tbuckley/cabot-search huggingface dataset:
Outcomes of adjuvant therapy in surgically staged uterine carcinosarcoma patients with minimal residual disease.
Authors: L. Tait, M. D. Hasselle, A. Meriwether, K. Wroblewski, S. D. Yamada, Y. Hasan
Journal: Journal of Clinical Oncology (2010)

e15513 Background: Uterine carcinosarcoma (UC) is a rare gynecologic malignancy with poor outcome. The purpose of this study is to evaluate multimodality treatment of UC in optimally cytoreduced patients. Methods: From 1997-2009, 33 patients with optimally debulked FIGO stage I-IV UC underwent adjuvant therapy with IRB approval for data collection. Exclusion criteria included extensive residual disease post-operatively or distant metastases. Patient characteristics, clinicopathologic variables and adjuvant therapy were analyzed. Recurrence-free-survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariate analysis (UVA) was performed using the log rank test. Results: Median age of patients was 66. Seventeen patients had FIGO stage I/II disease and 16 patients had stage III/IV disease. Eighteen had > 50% myometrial invasion, 17 had lymphovascular invasion, and 15 had involved pelvic lymph nodes. Median tumor size was 6.8 cm. Twenty patients (65%) received adjuvant chemotherapy. Seventeen received whole pelvic radiotherapy (4 with brachytherapy), and 5 received brachytherapy alone. The median survival was 7.1 years (95% CI, 1.8 to 10.5). The 1- and 5-year OS were 85% (95% CI, 67 to 93%) and 53% (95% CI, 33 to 70%), respectively. For the 15 patients alive without recurrence, the median follow-up was 2.1 years (range 0.9 to 10.8 years). On UVA for OS, only stage (I/II vs. III/IV) was significant (p < 0.01). Age ≥ 60 (p = 0.06) and adjuvant chemotherapy (p = 0.06) were borderline significant for worse OS. With median RFS time of 4.5 years (95% CI, 0.5 to not estimable) in 32 patients, the 1-year and 5-year RFS probabilities were 59% (95% CI, 40 to 74%) and 49% (95% CI, 29 to 66%), respectively. Only tumor size at the time of surgery had a statistically significant association (HR = 1.14, 95% CI [1.02, 1.27], p = 0.02, Cox proportional hazards regression) for RFS. Eleven (33%) and 7 (21%) patients had a component of locoregional and distant recurrence respectively. Conclusions: This analysis demonstrates that accurate staging, optimal debulking and multimodality adjuvant treatment results in 5 year OS of 53% which is favorable when compared with historical controls. No significant financial relationships to disclose.
MRI-US fusion targeted biopsy results in men with a history of prior cancer.
Authors: Cayce Nawaf, James Rosoff, Amanda Lu, Jeffrey Weinreb, Peter Humphrey, Angelique Levi, Peter Schulam, Preston Sprenkle
Journal: Journal of Clinical Oncology (2016)

88 Background: Appropriate risk stratification of men on active surveillance for prostate cancer is essential to identify men in whom it is safe to take this deferred treatment approach. This study evaluates upstaging rates using MRI-US fusion targeted biopsy in men who have had a prior positive standard 12-core biopsy. Methods: Between 12/2012 and 06/2015, 374 men with an indication for prostate biopsy underwent pre-biopsy mpMRI followed by 12-core standard trans-rectal mapping biopsy (Mbx) and MRI-Ultrasound fusion targeted biopsy (Tbx) of lesions identified on mpMRI. The combination of Mbx and Tbx, when both occurred, constitutes a fusion biopsy (Fbx). Men who underwent both Mbx with or without Tbx using the Artemis/Pro-Fuse system with a previous non-MRI-guided biopsy and a diagnosis of prior Gleason 6 prostate cancer were included. Patients without a lesion on MRI underwent Mbx only. Maximum Gleason scores (GS) were assigned on a per patient basis with Mbx GS available for all patients in the cohort and Tbx GS available only for patients with a lesion visible on MP-MRI. Clinically significant (CS) cancer was defined as GS ≥ 3+4. GS per patient was compared by chi-square and McNemar’s test. Results: 118 patients met inclusion criteria (Mean PSA = 6.9, Mean age = 62.5). 