tbuckley/cabot-search huggingface dataset:
Effect of intratumoral CD3+ and NKp46+ cells on tumor progression in resected colorectal liver metastases treated with neoadjuvant chemotherapy.
Authors: Matteo Donadon, Matteo Cimino, Kelly Hudspeth, Luca Di Tommaso, Max Preti, Massimo Roncalli, Domenico Mavilio, Guido Torzilli
Journal: Journal of Clinical Oncology (2016)

281 Background: The long-term outcome of patients resected for colorectal liver metastases (CLM) after neoadjuvant chemotherapy (CHT) depends by several tumoral and non-tumoral factors, such as the immune response to the tumor and to the CHT. The aim of this study was to investigate the impact of the pathological and immunological response in patients undergoing liver resection for CLM after CHT in regards to the long-term outcome. Methods: The immunoreactivity to CD3+ and NKp46+ cells inside the tumor, at the border between the tumor and the normal liver, and inside the normal liver was tested by computer-assisted image analyses in 121 patients undergoing liver resection for CLM between 2005 and 2013 preoperatively treated with oxaliplatin or irinotecan with or without bevacizumab or cetuximab. The survival was assessed in relation to several prognostic factors and to that immunoreactivity. Results: At univariate analysis T1/T2- and N0-status of the primary tumor, metachronous CLM, the radiological response, and the higher density of intratumoral CD3+ ( &gt; 1%) and of NKp46+ (mean &gt; 1) were found to be significantly associated with prolonged survival, but only intratumoral CD3+ ( &gt; 1%) and NKp46+ (mean &gt; 1) were significant on multivariate analysis (P = 0.005 and P = 0.004 respectively). On logistic regression analysis the metachronous CLM (OR = 2.781; P = 0.002), the use of irinotecan and cetuximab (OR = 3.891; P = 0.001) and the radiological response (OR = 3.219; P = 0.001) were found to be associated with increasing density of intratumoral CD3+ and NKp46+ cells. No significant associations were found with CLM number or size, CEA, or number of CHT courses. Combining the intratumoral CD3+ and NKp46+ cells density we defined four stages of survival (P = 0.003): patients presenting intratumoral CD3+ ( &gt; 1%) and NKp46+ (mean &gt; 1) had 100% overall survival at 5 years. Conclusions: Intratumoral CD3+ and NKp46+ cells density is a crucial prognostic factor in patients undergoing hepatic resection for CLM after CHT, and the kind of CHT seems related to their density. Further external validations are required to confirm our promising findings.
A review of how antineoplastic treatments impact the sexuality, fertility, and sexual function of adult patients with brain cancer: Implications for real-time treatment planning.
Authors: E. M. Dunbar, S. Savona, N. Ferree, P. A. Pumphrey
Journal: Journal of Clinical Oncology (2011)

2099 Background: There is an unmet need to understand how anti-neoplastic treatments impact the sexuality, fertility, & sexual function of adult brain cancer patients in both the immediate & short-term future. For ethical & practical reasons, the paucity of literature is predominantly retrospective & addresses either non-CNS cancers or adult sequela of childhood cancer treatment. The authors sought information immediately impacting “real-time” treatment planning for adult brain cancer patients. Methods: Search criteria included English-written PubMed articles before 12-2010 regarding adults >13yo. Subject/ key terms were combined to refine parameters: “neoplasm/cancer”, “infertility/fertility”, “sexual dysfunction/function/behavior”, “sexuality”, “brain”, “drug therapy/anti-neoplastic/chemotherapeutic/biologic/anti-angiogenic”, & common CNS chemotherapies. Articles focusing on “pituitary neoplasm/cancer” & surgery/radiation were excluded. Cross-reference with CINAHL & Web of Science provided no significant differences. Results: (manual when needed): 300+ citations (0 Meta/Systematic Reviews, 2 RCTs, 18 Reviews, 198 Cases/Other. Articles predominantly addressed sexual organ or other systemic cancers, childhood cancer survivors, & long-term sequela. No articles focused on adult brain cancer patients treatments nor the immediate/short-term impact of common CNS chemotherapies used in adult non-CNS cancers. Major themes included the scope of the problem, barriers to evaluation/treatment, & need for more research. 84 addressed spontaneous fertility after treatment, 86 addressed fertility-sparing/restitution success, & 13 addressed emotional sequela. Only 1 focused-group & 1 survey addressed information needs/barriers of patients at diagnosis. Conclusions: This search highlights the need for interdisciplinary research regarding information immediately impacting “real-time” treatment planning for adult brain cancer patients. Practical patient & provider resources, updated evidence, including pharmacology/toxicology cross-reference, will be provided at presentation.
Dendritic Cell Subsets in Bone Marrow and Peripheral Blood of Patients with Myelodysplastic Syndromes Display Numeric and Functional Defects
Authors: Nathalie van Leeuwen-Kerkhoff, Theresia M. Westers, Hetty J Bontkes, Shahram Kordasti, Ghulam J. Mufti, Tanja D de Gruijl, Arjan A van de Loosdrecht
Journal: Blood (2015)
Elevated pS6K levels in the sarcomatoid component of tumors derived from patients with metastatic renal cell carcinoma (mRCC).
Authors: Sumanta Kumar Pal, Tommy Tong, Miaoling He, Huiqing Wu, Xueli Liu, Courtney Carmichael, Clayton Lau, Rebecca A. Nelson, Robert A. Figlin, Jeremy Jones
Journal: Journal of Clinical Oncology (2013)

