tbuckley/cabot-search huggingface dataset:
Identifying patients at high risk for colorectal cancer: A pilot study of colonoscopy in patients with rectal bleeding in a low-income country.
Authors: Olusegun Isaac Alatise, Ibrahim S. Bello, Akinwunmi O. Komolafe, Olusegun Adekanle, T. Peter Kingham
Journal: Journal of Clinical Oncology (2015)

560 Background: Colorectal cancer (crc) is one of the most common cancers worldwide. There is an increasing incidence in low and middle income countries (LMICs). Patient outcomes are poor due to a lack of screening programs. Timely and efficient referral leading to earlier diagnosis of crc is imperative to improve survival. This study was initiated to determine the value of colonoscopy in patients with rectal bleeding for diagnosing crc in Nigeria. Methods: This is a prospective study of patients older than 45 years that present with rectal bleeding at 5 primary health care facilities in Ile-Ife, Nigeria. Patients were enrolled when they were referred for colonoscopy at the Endoscopy unit of Obafemi Awolowo University Teaching Hospitals. Data obtained included the socioeconomic, clinical, anthropometric, colonoscopy and histopathological parameters. Results: In this interim analysis, 68 patients were recruited into the study. The median age was 58.5 years (range 45-89 years). Median duration of rectal bleeding was 6 months (0.25 -360 months). Fifty six (82.4%) patients had seen a doctor regarding their rectal bleeding prior to the current episode for which they were referred. Changes in bowel habits and weight loss were found in 29 (42.6%) and 30 (44.1%) patients respectively. Crc was found in 14 (21%) patients and polyps in 11 (16.2%) patients. Hemorrhoids were found in 68% of patients. Of the 14 patients with crc, 10 had stage II or III disease (71.4%). Weight loss occurred in 14 (100%) of patients with crc, compared to 16 (30%) of patients without crc (p&lt;0.0001). Conclusions: Given the high specificity of rectal bleeding in predicting the possibility of occurrence of colorectal cancer and polyps, this symptom may be used to select patients needing screening in resource poor settings. [Table: see text]
Local therapy of primary disease and survival in non-small cell lung cancer metastatic to brain and other single organ sites
Authors: J. Lee, S. Taylor, B. N. Bekele, M. Debnam, E. Chang, P. K. Allen, D. Suki, D. D. Karp, D. J. Stewart, Y. Oh
Journal: Journal of Clinical Oncology (2008)

19020 Background: Standard therapy for non-small cell lung cancer (NSCLC) brain metastases is radiotherapy and/or surgical resection for all visible lesions. This practice has been able to palliate brain metastasis-related symptoms and to improve survival. Similarly, we hypothesize that local therapy for other sites of disease, particularly the primary tumor and locoregional lymph node metastases, may further improve survival. Methods: Patients with NSCLC metastatic to one organ site were identified in the M.D. Anderson Cancer Center Tumor Registry, Thoracic Radiation Oncology, and Neurosurgery databases, and survival was compared for patients who received definitive local therapy of primary disease - chest radiotherapy >/= 45 Gy (ChRT) or thoracic resection (TS) of their primary tumor and locoregional lymph nodes - versus those who did not. Results: 120 patients had brain as a solitary organ site of metastasis, and 115 (96%) received brain metastasis treatment with surgical resection, stereotactic radiosurgery (SRS), and/or whole brain radiotherapy (WBRT). Ten (8%) also received ablative local therapy of primary disease - 8 (6%) ChRT and 2 (2%) TS of primary tumor and locoregional lymph nodes. Another 221 patients had solitary organ sites of metastasis outside the brain, and 61 (28%) received palliative radiotherapy to them. Of these 35 (16%) also received ablative local therapy of primary disease - 33 (15%) ChRT or 2 (1%) TS. In those with brain as a solitary metastatic organ site, survival was a marked improved by ChRT or TS (p=0.00186, median survival 30 vs. 7 months). In those with non-CNS solitary organ sites of metastases, there is only a tendency towards improved survival in patients who received ChRT (median survival 12 vs. 8 months). Conclusions. For NSCLC patients with brain as a solitary organ site of metastasis, ChRT or TS markedly improves median survival. For those with non-CNS solitary organ sites of metastases, ChRT improves survival, but this benefit is lost in those who survive beyond one year. Patients with extracranial metastases rarely received local therapy for metastases, whereas brain metastasis patients invariably do. Our results suggest a potential benefit ChRT or TS in patients with oligometastatic NSCLC. No significant financial relationships to disclose.
Prevalence of atypical urine cytology in patients treated with gemcitabine-cisplatin (GC) for urothelial carcinoma (UC).
Authors: Kimberly R. Kruczek, Lu Wang, Guliz Barkan, Elizabeth Henry
Journal: Journal of Clinical Oncology (2015)

