tbuckley/cabot-search huggingface dataset:
2-<sup>18</sup>fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residuals: A retrospective validation of the SEMPET trial.
Authors: M. Bachner, P. Zucali, A. Horwich, K. Oechsle, Y. Loriot, A. Flechon, C. K. Kollmannsberger, J. R. Germa-Lluch, J. Oldenburg, M. De Santis
Journal: Journal of Clinical Oncology (2010)

4581 Background: The use of FDG-PET for the evaluation of postchemotherapy seminoma residuals has been recommended by several international guidelines. This is based on the prospective SEMPET trial including 56 PET studies. Our trial was designed to confirm these recommendations in a larger group of patients. Methods: Investigators from Europe and Canada were invited to contribute consecutive patient data. The eligibility criteria included: metastases of pure seminoma (testicular or extragonadal), negative tumor markers after first line or salvage platinum-containing chemotherapy (completed after 2001), CT evidence of clearly measurable residual masses ≥ 1cm in diameter after chemotherapy, a postchemotherapy FDG-PET scan evaluated by visual interpretation; and a follow-up of ≥ 24 months (unless relapse) or surgery of residual lesions. Results: By October 2009, 147 FDG-PET results from 17 institutions were contributed, of which 42 were ineligible, mostly due to insufficient follow-up (88%), 13 were rated equivocal and were not included in the final analysis. Interestingly, all patients with equivocal scans remained relapse-free. The results of the remaining 92 PET studies demonstrated 64 true negative (TN), 8 true positive (TP), 4 false negative (FN) and 16 false positive (FP). The interval between chemotherapy and PET scan was inadequate according to the current guidelines in 10/16 (63%) FP and in 2/4 (50%) FN scans. Excluding scans with inadequate timing, specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 91%, 80%, 57%, 97%, and 90%, respectively. Eight of 45 (18%) residual lesions ≥ 3cm contained viable tumor; 42/45 (93%) were correctly predicted by FDG-PET. Conclusions: These retrospective data confirm a high specificity, sensitivity, and NPV of FDG-PET for the evaluation of postchemotherapy seminoma residuals. Based on a small number of positive PET scans, the PPV was less reliable than previously reported. However, FDG-PET performed within the correct timeframe remains a valuable tool for clinical decision-making in this clinical setting, and allows to omit unnecessary surgery. No significant financial relationships to disclose.
Risk of breast fibrosis following irradiation using a breast-specific SBRT system compared with conventional APBI.
Authors: Z. A. Husain, S. J. Feigenberg, E. Nichols, J. Zhang, C. Yu, K. Prado, B. Yi, W. D'Souza, Y. Mutaf
Journal: Journal of Clinical Oncology (2011)

116 Background: To determine the dosimetric characteristics and risk of breast fibrosis using a normal tissue complication probability (NTCP) model in conjunction with a novel preoperative stereotactic radiotherapy system called the GammaPod. Results are compared with linac based post-lumpectomy APBI plans for the same cohort. Methods: The GammaPod breast SBRT system consists of a Co-60 irradiation unit in combination with an immobilization device with embedded fiducials. Eight patients were enrolled in an IRB-approved protocol and underwent CT scans in the prone position with breast immobilization. A preoperative target (GTV) was synthesized to match the tumor location and volume reported in imaging studies obtained prior to surgery (0.3-2.4 cc). The GTV was expanded by 1.5 cm to create a CTV, and a PTV was created using an additional 0.3 cm margin. The PTV was prescribed 25.5 Gy in 3 fx, which is radiobiologically equivalent to conventional APBI doses of 38.5 Gy in 10 fx. Following the radioablative experience in NSCLC, we also planned to deliver 60.0 Gy to the GTV+0.3 cm as a simultaneous boost in conjunction with the 25.5 Gy PTV prescription dose. For comparison, linac-based treatment plans were created for the same cohort following NSABP B-39 guidelines. Whole breast dosimetry was analyzed in terms of biologically equivalent dose (BED) and Lyman NTCP analysis was performed. Results: The volume of ipsilateral breast receiving 10, 20, 50, and 100% of the prescribed dose was substantially smaller in GammaPod vs. APBI plans, with cohort averages of 19.3, 13.0, 7.1 and 4.0% vs. 75.8, 67.3, 48.1 and 27.6% respectively (p&lt;0.001). Even though the PTV equivalent uniform BED (EUD) was substantially higher in GammaPod plans (87.9 Gy vs. 57.3 Gy), the ipsilateral breast EUD was still smaller in these plans, 18.9 ± 5.0 Gy vs. 47.2 ± 3.2 Gy (p&lt;0.001). Corresponding NTCP predictions for breast fibrosis rates following GammaPod and APBI treatments were 0.2 ± 0.1% vs. 2.8 ± 0.8% (p&lt;0.001), respectively. Conclusions: The GammaPod system improves upon traditional post-lumpectomy linac-based APBI by decreasing dose to the ipsilateral breast as well as the predicted rates of breast fibrosis.
Outcome analysis of stem cell transplantation in the elderly
Authors: Y.-K. Keung, L. Beaty, I. Molnar, J. Lovato, K. Zamkoff, J. Cruz, D. D. Hurd
Journal: Journal of Clinical Oncology (2004)

