tbuckley/cabot-search huggingface dataset:
Combination external beam and brachytherapy for intermediate- to high-risk prostate cancer: Comparison of high-dose rate (HDR) and seed (LDR) implant methods.
Authors: Sarah E. Daniel, Thomas Carion, Edward Schervish, Rene Frontera, Amr M. Aref, Cynthia Holland Browne, Todd Campbell, Paul J. Chuba
Journal: Journal of Clinical Oncology (2015)

90 Background: Maximizing the therapeutic ratio for intermediate to high risk localized prostate cancer may be accomplished by using a combination of external beam radiotherapy (EBRT) and radiation implant. Differences in implant methods could be expected to influence mortality. We compared outcomes for patients treated using combination EBRT and high dose rate (HDR) versus EBRT and low dose rate (LDR) seed implant methods. Methods: Between 12/1993 and 05/2010 there were 307 cases of combination therapy with analyzable data: 227 HDR + EBRT (HDRe) and 81 LDR + EBRT (LDRe) Intermediate risk patients had 1+ risk factors: PSA ≥ 10, Gleason score (GS) ≥ 7, or AJCC clinical stage ≥ T2b. High risk patients exhibited either 2+ of these risk factors or PSA ≥ 20, GS ≥ 8, or AJCC clinical stage ≥ T3. External beam radiation was 45 Gy in 1.8 Gy daily fractions using 3D conformal or IMRT methods. The prostate, seminal vesicles, and (in some patients) pelvic lymph nodes were treated. HDR brachytherapy was delivered one week prior to beginning EBRT. Afterloading HDR catheter needles were surgically implanted into the prostate. HDR dose was 21 Gy in three equal fractions of 7 Gy peripheral dose given over two days. LDR was performed 2-3 weeks after EBRT using I-125 or Pd-103 seeds and 109 or 90 Gy respectively. PSA failure was defined as “nadir plus two.” Results: HDRe and LDRe cases were well matched for pretreatment risk factors. There were 18 PSA failures in the HDRe group (7.9%) and 6 PSA failures in the LDRe group (7.4%). Adjusted Cox proportional hazard models showed no statistically significant difference between the treatment groups with regard to PSA failure. Hazard ratio for LDRe compared to HDRe was 0.82 (95% CI 0.28, 2.46; p=0.73). There were 26 deaths from any cause (11.45%) in the HDRe group and 11 deaths from any cause (13.58%) in the LDRe group. Adjusted Cox models showed no statistically significant difference between the treatment groups for survival. Hazard ratio for LDRe compared to HDRe was 1.49 (95% CI 0.68, 3.25; p=0.32). Conclusions: There were no statistically significant differences in PSA failure free survival or overall survival detected in LDRe versus HDRe patient groups.
A study of cell-free and concentrated ascites reinfusion therapy (CART) for intractable ascites associated with cancerous ascites.
Authors: Yuki Ueda, Kanji Katayama, Daisuke Fujimoto, Makoto Murakami, Yasuo Hirono, Takanori Goi, Akio Yamaguchi
Journal: Journal of Clinical Oncology (2015)

205 Background: Intractable ascites associated with cancerous ascites causes severe abdominal distention, loss of appetite, poor nutritional condition and reduce the quality of life. We treat patients suffering from cancerous ascites by Cell-free and Concentrated Ascites Reinfusion Therapy (CART). But, cancerous ascites contains a lot of cellular components, and it easily cause filter obstruction. So we applied new method of CART: KM-CART in cancerous ascites patients. This CART system has a filter cleaning function, so the system has less incidence of filter obstruction. We report on our experience on CART for patients with cancerous ascites. Methods: Since November 2009 to August 2014, we applied CART in 31 cases of cancerous ascites (gastric cancer, 13; colorectal cancer, 6; pancreatic cancer, 10; others, 2). Results: On average, 3.8kg (range 1.2-7.5kg) of ascites were filtrated and concentrated to 440g (70-1110g). In all cases abdominal distention disappeared and abdominal girth decreased. Side effect was only mild fever on 11 cases. Conclusions: CART is safe and effective treatment for patients with cancerous ascites. This treatment may be able to improve quality of life with peritoneal dissemination.
