tbuckley/cabot-search huggingface dataset:
Effects of the antiangiogenic drug bevacizumab on tumor perfusion and drug delivery of <sup>11</sup>C-labeled docetaxel in patients with non-small cell lung cancer (NSCLC): Implications for scheduling of antiangiogenic agents.
Authors: E. F. Smit, M. Lubberink, I. Bahce, M. Walraven, M. P. de Boer, H. N. Greuter, N. H. Hendrikse, J. Eriksson, A. D. Windhorst, P. E. Postmus, H. M. Verheul, E. H. Serne, A. A. Lammertsma, A. A. van der Veldt
Journal: Journal of Clinical Oncology (2011)

3059 Background: Current strategies combining anti-angiogenic drugs with chemotherapy provide clinical benefit in patients with advanced-stage NSCLC cancer. It has been hypothesized that pre-treatment with anti-angiogenic drugs may transiently normalize abnormal tumor vasculature and contribute to improved delivery of subsequent chemotherapy (Nat Med 2001;7:987-9). The purpose of the present study was to investigate this concept in NSCLC patients using a perfusion tracer ([15O]H2O), radiolabeled chemotherapy ([11C]docetaxel) and positron emission tomography (PET) before and after a single infusion of bevacizumab. Methods: A total of 70 PET scans were scheduled in 10 NSCLC patients. Patients underwent dynamic PET scans with [15O]H2O and [11C]docetaxel before, and at 5 hours and 4 days after IV administration of bevacizumab (15 mg·kg-1). An additional [15O]H2O scan was performed at 2 hours. Systemic effects of bevacizumab were investigated by assessing: (1) plasma levels of vascular endothelial growth factor (VEGF) using ELISA kits, (2) blood pressure, (3) cardiac output using [15O]H2O, and (4) microcirculation in the skin using capillaroscopy. Results: Two hours after bevacizumab administration, tumor perfusion did not change (Wilcoxon Signed Ranks test , P = 0.89). At 5 hours, however, both tumor perfusion and the net influx rate constant of [11C]docetaxel decreased significantly (P < 0.05 for both). These changes persisted until day 4 (P < 0.01 for both). Changes in tumor parameters were accompanied by a rapid decrease in circulating VEGF at 3 hours (P < 0.05) and a decline in cardiac output at 4 days (P = 0.05). The other systemic parameters remained unchanged. Conclusions: A single dose of bevacizumab induces a rapid and significant decline in tumor perfusion and [11C]docetaxel delivery in NSCLC tumors. These rapid changes in tumor parameters are not due to changes in cardiovascular parameters. The findings of the present study highlight the importance of drug scheduling for enhancing drug delivery to tumors and advocate further studies to optimize scheduling of anti-angiogenic drugs.
Use of two novel antibodies that detect tumor-specific antigens for the detection of colorectal cancer.
Authors: M. di Bari, A. Spila, P. M. Arlen, J. A. Bristol, M. Roselli, F. Guadagni
Journal: Journal of Clinical Oncology (2011)

e21082 Background: The early diagnosis of colorectal cancers remains an area of high unmet medical need, as underscored by the U.S. estimated combined, annual death rate of >89,000. These cancers are currently diagnosed with non-laboratory procedures that are often invasive and expensive. As an alternative diagnostic approach, we developed immunohistochemistry (IHC) tests based upon two unique promising novel tumor-specific monoclonal antibodies generated against a clinically tested human colon cancer vaccine. NPC-1C and 16C3 are two novel monoclonal antibodies that bind to antigen-specific targets expressed on colorectal cancer tissues and cells with little cross-reactivity to normal tissues. The NPC-1C antibody binds to a variant of MUC5AC whereas the 16C3 antibody binds to variants of CEACAM-5 and CEACAM-6. The aim of this study was to evaluate the use of the NPC-1C and 16C3 antibodies as potential new tools for colorectal cancer diagnosis and for future application as novel biological treatments for colorectal cancers. Methods: Paraffin-embedded colorectal cancer tissues were stained by immunohistochemistry (IHC) using the biotin-labeled NPC-1C and the biotin-labeled h16C3 at a concentration of 10 μg/ml. Results: Colorectal cancer cases (n=24, including colon cancer, sigmoid intestine cancer and rectum cancer) were stained by IHC with the monoclonal antibodies NPC-1C and 16C3. More than 70% of tested cases showed a specific positive staining for NPC-1C antibody and more than 85% of tested cases showed a specific positive staining for 16C3 antibody. Moreover, less than 8% of healthy normal colon tissues (n=20) stained positive for 16C3, and none of the normal colon tissues (n=8) stained positive with NPC-1C. Conclusions: Our results demonstrate that the NPC-1C and 16C3 antibodies specifically recognize target antigens expressed at high percentages (70-80%) of colorectal cancer cases and minimally cross-reacted with healthy colon tissues. From this preliminary sample set, our data suggest that these two antibodies may be considered as potential new tools for cancer diagnosis and for future therapies for life-threatening cancers.