363 Background: The prevalence of atypical urothelial cells (AUC) in the general population is estimated to range between 2-23% with known variability between individual pathologists’ use of this diagnosis. At our institution, the AUC rate for all urinary tract cytology (UTC) is 6.1%. Increased rates of urothelial atypia have been described in pts receiving certain systemic and intravesical therapies for UC. This may confound the use of UTC for post-therapy surveillance. Our objective is to describe the prevalence of urothelial atypia in pts treated with GC, as it is currently unknown. Methods: Patients who received at least one cycle of GC for UC at a single institution from 1/1/2007-9/30/2014 were identified. Demographics, clinical characteristics, treatment setting, number of cycles, and specimen type were recorded. Urine cytology reports were reviewed and tabulated. Results: Seventy-four pts treated with GC were identified. Median age at treatment was 65 (range 42-80); 58 (78%) were male. Median number of cycles was 4 (range 1-9). Treatment settings were: 15 (20%) neoadjuvant, 38 (51%) adjuvant, and 21 (28%) metastatic. Ten (14%) pts were previously treated with intravesical therapy (9 BCG, 1 mitomycin). Thirty-six (49%) pts had urine cytology available. Twenty-seven (75%) pts had at least 1 urine cytology within 12 months post-chemotherapy, with 44 total specimens. Nine (25%) pts had cytology performed &gt;1-year post treatment. Cytology specimens within 12 months post-chemotherapy were reviewed. Two out of 44 specimens had AUC (5%), with all other cases negative. The pts with AUC were male, received adjuvant therapy, had prior radical cystectomy with orthotopic neobladder reconstruction, and had no intravesical therapy. Conclusions: The prevalence of AUC in pts treated with GC was similar to the general population. Chemotherapy with GC does not appear to morphologically affect urothelial cells. If atypical UTC is seen in this population, the cause should be investigated, as GC does not appear to influence urothelial changes. Additional study is needed to characterize the impact of systemic therapy on urothelial atypia and to guide the use of urine cytology for post-therapy surveillance.
Palonosetron versus other 5-HT<sub>3</sub>–receptor antagonists for chemotherapy-induced nausea and vomiting prevention in patients with noncolon gastrointestinal cancers.
Authors: S. Balu, C. Craver, J. Gayle, D. Buchner
Journal: Journal of Clinical Oncology (2011)

129 Background: This study analyzed the risk of chemotherapy induced nausea and vomiting (N&amp;V) [CINV] associated with palonosetron versus other 5-HT 3 receptor antagonists (5-HT 3 -RAs) initiation among patients with non-colon gastrointestinal cancers receiving chemotherapy (CT) in a hospital outpatient setting. Methods: Patients diagnosed with any non-colon gastrointestinal cancer initiating any CT and antiemetic prophylaxis with palonosetron (Group 1) or other 5-HT 3 -RAs (Group 2) for the first time (index date) between 4/1/2007-3/31/2009 were identified from the Premier Perspective database. Patients included were aged ≥ 18 years, with no evidence of N&amp;V, CT, and antiemetic medication in the 6 month pre-index date period, and with at least 36 consecutive months of data. A negative binomial GLM regression analysis was done estimating the number of CINV events (identified through either ICD-9-CM codes for N&amp;V and/or volume depletion or CINV-related rescue medications 1 day after CT administration) in the follow-up period (first of 8 CT cycles or 6 months post index date) between the 2 groups (after matching on CT and specific CT cycle). Results: Of 658 identified patients, 215 initiated on palonosetron (Group 1; 32.7%). Group 1 patients were significantly younger [61.7 (SD: 11.3) vs. 62.2 (12.1) years; p = 0.0073], a higher percent received highly emetogenic chemotherapy (27.4% vs. 19.4%; p &lt; 0.0001), and comprised of less African Americans (7.0% vs. 13.3%). In the follow-up period, the unadjusted number of CINV events per patient per CT cycle for Group 1 patients was lower versus Group 2 patients, though statistically non-significant (4.7 vs. 5.2; p = 0.1714). However, after controlling for differences in demographic and clinical variables, the regression model predicted a statistically significant reduction (30.9%) in the total CINV events per patient per CT cycle in favor of Group 1 patients; p = 0.0086. Conclusions: In this analysis, patients with non-colon gastrointestinal cancers initiated on palonosetron were more likely to experience a significantly lower rate of CINV events per patient per CT cycle versus those initiated on other 5-HT3-RAs. [Table: see text]
Suppressive signals in colorectal cancer: RasGRP1 a new marker for anti-EGFR therapy?
Authors: Jeroen Roose, Philippe Depeille, Robert S. Warren
Journal: Journal of Clinical Oncology (2016)