475 Background: Consistent with other retrospective analyses, data from our institutional experience indicates that patients (pts) with sarcomatoid mRCC have a poorer outcome as compared to pts that lack sarcomatoid features (Pal SK, et al. Urol Oncol 2012). The preponderance of correlative studies to date focused on epithelial-to-mesenchymal transition (EMT) as a driver of sarcomatoid disease; however, the role of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling is poorly understood. Methods: Of 270 pts with mRCC in our institutional database, 21 pts were noted to have sarcomatoid features. Thirteen of these pts had available tissue from nephrectomy or diagnostic biopsy. An additional 13 pts with mRCC and available tissue were identified from the database who had a similar MSKCC risk stratification but lacked sarcomatoid features. Immunohistochemical staining were performed for moieties related to VEGF-mediated signaling (pS6K) and EMT (Twist, E-cadherin and N-cadherin). Results: Among matched pts with and without sarcomatoid features (n=13 for each group), 9 pts (69.2%) in each group had poor risk disease by MSKCC criteria, while the remainder had intermediate risk disease. Given our risk-matching approach, median survival was similar in both groups (6 mos in pts with no sarcomatoid features vs. 9 mos in pts with sarcomatoid features, p = NS). In evaluable specimens from pts with no sarcomatoid features, the proportion of cell staining positively for pS6K was 24.4%. A higher proportion of pS6K staining was found in pts with sarcomatoid mRCC, both in sarcomatoid components (60.0%) and non-sarcomatoid components (52.5%). Staining for N-cadherin, E-cadherin, and Twist were highly variable, and no observable differences between groups were identified. Conclusions: Although chemotherapeutic strategies are a common 1 st -line approach to sarcomatoid mRCC, the finding of higher pS6K staining in this population suggest the potential for currently approved targeted therapies in this disease. Prospective assessment of VEGF- and mTOR-directed therapies for sarcomatoid mRCC, as in ECOG 1808 (NCT01164228), should be encouraged.
Dying for advice: Code-status discussions between resident physicians and patients with advanced cancer—A national survey.
Authors: David Johnson Einstein, Katherine Levine Einstein, Paul Mathew
Journal: Journal of Clinical Oncology (2014)

83 Background: Patients with treatment-resistant advanced cancer rarely benefit from cardiopulmonary resuscitation (CPR) but infrequently discuss end-of-life care with a physician until hospitalized for deterioration. Admitting resident physicians may therefore conduct initial code-status discussions, but may elicit patients’ preferences without providing necessary guidance. Methods: We distributed a case-based survey to all United States internal medicine residency program directors, of whom 19 enrolled and forwarded the survey to their residents. 358 residents (response rate 22.0%) completed the survey. Results: Faced with a hypothetical case of an inpatient with treatment-refractory advanced cancer, nearly all residents felt CPR would not be helpful. Yet, fewer than half (46.7%) of residents were likely to discuss an estimate of prognosis and the value of CPR with the patient. Only 30% were likely to offer a specific recommendation on CPR. A majority (69%) of residents who were unwilling to make a recommendation stated that patients should make their decisions independently. Most residents report that a sense of responsibility is the primary reason to discuss code status independent of attending physicians, and that deference to patient autonomy prevented them from sharing knowledge of outcomes or offering guidance. Ultimately, a minority stated they were satisfied with end-of-life discussions. Conclusions: Internal medicine resident physicians in the United States are unlikely to share the poor prognosis or offer specific recommendations on CPR in treatment-refractory cancer principally because of a conflict with their concept of patient autonomy. Given the futility associated with CPR in this setting, these data define a major unmet need in training and practice.
Management of the primary site in stage IV non-small cell lung cancer: SEER analysis.
Authors: Sean Szeja, Savita V. Dandapani
Journal: Journal of Clinical Oncology (2016)