Definitive chemoradiation with full-dose gemcitabine for unresectable pancreatic cancer: A single-institution experience.
Authors: Jessica Zhou, Jincheng Shen, Matthew J Schipper, Theodore Steven Lawrence, Mary Uan-Sian Feng
Journal: Journal of Clinical Oncology (2013)

331 Background: Definitive chemoradiotherapy (chemoRT) for unresectable pancreatic cancer has traditionally involved 5-FU-based chemotherapy. We have a long-history of combining gemcitabine and radiotherapy and performed a retrospective review of patients (pts) treated in this manner over the past 13 years. Methods: After IRB approval, the records of pts who underwent definitive treatment with radiotherapy (RT) and concurrent gemcitabine-based chemotherapy at the University of Michigan from February 1999 – May 2012 were reviewed. 193 pts were identified. Mean radiation dose was 40.5 Gy (median 36 Gy, range 24-60 Gy) in 2.2 Gy fractions (range 1.6 to 2.8), and targeted only radiographically apparent disease. 32% of pts received ≥50 Gy, and IMRT was used for 33%. The majority (97.9%) of pts were treated with concurrent full-dose weekly gemcitabine at 1000mg/m2. 48% of pts received at least 1 cycle of chemotherapy prior to chemoRT, and 13% received 2+ cycles. 85% of pts received additional chemotherapy after RT. Cox proportional hazard models were used for survival analysis. Results: Treatment was well-tolerated, with 91% of pts completing RT without a toxicity-related treatment break. With a median follow-up of 10 months, median overall survival (OS) was 13.5 months. 1, 2, and 5 year OS was 57%, 25%, and 5%, respectively. On univariate analysis, pre-treatment CA 19-9 and KPS predicted for OS (p=0.02 and 0.04). Tumor diameter was marginally associated (p=0.06). Age, gender, comorbidities, RT dose, and change in CA 19-9 before or after RT did not predict for OS. With regards to local response to treatment, 1 pt achieved a radiographic complete response (CR) and 30% of pts had a partial response (PR). Distant disease relapse occurred in 52% of all pts, including metastatic disease in the liver in 30%, peritoneum 15%, and lung 14%. 11 pts (6%) had late gastric or duodenal bleeds. Conclusions: Definitive chemoRT utilizing full dose gemcitabine is well-tolerated and achieves survival outcomes which compare favorably with reported series on 5-FU based therapy.
The relationship of EGFR intron 1 (CA) and microsatellite polymorphism and the efficacy of EGFR-TKI in advanced NSCLC patients.