625 Background: Treatment of metastatic colorectal cancer (mCRC) is largely palliative, making potentially curative therapy via molecular inhibition of specific cellular targets in CRC is a highly sought-after goal. One target of considerable focus in both basic and clinical investigation in CRC is the Epidermal Growth Factor Receptor (EGFR). Despite widespread EGFR expression in CRC, clinical trials have shown modest benefit from the use of anti-EGFR blocking antibodies and tumors with activating mutations in KRAS (KRAS MUT ) do not benefit from EGFR blockade. Given the ubiquitous expression of EGFR in CRC, why does such a large subset of patients fail to benefit from anti-EGFR antibodies? Methods: We combine the analysis of genetic mouse models, CRC cell line, and CRC patient database information and tumor samples. Results: We recently reported that two structurally distinct types of RasGEFs, SOS1 and RasGRP1, are co-expressed in both normal intestinal epithelial cells and in CRC cells. We observed that EGFR signals in CRC cells with KRAS MUT result in even more RAS activation, arguing that RasGEFs load more RAS molecules with GTP following EGF stimulation. Indeed, we found that both SOS1 and RasGRP1 are activated downstream of the EGFR. Quite surprisingly, SOS1 and RasGRP1 have opposing functions here. Biochemically, RasGRP1 limits the amount of EGFR-SOS1-RAS signals. Biologically, knockdown of RasGRP1 expression in KRAS MUT CRC cells leads to increased tumor growth in a xenograft mouse model. Conclusions: We hypothesize that anti-EGFR therapy may lead to unwanted inhibition of the inhibitory EGFR signals when CRC tumor express significant levels of RasGRP1 protein. We will discuss our current research that focuses on RasGRP1 as a prognostic marker of CRC outcome but also as a diagnostic indicator for EGFR therapy.
First Trial of Humanized Anti-CD74 Monoclonal Antibody (MAb), Milatuzumab, in Multiple Myeloma
Authors: Jonathan Kaufman, Ruben Niesvizky, Edward A. Stadtmauer, Asher Chanan-Khan, David Siegel, Heather Horne, Nick Teoh, Matthew J. Leoni, William A Wegener, David M. Goldenberg
Journal: Blood (2008)
Multi-institutional phase II trial of single agent regorafenib in refractory advanced biliary cancers.
Authors: Heloisa P. Soares, Nishi Kothari, Amit Mahipal, Gregory M. Springett, Jongphil Kim, Fatima Tariq, Hanna Kelly Sanoff, Andrew Stewart Poklepovic, Richard D. Kim
Journal: Journal of Clinical Oncology (2016)