52 Background: One of every three non-small cell lung cancer (NSCLC) patients is diagnosed with terminal stage IV disease. As systemic treatments have evolved, other tumor sites such as kidney have demonstrated benefits of aggressive management of the primary location and oligo-metastases. The purpose of this study is to use the SEER database to evaluate survival outcomes associated with surgery (S) and radiation treatment (RT) of the primary site in stage IV NSCLC. Methods: Eligible patient cases had lung coded as the primary location. The analysis was limited to histology of squamous cell carcinoma or adenocarcinoma, M1 staging, had recorded extent of surgery and status of radiation, were taken from years 1998-2013 and grouped from 1998-00, 01-05, 06-10, 11-2013 for temporal analysis. Kaplan-Meier was used to estimate median overall survival (MOS) and lung cancer specific survival (CSS). Results: There were 41150 patients meeting inclusion criteria with median follow up of 4 months limited by survival. Treatment was S only to 494, RT only to 20346, S+RT to 731 and neither to 19579. Of the dual modality patients, 85 had RT before S, 525 after and 121 unknown order. Node negative surgical patients undergoing lobectomy had better median OS &amp; CSS (30 &amp; 35 m respectively) than all other surgical categories (eg. wedge resection with 13 &amp; 17m, pneumonectomy with 10 &amp; 15m). Median OS &amp; CSS decreased slightly from 5 to 3 and 6 to 4 months over the time from 2000-2013. In the subset with N0 disease, those receiving both S+RT observed an increase of median OS &amp; SS from 11 to greater than 35 months (median not reached in 2013) while no trend was seen for other treatment strategies, which were ~5 months in 2013. Conclusions: Potential sources of confounding and bias must be regarding when interpreting our findings. These include selection of patient for aggressive treatment, both local and systemic, the latter of which this database does not describe. Our findings demonstrate that, in stage IV NSCLC, aggressive management of the primary site with surgery and radiation in patients with limited local disease such as N0 lymph nodes is associated with prolonged survival.
Occurence of initiation and progression of colorectal cancer in the changed intestinal environment.
Authors: Seiji Ohigashi, Kazuki Sudo, Daiki Kobayashi, Osamu Takahashi, Takuya Takahashi, Takashi Asahara, Koji Nomoto, Hisashi Onodera
Journal: Journal of Clinical Oncology (2013)

416 Background: Use of new molecular biology–based methods of bacterial identification is expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. However, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset. We analyzed the intestinal environments to determine whether the changes differed with the stage of CRC or adenoma. Methods: We analyzed fecal microbiota, organic acid concentrations, and pH in CRC patients (n=93), individuals with adenoma (n=23), and individuals with normal intestinal tracts (n=27). After patient hospitalization, the feces of all subjects were collected before any administration of laxatives or antibiotics to prepare the bowel.Thirteen bacterial groups were enumerated in the fecal microbiota by using reverse transcription–quantitative PCR (RT-qPCR). Eight kinds of organic acid were quantified using high-performance liquid chromatography, and fecal pH was measured by pH meter. Results: The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log 10 cells/g of feces; p&lt;0.001), 5 groups of obligate anaerobe (Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, and Atopobium cluster), and 2 groups of facultative anaerobes (Enterobacteriaceae and Staphylococcus) were significantly lower in the CRC group than in the healthy individuals. While the concentrations of organic acids—particularly short chain fatty acids (SCFAs) such as acetic acid, propionic acid, and butyric acid—were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p&lt;0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs concentrations and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among T-stages or Dukes stages. Conclusions: CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.
Pathologic correlation of <sup>89</sup>Zr-Df-IAB2M antiprostate-specific membrane antigen (PSMA) minibody in patients with metastatic prostate cancer.
Authors: Michael J. Morris, Stephen Barnett Solomon, Jeremy C. Durack, Joseph A. O' Donoghue, Serge K. Lyashchenko, Ruan Shutian, Jorge A. Carrasquillo, Jason Stuart Lewis, Danny F. Martinez, Nicole A. Parada, Jennifer Keppler, Anna Wu, Victor E. Reuter, Wolfgang Weber, Howard I. Scher, Steven M. Larson, Neeta Pandit-Taskar
Journal: Journal of Clinical Oncology (2015)