Authors: S. Zhou, S. Ren, L. Yan, J. Zhang, C. Zhou
Journal: Journal of Clinical Oncology (2010)

e18051 Background: Intron 1 of the epidermal growth factor receptor (EGFR) gene contains a polymorphic simple sequence repeat (SSR) of 14-21 CA dinucleotides, which regulates the transcription and expression of EGFR, the length of these repeats is inversely related to EGFR expression, we evaluated the relationship of the (CA)n repeats with the efficacy of EGFR-TKI in advanced non-small cell lung cancer (NSCLC). Methods: Genomic DNA was isolated from peripheral blood lymphocytes (PBLs). Extracted DNA was amplified for EGFR intron1 by PCR and sequenced in an ABI3100 genetic analyzer. Results: 70 patients were enrolled with 37 males and 33 females, stage IIIB/IV: 6/64, PS 0-1/2-3: 43/27, adenocarcinoma/non-adeno: 58/12, the median age was 59 years old and the median progression-free survival (PFS) was 6.1 months. The EGF receptor (CA) n dinucleotide repeat lengths of both alleles were between 14 and 21. There was no significant association between homozygous or heterozygous status with baseline characteristics such as gender, age, performance status, histology, and stage or rash, however, patients with shorter repeats (any allele ≤ 17CA) had marginally significantly better clinical responses than patients with longer repeats (two alleles > 17CA) (p = 0.075, 10.8 months vs 5.2 months). Conclusions: EGFR (CA)n repeats maybe another biomarker to predict the effect of EGFR-TKI, patients with a low number of EGF receptor CA repeats (any allele ≤ 17 CA) are more likely to have a better clinical outcome than patients with a high number of CA repeats (both alleles > 17 CA) during targeted therapy with EGFR-TKI. No significant financial relationships to disclose.
Pain and quality of life (QoL) in patients with locally recurrent rectal cancer (LRRC)
Authors: M. Ikeda, Y. Fujie, M. Sekimoto, M. Yasui, T. Shingai, T. Hata, I. Takemasa, M. Ikenaga, H. Yamamoto, M. Ohue, M. Monden
Journal: Journal of Clinical Oncology (2005)

8249 Purpose: Although multimodality therapy for LRRC has been improving in prognosis, survival rate is still poor. Posttreatment pain is a common problem in patients with LRRC treated with either nonsurgical palliation or radical resection. Given the limited survival after treatment of LRRC, posttreatment pain and QoL are important parameters in the assessment of treatment. Patients and Methods: Patients with confirmed LRRC who had treatment at our institution were included in this study. Assessments of pain and QoL were carried out by two doctors. Severity of pain was assessed using the visual analog scale (VAS), and QoL was assessed using the Functional Assessment of Cancer Therapy- General (FACT-G) questionnaire. VAS score and FACT-G scores were analyzed using Mann-Whitney U tests. Results: Assessments of pain and QoL were performed 22 times in 20 patients. Median age 59 (range 50–68). Thirteen patients underwent surgery with curative intent (5 total pelvic exenteration, 3 low anterior resection, one abdominoperineal resection, 4 local excision). Sacral bone resection was performed in 7 patients. Seven patients treated with nonsurgical palliation consisting of chemotherapy, chemoradiation, or supportive care alone. Median VAS worst pain score in patients after resection without recurrence (n=10) was 31% and that after nonsurgical palliation (n=8) was 12%, but not statistically significant (p=0.06). All FACT-G scores between the two groups were comparable. Median VAS worst pain score in patients after resection with recurrence (n=4) was 62%. Median VAS worst pain score in patients after bony resection was greater than that without bony resection even without recurrence (44% vs 4%). All FACT-G scores with recurrence were significantly lower than those without recurrence irrespective of treatment. Conclusion: Patients with LRRC experience significant levels of pain after treatment. To avoid bony resection may have better results in pain control, but radical resection is necessary because tumor recurrence may cause severe pain and poor QoL. No significant financial relationships to disclose.
Duration of remission using I-131 tositumomab in patients with B-cell lymphoma relapsing after autologous stem cell transplant.