6654 Background: Stem cell transplantation (Tx) has been increasingly performed in more elderly patients. We report the outcome of patients over 65 who underwent autologous or syngeneic stem cell Tx in our institution. Methods: Between 1995 and 2003, 43 patients (pts) meeting eligibility criteria underwent autologous (n=41) or syngeneic (n=2) Tx. 5 received BM, 37 PBSC, and 1 BM+PBSC. Median age was 68 years (range 65–75). Diagnoses included 14 myeloma (MM), 22 lymphoma, 6 acute leukemia (AL), and 1 breast cancer. 30 pts received high dose chemotherapy alone and 13 received TBI plus cyclophosphamide. Survival analysis was performed using Cox proportional hazards regression and logrank tests. Logistic and linear regression, for dichotomous and continuous outcomes respectively, with Chi sq tests were used to assess associations with age as a continuous variable. Results: There were 2 Tx-related deaths (4.7%) by 100 days (1 VOD; 1 sepsis). 38 patients developed febrile neutropenia of which five had bacteremia and 14 required empiric amphotericin. Engraftment, ANC>500 and platelet>20,000, was achieved at medians of 10 days and 18 days, respectively. Among 23 pts with residual disease prior to Tx, 18 (78%) achieved complete remission after Tx. 18 pts had died; 9 died of recurrent disease, 1 VOD, 4 sepsis, 1 COPD, 1 glioblastoma multiforme and 2 of causes unknown. Median survival of all cases was 2.0 years; that of AL was 9.0 months, lymphoma 22.4 months, myeloma median not reached (p<0.001). Overall survival or engraftment was not associated with the age at Tx. Median hospital stay after Tx was 14 days (range 11–56). Each additional year in age >65 was associated with an additional 1.2 days in the length of hospital stay (p<0.001). There was no significant difference in the ages of the pts with or without infectious complications (p=0.20), and of those with or without cardiac complications (p=0.73). Conclusions: Autologous and syngeneic stem cell Tx is well tolerated in the older pts. Although there is a longer hospital stay in the more elderly, there is no significant correlation between age and infectious or cardiac complications. The time to engraftment and overall survival are not adversely affected by the age at Tx. No significant financial relationships to disclose.
Expression of programmed death ligand 1 (PD-L1) by non-Hodgkin's lymphomas (NHL) and effect on tumor-associated T cells
Authors: D. J. Andorsky, R. Yamada, K. Steward, S. De Vos, J. Said, J. Timmerman
Journal: Journal of Clinical Oncology (2009)

