tbuckley/cabot-search huggingface dataset:
Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients.
Authors: Elias J. Anaissie, Marisa H. Miceli, Li Dong, Fariba Saghafifar, Giampaolo Talamo, Klaus A. Hollmig, Guido Tricot, Bart Barlogie
Journal: Blood (2004)
Pre-Clinical Evaluation of the Anti-CD22 Immunotoxin CAT-8015 in Combination with Chemotherapy Agents for Childhood B-Precursor Acute Lymphoblastic Leukemia (Pre-B ALL).
Authors: Yachna Ahuja, Maryalice Stetler-Stevenson, Robert J. Kreitman, Ira Pastan, Alan S. Wayne
Journal: Blood (2007)
Longitudinal assessment of quality of life (QOL) of patients (pts) with ovarian cancer (ovca) receiving high-dose or conventional-dose chemotherapy (CDCT)
Authors: D. C. Bodurka, C. C. Sun, C. B. Weaver, D. L. Bethancourt, M. A. Fitzgerald, J. K. Wolf, D. M. Gershenson, J. J. Kavanagh, M. F. Munsell, M. L. Donato
Journal: Journal of Clinical Oncology (2005)

5065 Background: There is a perception that pts receiving high-dose chemotherapy with autologous stem cell support (HDCT) experience long-term detriments to overall QOL. To assess if changes in QOL differ between women receiving HDCT and CDCT, a prospective single-institution study was conducted to longitudinally assess QOL of ovca pts enrolled on a phase II trial of HDCT and newly diagnosed pts scheduled to begin CDCT. Methods: The FACT-O was used to assess QOL at 4 time points (T1, T2, T3, T4) in two groups of pts. CDCT consisted of 6 cycles of platinum/paclitaxel. HDCT consisted of mobilization regimen (MOB) of ifosfamide/etoposide, followed by high-dose topotecan, melphalan and cyclophosphamide (TMC). For CDCT pts, T1= pre-cycle #1 and T2 =cycle #6. For HDCT pts, T1=MOB and T2 = post-TMC (during engraftment). For all pts, T3 and T4 occurred at 3 and 6 months follow-up, respectively. The FACT-O consists of 4 domains [physical (PHYS), social (SOC), emotional (EMO), and functional well-being (FUNC)] and the ovca subscale (OV). The Mann-Whitney U test was used to compare changes in pts’ QOL scores. Results: To date, 39 HDCT and 19 CDCT pts have participated. All patients were alive at T4. At T1 CDCT pts had worse FUNC (p=.006) and OV (p=.009) scores than HDCT pts; however PHYS, SOC and EMO scores were similar between both groups. At T2, HDCT pts had worse PHYS (p=.003), FUNC (p=.04) and OV (p=.03)scores than CDCT pts. HDCT pts had significantly worse changes than CDCT pts from T1 to T2 for PHYS, FUNC and OV (p<.001). Both HDCT and CDCT pts had better PHYS, FUNC and OV scores at 3 months and 6 months follow-up compared to each group’s baseline scores (p=.02 to .006) At 3 months follow-up, HDCT pts reported higher PHYS (p=.04), FUNC and OV scores than CDCT pts. At 6 months follow-up, both groups reported identical levels of PHYS, FUNC and OV well-being. Conclusions: Compared to CDCT pts, HDCT pts reported lower PHYS and FUNC well-being during treatment, however, both groups of women returned to normal or better levels in all QOL domains compared to their pre-treatment levels. Our data suggest that pts receiving HDCT return to normal QOL and may exceed levels reported by CDCT pts. No significant financial relationships to disclose.
Patient expectations of palliative cancer treatment for noncurable malignancies: A pilot study.
Authors: Katherine E. Faricy-Anderson, Susan M. Allen, Nancy J. Freeman, Vincent Mor
Journal: Journal of Clinical Oncology (2014)