Distribution and timing of distant metastasis (DM) after definitive therapy for patients with esophageal and esophagogastric junction (E-EGJ) cancer.
Authors: Hironori Shiozaki, Kazuki Sudo, Roopma Wadhwa, Wayne Lewis Hofstetter, Heath D. Skinner, Ritsuko Komaki, Jeffrey H. Lee, Brian Weston, Manoop S. Bhutani, Dipen M. Maru, Mariela A. Blum, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2014)

105 Background: For localized E-EGJ cancer patients, the preferred therapy is chemoradiation (CRT) followed by surgery (TMT). Definitive CRT (BMT) has been also established for the patients who do not qualify for surgery. Distribution and timing of distant metastasis has not been described. Methods: Between 2002 and 2013, 629 patients with localized E-EGJ cancer who underwent TMT or BMT were reviewed the distribution and timing of DM over time. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: The median follow-up time was 37.2 months (interquartile range: 17.8-65.0) among patients with data that were censored. Among 356 patients with TMT, 33% (119) developed DM as their first relapse. Among 273 patients with BMT, 40% (109) developed DM. Following TMT and BMT, 91% and 96% of DM were diagnosed within 2 years of treatment, respectively. The 7 most common anatomic sites of DM were: lung (20% of DM for TMT and 17% of DM for BMT), distant lymph node (13% and 20%), liver (14% and 11%), peritoneum (10% and 13%), bone (6% and 11%), brain (8% and 8%) and pleura (7% and 5%). The median OS from DM were 10.2 months (95% CI: 7.8-12.7) for TMT patients and 7.8 months (95% CI: 5.7-9.9) for BMT patients. The median OS of patients with pleura metastasis was the shortest (1.5 months [95% CI: 1.0-2.1] for TMT and 3.5 months [95% CI: 3.3-3.6]) for BMT. Conclusions: After TMT and BMT, 33% and 40% of patients had DM and most DM occurred within 2 years (91% and 96%). Common sites of DM sites are lung, distant lymph node and liver. The risk factors associated with DM need to be elucidated. Supported by UT M. D. Anderson Cancer Center Multidisciplinary Research G rants, CA138671, CA172741, CA129926 from NCI (JAA) and Generous Donors. [Table: see text]
Gene expression profiling of prostate tissue based on variable expression of 5-alpha reductase 2.
Authors: Keyan Salari, Seth Bechis, Rongbin Ge, Jian Hong, Aleksander Otsetov, Zongwei Wang, Chin-Lee Wu, Shahin Tabatabaei, Aria F. Olumi
Journal: Journal of Clinical Oncology (2016)

143 Background: Androgen signaling plays a central role in the pathophysiology of both benign and malignant prostatic disease. We previously showed that some men carry epigenetic modifications of the 5-alpha reductase (AR) promoter that modulate gene expression, raising the hypothesis that there may be molecular heterogeneity underlying the variability in clinical response to 5-AR inhibitors for management of benign and malignant prostatic diseases. In this study, we performed whole-genome expression profiling of prostatic tissue based on variable expression of 5-AR2 to determine whether molecular subtypes of clinical relevance could be identified. Methods: Prostatic tissue specimens were obtained from 22 patients with symptomatic BPH undergoing prostate debulking surgery. 5-AR2 protein expression was measured by immunohistochemistry, and 5-AR2 promoter methylation determined by PCR. RNA was extracted from each specimen and whole-genome expression profiling was performed using Illumina Human BeadChip Arrays. Gene expression data was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Results: Unsupervised hierarchical clustering identified two subtypes of patients with distinct gene expression signatures. Among the most differentially expressed genes were several notable androgen-regulated genes, including TMPRSS2, NKX3-1, AZGP1, KLK3 (encoding the PSA protein) and multiple other members of the kallikrein family of serine proteases (all P&lt; 0.001, FDR &lt; 0.02). Multiple gene sets composed of androgen-regulated genes and androgen receptor target genes were found to be significantly enriched in one of the two subtypes. Interestingly, patients from this Androgen-Up subtype were also noted to have a higher frequency of 5-AR2 promoter methylation (though not statistically significant). Conclusions: Our findings suggest that there are distinct molecular subtypes among prostatic tissues with variable expression of 5-AR2, driven by differences in androgen gene regulation. These differences may partially explain the variable response to 5-AR inhibitors and thereby inform clinical strategies for devising therapies for benign and malignant prostatic disease.