220 Background: IAB2M is a novel anti-PSMA minibody (Mb) based on the humanized J591 antibody that targets the extracellular domain of PSMA. The Mb has been engineered to remove Fc-Rn interactions and reduce the molecular weight relative to J591. The result is faster blood pool clearance, for a more favorable imaging schedule, while retaining bivalent targeting of PSMA. We have previously reported on the pharmacokinetics, dosimetry, and lesion uptake of IAB2M(Pandit-Taskar et al, WMIS 2014). Here we report the correlation between imaging and pathology of biopsies of PSMA avid lesions. Methods: Following standard imaging (SI) of CT/MRI, bone scintigraphy (BS), and FDG PET, 5 mCi of 89 Zr-Df-IAB2M was administered intravenously. Escalating minibody doses of 10, 20, and 50 mg were delivered, with cohort expansion at 10 and 20 mg. Whole body PET/CT scans were serially performed at various time points:1-2 h, 24 h, 48 h, and 72-144 h post injection. Metastases identified on PET were confirmed, where possible, with bx’s in the following preference: concordant IAB2M and FDG positivity, IAB2M, and FDG mismatch, or a mismatch between SI and any PET. Results: 24 patients (pts) with metastatic prostate cancer were scanned (11 at 10, 7 at 20, and 6 at 50 mg Mb doses). A total of 15 bxs (7 soft tissue, 8 bone) were performed on 14 pts; the histopathologic correlation is summarized in the table below. 13 lesions were identified by IAB2M, 11 by FDG, and 14 by SI. Of these, 12/13 (92.3%), 10/11 (90.9%), 12/14 (85.7%) were biopsy positive for cancer, respectively. 2 bone lesions were not identified by IAB2M, evident on other imaging modalities, and were both neg by bx. Overall bx concordance (pos/pos, neg/neg) with imaging was: IAB2M 14/15 (93%) vs. BS/CT 13/15 (86%) vs. FDG 12/15 (80%). Conclusions: An ongoing analysis of IAB2M imaging showed a high concordance with pathologic findings in patients with metastatic prostate cancer. Clinical trial information: NCT01923727. [Table: see text]
Advanced radiation oncology technology within the Veterans Health Administration (VHA).
Authors: George A. Dawson, Alice V. Cheuk, Shruti Jolly, Ruchika Gutt, Helen Fosmire, Stephen T. Lutz, Mitchell Steven Anscher, Michael Philip Hagan, Drew Moghanaki, Lori Hoffman-Hogg, Maria D. Kelly
Journal: Journal of Clinical Oncology (2014)

52 Background: The rapid evolution of technology in the treatment of cancer has paralleled other technological advancements in modern society. Intensity Modulated Radiotherapy (IMRT), Image Guided Radiotherapy (IGRT), Brachytherapy (BT), Cone Beam Computed Tomography (CBCT), Stereotactic Radiosurgery (SRS), and Stereotactic Body Radiotherapy (SBRT) facilitate treatment with higher, more conformal radiation doses, potentially improving cancer control while reducing normal tissue toxicity. Recent Surveillance, Epidemiology and End Results (SEER) program data and physician surveys indicate prostate BT is declining and the integration of SRS and SBRT is slower compared to IMRT. As utilization of technology increases, an understanding of its availability within the VHA is necessary to ensure quality and patient safety. Methods: An electronic survey was sent to 82 Radiation Oncologists (ROs)at 38 active VHA Radiation Oncology Centers with subsequent follow-up phone calls. The survey occurred from May-June 2014. ROs were queried on the availability of advanced RT technologies including IMRT, IGRT, BT, CBCT, SRS and SBRT at their facility. Practitioner specific details: years in practice, academic appointment and VHA employment status were collected. Results: Responses were obtained from 62 ROs representing 75% of VHA ROs and 34 or 89% of facilities. Full time VHA employees made up 60% of respondents with 35% in practice for &lt;5 years and 34% practicing for &gt;20 years; 71% held an academic appointment. The Table shows on site availability of advanced RT technologies within the 34 VHA sites that responded. Conclusions: For veterans receiving cancer treatment, VHA ROs are able to routinely use IMRT and IGRT with CBCT capabilities. However, stereotactic (SRS and SBRT) and BT services are less available, and may require referrals externally or to other VHA facilities. Limited availability of SRS and SBRT parallels the community experience. Likewise the decreasing utilization of BT is common to the VHA and private sector. SBRT, SRS and BT require significant expertise and technology. [Table: see text]
The best combination treatment of patients with advanced nasopharyngeal carcinoma.
Authors: F. Li, X. Zhang, L. Chen, H. Chen, B. Liang, Y. Dai, G. MA, J. Zheng
Journal: Journal of Clinical Oncology (2011)