194 Background: Many people with advanced non-curable malignancies have unrealistic expectations of palliative cancer treatment including a belief that treatment may cure their cancer. However, qualitative data describing how patients define “cure” or other treatment goals are lacking. We initiated a pilot study to assess patient understanding of the goals of palliative anti-cancer treatment. Methods: Patients with advanced non-curable malignancy were eligible. Enrolled patients completed a structured interview with both quantitative and qualitative components to assess their understanding of treatment goals and their perceptions of clinical interactions. Additional data included age, race/ethnicity, education, type of malignancy, co-morbidities, and palliative care involvement. Results: We enrolled 30 patients initiating non-curative anti-cancer treatment. Ages ranged from 58 to 92 years. The most common malignancies were lung (33%) and prostate (17%) cancer. Ninety-three percent reported that their doctors explained things in “a way you can understand” and provided “as much information as you want” about treatment. However, only 53% accurately reported that treatment was “not at all likely” to cure their cancer; 40% reported some chance of cure; and 7% weren’t sure. Patient-reported definitions of “cure” ranged from “make it go away” to “no further symptoms” to “less pain.” Of those who reported some chance of cure, about half defined cure as eradication but half used more traditionally palliative language. Overall, 80% reported that treatment was “very” or “somewhat” likely to help them live longer and their definitions of “live longer” ranged from “wake up the next morning” to “20 more years” to “live to 105.” Conclusions: Patient-reported definitions of “cure” and other treatment goals vary widely and a substantial number of patients report unrealistic expectations. These results suggest the need for an intervention to improve patient-physician communication to ensure that patients fully understand the goals of their palliative treatments. “The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.”
Correlation of peripheral blood lymphocyte counts with outcome and histopathologic features of lymphocytic inflammation in patients with stage II colorectal carcinoma.
Authors: Hector Hugo Li-Chang, Naziheh Assarzadegan, David Messenger, Andrea Grin, Christopher Howlett, Richard Kirsch
Journal: Journal of Clinical Oncology (2014)

475 Background: The prognostic importance of the local antitumor immune response in colorectal carcinoma (CRC) is well established. Recent studies suggest that systemic antitumor immunity may also impact on survival. This study aimed to determine the relationship between peripheral blood lymphocyte counts (PBLCs), reactive features in regional lymph nodes, local tumoral/peri-tumoral lymphocytic inflammation and survival in stage II CRC. Methods: Resection specimens from 185 patients with stage II CRC were assessed for peri-tumoral lymphocytic inflammation, tumor-infiltrating lymphocytes, lymph node yield, lymph node size, and reactive changes in individual lymph nodes. Reactive changes were scored semi-quantitatively and given a reactivity [R] score of 1-4 based on the presence and size of germinal centers. Pre-operative PBLCs and neutrophil counts were recorded. Results: Lower peripheral lymphocyte counts were associated with advanced age (p = 0.016), T4 disease (p = 0.006), venous invasion (p = 0.006), lymph node yields &lt;12 (p = 0.024), smaller mean nodal diameters (p = 0.021), absence of tumor-infiltrating lymphocytes (p = 0.002) and fewer highly-reactive lymph nodes (R score 4) per case (p = 0.032). Cox regression analysis revealed that advanced age (Hazard Ratio, 1.03 per year [95% confidence interval, 1.01-1.05]; p = 0.015) and higher peripheral lymphocyte counts (HR, 0.52 per 1x10 9 cells/L [95% CI, 0.31-0.86]; p = 0.011) were independently predictive of disease-free survival. Neutrophil counts were not associated with outcome. A higher neutrophil to lymphocyte ratio was associated with worse survival on univariate, but not multivariable analysis. Conclusions: The PBLC is an independent predictor of survival in stage II CRC, and is significantly associated with the immune status of regional lymph nodes and the local lymphocytic immune response.
The Majority of Patients with Relapsing Light Chain (AL) Amyloidosis Are Not Eligible for Enrollment Onto Clinical Trials: Using Screen Failures to Define Major Unmet Medical Needs
Authors: Heather Landau, Raymond L. Comenzo, Tasneem Balasinorwala, Melissa Warner, Ola Landgren, Sergio A. Giralt, Hani Hassoun
Journal: Blood (2015)
Effect of sunitinib pretreatment on yield from tumor-infiltrating lymphocyte (TIL) cultures in patients with renal cell carcinoma.
Authors: Axel Bex, Aurelie Guislain, Hester van Boven, Christian U. Blank
Journal: Journal of Clinical Oncology (2012)