Authors: D. D. Shepard, J. Estes, K. A. Griffith, M. S. Kaminski
Journal: Journal of Clinical Oncology (2010)

8071 Background: Despite progress in systemic therapy, advanced stage indolent B-cell non-Hodgkin lymphoma (NHL) is considered incurable. Long-term remissions are attainable with both autologous stem cell transplant (ASCT) and radioimmunotherapy (RIT). ASCT has been performed on younger pts in first or second relapse, but options for salvage post-ASCT may be limited and poorly tolerated. We present an update of our original single-center phase I/II study of RIT in post ASCT relapsed pts. Methods: From 4/24/1990 to 1/17/1996, 59 adult pts with relapsed/refractory B-cell NHL and <25% bone marrow (BM) involvement by NHL were treated with I-131 tositumomab. Separate dose escalations using total body radiation dose (TBD) were performed in pts with or without prior ASCT. Results: Twelve pts who had prior ASCTs received TBDs of 33-93 cGy. The maximally tolerated TBD was established at 45 cGy, as opposed to 65- 75 cGY for non-ASCT pts. Median pt age was 46. Ten pts had stage III/IV disease with 4 having BM involvement, 7 had prior radiation therapy and 7 had >4 prior chemo regimens. Three pts had low grade follicular, 6 transformed low grade, and 3 de novo aggressive NHL (2 DLBCLs and 1 mantle cell). Four pts had > 500 grams tumor burden and 2 had elevated LDH. Median time from transplant to RIT was 26 months (range 9 to 59) with 5 pts receiving interim chemo. 7 pts were treated with > 45 cGy TBD. Dose limiting toxicity was hematologic with Gr III/IV neutropenia in 6 pts, Gr III/IV thrombocytopenia in 5 and Gr IV anemia in 1 pt. The median overall survival was 7.6 yrs for all 12 pts with a progression free survival of 6 months. Seven pts responded (5 CRs and 2 PRs). Responses ranged from 0.25-15.3 yrs (median 6.8) with 3 pts remaining in CR at 13, 13.6, and 15.3 yrs representing 1 follicular and two transformed follicular NHLs. Conclusions: RIT with I-131 tostitumomab is feasible for B-cell NHL pts relapsing after ASCT and can result in remissions lasting more than a decade. Additional studies in this population are warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Impact of body mass index (BMI) and weight changes on recurrence and survival in stage III colon cancer (CC).
Authors: Joanna Vergidis, Sina Alipour, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2012)

3560 Background: Research suggests that physical activity can lower the risk of relapse and mortality from CC. It is unclear if such potential benefits are mediated through an effect on weight. Our aims were to 1) evaluate the impact of pre-treatment BMI on recurrence and survival in early stage CC, 2) examine how weight gains and losses from baseline may affect outcomes, and 3) explore if the effects of different body compositions are modified by adjuvant therapy (AT). Methods: Patients (pts) diagnosed with stage III CC from 2006 to 2008, evaluated at any 1 of 5 cancer centers in British Columbia, and who had their weights measured serially throughout their AT period were reviewed. Using Cox proportional hazards models, we compared outcomes among a) BMI&lt;25 [normal] vs. 25-30 [overweight] vs. &gt;30 [obese] and b) weight increase or decrease of &lt; vs. &gt;/=5% and &lt; vs. &gt;/=10%, while controlling for confounders. Results: A total of 821 pts were included: median age was 65 years, 50% were men, and 83% were ECOG 0/1. At baseline, 43, 37, and 20% were normal, overweight, and obese, respectively. Compared to pts with normal BMI, those who were overweight or obese did not show an increased risk of recurrence (HR 0.81, 95%CI 0.42-1.58 and HR 1.09, 95%CI 0.48-2.51, respectively, p trend=0.74) or death (HR 0.54, 95%CI 0.26-1.13 and HR 0.62, 95%CI 0.22-1.74, respectively, p trend=0.24). A number of pts experienced weight gain or loss during their AT period, but none of these weight changes affected outcomes (Table). Receipt of AT did not modify the effects of BMI or weight change. In Cox models, advanced age and poor performance status were the main factors that consistently correlated with an increased risk of recurrence and death (p&lt;0.05). Conclusions: Neither baseline BMI nor short-term weight changes during AT appear to affect outcomes in stage III CC. Physical activity likely exert its benefit on relapse and survival by influencing long-term weight changes or acting via other alternative mechanisms. [Table: see text]
Early detection to neoadjuvant chemotherapy response in locally advanced rectal cancer using <sup>18</sup>F-FDG PET.