Distributions of FcγRIIa-131 and FcγRIIIa-158 polymorphisms and clinical response to cetuximab in Japanese patients with metastatic colorectal cancer (mCRC).
Authors: H. Fukushima, T. Yoshino, K. Yamazaki, T. Nishina, S. Yuki, S. Kadowaki, E. Shinozaki, T. Yokota, S. Kajiura, T. Yamanaka
Journal: Journal of Clinical Oncology (2011)

565 Background: Polymorphisms in fragment C receptor (FcγR) are expected as a predictive biomarker of cetuximab (Cmab). Previous studies have convincingly confirmed the distributions (dists) of FcγR polymorphisms in Western population and shown the existence of linkage disequilibrium (LD) between FcγRIIa and FcγRIIIa polymorphisms. Meanwhile, the dists in Asian population have been unknown but a few studies for non-cancer patients have suggested the difference in dists between Asian and Western populations. We investigated the dists of FcγR polymorphisms and their association with clinical response to Cmab in Japanese mCRC patients. Methods: Ninety-three patients with irinotecan/oxaliplatin/5-FU-refractory mCRC and treated by Cmab plus irinotecan or Cmab monotherapy were retrospectively registered from 8 centers in Japan. FcγR polymorphisms were determined from genomic DNA extracted from peripheral blood samples based on the Multiplex allele-specific PCR method. Comparisons according to FcγR polymorphisms were evaluated using Fisher's exact test for response rate (RR) and log-rank test for progression-free survival curves (PFS). Results: The dists of FcγRIIa HH/HR/RR and FcγRIIIa VV/VF/FF were 68/30/2% and 4/40/56%, respectively (Table). The absence of LD between FcγRIIa and FcγRIIIa polymorphisms was confirmed (GENEPOP, p=0.526; Linkdis, p=0.146). Of 74 patients with KRAS wild-type and treated by Cmab plus irinotecan, no difference according to FcγR polymorphisms was observed in either RR (IIa: HH 37% vs. HR/RR 36%, p=1.00; IIIa: VV/VF 39% vs. FF 35%, p= 0.81) or PFS curves (IIa: HH vs. HR/RR, p=0.84; IIIa: VV/VF vs. FF, p=0.09). Similar results were seen in patients treated by cetuximab monotherapy. Conclusions: This study clarified an ethnic difference in the frequencies of FcγR polymorphisms. Associations between the polymorphisms and clinical response to Cmab did not reach a statistical significance. [Table: see text] No significant financial relationships to disclose.
Perivascular Human Umbilical Cord Cells Are Capable of Long Term Culture and Respond to Chemotactic Gradient in an In Vitro-Model of Alveolar Damage.
Authors: Tiziana Montemurro, Gabriella Andriolo, Gaia Weissmann, Mariarosa Colnaghi, Rosaria Giordano, Paolo Rebulla, Fabio Mosca, Lorenza Lazzari
Journal: Blood (2006)
Use of genetic variants in formyl peptide receptor 2 (FPR2) to predict tumor recurrence in stage II colon cancer.