8526 Background: PD-L1 is expressed on antigen presenting cells and inhibits activation of T cells through its receptor, PD-1. PD-L1 is aberrantly expressed on epithelial malignancies and may prevent an effective host anti-tumor immune response. The role of PD-L1 in NHL is unknown. Methods: PD-L1 expression was analyzed in 16 NHL cell lines by flow cytometry (FC) and in 111 lymphoma specimens by immunohistochemistry (IHC) (n=92) or FC (n=19). In functional studies, irradiated anaplastic large cell lymphoma (ALCL) cells were co-cultured with allogeneic T cells in the presence of anti-PD-L1 blocking antibody, and IFNγ secretion and thymidine incorporation was used to assess T cell function and proliferation. To further test tumor-T cell interactions, malignant ascites from a patient with ALK+ ALCL and peripheral blood mononuclear cells from a patient with leukemic mantle cell lymphoma, both containing PD-L1-expressing tumor cells and tumor-associated T cells, were stimulated with phytohemagglutinin (a polyclonal T cell activator) and incubated with anti-PD-L1 antibody. Levels of 16 inflammatory cytokines were measured as an assessment of T cell activity. Results: All 9 B cell lymphoma lines were negative for PD-L1, while all 5 ALCL cell lines were strongly positive. One T-cell ALL line was positive, and one peripheral T cell lymphoma was negative. Strong PD-L1 staining was detected by IHC in all 14 ALCL specimens and in 83% of diffuse large B cell lymphomas (DLBCL) analyzed (n=35). Activity of allogeneic T cells co-cultured with irradiated ALCL cells, as measured by IFNγ secretion and proliferation, was markedly enhanced in the presence of anti-PD-L1 blocking antibody. In the autologous setting using cultures of ALCL and mantle cell lymphoma specimens containing host T cells, secretion of inflammatory cytokines by tumor-associated T cells, including GMCSF, IFNγ, IL-1, IL-6, IL-8, TNFα, and MIP1α, were increased by incubation with anti-PD-L1 antibody. Conclusions: PD-L1 is highly expressed in ALCL and in a majority of DLBCL. Blockade of tumor-associated PD-L1 promoted activation of adjacent T cells. PD-L1 may play a role in thwarting an effective anti-tumor immune response and represents an attractive target for lymphoma immunotherapy. No significant financial relationships to disclose.
Phase I/II study of novel HLA-A24 restricted DEPDC1 and MPHOSPH1 peptide vaccine for bladder cancer.
Authors: W. Obara, T. Tsunoda, K. Yoshida, M. Kanehira, R. Takata, T. Katagiri, T. Miki, T. Shuin, Y. Nakamura, T. Fujioka
Journal: Journal of Clinical Oncology (2010)

e13122 Background: We had previously reported that M-phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) were identified as oncogenes by genome-wide expression profile analysis of bladder cancer by cDNA microarray. We also identified that MPHOSPH1 and DEPDC1 derived epitope peptides, which induce specific cytotoxic T lymphocytes (CTL) against bladder cancer expressing MPHOSPH1 and DEPDC1 in HLA-A24 restricted fashion. We conducted a phase I/II study of a vaccine treatment using these novel peptides and assessed both the safety and efficacy for patients with advanced bladder cancer. Methods: The main eligibility criteria was advanced bladder cancer patients who already resistant to the standard chemotherapies or radiotherapy, having HLA-A*2402 genotype and expression of MPHOSPH1 or DEPDC1 on tumor tissues by immunohistochemistry. MPHOSPH1-278 (IYNEYIYDL) and/or DEPDC1-294 (EYYELFVNI) peptides (each of 1mg/body) were subcutaneously injected with Montanide ISA 51 adjuvant. Patients were vaccinated on day 1, 8, 15, and 22 of each 28-day treatment cycles. The primary endpoint was evaluation of safety and the secondary end points were immunological and clinical response. Results: Six patients were enrolled in phase I part. Vaccinations were well tolerated without serious adverse events. Inductions of antigen-specific CTL response were recognized in four out of six patients. A total of 15 patients were enrolled in the phase I/II study. One patient with multiple lung metastasis and another two patients with bladder invasion showed objective response with necrosis in image analysis. The clinical and immunological reaction was recognized for synchronization. Six patients showed stable disease for more than 4 months. Conclusions: Our experience data suggest that novel MPHOSPH1 and DEPDC1 epitope peptide vaccine treatment is tolerable and may be an effective for patients with bladder cancer. As the next study, peptide vaccine against recurrence prevention after TUR for non-muscle-invasive bladder cancer is now in progress. No significant financial relationships to disclose.
A comparison of patient-reported outcomes (PROs) in National Cancer Institute-sponsored cancer treatment trials conducted during two time periods: 1999–2003 and 2003–2008
Authors: A. M. O'Mara, A. M. Denicoff, B. Reeve, R. Burns, T. Trimble
Journal: Journal of Clinical Oncology (2009)

