D. Grand, R. Guimbaud, K. Gordien, S. Valmary, E. Delabesse, M. Danjoux, E. Tournier, S. Kirzin, P. Brousset
Journal: Journal of Clinical Oncology (2010)

3571 Background: Treatment of metastatic colorectal cancer with anti-EGFR is restricted to patients with wild-type KRAS tumor. The detection of KRAS mutation is easy to perform using several methods of molecular biology. The aims of this work were to analyze the impact of different factors for detection of KRAS mutations in routine practice. Methods: 441 KRAS mutation analyses were performed between October 2008 and June 2009 on formalin fixed and paraffin-embedded tumour samples (89%) and cryopreserved samples (11%). 287 cases were surgical samples and 96 were biopsies. Majority of samples were primary tumors (77%) with only 13% of metastases. A microscopic examination before DNA extraction was systematically performed to control the percentage of tumour cells in the sample with macrodissection in two third of cases for enrichment into tumour cells. Results: Using a sensitive method to detect KRAS mutations at codon 12 and 13 (screening by HRM PCR and mutation identification by TaqMan probes), we detected 39 % of KRAS mutation with only 6% of DNA amplification failure. The frequency of the various mutations was roughly similar to that described in the literature (G12D: 42%, G12V: 23.4%, G13D: 21%, G12C: 4.8%, G12S: 3.61%, G12A: 1.8%, G12R: 06%). More interesting, the detection rate of the mutations clearly decreased with the percentage of tumour cells (TC) in the extracted samples (TC > 50% [n = 378]: 41%, 20-50 TC% [n = 44]: 27%, TC < 20% [n = 5]: 0%) (p = 0.039). The detection rate of mutations seems to be more important in metastatic tumours (n = 58) than in primary tumours (n = 344): 48% vs. 38% respectively. The type of material (biopsy vs. surgical specimen) had no impact. Conclusions: In colorectal cancer, tissue samples that contain less than 50% of tumor cells can give rise to false-negative results for KRAS mutation detection. Frequency of KRAS mutations seems higher in metastatic than in primary tumours. No significant financial relationships to disclose.
FRI0172 Utility of Swedish Register Data in Classifying Systemic Lupus
Authors: E. Arkema, A. Jönsen, L. Rönnblom, C. Sjöwall, E. Svenungsson, J.F. Simard
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a quite rare disease, making it a challenge to achieve an adequate sample size for many research questions. <h3>Objectives</h3> Our aim was to employ data mining techniques to identify a classification algorithm using national register data in Sweden. <h3>Methods</h3> Clinically confirmed SLE cases were pooled from 4 major clinical centers in Sweden (Linköping, Lund, Stockholm and Uppsala), excluding cases with &lt;4 ACR criteria. We identified a population of non-SLE comparators by randomly selecting individuals from the National Population Register matched on age, sex and county to individuals with SLE from national registers. Both cases (N=940) and comparators (N=24,370) were restricted to adults (&gt;16y) living in Sweden Jan 1, 2010. Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the study population. Two different methods (classification tree analysis and penalized least absolute shrinkage and selection operator (LASSO) regression) generated an algorithm to identify cases from non-cases in men and women separately. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Sensitivity analyses used a second general population comparator group and elastic net regression to allow collinear predictors. <h3>Results</h3> Both the classification tree and LASSO methods identified only 1 variable as the best discriminator between cases and non-cases: ≥1 SLE ICD code in a specialized clinic (sensitivity=0.99, PPV=0.98 in women). Results in men were similar. Standardized PPVs were high. Sensitivity analyses added several predictors, such as inpatient and outpatient visits and medications. <h3>Conclusions</h3> The use of an SLE ICD code in a specialized clinic to distinguish between cases and non-cases performed well. Additional algorithms were identified in sensitivity analyses. It is possible to identify individuals with SLE among thousands of people in Sweden, however validation studies (currently underway) are necessary to assess the magnitude of potential misclassification. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4550
Pulmonary metastasis (PM) of testicular choriocarcinoma: Can we omit resection of residual PM after induction chemotherapy?