Authors: Junichi Hasegawa, Junichi Nishimura, Yoji Ogawa, Ho Min Kim, Toshiki Hitora, Masahiro Murakami, Masaki Hirota, Masato Yoshikawa, Masakazu Ikenaga, Junzo Shimizu, Shoki Mikata, Hideaki Miwa
Journal: Journal of Clinical Oncology (2014)

440 Background: Early detection of treatment response of neoadjuvant chemotherapy (CTx) for locally advanced rectal cancer may spare patients the toxicity of ineffective CTx. We evaluated prospectively tumor response with 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) in the early course of preoperative CTx. Methods: A total of 15 patients with locally advanced rectal cancer (T3 or T4 and N0-N2) received neoadjuvant CTx (XELOX or XELOX+bevacizumab). Patients underwent 18 F-FDG PET before CTx, at the end of first cycle of CTx (12-38 days: median 15days), and before surgical resection. Scans were interpreted using SUVmax parameter. Magnetic resonance imaging (MRI) was undergone before CTx, at the end of 2 cycles of CTx (25-54 days: median 38 days), and before resection. The tumor longest diameter was measured by MRI T2-weighted images. After resection, SUVmax and diameter were compared with the Tumor Regression Grade (TRG). Results: Of 15 patients, TRG1 was in 1 patient, TRG2 was in 5 patients, and TRG3 was in 9 patients. We divided into 2 groups, non-responder (NR) group was TRG1 and TRG2, and responder (R) group was TRG3. There was no significant difference as for clinicopathological parameters before CTx including tumor diameter and SUVmax. The tumor size before surgery was significantly smaller in R group than NR group (22.2 mm vs. 35.0 mm; p = 0.017). SUVmax in R group was significantly lower at the end of first cycle of CTx (4.9 vs. 9.3; p = 0.023), and before surgical resection (3.2 vs. 10.3; p = 0.007) than that in NR group. Conclusions: In this study, 18 F-FDG PET at the end of first neoadjuvant CTx successfully predict pathological response of locally advanced rectal cancer.
A phase ll study of trastuzumab in combination with triweekly S-1 plus CDDP in HER2-positive advanced gastric cancer (HERBIS-1).
Authors: Naotoshi Sugimoto, Junji Tanaka, Masahiro Tsuda, Wataru Okamoto, Hiroyuki Okuda, Hiroshi Imamura, Toshio Shimokawa, Daisuke Sakai, Yukinori Kurokawa, Yoshito Komatsu, Chikashi Ishioka, Toshimasa Tsujinaka, Hiroya Takiuchi, Hiroshi Furukawa
Journal: Journal of Clinical Oncology (2013)

70 Background: S-1, an oral fluoropyrimidine, plus cisplatin (SP) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer (AGC). Although ToGA study demonstrated that trastuzumab (T-mab) in combination with capecitabine plus cisplatin or fluorouracil plus cisplatin improved the overall survival of patients (pts) with HER2-positive AGC, there was no study evaluating the efficacy and the safety of T-mab in combination with SP regimen. Methods: Eligibility criteria included gastric or esophagogastric junction adenocarcinoma; HER2-positive confirmed by IHC and/or FISH (IHC 3+ or IHC 2+ and FISH positive); unresectable or recurrent; measurable lesion; no history of chemotherapy or radiotherapy; age≤75; ECOG PS of 0-1; and adequate organ function. Pts received S-1 at 40–60 mg depending on body surface area, po bid, day 1-14, and cisplatin 60 mg/m 2 , iv, day 1, plus T-mab 8 mg/ kg, iv, day 1 (6 mg/ kg, iv, d1 from 2nd course), repeated every 3 weeks until disease progression. Primary endpoint was response rate assessed by the RECIST (ver 1.1). The planned sample size was 50 based on the threshold response rate of 35%, the expected rate of 50%, power of 80%, and 1-sided α of 0.1. Results: A total of 56 pts were enrolled from July 2011 to May 2012. Two pts were ineligible with inadequate renal function and no measurable