Authors: W. Zhang, M. J. Labonte, D. Yang, Y. Ning, A. Gerger, P. O. Bohanes, T. Winder, A. B. El-Khoueiry, S. Iqbal, H. Lenz
Journal: Journal of Clinical Oncology (2011)

408 Background: The formyl peptide receptor (FPR) is a G-protein-coupled receptor (GPCR) that mediates chemotaxis of phagocytic leucocytes induced by bacterial and host-derived chemotactic peptides. Recent studies found that it is selectively expressed in highly malignant gliomas and contributes to tumor growth and angiogenesis by mediating tumor cell chemotaxis, proliferation and production of chemokines and VEGF. Previously we demonstrated that polymorphisms in the VEGF pathway predict tumor recurrence in adjuvant colon cancer. Here we tested the hypothesis that two genetic variants in the FPR2 gene (rs17834679 and rs17694990) may predict tumor recurrence in a cohort of adjuvant colon cancer patients. Methods: Between 1992 and 2007, blood samples were obtained from 234 adjuvant colon caner patients (109 with stage II and 125 with stage III) at the USC medical facilities. Genomic DNA was extracted from peripheral blood and two potentially functional genotypes (rs17834679 and rs17694990) within the FPR2 gene were determined utilizing the PCR-RFLP technique. The median follow-up was 4.4 years (range: 0.3- 16.8). Ninety of 234 patients (38.5%) developed tumor recurrence with a 3-year probability of 0.34 ± 0.05. Results: In multivariable Cox proportional hazards regression analysis, FPR2 polymorphism rs17834679 was significantly associated with time to tumor recurrence (TTR) in stage II colon cancer (adjusted P = 0.027). Patients with CC genotype were at greatest risk of developing tumor recurrence (adjusted hazard ratio [HR]: 2.819 [95%CI: 1.127-7.051]) compared to those with GC and GG genotypes. In the dominant inheritance model, patients with any G allele had longer TTR (16.8 years+, median was not reached) compared to those with CC genotype (median TTR 5.4 years [95%CI: 3.2-10.7]; p=0.007, log-rank test). There are no significantly associations between FPR2 polymorphisms and TTR in stage III colon cancer. Conclusions: Polymorphisms in the FPR2 gene may serve as molecular markers for tumor recurrence in stage II colon cancer, indicating that the analysis of genetic variants of FPR2 may help to identify patient subgroups at high risk for tumor recurrence. No significant financial relationships to disclose.
Phase II trial of NGR-hTNF and doxorubicin in relapsed small cell lung cancer (SCLC).
Authors: M. G. Vigano', R. Cavina, S. Novello, F. Grossi, A. Santoro, V. Gregorc, G. Scagliotti, I. M. Garassino, G. Rossoni, M. G. Levra, C. Genova, F. Caligaris-Cappio, A. Lambiase, C. Bordignon
Journal: Journal of Clinical Oncology (2011)

7077 Background: NGR-hTNF, a selective vascular targeting agent, improves the intratumoral doxorubicin penetration by normalizing tumor vasculature and decreasing tumor interstitial fluid pressure. A phase I trial previously selected NGR-hTNF 0.8 µg/m2 + doxorubicin (D) 75 mg/m2 for further testing. Methods: SCLC pts relapsing after a platinum-based regimen received every 3 weeks NGR-hTNF until progression (PD), while D dose was capped at 550 mg/m2. The trial had 2-stage design with a total of 27 patients (pts) to be accrued. Progression-free survival (PFS) was primary study aim. Results: 28 pts (median age: 63 years; M/F: 19/9; PS 0/1-2: 13/15) were recruited. Prior treatment lines ranged from 1 to 3. Median treatment free interval from last line was 2.8 months (95% CI, 1.0-3.9), with 16 pts being platinum resistant (pl-R; PD ≤ 3 months) and 12 pts platinum sensitive (pl-S; PD > 3 months). Baseline neutrophil-to-lymphocyte ratio (NLR), an index of systemic host immune response to tumor, was ≤ or > 4 (median value) in 18 and 10 pts, respectively. 114 cycles were given (median 3; range 1-10) and 13 pts (46%) received ≥ 4 cycles. NGR-hTNF did not increase D related toxicity. No grade 3-4 toxicities related to NGR-hTNF were noted, while grade 1-2 events were transient chills (61%). The disease control rate was 55% (95% CI 35-74), including 6 partial responses (PR; 22%) and 9 stable diseases (SD; 33%). Median PFS was 3.2 months (95% CI 2.6-3.8). Pts with PR or SD had median PFS of 6.3 and 4.1 months, respectively. With median follow-up of 19.3 months, the 6-month and 1-year overall survival (OS) rates were 49% and 34%, respectively. By subset analyses, response rates were 19% and 27%, median PFS were 2.7 and 4.1 months, and 1-year OS were 27% and 42% for pl-R and pl-S pts, respectively. Median PFS and 1-year OS were 3.3 months and 27% in pts with brain metastases (n=9) and 4.1 months and 44% in pts pretreated with ≥ 2 regimens (n=8), respectively. By Cox analyses both PFS and OS did not correlate with age, sex, PS and platinum sensitivity, while only NLR was associated with OS (HR=0.30). The 1-year OS in pts with NLR < or ≥ 4 were 48% and 10%, respectively (p=0.01). Conclusions: Further development of NGR-hTNF plus doxorubicin in platinum resistant or sensitive SCLC is of interest.