Authors: A. Tryakin, M. Fedianin, B. Polockij, B. Ahmedov, J. Sergeev, T. Zakharova, A. Mitin, I. Fainstein, A. Garin, S. Tjulandin
Journal: Journal of Clinical Oncology (2008)

16065 Background: Metastatic choriocarcinoma is the most aggressive subtype of nonseminomatous germ cell tumors (NSGCT) that tends to early spread into viscera, especially lungs. Resection of all post-chemotherapy residual tumors has become a standard option in metastatic NSGCT. However multiple metastases of choriocarcinoma frequently involve retroperitoneal lymphnodes, liver, and both lungs. In this setting it is difficult (and often just impossible) to achieve “no evidence of disease” (NED) status. We performed an analysis to review the outcome of patients (pts) with choriocarcinoma who became marker-negative after induction chemotherapy (CT) with their residual PM left. Patients and Methods: 43 CT-naïve pts with metastatic NSGCT, PM and baseline hCG level > 50000 IU/l were treated in our center from 1993 to 2006. 20 out of them completed induction CT, became marker-negative and still had residual PM. Median pre-treatment hCG level was 250000 IU/l (range, 54900–3260000). 18 (90%) pts had testicular primary tumor. Induction CT-regimens were T-BEP (40%), BEP (40%), C- BOP-3BEP (20%). Median follow-up was 42 (range, 14–107) months. Results: 15 (75%) out of 20 pts had residual tumor resections. 4 out of them underwent resections of two metastatic sites (RPLND - 10 pts, lung resections - 6 pts, liver resections - 3 pts). No viable tumor was found in resected masses. Mature teratoma arose more often in RPLN - 5 (50%) pts compared with lung metastases - 1 (17%) pt (it was a solitary residual PM). Despite surgery 17 (85%) pts could not achieve NED status mostly due to nonresected multiple residual PM. Two (10%) pts relapsed: occurrence of brain metastases in both of them without progression of PM (one pt previously underwent resection of a gross PM and second one - RPLND). Conclusion: Resection of PM has no influence on patients’ outcome in metastatic choriocarcinoma pts with multiple residual PM, who achieved marker-negative status after induction CT. No significant financial relationships to disclose.
Prognostic information (PI), psychological well-being, and quality of life for advanced cancer patients (ACP) in phase I trials and their spousal caregivers (SC).
Authors: Fay J. Hlubocky, David Cella, Tamara Sher, Bonnie Yap, Mark J. Ratain, Christopher Daugherty
Journal: Journal of Clinical Oncology (2013)

9520 Background: The impact of the physician’s (MD) disclosure of PI on the psychological well-being and quality of life (QoL) of clinical trial subjects with terminal disease on Phase I trials has not been formally evaluated. Methods: A prospective cohort of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) utilizing various measures including: state-trait anxiety (STAI-S/T), depression (CES-D), quality of life/QoL (FACIT-Pal), and global health (SF-36). Semi-structured interviews of ACPs also evaluated MD-Pt communication re prognosis and worry about ACP death. Results: 100 subjects (50 Phase I ACPs and 50 SC) were separately interviewed at T1 and T2. For the population as a whole: median age 62 (28-78y); 51% male; 100% married; 88% Ca; 68% &gt; HS educ; 56% GI dx; 54% income &lt;$65,000 yr. At T1, 45% of ACPs acknowledged having a discussion re life expectancy with MD; 35% stated the MD gave a prognostic timeframe; and 41% reported worry re death. For SC at T1, 62% recalled a prognosis discussion with the MD; 50% stated MD gave a timeframe; 53% reported PI disclosure was initiated by the MD; 66% reported worry re ACP death. At T2, rates remained consistent for both ACP and SC with the exception of increased reported worry re ACP death at 55% and 70% respectively. At T2, ACP who denied a prognosis was given by the MD had higher STAI-S (35 ± 10 v 29 ± 9, p=0.03) and CES-D scores (16 ± 12 v 7 ± 4, p=0.01); and lower FACT-Pal scores (128 ± 18 v 153 ± 24, p=0.01). SC with acknowledgement of a prognostic timeframe given by the MD had higher STAI-S anxiety (39 ± 16 v 35 ± 14, p=0.04) at T2. Regression analyses revealed that ACP with acknowledgement of a prognostic timeframe given by the MD had poorer FACIT-Pal QoL over time. Also, SC with acknowledgement of a prognostic timeframe at T2 was negatively associated with SF-36 scores. ACP and SC qualitative responses re PI disclosure revealed salient themes: hope for a positive outcome or prolonged survival; stabilization of disease; emotional distress; ambivalence/fear; acceptance. Conclusions: Physician disclosure of a prognostic timeframe is negatively associated with QoL among clinical trial subjects and SC in phase I trials.