lesion. Characteristics of 54 eligible pts were as follows: median age of 66 (range 34-75), M/F: 42/12, PS0/1: 42/12, unresectable/recuurent: 51/3, and IHC 2+/3+: 9/45. As one patient did not receive the protocol treatment due to the rapid progression of tumor, the efficacy and the safety analyses were conducted in the full analysis set of 53 pts. The confirmed response rate assessed by the independent review committee was 68%, and the disease control rate was 94%. The response rate without interval confirmation was 75%. The grade 3/4 adverse events (&gt;5% of pts) were as follows: neutropenia 30%, leucopenia 8%, anorexia 21%, diarrhea 8%, hypoalbuminemia 8%, vomiting 6%, and increased creatinine 6%. Conclusions: T-mab in combination with triweekly SP regimen showed promising antitumor activity and manageable toxicities in pts with HER2-positiveAGC. Clinical trial information: UMIN000005739.
Two-stage hepatectomy for colorectal metastases: Association of a good pathologic response to intensified preoperative chemotherapy with second stage completion and longer survival.
Authors: François Quenet, Marie-Hélène Pissas, Hugo Gil, Lise Roca, Sebastien Carrere, Mathias Alline, Philippe Rouanet, Bernard Saint-Aubert, Helene de Forges, Lakhdar Khellaf, Emmanuelle Samalin, Fabienne Portales, Olivia Sgarbura, Marc Ychou, Frederic Bibeau
Journal: Journal of Clinical Oncology (2016)

666 Background: The two-stage surgical resection (TSR) of bilobar colorectal liver metastases (CRLM) is widely used and has shown encouraging survival results. The risk of drop-out after the first-stage hepatectomy remains high and associated with poor survival rates. Our objective was to evaluate the predictive factors of long-term survival, based on the pathologic response to an intensified systemic chemotherapy administered preoperatively. Methods: Data from 899 patients treated for CRLM in our institution were collected prospectively between January 2003 and August 2013. We evaluated the pathologic response to preoperative chemotherapy, and its impact on the second-stage completion and on survival. Results: Sixty-seven patients were eligible for the TSR first stage. All patients underwent an intensified chemotherapy in combination with a biotherapy (Bevacizumab or Cetuximab) in 38cases. The Tumour Regression Grade (TRG), the Blazer grade, and the modified-TRG were used to classify patients as responders (TRG and mTRG 1-3, Blazer 0-1) or non-responders (TRG and mTRG 4-5, Blazer 2) after the first stage. Responders in the three classifications (TRG: p = 0.033; mTRG: p = 0.03, Blazer:p = 0.005), and initial metastases number (p = 0.001) were independent predictive factors for the second-stage completion. Triple chemotherapy were associated with responders in the three classifications (TRG and mTRG: 73.7% versus 26.3% p &lt; 0.0001 ; Blazer : 84.2% versus 15.8% p = 0.001). Median overall survival (OS) of patients who completed TSR was significantly different (44, 84 versus18,39 months; p &lt; 0.0001). There was no statistical difference in OS and recurrence-free survival between the responders and non-responders. Conclusions: A good pathologic response to intensified preoperative chemotherapy is associated with completion of the second stage of TSR, and thus with a longer survival. Knowing this response before the first-stage resection may allow avoiding useless resections for patients who will not benefit from this strategy.
Global DNA Methylation Status of CD4+ T-Cell Population in Mielodysplastic Syndromes.
Authors: Angel Guerra-Moreno, Carlos Palacio, Noemí Martínez-Morgado, Margarita Ortega, Maida Navarrete, Carmen Sánchez-Morata, Laura Gallur, Javier Bueno, Teresa Vallespi
Journal: Blood (2009)