Effect of combined lymphocyte and monocyte recovery on survival post myeloablative allogeneic hematopoietic stem cell transplant for acute leukemia.
Authors: M. Thoma, T. Huneke, L. DeCook, N. Johnson, R. Wiegand, M. R. Litzow, W. J. Hogan, L. F. Porrata, S. G. Holtan
Journal: Journal of Clinical Oncology (2011)

6561 Background: Many previous studies of immune reconstitution (IR) post-allogeneic hematopoietic stem cell transplantation (HSCT) have focused on lymphocyte recovery. Recognizing that IR involves complex interactions between innate and adaptive immune systems, we hypothesized that monocyte recovery along with lymphocyte recovery could provide additional prognostic information. Methods: To test our hypothesis, we analyzed data from 135 consecutive patients undergoing myeloablative allogeneic HSCT for AML and ALL. The absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) were determined longitudinally at days +15, +30, +60, +100 and correlated with outcomes. Results: At the day +30 time point, both ALC and AMC > 0.3 x 109 cells/L were strongly associated with improved survival (OS 29.6 months vs. 5.4 months, p=0.006 and 25.3 months vs. 5.1 months, p=0.01 respectively), a pattern that continued through the day +100 evaluation. Multivariate analysis including age at transplant, CD34+ cell dose, related vs. unrelated HSCT, and grade of acute GVHD revealed the following independent prognostic factors: age at transplant (RR 4.31, 95% CI 1.45 – 13.7, p=0.008), day +100 ALC > 0.3 x 109 cells/L (RR 0.34, 95% 0.16 – 0.82, p=0.02) and day +100 AMC > 0.3 x 109 cells/L (RR 0.33, 95% CI 0.18 – 0.67, p=0.002). To further explore whether any patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort. Four clusters of patients were identified, clusters A-D. Patient clusters B and D demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters A and C (57.8 months vs. 19.7 and 4.4 months, respectively, p<0.001). Conclusions: IR is paramount to the success of transplant as a therapeutic modality for high-risk hematologic malignancies. Our data suggests that monocyte/macrophage reconstitution may be as important as, and supportive to, lymphocyte recovery post allogeneic HSCT.
Impact of sarcopenia on short- and long-term outcomes in patients with gastric cancer.