TPS468 Background: Currently, there is no standard second line treatment for patients with advanced biliary tract cancer (BC) who have failed prior systemic therapy. Aberrant activation of the Ras/Raf/MEK/ERK pathway occurs in more than 60% of BC indicating the importance of this pathway in biliary carcinogenesis. Furthermore anti-angiogenic agents such as the VEGF-antagonist bevacizumab, and the multikinase inhibitor sorafenib have been tested in BC in the first line setting with modest activity. Regorafenib is an oral multi-kinase inhibitor that targets multiple membrane-bound and intracellular kinases including VEGF, the Ras/Raf/MEK/ERK and PDGFR- ß pathways. Given the pivotal role of these pathways in biliary cancer biology, the clinical evaluation of regorafenib represents a novel and rational approach to treat this disease. Methods: This is a multi-institutional phase II single arm single-stage design trial using regorafenib as single agent. Patients with histologically or cytologically-proven locally advanced or metastatic biliary tract carcinomas that failed no more than 2 prior line of systemic chemotherapy are eligible for this study. Patients must have measurable disease per RECIST 1.1 criteria and never been treated with VEGF inhibitors. Patients will receive regorafenib 160 mg daily (21 days on and 7 days off) and will be evaluated for response every 2 cycles (1cycle = 28 days). The study’s primary endpoint is 6 month overall survival. Secondary endpoints are to define disease control, progression-free survival and toxicity related to treatment. Correlative biomarker studies using plasma samples will be performed to investigate levels of 40 relevant proteins associated with the above-mentioned pathways in the attempt to identify predictive markers of drug benefit. As per September 2015, twelve of the 39 planned patients have been accrued for the study. In addition to Moffitt Cancer Center, this trial will enroll patients at the UNC Lineberger Comprehensive Cancer Center and VCU Massey Cancer Center. Clinical trial information: NCT02115542.
Clinical and genetic characteristics of multiple primary cancers (MPC) in groups of familial and sporadic breast cancer (BC).
Authors: V. D. Petrova, E. L. Sekerzhinskaya, I. A. Selezneva, T. V. Sinkina, S. A. Terekhova, U. A. Boyarskikh, N. A. Ermolenko (Kostrykina), M. L. Filipenko, A. F. Lazarev
Journal: Journal of Clinical Oncology (2011)

e11047 Background: MPC represents the interest for their prognosis and more effective treatment. The objectives of our research was to investigate clinical and genetic characteristics of MPC among women with familial and sporadic BC. Methods: The research is based on data of 1407 Caucasian women with BC aged 20-79 years (555-familial BC, 852– sporadic BC), control group consisted of 1006 women without a history of cancer. In all groups were analyzed more than 100 phenomic and genotypic factors. Processing of the results was performed using modern methods of biomedical statistics. Statistically significant differences taken at p<0.05. Genotyping was carried out by real-time PCR using competitive Taq-Man probes or with allele-specific PCR using SYBR Green intercalating dye. Results: Specific weight of MPC in group of familial BC [18,0% (14,74-21,26] was higher than in group of sporadic BC [2,0% (1,04-2,96)]. Among women with familial BC with MPC premenopause status met more rapidly [10,1 (4,06-16,14)] than in the group of sporadic BC with MPC [5,0 (1,26-8,74)]. Specific weight of BRCA-negative cases and FGFR-mutations were higher in familial group with MPC than in the group of sporadic BC with MPC [68,7% (59,38-78,02) against 40,0% (18,10-61,90); 3,0% (0,42-6,42) against 35,0% (13,66-56,34)]. Patients with triple negative and HER2neu positive BC met more frequently in familial group with MPC than in the group of sporadic BC with MPC. Reproductive factors such as obesity, aborts and others also had significance. Conclusions: Clinical and genetic characteristics of MPC in group of familial BC have different characters as against as group of sporadic BC.
Performance characteristics of PSA in patients undergoing radical prostatectomy.
Authors: Jen-Jane Liu, James D Brooks, Michelle Ferrari, Rosie Nolley, Joseph C. Presti
Journal: Journal of Clinical Oncology (2012)