e16018 Background: To evaluate Radiotherapy, Platinum, 5-FU and Nimotuzumab combine therapy in treatment of advanced nasopharyngeal carcinoma. Methods: From January 2010 until October 2010, 268 patients with pathologically diagnosed advanced Nasopharyngeal carcinoma, stage II to IV with partial metastases combine treated with Nimotuzumab, chemo-radiotherapy were collected. Among 268 patients 241 were qualified for analysis by SAS program. Generally, patients were receiving a total dose of 45Gy-72Gy radiotherapy, and mainly receiving combination of chemotherapy program of Platinum, and all patients were receiving 100-200mg of Nimotuzumab treatment over the same period, once a week. Results: There were 241 cases medical records can be analyzed. Patients aged 37-75 years-old with median age of 60.2. Male and female ratio was 3.46:1. Pathology diagnosed as squamous cell carcinoma. Cancer staged as IV, III and II were 38.2%, 53.7% and 9.1%, and with 64.73% of them with metastasis. Seven patients(2.91%) had adverse events which considering doubt as due to treatment, including chills, fever, rash, oral mucositis and allergy. No patient had significant fatigue, thrombocytopenia, decreased white blood cells count. No other sensory abnormalities, such as sepsis, herpes zoster, bilirubin and heart discomfort were observed. Conclusions: Nimotuzumab combined with chemo-radiotherapy for patients with advanced carcinoma is well tolerated and safe. Radiotherapy, Platinum, 5-FU and Nimotuzumab combine therapy can be considered as the best treatment regimen for patients with advanced nasopharyngeal carcinoma.
A phase II multicenter study of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) chemotherapy with pegfilgrastim support in patients (pts) muscle-invasive urothelial cancer (MIUC): Safety, pathologic, radiologic, and molecular correlates.
Authors: Toni K. Choueiri, Susanna J. Jacobus, Angela Q. Qu, Christopher Sweeney, Leonard Joseph Appleman, Christopher P.G. Tretter, Glenn J. Bubley, Aymen Elfiky, Rachel Park, Edward C. Stack, Sabina Signoretti, Meghara K. Walsh, Graeme Steele, Michelle S. Hirsch, Katherine Maragaret Krajewski, Mary-Ellen Taplin, Jonathan E. Rosenberg, Robert W. Ross
Journal: Journal of Clinical Oncology (2013)

278 Background: ddMVAC is associated with high responses rate (RR) in advanced urothelial cancer (UC). We embarked on a study in MIUC to determine pathologic RR and its correlation with clinical and radiological outcomes as well as DNA excision repair pathway biomarkers (ERCC1, PAR, BRCA1, and BRCA2). Methods: Patients with cT2-T4, N0-1, M0 UC, and adequate kidney and marrow function were enrolled on a prospective multicenter phase II trial. Four cycles of ddMVAC were given followed by radical cystectomy (RC). The primary endpoint was pathologic downstaging to &lt;pT1N0M0. The treatment would be considered effective if 17 of 37 eligible patients (46%) met the primary endpoint (85% power, 1-sided type I error 0.1). Secondary endpoints included safety, imaging response (by contrast-enhanced imaging, largely MRI), and biomarker correlates. Results: Between 12/08 and 4/12, 39 pts (cT2:42%; cT3:42%, cT4:16%, N1:45%) were enrolled. 91% had bladder primary, and 95% received 4 cycles of ddMVAC. Median follow up was 18 months. One patient developed distant metastases before RC. Of 39 eligible pts, 49% (90% CI 35-63) downstaged to &lt;pT1N0M0 (pT0N0=26%), and the primary endpoint was met. 14/17 (82%) of pts with cN1 disease had pN0 at surgery; no pts with cN0 was found to have pN(+). Toxicities &gt;Grade 3 related to chemotherapy were observed in 10% of pts and included mucositis, hand-foot skin reaction, hypokalemia and neutropenia. No neutropenic fevers were seen. Median and 18-month disease-free survival (DFS) is provided in Table. Tissue biomarker analyses will be presented. Conclusions: ddMVAC regimen is well tolerated and results in significant pathologic and radiologic downstaging in pts with MIUC. Clinical trial information: NCT00808639. [Table: see text]