40 patients (34%) were upstaged by Fbx to Gleason ≥ 7. Of those upstaged, 17 men (14%) would have been missed by Mbx alone, in comparison to 7 (6%) that were missed by Tbx alone. Total number of prior biopsies (p = 0.28) and number of years on Active Surveillance (p = 0.22) were not related to upgrade on Fbx. Older men (65.3 vs. 60.9, p = 0.033) and those with higher PSA (8.7 vs 5.8, p = 0.002) were more likely to be upgraded on Fbx. Tbx was more likely to identify CS cancer than Mbx (85% vs 56%; p &lt; 0.012). Conclusions: MP-MRI Fusion biopsy more accurately stratifies men with a previous prostate biopsy than those receiving a template mapping 12-core biopsy alone. Tbx should be strongly considered before enrolling a patient in active surveillance since up 14% of clinically significant cancer would have been missed with a 12-core biopsy alone. [Table: see text]
A 17-gene genomic prostate score (GPS) as a predictor of biochemical (BCR) and clinical recurrence (CR) in men with surgically treated intermediate- and high-risk prostate cancer (PCa).
Authors: Eric A. Klein, Nan Zhang, Michael Crager, Tara Maddala, Phillip G. Febbo, Shibu Thomas, Michael Gormley, Deborah Sokol Ricci, Sara Moscovita Falzarano, Cristina Magi-Galluzzi, H. Jeffrey Lawrence
Journal: Journal of Clinical Oncology (2016)

104 Background: The biopsy-based GPS (scale 0-100) is validated as an independent predictor of adverse pathology in men with low- and intermediate-risk PCa. We wished to examine the association of GPS with BCR and CR in higher-risk disease. Methods: We performed exploratory analyses of data from a prior development study of radical prostatectomies from 441 men with AUA low-, intermediate- and high-risk disease, using a cohort sampling design (Klein et al. Eur Urol 2015). Multivariable Cox proportional hazards models were employed with the cohort sampling weights. Since these data were used in the selection of genes and coefficients for GPS, hazard ratios (HR) and other estimates based on GPS were corrected for regression to the mean (RM), and Storey’s method was applied to hypothesis tests for GPS to control the false discovery rate (FDR). Results: All estimates are RM-corrected. Broad, overlapping ranges of GPS values were observed across all AUA risk groups. GPS was strongly associated with BCR (HR 1.64 for 20 GPS units, p&lt;0.001, FDR q-value &lt; 0.1%) and CR (HR 2.79 for 20 GPS units, p &lt; 0.001; FDR q-value &lt; 0.1%), after adjusting for AUA risk group. Intermediate-risk patients with GPS &gt; 40, who represented 41% of all intermediate-risk patients, had estimated 3-year BCR risk and 10-year CR risk similar to high-risk patients (Table). Conversely, high-risk patients with GPS≤ 40, who represented 63% of all high-risk patients, had a 3-year BCR risk and a 10-year CR risk similar to men with intermediate-risk disease. High-risk patients with GPS &gt; 40 had 3-year BCR risk of almost 50% and 10-year CR risk of 35%. Conclusions: GPS appears to provide improved risk stratification for BCR and CR in AUA intermediate- and high-risk PCa. These findings require confirmation in an independent cohort of patients. [Table: see text]
Safety and efficacy of neoadjuvant combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil, and oxaliplatin with intravenous (iv) cetuximab in patients with unresectable liver metastases from colorectal cancer (CRC): Interim report from OPTILIV—A European multicenter phase II trial.