Authors: Fumiko Hirata, Taiichi Kawamura, Noriyuki Nishiwaki, Keiichi Fujiya, Hayato Omori, Wataru Takagi, Taichi Tatsubayashi, Shinsaku Honda, Makoto Hikage, Rie Makuuchi, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Yusuke Kinugasa, Teiichi Sugiura, Katsuhiko Uesaka, Masanori Terashima
Journal: Journal of Clinical Oncology (2016)

19 Background: Depletion of skeletal muscle in aged people (sarcopenia) regarded as a poor prognostic factor in various cancers. The aim of this study was to assess the impact of preoperative sarcopenia on postoperative short- and long-term outcomes in patients with gastric cancer underwent curative resection. Methods: A total of 881 patients who underwent R0 resection for gastric cancer aged 65 or older between June 2003 and March 2011 were included in this study. Muscle mass was assessed by measuring percentage of arm muscle area (%AMA). Preoperative sarcopenia was defined as aged 65 or older, %AMA &lt;80%, and decline in grip strength ( &lt;25kg in men, &lt;20kg in women), according to algorithm suggested by European Working Group on Sarcopenia in Older People (EWGSOP) with slight modification. Relationship between sarcopenia and short- and long-term outcomes were evaluated using uni- and multi-variate analysis. Results: Of 881 patients, sarcopenia was diagnosed in 62 patients (7.0%). Incidence of sarcopenia was significantly higher in patients with aged (75 or older), female, low BMI (18.5 or less) and poor PS (2). There was no significant difference of operation time or blood loss between sarcopenic and non-sarcopenic patients. Postoperative complications (Clavien–Dindo classification grade III or higher) was observed in 124 patients (14.1%). Multivariate analysis revealed that T stage and intraoperative blood loss were significant independent risk factors for postoperative complications. The incidence of postoperative complication was similar regardless of the sarcopenia status. The 5-year survival rate was tended to be worse in the sarcopenic patients (67.7%) than in the non-sarcopenic patients (78.4%) (p = 0.058). Multivariate analysis demonstrated that age (75 or older), male, total gastrectomy, D2 lymph node dissection, and sarcopenia were selected as independent prognostic factors for gastric cancer. Conclusions: Preoperative sarcopenia determined by %AMA seems not to be a risk for postoperative morbidity. However, sarcopenia appears to be a significant prognostic factor in patients with gastric cancer underwent curative resection.
Disrupting TNF signaling in pancreatic cancer: A phase I/II clinical study in patients with advanced disease
Authors: K. V. Kosuri, T. Bekaii-Saab, J. Bender, T. Criswell, Y. Kane, T. Chidiac, D. Young, D. Guttridge, M. Caligiuri, M. Villalona-Calero
Journal: Journal of Clinical Oncology (2005)

4103 Background: Pancreas adenocarcinoma is one of the most intractable and debilitating cancers. Tumor necrosis factor (TNF) is implicated through paracrine effects in promoting symptoms of asthenia, anorexia and abdominal pain, and through activation of NF-kB in decreasing incorporation of myoD RNA into muscle mass, leading to wasting. Strategies aiming to disrupt TNF signaling may result in increased quality of life (QOL) and delayed tumor progression. Materials and Methods: This phase I/II study evaluated feasibility and efficacy of the combination of etanercept, a recombinant human TNF receptor that binds and renders TNF biologically inactive, with gemcitabine (GEM) in 25 chemonaive pts with metastatic PCA. Pts received GEM at 1000 mg/m2 given once weekly for 7 weeks and 1 week off for cycle 1 and then weekly for 3 weeks out of 4. Etanercept was given at a dose of 25 mg subcutaneously twice weekly starting 7 days prior to chemotherapy. QOL (FACT Hep) and peripheral blood mononuclear cells for Real Time PCR determination of TNF, IL-1b, IL-6, IFNγ, IL-10, IL-12 and NFκB (ELISA) were collected at multiple time points, in both, pts receiving the combination and in 10 control pts receiving GEM only. Results: An abbreviated Phase I study demonstrated safety of the combination in 6 pts.Efficacy data on 24 pts showed 3 partial responders (13%), 8 stable disease and 13 progressors(using RECIST criteria).The tumor control rate (CR+PR+SD) was 46% and the proportion of pts who are free of disease progression at 6 months was 17% (4/24). 13 pts had data collected for clinical benefit response, with 3 responders (23%) identified.The most common G3/4 toxicities included neutropenia (25%) and nausea (13%). Molecular correlative and QOL data will be presented at the meeting. Conclusions: The combination of etanercept and GEM is active and well tolerated. Correlative and QOL data should offer further insight on the role of TNF signaling disruption. (Supported by NCI R21CA101360) No significant financial relationships to disclose.