6618 Background: Over the past decade, the U.S. National Cancer Institute (NCI) support for incorporating Patient-Reported Outcomes (PROs) into disease treatment clinical trials has grown considerably, both in the number of trials, as well as the types of research questions being addressed and the measures used to answer the questions. This presentation will compare the breadth of NCI supported Phase III treatment trials in breast, colo-rectal, lung, and prostate cancers that include PRO secondary endpoints activated during two time periods: 1999–2003 and 2003–2008. Both time periods will be compared to identify the number and type of PRO measures; in addition the targeted PRO domain will be examined by cancer site. Methods: For this study, PRO was broadly defined to include any self-report questionnaire that gathered data on the potential impact that disease treatment might have on patient functioning, quality of life, or symptoms. Using the terms, 'protocol title, lead disease, phase III, quality of life, and instrument name,’ a search was conducted of the NCI database containing breast, colo-rectal, lung, and prostate Phase III treatment trials activated during the two time periods. If a scale was used more than once or if different versions of the scale were used, i.e., FACT-G and FACT-BR, it was only counted once. Results: Between 1999 and 2003, 42 phase III trials in the four major cancers were activated, with 15 trials having one or more PROs as secondary endpoints. Between 2003 and 2008, 50 phase III trials in the four major cancers were activated, with 28 trials having one or more PROs as secondary endpoints. Although the data reveal a 20% increase in the number of phase III trials in the 4 diseases between the two time periods, the number of trials with PRO endpoints has doubled. Conclusions: This significant increase in the use of PROs in phase III trials gives investigators additional data to fully analyze the impact of new treatments. These PRO data will provide researchers, clinicians, and future patients with a more in-depth understanding of the potential for new cancer therapies and technologies to extend both the quantity and quality of life. No significant financial relationships to disclose.
Effect of neuropilin-2 expression on TGF-β1-epithelial-mesenchymal transition in colorectal cancer cells.
Authors: C. Grandclement, R. Bedel, B. Kantelip, E. Viel, J. Remy Martin, C. Ferrand, X. B. Pivot, P. Tiberghien, C. Borg
Journal: Journal of Clinical Oncology (2011)

414 Background: Initially characterized as neuronal receptors, Neuropilins (NRPs) were also found to be expressed in endothelial cells and subsequently were shown to play a role in the development of the vascular system. NRP family consists of two genes, neuropilin-1 (NRP1) and neuropilin-2 (NRP2).The multiple functions of NRPs were recently highlighted by the identification of NRP role in oncogenesis. In this study, we first confirmed the role of NRP2 in tumor progression. We also extended the understanding of NRP2 oncogenic functions by investigating the ability of NRP2 to orchestrate epithelial-mesenchymal transition (EMT) in colorectal cancer cells. Methods: We have generated human colon cancer cell lines transfected with NRP2 transgene or siRNA to investigate NRP2 involvement in EMT. First, the oncogenic functions of NRP2 were studied in vitro by MTT, soft agar, invasion assays and in vivo using xenografts experiments. Ability of NRP2 to orchestrate EMT was then investigated by flow cytometry, immunohistochemical (IHC) staining, western-blotting and quantitative real-time PCR. Results: IHC staining revealed that NRP2 is expressed in human colon and breast carcinomas while it is not expressed in healthy tissues. Then, we confirmed that NRP2 increases tumor proliferation, colony formation, invasion and xenograft formation. Moreover, NRP2-expressing cells displayed an immunohistochemical phenotype of EMT characterized by the loss of E-Cadherin and an increase of vimentin. Furthermore, NRP2 expression promotes transforming-growth factor-β1 (TGF- β1) signaling, leading to an increased phosphorylation of the Smad2/3 complex in colorectal cancer cell lines. Specific inhibition of NRP2 using siRNA or treatment with specific TGFβRI kinase inhibitors prevented this phosphorylation and the EMT, suggesting that NRP2 cooperates with TGFRI to promote EMT in colorectal carcinoma. Conclusions: Our findings have reinforced the essential role of NRP2 in cancer progression and demonstrated that NRP2 expression confers to tumor cell lines the hallmarks of EMT. Moreover, in the current work, we present evidence for the therapeutic value of NRP2 targeting. No significant financial relationships to disclose.
The effect of bi-weekly pegylated liposomal doxorubicin pharmacokinetics in elderly women with metastatic breast carcinoma
Authors: M. Gusella, U. Basso, F. Pasini, E. Ferrazzi, A. Bononi
Journal: Journal of Clinical Oncology (2008)

