tbuckley/cabot-search huggingface dataset:
Conversion to complete surgical treatment using hepatic artery infusional chemotherapy in patients with unresectable liver metastases from colorectal cancer.
Authors: John Brian Ammori, Nancy E. Kemeny, Andrea Cercek, Ronald P. DeMatteo, Peter J Allen, Philip Paty, Yuman Fong, William R. Jarnagin, Michael Ian D'Angelica
Journal: Journal of Clinical Oncology (2012)

472 Background: Hepatic artery infusional (HAI) chemotherapy effectively treats colorectal liver metastases (CRLM). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on the conversion to complete resection and/or ablation (R/A) and long term outcomes. Methods: All patients with initially unresectable CRLM treated with HAI and systemic chemotherapy from 2000-2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Results: 373 patients were included. 296 (79 %) were previously treated and 77 (21 %) were chemo naïve. 115 (31 %) were on protocol and 258 (69 %) were not on protocol. 93 patients (25%) subsequently underwent complete R/A (conversion group). Of the 115 protocol patients, 47 (41 %) underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16% during 2000-2003 to 30% during 2004-2009. 43% of patients who were chemotherapy-naïve prior to HAI therapy eventually underwent complete R/A, compared to 15% who were initially treated with systemic therapy (p&lt;0.001). Factors associated with conversion on multivariate analysis were more recent treatment (2004-2009), no prior chemotherapy, and a clinical risk score &lt; 3. Overall survival was greater in the conversion group, with a median and predicted 5-year survival from the time of HAI pump placement of 54 months and 49%, compared to 19 months and 6%, respectively (p&lt;0.001). Conclusions: One-quarter of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Conversion was more likely in patients who were chemotherapy-naïve (43 %), had a clinical risk score &lt; 3, and were treated in the more recent era. Survival in the conversion group was significantly better.
Oxaliplatin, irinotecan, and PK-adjusted 5-fluorouracil within a multidisciplinary approach in patients with locally advanced pancreatic cancer (LAPC): Preliminary results.
Authors: Patricia Martin Romano, Azucena Aldaz, Ana Chopitea, Fernando Pardo, Leire Arbea, Jose Carlos Subtil, Fernando Rotellar, Carlos Garzon, Laura Zufia, Iosu Sola, Jose Luis Solorzano, Eduardo Castanon, Javier Rodriguez
Journal: Journal of Clinical Oncology (2014)

356 Background: Neoadjuvant therapy is an increasingly used approach in LAPC patients (pts) but the optimal sequence remains to be defined. We evaluated the feasibility and efficacy of induction chemotherapy (ICT) with pharmacokinetic (PK) monitoring, chemo-radiotherapy (CRT) and surgery. Methods: Borderline resectable and unresectable LAPC pts with EUS stages T3-4/N+ were included. Pts were planned to receive 4 cycles of biweekly ICT with Oxalipatin (85mg/m²), Leucovorin (400mg/m²), Irinotecan (150mg/m²) and 5-FU (initial dose of 3200mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1.) After ICT, pts with no progressive disease received CRT (50.4 Gy, daily concurrent Capecitabine and weekly Oxaliplatin). Surgery was planned 4 to 6 weeks after the completion of CRT. Pathological response was graded according to the CAP classification. Toxicity was recorded according to the NCI-CTCAE 4.0. Results: From November 2011 to February 2013, 13 LAPC treatment-naïve (M/F: 11/2) pts were enrolled (T4; 30.8%, N+; 61.5%, 8 borderline resectable, 5 unresectable due to celiac abutment (2 pts), SMA and celiac encasement (1 pt), unreconstructible SMV and portal occlusion (2 pts). Median age was 63. During ICT, 5- FU dose had to be increased from baseline in 30.7% pts. Grade 3-4 ICT-related toxicities were neutropenia (6 pts) and diarrhea (1 pt). During CRT, grade 3 toxicity included neutropenia (2 pts), thrombocytopenia (1 pt), diarrhea (1 pt), asthenia (1 pt) and mucositis (1 pt); three pts required hospital admission in hospital. Twelve pts completed the whole neoadjuvant program. Ten pts proceeded to surgery with an R0 resection rate of 76.9%. Pathological response was CAP 0 (no viable cells) and CAP 1 (small groups of cancer cells) in 20% and 50% of pts, respectively; ypT0 and ypN0 rates were 20 and 60%. After a median follow-up of 12 months, the 12-month actuarial median PFS and OS were 80% and 75%, respectively. Conclusions: This neoadjuvant strategy seems feasible and promising although a longer follow-up is required. 5-FU PK modulation may contribute to a better therapeutic index.
Phase I study of OSI-211 (liposomal lurtotecan) in combination with liposomal doxorubicin (LD) every 3 weeks in patients (pts) with advanced solid tumors; final analysis suggests benefit in refractory ovarian cancer (OC)
Authors: D. S. Mendelson, M. Brewer, M. Janicek, E. Breitenbach, E. Barrett, M. Hamilton, M. Ptazynski, C. van Duym, M. Gordon
Journal: Journal of Clinical Oncology (2005)