419 Background: Targeted therapies achieve response rates up to 50% in metastatic RCC, but durable complete remissions are very rare. Therefore additional therapeutic options are warranted. Adoptive transfer (ACT) of tumor infiltrating lymphocytes (TIL) has revealed response rates of up to 72% in melanoma patients and may lead to consolidation of responses upon sunitinib in RCC. Recent data suggest that sunitinib influences lymphocyte infiltration and regulatory T cells (Treg) into tumor, dendritic cells (DC), and myeloid derived suppressor cells (MDSC) in animal models, but impaired proliferation and function of human T cells and was unable to improve human DC activity in vitro. Methods: We compared TIL grown from primary tumors pretreated with 2 courses sunitinib prior to cytoreductive nephrectomy to TIL generated from treatment-naïve RCC. Patients took part in a phase II trial of presurgical sunitinib registered under EudraCT 2006-006491-38 and gave written informed consent. From 6 pretreated primary tumors and 6 untreated controls sterile tumor material was obtained and digested with collagenase, hyaluronidase and DNase to obtain tumor single cell suspension. This TIL/tumor suspension was cultured for up to 25 days in 6000IU/ml interleukin 2 (IL-2) and rapidly expanded by anti-CD3+IL-2 stimulation. Results: TIL harvested after coculture with tumor cells yielded 36+/−SD fold expansion from non-pretreated tumors versus a 128+/−SD fold expansion from tumors from patients that had been pretreated with sunitinib (p=0.015). Phenotypic analysis of culture product indicated a higher content of natural killer (NK) cells from treatment naïve TIL cultures, while sunitinib pretreatment skewed towards NK T cells. Interferon-gamma-production was not different on a per cell level.Rapid expansion after culture using anti-CD3/IL-2 induced 100-200 fold expansion towards a content of more than 75% T cells with no significant differences between both groups. Conclusions: Sunitinib in vivo pretreatment improves TIL grow during initial culture and does not impair function or rapid expansion, allowing higher final yield of TIL for ACT studies in RCC.
Prognostic and predictive value of tumor-infiltrating immune cells in Japanese patients with stage II/III gastric cancer.
Authors: Sophie Earle, Toru Aoyama, Alexander I. Wright, Darren Treanor, Yohei Miyagi, Lindsay C. Ward, Tomio Arai, Jeremy D. Hayden, Takaki Yoshikawa, Helene H. Thygesen, Heike I. Grabsch
Journal: Journal of Clinical Oncology (2014)

46 Background: Since the ACTS-GC trial, Japanese patients with stage II/III gastric cancer (GC) receive adjuvant S1 chemotherapy. However, selection of patients (pts) by TNM stage does not predict benefit from adjuvant S1 with certainty. Thus, there is an urgent clinical need to identify predictive biomarkers. Increasing evidence suggests tumor immune cell infiltration may be related to GC pts prognosis. We tested the hypothesis that extent and type of immune cell infiltration in GC is related to benefit from adjuvant chemotherapy. Methods: Tissue microarrays from 252 GC resections (109 pts treated by surgery alone (S), 143 pts treated by surgery and adjuvant S1 chemotherapy (SC)) from the Kanagawa Cancer Center Hospital (Yokohama, Japan) were investigated by immunohistochemistry for common leucocytes antigen (CD45), neutrophils (CD66b), macrophages (CD68 and CD163), T-cell subtypes (CD45R0, CD8, CD3), B-cells (CD20) and Treg cells (FOXP3). Staining was quantified as percentage immunoreactivity/area by automated image analysis. Relationship with overall survival was analyzed. A Cox regression model was used to identify independent prognostic markers and treatment interaction effect. Results: The hazard ratio of S1 was 0.694 in this GC cohort which is similar to the results of the ACTS-GC trial. CD45 and CD45R0 were independent prognostic markers in the S group only (CD45 p=0.032, CD45R0 p=0.003). A treatment interaction effect was seen for CD45, CD45R0, and CD68 (p value for test of interaction: CD45 p=0.062, CD45R0 p=0.082, CD68 p=0.057). Survival in the SC group was significantly poorer compared to the S group for CD45&gt;56% or CD68&gt;7% (p&lt;0.05). Conclusions: This is the first study to investigate the relationship between tumor immune cell infiltration at time of surgery and benefit from adjuvant chemotherapy. Our results indicate that GC patients with high intratumoral levels of CD68, CD45, or CD45R0 positive immune cells might not benefit from adjuvant S1 chemotherapy. These findings require validation in a second independent dataset before conducting a prospective study stratifying patients with stage II/III GC based upon extent of CD45, CD45R0, or CD68 immune cell infiltration for adjuvant treatment.
Study of PSMA-targeted <sup>18</sup>F-DCFPyL PET/CT in the evaluation of men with an elevated PSA following radical prostatectomy.
Authors: Michael A. Gorin, Steven P. Rowe, Margarita Mana-ay, Zsolt Szabo, Edward M. Schaeffer, Phuoc T. Tran, Mohamad E. Allaf, Curtiland Deville, Steve Y. Cho, Kenneth J. Pienta, Martin G. Pomper, Ashley Ross
Journal: Journal of Clinical Oncology (2016)