199 Background: The Prostate Cancer Prevention Trial demonstrated that the performance characteristics of PSA are improved for diagnosis of high grade disease. We assessed the performance of PSA for determining total and high grade cancer volume in a radical prostatectomy series. Methods: We identified 1307 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (n=658) and T2 (n=549) disease who had surgery between 1988 and 2002 and detailed morphometric mapping by a single pathologist. Patients with T1c and T2 disease were analyzed separately as the indication for biopsy was different in these two populations (elevated PSA versus abnormal DRE). We generated receiver operating characteristic (ROC) curves for PSA based on total tumor volume and volume of Gleason 4 or 5 disease and compared the areas under the curve (AUC) for different cut points of total and high grade cancer volume. Results: For patients with clinical stage T1c disease, as total and high grade cancer volumes increased, so did the AUC for PSA performance. There was a significant difference in AUC for PSA for total cancer volumes greater than 0.5 cc (AUC=0.62) compared to greater than 2 cc (AUC=0.72, p=0.02), and also between volumes greater than 2 cc (AUC=0.72) and 5 cc (AUC=0.79, p=0.0003, Fig.1). The AUC for PSA performance for volume of high grade disease increased from 0.66, to 0.68, to 0.76 for Gleason 4 or 5 volumes of 0, 0.5, and 3 cc, respectively (Fig. 2). For patients with clinical stage T2 disease, the AUCs for total or high grade cancer volume were not different across cut points, but were overall higher compared to the T1c group. Conclusions: In T1c patients, PSA performance improved in a stepwise fashion with higher total and high grade cancer volumes as evidenced by improved receiver operating characteristics. In T2 patients, no similar trend was observed, although overall PSA performance was improved compared to T1c patients. Prior studies show that PSA performs better for the detection of high grade disease; here, we show that PSA performs better in predicting volume of high grade disease in radical prostatectomy specimens.
Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreatic cancer.
Authors: J. Huang, J. M. Robertson, J. H. Margolis, S. Balaraman, G. S. Gustafson, P. V. Khilanani, L. Nadeau, R. P. Jury, B. McIntosh
Journal: Journal of Clinical Oncology (2011)

287 Background: To retrospectively compare the efficacy and toxicity of full-dose gemcitabine-based chemoradiotherapy (GemRT) vs. 5-fluorouracil (5-FU)-based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC). Methods: From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n=38) or GemRT (n=55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000 mg/m 2 weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact. Results: Eighty-eight of 93 patients have died, and only one was lost to follow-up after developing DM. The median OS was 11.2 months (range 1.5-96). Patient characteristics (including Zubrod score, age, tumor stage, nodal stage, tumor location, and grade) were not significantly different between treatment groups. The OS was significantly better for GemRT compared to 5FURT (median 12.5 months vs. 10.2 months; 51% vs. 34% at 1 year; 12% vs. 0% at 3 years; 7% vs. 0% at 5 years; respectively; p=0.04), although the two groups had same DM (34% at 1 year). GemRT cohort was more likely to receive gemcitabine before or after chemoradiotherapy than 5FURT cohort (85% vs. 37%, p&lt;0.001). Of the subset who received gemcitabine either before or after chemoradiotherapy, OS was still significantly better for GemRT without concurrent erlotinib compared to 5FURT (median 15.1 months vs. 10.7 months; 70% vs. 36% at 1 year; 21% vs. 0% at 3 years; 11% vs. 0% at 5 years; respectively; p=0.005), as was the rate of DM (23% vs. 45%; respectively; p=0.04). The subsequent hospitalization, percent of survival time spend in the hospital, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups. Conclusions: Full-dose GemRT was associated with improved OS compared to standard 5FURT. This approach yielded a moderate number of long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity. No significant financial relationships to disclose.
Empowering bereaved parents in the development of a comprehensive bereavement program.
Authors: Jennifer Malia Snaman, Charlene Phillips, Deena R. Levine, Justin N. Baker
Journal: Journal of Clinical Oncology (2015)

47 Background: The death of a child poses special challenges to both bereaved families and staff. Each individual's grief journey is unique and ongoing; however, common themes and support systems help to define successful bereavement services. Bereaved parents who have experienced the loss of a child have special insight and can help to identify the key components necessary for the development and implementation of a comprehensive bereavement program. Methods: The bereavement program at St. Jude Children’s Research Hospital is multifactorial and involves both supportive services and useful resources that have been developed by parents who have lost a child to cancer at our institution. Results: The program begins with anticipatory bereavement services prior to death by the bereavement coordinator and Palliative Care team. Following the child’s death, a bereaved parent mentor is offered and available. These mentors have been trained how to identity and triage abnormal or concerning behaviors and how to obtain additional psychosocial support for at risk families. The materials include a parent-created a resource manual with parent and sibling with recommended books, websites, and other helpful references. Parents developed a booklet containing reflective pieces and several videos describing difficult moments in their grief journey to provide a support to other parents, siblings, and staff. Finally, they designed and illustrated communication cards to be sent to all bereaved families at key time points during the first two years following a child’s death. Conclusions: The innovative nature of this program with multiple components of the parent-driven comprehensive bereavement program can serve as a paradigm for the development of others programs and for the field of hospice and palliative medicine as a whole.