2074 Background: OSI-211 is a topoisomerase (topo) I inhibitor in liposomal formulation. In vivo efficacy of the liposomal preparation is greater than native lurtotecan or topotecan and allows combination therapy with LD in murine xenograft tumor models. In the clinic, combinations of topotecan and LD have been too toxic and/or demonstrate limited benefit. Methods: We performed a Phase I trial to evaluate the safety and pharmacokinetic (PK) interactions of the combination of OSI-211 and LD in subjects naive to topo I therapy with two or fewer prior chemotherapy regimens. Cohorts of 3–6 pts accrued to escalating doses of OSI-211 (0.3, 0.6, 0.9, 1.2 mg/m2/day) administered days 1–3 with fixed dose LD, 30mg/m2 day 1 of each 21-day cycle. At the MTD, additional pts with OC were enrolled. Results: Fifteen pts (5M/10F) were treated on study, median age 63 years (range 49–82) and a median ECOG =1. MTD and recommended phase II dose for OSI on this schedule is 0.9 mg/m2/day. The primary DLT is myelosuppression. Cumulative marrow toxicity is not apparent with this schedule (mean # cycles 7; range 2–26). Liposome-related infusion reaction occurred in 1 pt during LD infusion and was not encountered with OSI-211 administration. Analyses of the PK data are currently ongoing, and PK for both OSI-211 and LD will be presented. Responses were observed in OC (3), refractory NSCLC (1/2 pts), small cell lung CA (1), endometrial CA (1), gastric CA (1) and breast CA (1). The 7 patients with OC achieved a with median TTP of 29.1 weeks (range 25.1–56.4). One of these pts experienced a major relief in ascites. Conclusion: In this first ever trial of two liposomal agents therapy with OSI-211 and LD on this schedule is safe and effective palliative therapy of advanced CA also well tolerated; the preliminary activity seen in pts with OC might deserve further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI OSI
A pilot study of the safety, efficacy, and effects on functional imaging of the combination of cG250 and sunitinib in patients (pts) with advanced renal cell carcinoma (RCC).
Authors: M. Ciprotti, I. D. Davis, D. W. Pook, F. T. Lee, T. Cavicchiolo, S. T. Lee, B. Chappell, G. J. O'Keefe, H. Tochon-Danguy, F. E. Smyth, W. Hopkins, A. M. Scott
Journal: Journal of Clinical Oncology (2011)