299 Background: Positron emission tomography/x−ray computed tomography (PET/CT) utilizing radiotracers targeting prostate membrane specific antigen (PSMA) offer the promise of improved sensitivity for visualizing low volume sites of prostate cancer. In this study we evaluated the sensitivity of PET/CT using 18 F-DCFPyL, a novel small molecule ligand of PSMA, for imaging sites of disease in men with an elevated PSA following radical prostatectomy. Methods: Patients with an elevated PSA following radical prostatectomy (defined as ≥ 0.2 ng/mL) were imaged with CT or magnetic resonance imaging (MRI) of the abdomen and pelvis, 99m Tc-methylene diphosphonate bone scan and 18 F-DCFPyL PET/CT. Conventional imaging studies (CT, MRI and boen scan) were clinically reviewed by readers blinded to the PET/CT scan results. Similarly, PET/CT scans were blindly reviewed and then the sensitivity of this novel imaging test was compared to that of conventional imaging. Results: In total, 12 men with a median PSA of 0.34 ng/mL (range 0.2 to 11) were imaged as part of this study. 2 (16.7%) patients had persistently elevated PSA values after surgery and 10 (83.3%) had values which were initially undetectable but then rose to ≥ 0.2 ng/mL. On conventional imaging, only 4 (25.0%) patients had at least 1 detectable site of disease. This included 1 patient with a local recurrence detected on MRI and 3 patients with bony lesions detected on bone scan. In contrast, 9 (75.0%) patients had areas of detectable disease on PET/CT. This included 3 (25.0%) patients with a local recurrence, 3 (25.0%) with lymph node metastases, 2 (16.7%) with bony lesions and 1 (8.3%) with both lymph node and bone findings. All lesions detected on conventional imaging had corresponding areas of radiotracer uptake on PET/CT. Conclusions: 18 F-DCFPyL PET/CT appears to be more sensitive for detecting areas of prostate cancer recurrence in patients with an elevated PSA following radical prostatectomy. Future work aims to more precisely define the sensitivity of this imaging test in a larger patient cohort. Clinical trial information: NCT02523924.
Prostate-specific antigen doubling-time (PSA DT) before onset of chemotherapy as survival predictor for hormone refractory prostate cancer (HRPC) patients
Authors: F. Scotte, E. Banu, S. Oudard, A. Banu, J. Medioni, E. Fabre Guillevin, A. Mejean, E. Fontaine, N. Thiounn, J. M. Andrieu
Journal: Journal of Clinical Oncology (2005)

4551
Growth factor and cytokine antibody array analysis of human hormone refractory prostate cancer (HRPC) tumor specimens and sera
Authors: G. R. Macvicar, R. D. Loberg, K. Tantivejkul, K. J. Pienta
Journal: Journal of Clinical Oncology (2005)

4686 Background: Tumor cells exist in a complex microenvironment in the circulation and in metastatic lesions. Several growth factors and cytokines are important in the tumor-stromal interactions and are essential for circulation and metastasis. To identify molecules involved in the metastatic process, we applied HRPC patient samples to cytokine and growth factor arrays. We hypothesized that there is a distinct expression pattern of cytokines and growth factors between normal and malignant specimens. Methods: Serum was isolated from peripheral blood of 13 HRPC patients, and 6 normal controls. Normal and tumor prostate and bone specimens were procured from a single HRPC patient as part of the University of Michigan’s Rapid Autopsy Program, and protein lysates were extracted for analysis. 5ug/ul serum and 500ug protein from tissue lysates were reacted with cytokine and growth factor arrays. Arrays were analyzed with imaging software for chemiluminescent intensity. Results: 10 HRPC patients were receiving chemotherapy at time of serum collection. HRPC patients had an average age of 67.8 years and an average PSA of 1233.9ng/mL. 2 HRPC patients had a Gleason Score of 5, and 2 had a Gleason Score of 7. Gleason Scores of 8, 9, or 10 were reported in 7 patients, and the Gleason Score was not known for 2 patients. Normal controls had an average age of 63.7 years and PSA values < 4ng/mL. The following cytokines and growth factors had over a two-fold increase in expression in HRPC sera compared to normal controls: GM-CSF, IL-2, IL-6, IL-8, MCP-2, MCP-3, MIP-1a, MSP-a, sgp130, ICAM-1, sTNF-RII, TNF-RI. The bone metastasis expressed EGF, FGF-6, IGFBP-1, IGFBP-2, IL-3, IL-6, MCP-1, MDC, MIG, NAP-2, PARC, SCF, TGF-b1, TGF-b3, TNF-b, HGF, and IL-8 at twice the level as in normal bone. At least a two-fold increase in G-CSF, IL-17, IL-8, VEGF-D, and NAP-2 was seen in the bone metastasis relative to the prostate primary tumor. Conclusions: IL-8 was expressed at a greater level in serum and prostate tumor tissue than in normal controls. Metastatic bone also expressed IL-8 at a greater level than in primary prostate tumor tissue. IL-8 may play a key role in the metastatic process. Funding support: DOD PC01–693 and NIH 1 RO1 CA102871. No significant financial relationships to disclose.
Team training in adult oncology.
Authors: Anne Gross, Susan Mann, Michael Kalfin, Sharon Lane, Saul Weingart, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2012)