Authors: M. Ducreux, P. Rougier, D. Smith, C. N. J. Focan, P. F. Innominato, M. Bouchahda, Y. Ajavon, D. Castaing, T. De Baere, A. Karaboué, C. Lepere, V. Boige, R. Adam, F. Levi
Journal: Journal of Clinical Oncology (2011)

e14102 Background: HAI of chronomodulated irinotecan (I), 5-Fluorouracil (F) and oxaliplatin (O) (chronoIFO) as well as HAI of O combined with iv F and leucovorin allowed complete macroscopic resections of CRC liver metastases in patients with prior failure on systemic chemotherapy (Bouchahda, Cancer 2009; Goere, Ann Surg 2010). Purpose: To evaluate the resection rate of CRC liver metastases through combining HAI of IFO with cetuximab (Cet) in the first prospective European trial (Lévi, ASCO 2010, TPS#198). Methods: Patients with wt KRAS CRC and unresectable liver metastases receive iv Cet (500 mg/m2, D 1 10:00-12:30) and chrono or conventional HAI of I (180 mg/m2 D1), F (2800 mg/m2/d D2-D3/4), and O (85 mg/m2 D2-3/4) q2 weeks. Grade 3-4 toxicities were managed with dose adaptation and/or supportive measures. Results: 23 patients (9F, 14 M; 33-76 y; PS 0-1) completed full assessment. They had bilateral liver lesions (82%), a median of 7 metastases [2-30; largest diameter, 38 mm (11-150)] and received ≥2 prior iv chemotherapy lines (61%). A median of 4 protocol courses (1-12) was given. Main grade 3-4 toxicities per patient were neutropenia (39%), abdominal pain (30%), fatigue (22%), and leukopenia (17%). An objective tumor response was achieved in 10/23 patients (43.4%). Seven patients underwent liver surgery (30.4%). 17 pts are alive with a median follow up of 16 months. One responding patient with 25 metastases measuring up to 6 cm and involving all liver segments had pathologic complete response in 24 of 25 lesions removed through three-stage hepatectomy. Conclusions: OPTILIV offers a safe and unusually effective treatment option. The trial aims at accruing 48 eligible patients to provide a statistical estimate of the complete macroscopic resection rate and survival in patients with liver metastases from refractory colorectal cancer receiving intravenous cetuximab and hepatic artery infusion of triplet chemotherapy.
Retrospective analysis of patients with male breast cancer: Report from O.R.I.O.N. collaborative group
Authors: D. G. Generali, M. C. Garassino, S. Lonardi, A. Bettini, R. Rossello, O. Martelli, E. Collova, I. Rampinelli, A. Mancuso, C. Saggia, V. Torri
Journal: Journal of Clinical Oncology (2008)

11594 Background: Male breast cancer is an uncommon disease, 1%(0.7 %) of all breast cancer. Its aetiology, clinical behaviour and treatment are not well-known. The objective of our report was to analyze the form of presentation and the clinical evolution of patients with male breast cancer studied from 1987 to 2006. Methods: A total of 142 men with a diagnosis of breast carcinoma were registered and treated at the cancer-based hospitals linked to ORION collaborative group. 138 men had nonmetastatic breast carcinoma at diagnosis and were included in this analysis. Patients’ charts were retrospectively reviewed to obtain details of patient characteristics, adjuvant therapy, and outcomes. Analysis was performed with descriptive statistics; the log-rank test was used to compare outcomes. Results: The median patient age was 61.9 years (range, 38–84 yrs). Positivity for family cancer history: 16 out of 123 cases, 3 were unknown. Pathological characteristics included: pT1 tumors 22 pts (15.5%); pT2a 33 (23%), pT2b 18 (12.5%), pT3a 48 (34%), pT3b 17 (12%), pT4, 4 (3%); infiltrating ductal carcinomas in 82.4% of cases; axillary lymph node involvement in 71 (50%); 61 patients with ER and PgR+ve tumors, 22 pts negative, 15 pts unknown. Median follow-up was 5.2 years (range 0.5–16.7 yrs). After surgery 48 (33.8%) pts received RT, 100 pts received adjuvant chemotherapy or hormonotherapy and 42 patients did not receive any treatment. The 10-year DFS and OS rates for men with T1 or T2 disease were 47% and 80%, whereas for men with T3 or T4 they were 48% and 44%, respectively. Conclusions: Our data confirmed what is reported in literature and as expected, early stages had a better DFS and OS. Further biological studies are required for a deep understanding of this rare disease and to use the best therapeutical strategy for improving the outcome. No significant financial relationships to disclose.