TPS142 Background: cG250 is an IgG1 kappa chimeric monoclonal antibody that binds to G250 (CAIX/MN), a heat-sensitive transmembrane cell-surface antigen homologous to carbonic anhydrase. CAIX/MN is present on more than 85% of RCC but expression in normal tissues is restricted to the gastric epithelium, biliary ducts, and some pancreatic acini. Previous studies have demonstrated excellent tumor targeting properties and safe administration either as cold antibody or labelled with various radioisotopes. A phase I multiple dose study completed at our site showed that cG250 is safe, has a long half-life and targets RCC effectively. We hypothesized that combination of cG250 and sunitinib would induce beneficial clinical effects by targeting complementary signalling pathways and that sunitinib’s acute effects on tumor vasculature would influence cG250 biodistribution, tumor metabolism and tumor blood flow. This ongoing study examines the safety and tolerability of coadministering cG250 with sunitinib in pts with metastatic clear cell RCC. Methods: The primary endpoint is toxicity. Secondary endpoints are antitumor effects; human anti-chimeric antibodies; impact of cG250 and sunitinib co-administration on tumor glycolytic metabolism assessed by 18F-FDG PET and on tumor blood flow assessed by 15O-H2O PET; biodistribution and tumor targeting assessed by 124I-cG250 PET scans; circulating pharmacokinetics of cG250 and 124I-cG250. Eligibility includes measurable metastatic or unresectable clear cell RCC with at least one lesion ≥2 cm assessable by PET imaging. Prior exposure to VEGF-targeting agents or multi-kinase inhibitors other than sunitinib is not permitted. cG250 is administered weekly at a dose of 10 mg/m2/week for 5 weeks, followed by 2 weeks without treatment. The 1st and 5th dose is trace-labelled with 124I to evaluate biodistribution and pharmacokinetics. Sunitinib is commenced on day 8 of cycle 1 at 50 mg for 4 weeks for sunitinib-naïve participants or continued at the same dose for those already receiving sunitinib. Up to 2 cycles are given. Five of the planned 14 pts have been enrolled.
Reduced-Intensity Unrelated Cord Blood Transplantation for Adult Patients with Severe Aplastic Anemia
Authors: Hisashi Yamamoto, Daisuke Kato, Naoyuki Uchida, Kazuya Ishiwata, Shinsuke Takagi, Masanori Tsuji, Hideki Araoka, Mayumi Yoshimi, Madoka Narita, Kimiko Sagawa, Naofumi Matsuno, Kazuhiro Masuoka, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
Journal: Blood (2008)
The use of electromagnetic transponder beacons to reduce planning target volume (PTV) margins in post-prostatectomy patients undergoing adjuvant or salvage radiation therapy.
Authors: Madeera Kathpal, Stephanie Ninneman, Raywin Rufus Huang, Stacie Wendt, Cynthia Malmer, Timothy Brand, John B. Halligan, Joseph P. Brooks, Michael Brown, Brent Tinnel, Dusten Macdonald
Journal: Journal of Clinical Oncology (2013)

233 Background: We determined necessary PTV margins when beacons are used to localize the prostatic fossa in post-prostatectomy patients. We hypothesized beacon localization would allow for decreased PTV margins and increased normal tissue sparing. Methods: 10 patients requiring post-prostatectomy radiation were treated on this IRB-approved prospective study. Each patient had 3 beacons placed in the prostatic fossa. Daily radiation was localized by beacons and a cone-beam CT (CBCT) taken for analysis. By measuring differences between the treated clinical target volume (CTV) and relevant anatomy on 5 equally-spaced axial CT slices we calculated necessary PTV margins for each fraction. We then auto-fused each CBCT scan with the treatment planning scan, recorded the shifts incurred, and repeated our measurements, representing a hypothetical CBCT - localized treatment. We report a PTV margin for each technique that would cover the CTV during 90% of all 304 fractions analyzed. We also used intra-fraction motion data to produce a worst-case estimate of required PTV bladder margins. Results: The average shifts from the beacon to CBCT- localized isocenter were 2.9, 3.2, 1.0 mm and 0.58 degrees in the vertical, longitudinal, lateral, and rotational planes, respectively. Necessary PTV margins for beacon and CBCT localization are listed in the Table. Conclusions: Beacon localization “attaches” the CTV to the bladder, allowing a decrease in PTV margin or the amount of posterior bladder included in the CTV. This could lead to decreased rates of bladder toxicity. Clinical trial information: NCT01624623. [Table: see text]
The presence of intraductal carcinoma of the prostate in needle biopsy as a prognostic parameter for prostate cancer patients with distant metastasis.
Authors: Masashi Kato, Toyonori Tsuzuki, Kyosuke Kimura, Naoto Sassa, Yasushi Yoshino, Akitoshi Fukatsu, Tohru Kimura, Ryo Ishida, Momokazu Gotoh
Journal: Journal of Clinical Oncology (2015)