12005 Background: Doxorubicin formulated in polyethylene-glycol coated liposomes (PLDox) have a prolonged circulation time and a different toxicity profile compared with the free drug; it has been demonstrated that its pharmacokinetics correlate with toxicity, when administrated at standard doses and schedules in young patients. To further decrease side effect risk in elderly breast cancer patients a PLD schedule have been proposed with reduced doses (20 mg/m2) and dose intensity maintained by shortening time between administrations (15 days).The aim of our ongoing study is to monitor doxorubicin plasma levels during the first two cycles and to evaluate if this procedure can help treatment design. Methods: Five women have been enrolled, aged between 74 and 78 years, affected by liver or bone metastasis by breast cancer, previously treated with anticancer drugs and refractory to hormone therapy. Blood samples were obtained 10 minutes, 1 hour, 24 hour, 72–96 hours, 7 and 14 days after the end of one-hour drug infusion during the first two cycles and Dox quantitated using a high performance liquid chromatography method. Results: PLDox pharmacokinetic was characterized by a long T1/2, ranging from 85 to 140 hours (longer than values reported for younger patients, mean =65–80 hours); in all cases, at the 15th day, when the second dose was scheduled, the drug was not completely eliminated and patients had residual Dox plasma level between 0.4 and 2.6 mg/L. Consequently, from the first to the second cycle an increase was observed both in Cmax and AUC by 12% and 23%, respectively. Palmar-plantar erythrodysesthesia (PPE) was the most frequent side effect. Leukopenia/neutropenia compared in two patients, complicated by prolonged fever in one case. Four patients discontinued chemotherapy because of toxicity and only one patient completed the 12 scheduled cycles, reporting a partial response. Conclusion: In our small sample of elderly breast cancer patients, a very long time of PLD elimination emerged. Drug plasma level monitoring seemed to suggest that in case of a bi-weekly administration schedule, even if with reduced doses, a drug accumulation can occur inducing treatment discontinuation. Founded by CARIPARO Foundation No significant financial relationships to disclose.
The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma
Authors: Monica Venere, Craig Horbinski, James F. Crish, Xun Jin, Amit Vasanji, Jennifer Major, Amy C. Burrows, Cathleen Chang, John Prokop, Quilian Wu, Peter A. Sims, Peter Canoll, Matthew K. Summers, Steven S. Rosenfeld, Jeremy N. Rich
Journal: Science Translational Medicine (2015)

The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive and hence termed "go or grow." We identified a molecular target that shuttles between these disparate cellular processes-the molecular motor KIF11. Inhibition of KIF11 with a highly specific small-molecule inhibitor stopped the growth of the more treatment-resistant glioblastoma tumor-initiating cells (TICs, or cancer stem cells) as well as non-TICs and impeded tumor initiation and self-renewal of the TIC population. Targeting KIF11 also hit the other arm of the "go or grow" cell fate decision by reducing glioma cell invasion. Administration of a KIF11 inhibitor to mice bearing orthotopic glioblastoma prolonged their survival. In its role as a shared molecular regulator of cell growth and motility across intratumoral heterogeneity, KIF11 is a compelling therapeutic target for glioblastoma.
Attitudes toward clinical research: an analysis of 922 patients in a university-based tissue repository
Authors: D. W. Rasco, Y. Xie, J. Yan, J. R. Sayne, D. E. Gerber
Journal: Journal of Clinical Oncology (2008)

6551 Background: Historically, participation rates in cancer clinical trials have been low. The degree to which this reflects patient preferences versus extrinsic factors (study availability, exclusion criteria, etc) is not clear. We therefore examined willingness to consider participation in future research among subjects enrolled in a university-based tissue repository. Methods: We examined a database of patients who had provided tissue and/or serum to a tissue repository. We reviewed subject responses to two questions asked at the time of consent: “May we contact you in the future (1) to obtain follow-up medical information and (2) to take part in more research?” We analyzed the association between these responses and subject characteristics using univariate analysis and multivariate logistic regression. Results: Of 922 subjects, 67% were women; median age was 57 years. 82% had a cancer diagnosis, 13% had a benign condition, and 5% were normal controls. Overall, 15.1% (95% CI, 12.8–17.5%) of subjects answered “No” to question #1 (medical follow-up), and 16.9% (95% CI, 14.5–19.4%) of subjects answered “No” to question #2 (future research). Individual subject responses to the 2 questions were highly correlated (P<0.00001). In univariate analysis, the likelihood of declining contact for future research was significantly associated with cancer type (P=0.003): patients with genitourinary malignancies were most likely to decline (25%); patients with upper aerodigestive malignancies were least likely to decline (8%). Declining contact for future research was not associated with subject age, gender, race, primary language, or location (public vs. private hospital). In multivariate analysis, cancer type (P=0.0015) and gender (P=0.035) were associated with subject responses. Conclusions: In this population, 17% of patients declined contact for participation in future research. These patients were more likely to be male and to have genitourinary malignancies. Importantly, socioeconomic and cultural factors did not appear to impact potential interest in future research participation. These data may be useful for targeting efforts to increase participation in cancer clinical trials. No significant financial relationships to disclose.