Treating HIV+ patients for non-AIDS-defining cancers (NADCs) in the era of targeted chemotherapy: An AIDS malignancy consortium study of sunitinib in patients on ART.
Authors: J. F. Deeken, R. T. Mitsuyasu, R. F. Little, S. P. Ivy, R. F. Ambinder, M. A. Rudek, J. Y. Lee, P. C. Moore, K. Mosby, B. J. Dezube
Journal: Journal of Clinical Oncology (2010)

TPS161 Background: The cumulative NADC incidence is approaching that of AIDS-defining cancers in HIV-infected persons in populations where effective antiretroviral therapy (ART) is commonly used. Marked increases in risk are seen in certain cancers, including lung, liver, head and neck, anogenital, and Hodgkin's lymphoma. Treatment of NADCs may be complicated by drug-drug interactions between ART and chemotherapy, including ART-mediated induction or inhibition of metabolizing enzymes, especially of the CYP450 family. To study these interactions, with the goal of formulating treatment recommendations on the use of targeted anticancer agents to treat NADCs in HIV+ patients, the AIDS Malignancy Consortium has launched the first clinical study to address this emerging epidemic. Sunitinib is a multi-targeted TKI of PDGFR, VEGFR1/3, KIT, FLT3, SCF, and RET. It is a prodrug which is metabolized into the active metabolite SU012662 by CYP3A4, which is then further inactivated by CYP3A4. Methods: The primary objectives of AMC 061 is to determine the safety and to investigate the effect of ART on the PK of sunitinib in HIV+ cancer patients. Secondary objectives include investigating: the efficacy of using sunitinib to treat NADCs; the effects of sunitinib on ART pharmacokinetics, CD4 count, and HIV viral load; and pharmacogenetic correlations. Subjects are stratified into three groups based on their ART therapy: (1) non- nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy, (2) non-ritonavir protease inhibitor (PI)-based therapy, and (3) ritonavir PI-based therapy. A phase I dose escalation design is used to determine the MTD of sunitinib (25, 37.5, or 50 mg daily) in each group, with both inter- and intra-patient dose escalation allowed. Between 21 and 42 patients will be enrolled. Intensive PK and PD monitoring is performed throughout Cycle 1. The trial was initiated in late 2009, and is open at AMC sites and those of the NCI Organ Dysfunction Working Group. As of 1/2010, three patients have been enrolled. Treatment has been well tolerated and no DLTs have been experienced. Updated information on the safety and initial PK analyses will be presented. No significant financial relationships to disclose.
Multicenter feasibility study of 5-FU, leucovorin, plus paclitaxel (FLTAX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake.
Authors: H. Takiuchi, H. Yasui, T. Nishina, D. Takahari, N. Nakayama, K. Taira, H. Kusaba, N. Fuse, S. Hironaka, T. E. Nakajima
Journal: Journal of Clinical Oncology (2011)

119 Background: Oral fluoropyrimidine plus cisplatin is widely used as a standard treatment for advanced gastric cancer, but patients (pts) with severe peritoneal metastasis often cannot tolerate this regimen. The aim of this study was to assess the feasibility of fluorouracil (5-FU), leucovorin (LV), plus paclitaxel (PTX) for peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake. Methods: Peritoneal disseminated gastric cancer with massive ascites or inadequate oral intake were enrolled in Part I (Level 1 (n=6): 5-FU bolus/l- LV div 2hr/PTX div 1hr = 500/250/60, Level 2 (n=6): 600/250/80 mg/m 2 (day1, 8, 15, q4w) to determine dose-limiting toxicity (DLT) and recommended dose (RD). In Part II (n=19), primary endpoint was completion rate of 2 cycles to evaluate the feasibility of this regimen at RD level. Results: One of Level 1 pts had DLT with grade 4 gastrointestinal perforation. Two of Level 2 pts had DLT (grade 3 febrile neutropenia and grade 3 infection with normal neutrophils) and treatment-related death (TRD) was observed in one patient due to pneumonia with grade 4 neutropenia. The RD was determined to be Level 1. Twenty-five patients were enrolled at RD level: first-line/second-line=18/7, performance status 0/1/2=1/19/5. The completion rate of 2 cycles was 92% and objective response rate of ascites was 45%. Grade 3 or 4 neutropenia was observed in 12% (febrile neutropenia in 8%). Five patients out of 7 second-line patients died within 30 days after last administration of FLTAX (TRD: 1 and disease progression: 4). Conclusions: RD of FLTAX regimen was 5-FU/l-LV/PTX=500/250/60 mg/m 2 . This regimen was feasible as the first-line treatment against peritoneal disseminated gastric cancer patients with massive ascites or inadequate oral intake. [Table: see text]
Effect of preoperative bilirubin on outcomes of completely resected hilar cholangiocarcinoma: A multi-institutional analysis.