27 Background: In outpatient oncology, clinicians working in various locations and at different times, rely on each other for information to coordinate and manage care. Increasingly complex treatment algorithms magnify risk for adverse events precipitated by failures of communication/coordination. We implemented team training in 16 adult practices across five campuses (community and academic) to reduce errors and increase efficiency/quality. Methods: 1,000+ MDs, NPs, PAs, RNs, pharmacists, and support staff were trained in teamwork concepts. Interventions and methods included baseline data collection on key clinical processes, (e.g. same-day chemotherapy changes not communicated to treating RN); observations and interviews with teams; “train-the-trainer” sessions; identification of “pain points”; interdisciplinary "process meetings" to develop agreements, tools and systems changes to support better communication/efficiency; trained all staff; collected data six months post-training. Results: Despite infrequency of noncommunicated same-day changes in chemotherapy at baseline (~2%), an improvement trend was seen (chi-square p=0.068). Incidence of missing infusion orders, not associated with an MD visit, decreased significantly. Providers reported fewer unnecessary pages. Nurses reported quicker, more reliable responses to pages sent. Staff reported improved practice efficiencies and safer, respectful work environments. Qualitative interviews elicited patient perceptions of communication, teamwork, and care coordination. Patients’ quantitative perceptions of teamwork improved significantly. Conclusions: Team training improved communication, task coordination, interactions with team members, staff perceptions of efficiency, quality, and safety and patient perception of teamwork in the outpatient practices of a comprehensive cancer center. [Table: see text]
Clinical recommendations for EGFR mutation testing in non-small cell lung cancer (NSCLC): Results from a European workshop.
Authors: R. Pirker, F. Herth, K. M. Kerr, M. Filipits, D. Grunenwald, H. H. Popper, R. Rosell, E. Smit, F. Cappuzzo, R. A. Stahel
Journal: Journal of Clinical Oncology (2010)

e18038 Background: Gefitinib has received European approval for the treatment of adult patients (pts) with locally advanced or metastatic NSCLC with activating mutations of the epidermal growth factor receptor (EGFR) tyrosine kinase. In Europe EGFR mutation testing is not well established, preventing access to new targeted therapies for NSCLC pts. Methods: An IASLC-ETOP European multidisciplinary workshop developed recommendations to facilitate implementation of standardized EGFR mutation testing in clinical practice. Results: The treating physician makes the decision to request EGFR mutation testing; the results of which should be available within 7 working days. All pts with NSCLC may eventually be tested, but exceptions may be made when likelihood of mutation is low. There was no consensus agreement on pre-screening algorithms. At diagnosis, the most accessible tissue is usually sampled, but re-biopsy at recurrence or disease progression should be considered. More data on potential heterogeneity between different biopsy sites are also needed. Sampling techniques include needle core biopsy, transbronchial biopsy, endobronchial biopsy, computed tomography-guided needle biopsy, mediastinoscopy, video-assisted thoracic surgery and thoracotomy. Further studies are needed to evaluate the use of cytology samples. Tumor specimen handling needs to be standardized. Fixation with 10% neutral-buffered formalin is optimum. Tumor cell enrichment of samples may be needed, depending upon the sensitivity of the test used. The tumor to normal cell ratio is important, although the minimum tumor cell number is ill-defined: ideally 200-400 cells are used. Various methods can be used to detect EGFR mutations: direct sequencing, ARMS, length analysis, dHPLC etc. Some tests only seek the most common activating mutations, others detect all mutations. Ideally pathologists should report tumor histology and mutation status concurrently, including sample size/quality, tumor nuclei percentage, methodology used, exons tested and mutation present/absent. Reference laboratories may be helpful. Conclusions: These recommendations will help to optimize routine EGFR mutation testing in Europe. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Lilly, Merck Serono, Roche, Roche/Genentech/OSI AstraZeneca, Boehringer Ingelheim, Lilly, Menarini, Merck, Merck Serono, Roche Roche