Biweekly nonpegylated liposomal doxorubicin (M) and docetaxel (T) as neoadjuvant treatment in patients with stage II-III breast cancer
Authors: I. Alvarez, A. Modolell, J. I. Mayordomo, J. Janariz, M. Centelles, J. M. García, P. Puerto, C. Diego, C. Madroñal, M. A. Burillo-R Andres
Journal: Journal of Clinical Oncology (2007)

11049 Background: We have previously reported (ASCO 2006) the efficacy and toxicity of 4 courses of M (75mg/m 2 ) and T (75mg/m 2 ) with G-CSF support in a 21 day schedule as neoadjuvant treatment in patients with resectable breast cancer. Aim: To evaluate the clinical and pathological response rate (RR) and toxicity of biweekly M and T given prior to surgery in patients with breast cancer. Methods: Patients with histological confirmation of breast cancer (stage II-III and inflammatory), age &gt;18 years, left ventricular ejection fraction &gt; 45% and adequate bone marrow, renal and hepatic function were included in the study. Prior systemic therapy, radiotherapy or surgery for breast cancer were not allowed. The treatment was: M (60 mg/m 2 ) and T (60mg/m 2 ) each in 1 hour infusion, with subcutaneous G-CSF (5 mcg/kg) support on days 4–9. Courses were repeated every 14 days. Patients received 6 courses prior to surgery. Results: To date 45 patients have been enrolled; 20 who have completed therapy and underwent surgery (except for patients with progression) were included in this interim analysis. Median age: 48 years (38–63), ECOG PS 0: 90%, ECOG PS1: 10%, postmenopausal: 35%. Histology was infiltrating ductal carcinoma in 80%. Patients received a total of 110 courses (median 6, range 2–6). Efficacy: Of 19 evaluable patients, 4 achieved a clinical complete response (cCR) (21%), 12 partial response (cPR) (63%), 1 stable disease (cSD) (5%) and 2 progressive disease (cPD) (10%), resulting in a clinical response rate (cRR) of 84%. Surgery was performed in 17 (85%) patients, 4 (23%) of them had pathological complete response (pCR), 12 (70%) partial response (pPR), 1 (6%) stable disease (pSD), resulting in a pathological RR of 93%. Median time to progression and overall survival have not been reached. Toxicity: Hematological grade III/IV toxicities per patient were neutropenia (10%), febrile neutropenia (10%) and thrombocytopenia (5%). Non-hematological grade III/IV toxicities per patient were mucositis (10%), nausea/vomiting (10%) and epigastralgia (10%) Conclusions: Six courses of T and M every 14 days with G- CSF support as induction treatment in stage II and III breast cancer are active and well tolerated. No significant financial relationships to disclose.