Authors: Harveshp Mogal, Rebecca Dodson, Nora Fino, Cecilia Grace Ethun, Timothy M. Pawlik, George A. Poultsides, Thuy Tran, Kamran Idrees, Ryan C. Fields, Linda Jin, Sharon M. Weber, Ahmed I. Salem, Robert C. G. Martin, Charles Raben Scoggins, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel, Perry Shen
Journal: Journal of Clinical Oncology (2016)

326 Background: Perioperative and long-term outcomes of patients with Hilar cholangiocarcinoma (HC) and preoperative hyperbilirubinemia have not been clearly defined. Methods: Patients with HC undergoing hepatectomy with a complete (R0/R1) resection between 2000 and 2014 were identified within a 10-institution prospectively maintained database. Using receiver operating characteristic curves from logistic regression models, a peak bilirubin cutoff point that minimized the difference between the sensitivity and specificity, was determined. Factors affecting perioperative complications were estimated using logistic regression. Results: 191 of 328 (58.2%) patients who underwent complete resection with a hepatectomy, with available preoperative bilirubin data were analyzed. 37.2% (n = 71) had bilirubin &gt; 7.9. Patients with higher preoperative bilirubin were more likely to have a higher CA 19-9 (1776±3721.5 vs 302.1±518.6, p = 0.0006), more comorbidities (1.6±0.8 vs 1.4±0.9; p = 0.002), preoperative biliary drainage (PBD) (91.4% vs 75.6%, p = 0.007), positive lymph nodes (48.5% vs 31.5%, p = 0.025) and perioperative death (14.5% vs 5.2%, p = 0.0292). Multivariate analysis identified PBD (OR 3.2, CI 1.4-7.5; p = 0.008) and smoking (OR 2.3, CI 1.2-4.4; p = 0.016) to be independent predictors of any and major complications. Peak bilirubin &gt; 7.9 (OR 3.1, CI 1.1-8.9; p = 0.04) and preoperative systemic sepsis (PSS) (OR 5.0, CI 1.2-21.5; p = 0.03) were associated with increased risk of postoperative mortality. However, on multivariate analysis only PSS was significant (OR 14.4, CI 2.2-93.9; p = 0.005); 5/13 (23.1%) of patients with PSS died within 30 days after surgery. Conclusions: PSS portends increased operative mortality in HC patients undergoing hepatectomy, independent of preoperative peak bilirubin levels. Prevention and aggressive treatment of PSS should be the priority in the preoperative optimization of these patients.
ABI-007 in the treatment of unresectable or recurrent gastric cancer refractory to fluoropyrimidine-containing regimen: Updated data from the multicenter phase II study.