237 Background: The presence of intraductal carcinoma of the prostate (IDC-P) is an adverse prognostic factor for prostate-specific antigen (PSA) failure, progression-free survival, and cancer-specific survival (CSS) in localized prostate cancer patients. However, there is no data indicating whether the presence of IDC-P can influence outcome in prostate cancer patients with distant metastasis at presentation. We aimed to evaluate whether IDC-P in needle biopsies is also an adverse prognostic parameter for CSS in prostate cancer patients with distant metastasis. Methods: We retrospectively evaluated 159 prostate cancer patients with distant metastasis who presented at the hospitals that the authors are affiliated with between 2002 and 2012 and reviewed the slides prepared from prostate needle biopsy specimens. Data on the patient age, performance status, clinical T stage, serum PSA, C-reactive protein, alkaline phosphatase (ALP), hemoglobin (Hb), albumin, serum calcium, biopsy Gleason score (&gt; 8 or not), the presence of Gleason pattern 5, the percent of the core involved with cancer, and the maximum percent of a core involved with cancer were analyzed. Patient characteristics were analyzed using the Fisher's exact test. Multivariate Cox proportional hazard regression models were developed to predict CSS. Results: Patient median age was 73 years (range 47–90 years). The median serum PSA was 290 ng/mL (range 4.18–10,992 ng/mL). The median follow-up period was 36 months (range 3–120 months). IDC-P component was detected in 103 (64.8%) patients. There were 82 patients who died of the disease and 6 patients who died of other causes. Using univariate analysis, IDC-P (p = 0.0001), the presence of Gleason pattern 5 (p = 0.005), the percent of the core involved with cancer (p = 0.002), Hb (p = 0.001), and high ALP (p = 0.002) were all shown to be significantly associated with CSS. In the multivariate analysis, only IDC-P (p = 0.016; hazard ratio, 2.187) was significantly associated with CSS. Conclusions: The presence of IDC-P in needle biopsy is a prognostic parameter for CSS in patients with distant metastasis at presentation.
Phase I/II trial of clofarabine in refractory and/or relapsed non-hodgkin’s lymphoma (NHL)
Authors: C. Nabhan, W. Fried, A. Galvez, P. Venugopal, P. Gozun, J. D. Bitran
Journal: Journal of Clinical Oncology (2008)

8564 Background: Clofarabine (CLO) is a second generation nucleoside analogue with known activity in acute leukemia and myelodysplasia. Given the lack of standard therapy in refractory and transplant-ineligible relapsed NHL, we investigated the activity of CLO in this patient (pt) population regardless of histology. Methods: Eligible pts had relapsed and/or refractory NHL with measurable disease, ECOG performance status ≤ 2, and adequate renal, cardiac, liver, and bone marrow function (unless cytopenias were disease- related). CLO was given intravenously over 1-hour days 1–5 every 28 days for 6 cycles maximum. All pts received anti-viral and anti- pneumocystis carinii prophylaxis. A standard 3x3 phase I study design was used with CLO 4 mg/m2 in cohort 1 and subsequent cohorts escalated by 2 mg/m2. Once the maximum tolerated dose (MTD) was determined, the phase II portion of this study was initiated at the MTD. All pts were followed until disease progression. Results: To date, 14 pts have been enrolled with 7 patients each in the phase I and II portions. Including all pts, median age was 78 years (27–84), median number of prior therapies was 2.5 (1–8), and 3 pts (21%) relapsed after autologous stem cell transplantation. Histologies included 4 diffuse large cell, 3 small lymphocytic, 2 anaplastic large cell, 2 mixed large cell/follicular, 1 follicular, 1 refractory marginal zone, and 1 Richter’s transformation. Median CLO cycles were 2.5 (1–6). Grade 3/4 non-hematologic toxicities were: 1 (7%) grade 3 pleural effusion and 2 (14%) grade 3 fatigue. All pts required growth factor support and 2 pts on the phase II portion required a dose reduction. Thrombocytopenia was the dose-limiting toxicity at 6 mg/m2 in 2/6 patients. The MTD and recommended phase II dose was 4 mg/m2. Responses: 2 (14%) complete responses lasting 4 and 12+ months, 3 (21%) partial responses, 1 minor response, and 1 stable disease. The overall response rate was 35% for this heavily pretreated pt population. With a median follow up of 5 months (1–13), the median duration of response has not been reached and 6 patients remain alive (42%). Conclusions: To our knowledge, this is the first report to establish clinical activity with CLO in refractory and/or relapsed NHL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme Genzyme
Shed alcam as a biomarker for urogenital cancers.
Authors: Shanna Arnold, Celestial Jones-Paris, Amanda Georgia Hansen, Oluwole Fadare, Peter Clark, Andries Zijlstra
Journal: Journal of Clinical Oncology (2012)