UW-01: A randomized comparison of three doses of weekly docetaxel as 1st-line chemotherapy in stage IV breast cancer
Authors: J. R. Gralow, D. Chielens, G. Schuster, B. Storer, M. J. McCleod, R. E. Smith, N. M. Chowhan, V. Gressler, G. Miletello
Journal: Journal of Clinical Oncology (2006)

10522 Background: Docetaxel (DOC) is an active agent in the treatment of breast cancer. The optimal dose and dosing interval for DOC, with respect to balancing efficacy and toxicity, has yet to be determined. In this multi-center, randomized phase III trial, we attempted to compare 3 doses of single-agent weekly DOC. Methods: Patients with documented evaluable or measurable stage IV breast cancer and no prior metastatic chemotherapy were eligible. Prior adjuvant chemotherapy was permitted if ≥ 6 months had elapsed. Adjuvant exposure to DOC was allowed if ≥ 1 year prior. All patients received intravenous weekly DOC, 3 out of 4 weeks. Patients on Arm A received doses of 25 mg/m 2 , Arm B received 30 mg/m 2 , and Arm C received 35 mg/m 2 . The primary study outcome was time to progression (TTP). Secondary endpoints included toxicity, response rate (RR), and overall survival (OS). Targeted accrual was 600 patients. Results: The study was stopped early for feasibility reasons (poor accrual) after a total of 108 patients were enrolled at 49 U.S. sites. The median patient age was 63 years. Grade 3, 4 non-hematologic toxicity was 22%, 22%, and 23% in Arms A, B and C respectively. Nail toxicity of any grade occurred in 2 patients in Arm A, 6 patients in Arm B, and 7 patients (2 of which were grade 3) in Arm C. TTP for Arm A was 19 weeks (95% confidence intervals [CI] 10–23), 28 weeks for Arm B (95% CI 15–38), and 24 weeks for Arm C (95% CI 12–37). There was a marginally significant difference in TTP between arms A and C (HR = 1.7, 95% CI = 1.0–2.8, p = 0.05), but not between arms B and C (HR = 1.0, 95% CI 0.6–1.7, p = 0.94). RR was 26%, 27%, and 31% in Arms A, B and C, respectively. Median survival was 77 weeks for Arm A (95% CI 53–115), and 96 weeks for arm B (95% CI 53-undetermined); it has not yet been reached for Arm C. Discussion: The interpretation of study results is limited due to early stopping and resultant loss of statistical power. For the primary study endpoint, TTP, the lowest (25 mg/m 2 ) dose may be less than optimal, but there was no observed difference between the intermediate (30 mg/m 2 ) and highest doses (35 mg/m 2 ) of weekly DOC. Grade 3, 4 non-hematologic toxicities were similar between the 3 arms. [Table: see text]
Phase II study of hydroxyurea for unresectable meningioma (Southwest Oncology Group S9811)
Authors: L. J. Swinnen, C. Rankin, E. J. Rushing, H. F. Laura, D. M. Damek, G. R. Barger
Journal: Journal of Clinical Oncology (2009)

2063 Background: Meningiomas account for 15%-18% of CNS tumors. Although benign, recurrence is seen in 16%-39% of cases, depending on the extent of resection possible. Tumor location may make further resection hazardous. Chronic hydroxyurea (HU) was reported to produce well documented objective responses in a small series of patients, with gradual regression occurring over 6–10 months. Induction of apoptosis was furthermore demonstrated with HU in primary benign meningioma explant cultures. The S9811 phase II trial was undertaken to estimate the objective response rate, if any, of unresectable benign meningioma to this HU regimen. Methods: Eligibility required unresectable, measurable, residual or recurrent, histologically-proven benign meningioma. Progressive tumor or progressive neurologic deficit was required. No prior cytotoxics, no radiation therapy for &gt;1 year. Age &gt; 18, adequate hematologic reserve, PS 0–2. HU 20 mg/kg/day po was given for up to 2 years if there was no progressive disease. Single-stage accrual of 38 pts would have allowed detection of 5% null hypothesis response probability vs. 20% with 90% power; the 28 pts actually accrued provide 81% power. Results: Between November 98 and June 2005, 29 pts were accrued, with study closure due to slow accrual. 1 ineligible. Response assessment showed CR+PR 0% (95% CI 0–12%); SD 71% (95% CI 51–87%); PD 21% (95% CI 8–41%); undetermined 7%. Median PFS was 27 months. (95% CI 12–29 months.); 3-year PFS 43% (95% CI 25–61%). Median OS has not been reached. Seven patients were removed from study for toxicity (5/7 hematological). Toxicity was mainly hematologic: 11/28 (39%) grade 3, 2/28 (11%) grade 4. Grade 3 non-hematologic toxicity was seen in 7/28 (25%). Conclusions: Chronic HU therapy for unresectable benign meningioma resulted in an estimated objective response rate of &lt; 12%. Whether the stable disease rate seen differs in any way from what can be expected from the natural history of meningioma cannot be determined from this phase II study design. No significant financial relationships to disclose.