Authors: Hiroya Takiuchi, Yasutsuna Sasaki, Tomohiro Nishina, Hirofumi Yasui, Kei Muro, Akihito Tsuji, Wasaburo Koizumi, Yasushi Toh, Takuo Hara, Yoshinori Miyata
Journal: Journal of Clinical Oncology (2012)

90 Background: ABI-007 is a novel Cremophor-free nanoparticle albumin-bound paclitaxel. Cremophor-free formulation allows administration using a shorter infusion schedule (30 minutes) and without the need for premedicaion to prevent solvent-based hypersensitivity reactions.This single arm phase II study evaluated the efficacy and safety of ABI-007 given every three weeks to unresectable or recurrent gastric cancer patients (pts) who had received one prior chemotherapy regimen containing fluoropyrimidine and developed disease progression (PD) or recurrence. Methods: Eligibility include: histologically or cytologically confirmed gastric adenocarcinoma , received one prior regimen containing fluoropyrimidine analogs and developed PD or recurrence, age: 20 - 74, at least one measurable lesion by RECIST(1.0), PS:0-2, adequate organ function and written informed consent. Study duration was until PD or unacceptable toxicity developed. Pts received ABI-007 260 mg/m 2 , i.v. on day 1 of each 21 day cycle) without premedication. The primary endpoint was overall objective response rate (ORR). Results: From April 2008 to July 2010, total of 56 pts were enrolled, 55 received the study treatment, and 54 pts were evaluable for response. Median age was 64, Male/Female was 43/12, PS:0/1/2 was 33/22/0 and number of sites of metastasis corresponding was 1/2/≥3:19/21/15. ORR was 27.8% (15/54; 95%CI, 16.5-41.6) and DCR (disease control rate:CR+PR+SD) was 59.3% (32/54, 95%CI, 45.0-72.4) for all evaluable patients. One confirmed CR was observed. Median progression–free survival was 2.9 months (95%CI, 2.4-3.6), and median overall survival was 9.0 months (95%CI, 6.6-11.5). The most common grade 3/4 toxicities were neutropenia (49.1%), leucopenia (20.0%), lymphopenia (10.9%); and peripheral sensory neuropathy (23.6%). Conclusions: These data demonstrate that ABI-007 showed promising activity with well-tolerated toxicities for previously treated unresectable or recurrent gastric cancer pts.
Who gets treated at commission on cancer-approved programs and does it make a difference in survival?
Authors: Vincent Caggiano, Carol Parise
Journal: Journal of Clinical Oncology (2013)

114 Background: Commission on Cancer (CoC) approval has promoted improvements in cancer care in the United States. The purpose of this study is to determine if there are differences in who is treated at CoC approved versus non-approved sites and if CoC approval is associated with survival. Methods: We examined 130,655 cases of stages I-IV first primary female invasive breast cancer from the California Cancer Registry diagnosed between 2000-2010. Odds ratios (95% CI) adjusted for stage, age, grade, year of diagnosis, and ER/PR/HER2 were computed to determine if there were differences by race: white, black, Hispanic, Asian/Pacific Islander (API) and American Indian (AI); SES (low, intermediate, high) or location (urban versus rural) in the likelihood of treatment at CoC sites. Cox regression was used to assess the risk of cancer specific mortality at CoC approved versus non-approved sites. Results: CoC-approved hospitals were more likely to be urban (89%) than rural (11.2%). Race and SES were associated with being treated at CoC sites. In the lowest SES group, blacks (OR=0.82; 95% CI=0.77, 0.89) and Hispanics (OR=0.90; 95%CI=0.86, 0.95) were less likely than whites to be treated at CoC sites. Similar ORs were seen in the intermediate SES group for blacks and Hispanics. In the highest SES stratum, blacks (OR=0.67; 95%CI=0.62, 0.74), Hispanics (OR=0.76; 95%CI=0.72,0.81), and APIs (OR=0.79; 95%CI=0.75,0.83) were less likely to be treated at CoC sites. Unadjusted survival was better for CoC sites (87% vs 85%). For Stage I, only whites treated at CoC approved sites had decreased risk of mortality (HR=0.86; 95%CI=0.79, 0.95). For Stage 2, whites (HR=0.87; 95%CI=0.82, 0.93) and APIs (HR=0.71; 95%CI=0.59, 0.86) had decreased risk of mortality. Blacks (HR=0.82; 95%CI=0.70,0.99) had slightly decreased risk of mortality. For stages III and IV, no difference in risk of mortality was apparent for any race at CoC-approved sites. Conclusions: Patients treated at CoC approved sites vary by race/ethnicity and SES. While the risk of mortality is reduced for some race/ethnicities in Stages 1 and 2 when treated at CoC-approved sites, for stages III and IV patients, CoC-approval does not make a difference in risk of mortality.