50 Background: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is thought to be involved in tumor cell adhesion, migration and metastasis. The ectodomain responsible for adhesion is proteolytically shed. Elevated shedding of ALCAM ectodomain is associated with malignant progression. Considering the proximity of urogentical cancer to both urinary secretions and hematogenous circulation we investigated if ALCAM shed into urine and/or blood could act as a prognostic or diagnostic marker of disease and patient outcome. Methods: Shed ALCAM in serum and urine was measured by ELISA while ALCAM shedding in tissues was detected with a unique immunohistochemical approach. ALCAM shedding was correlated with patient parameters including tumor stage, metastasis, recurrence, overall and disease-specific survival. Results: ALCAM shedding was compared across tissue and fluids from normal age-matched healthy adults, non-urological neoplasia, and non-cancer patients. Elevated ALCAM shedding was readily detected in fluids and tissue from patients with urogenital cancers. However, only the detection of shedding in tissue and urine correlated significantly with disease progression and patient outcome. Specifically, shed ALCAM detected in urine collected from bladder cancer patients undergoing cystectomy (Vanderbilt 2000-2010) correlated strongly with patient outcome. Urine ALCAM correlates positively with invasiveness (80%), and is predictive of recurrence as well as survival (HR=10.2 and 2.9). Urinary ALCAM ROC curves show the optimal sensitivity and specificity of predicting recurrence (90 and 68%) and survival (62 and 83%). Conclusions: We show for the first time that cleaved ALCAM is detectable in the urine and that urinary ALCAM is a novel biomarker in urogenital cancers. ALCAM shedding is marker of cancer progression and patient outcome with high specificity and accuracy. Evaluating levels of shed ALCAM in urine offers a unique and effective method to diagnose, assess, and stratify patients with urogenital cancers. We find this correlation particularly exciting because ALCAM is functionally involved in cancer progression and therefore reports on cellular behavior rather than mere presence of neoplastic disease.
Overexpression of a set of genes in mesothelioma versus parietal pleura may explain its chemo- and radio-resistance
Authors: O. D. Roe, E. Anderssen, E. Helge, C. Hild Hakvaag Pettersen, H. Sandeck, E. Larsson, S. Lundgren
Journal: Journal of Clinical Oncology (2008)

13506 Background: Malignant mesothelioma is a tumour highly resistant to most conventional chemotherapy and radiation. Little is known about the molecular basis for mesothelioma therapy resistance. Differential gene expression of mesothelioma versus normal pleura could elucidate some issues related to resistance and lead to discovery of new therapeutic targets. Methods: Needle biopsies from five patients with mesothelioma were obtained and snap-frozen in liquid nitrogen. Normal visceral and parietal pleura were obtained by Video Assisted Thoracoscopy from six cancer-free patients with spontaneous pneumothorax, anatomically dissected and snap-frozen in liquid nitrogen. Adjacent tissue was formalin-fixed and Hematoxylin-Eosin- Safran (HES) stained for analysis of cell types. RNA was extracted and analyzed with the Affymetrix Human Genome U133 Plus 2.0 Chip oligoarray of 39 000 genes. Principal Component Analysis was used to discover tissue with similar gene expression patterns and differentially expressed genes were identified by a modified T -test. KEGG Pathways and biological processes gene ontology (GO) terms that were overrepresented among the differentially expressed genes were identified. Cell specific expression of proteins encoded by some of the overexpressed genes was detected by immunohistochemistry. Results: Six mesothelioma samples and ten normal (seven parietal and three visceral) samples were analyzed. Parietal, visceral pleura and mesothelioma had distinct expression profiles. When parietal pleura and tumor were compared, several key genes encoding proteins known to confer chemo- resistance (e.g. TOP1, TOP2A, TYMS, BIRC5/Survivin, TUBB and 12 proteasome genes) and radio-resistance by several DNA-repair and DNA- damage checkpoint genes (e.g. BRCA2, FANCA, FANCD2, RAD51) were overexpressed in tumour. Conclusion: Mesothelioma resistance to therapy is reflected in the gene profile where many known genes related to chemo-and radio-resistance are significantly over- expressed. Specific suppression of some selected genes or gene products could lead to increased anti-tumour effect of conventional chemo- and/or radiotherapy. No significant financial relationships to disclose.