tbuckley/cabot-search huggingface dataset:
Risk of colorectal cancer after diagnosis of prostate cancer: A population-based study.
Authors: Danielle Nicole Desautels, Zoann Nugent, Alain Demers, Salaheddin Mahmud, Piotr Czaykowski, Harminder Singh
Journal: Journal of Clinical Oncology (2015)

3606 Background: Prior studies on risk of colorectal cancer (CRC) among survivors of prostate cancer (PC) have not controlled for important confounding factors such as competing risk of death and other cancers, and comorbidities. We assessed the risk of CRC (overall, sub-site- and treatment-specific) among PC survivors. Methods: A historical cohort study was performed by linking the Manitoba Cancer Registry and the Manitoba Health administrative databases. Each subject diagnosed with PC as his first cancer between 1987 and 2009 was age-matched with up to five men with no history of invasive cancer on the index date (date of PC diagnosis). All subjects were followed up to the date of diagnosis of CRC or another cancer, death, migration from the province, or study end-point (December 31, 2009). Competing-risk proportional hazard models were used to compare the CRC incidence rates with adjustment for age, history of lower gastrointestinal endoscopy, intensity of health care visits, diabetes and socio-economic status. There were three mutually exclusive (and competing) outcomes: CRC, another primary cancer, and death. Time dependent analysis was performed to assess effect of radiation treatment. Results: 14,164 men with PC and 69,051 controls were followed for a total of 559,081 person-years. Men diagnosed with PC had an increased risk of subsequently being diagnosed with CRC (all CRC: hazard ratio (HR) 1.14; 95% confidence interval (CI): 1.02-1.27; rectal cancer: HR 1.36; 95%CI: 1.09-1.71). Among men with PC, treatment with radiation was associated with increased risk for rectal/rectosigmoid cancer (HR 2.06; 95%CI: 1.42-2.99) compared to men with PC not treated with radiation, with the majority of excess cases being diagnosed within 5 years from PC diagnosis. Conclusions: Following a diagnosis of PC, the probability of diagnosing a CRC is increased, in particular rectal cancer among those treated with radiation. CRC screening soon after PC diagnosis should be considered.
Phase 1b study with PEGylated human IL-10 (AM0010) with 5-FU and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma (PDAC).
Authors: J. Randolph Hecht, Aung Naing, Gerald Falchook, Manish R. Patel, Jeffrey R. Infante, Raid Aljumaily, Deborah Jean Lee Wong, Karen A. Autio, Zev A. Wainberg, Milind M. Javle, Johanna C. Bendell, Shubham Pant, Peter Van Vlasselaer, Gail Linda Brown, Martin Oft, Kyriakos P. Papadopoulos
Journal: Journal of Clinical Oncology (2017)

399 Background: The benefit of adding nal-irinotecan or oxaliplatin to 5-FU in second-line therapy for PDAC is relatively small and it has been refractory to immune therapies. The success and the durability of immunotherapy is thought to depend on the activation and expansion of intratumoral, tumor specific cytotoxic CD8+ T cells which are absent in most PDACs. AM0010 stimulates the survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune stimulation and prolonged stable disease in PDAC patients (pts) with single agent AM0010 was recently presented. Irinotecan may eliminate cytotoxic T cells. Treatment with platinum or 5-FU may activate immune responses to cancer and AM0010 has synergistic anti-tumor function with both in preclinical models. In this phase 1b clinical study, the efficacy of AM0010 with FOLFOX was explored in patients with PDAC. Methods: PDAC pts progressing on a median of 1 prior therapy (range 1-3) were treated daily with AM0010 in combination with FOLFOX (n=20). Tumor responses were monitored using irRC. Immune responses were monitored using analysis of serum cytokines, activation of blood derived T cells and peripheral T cell clonality. Pretreatment samples were analyzed by IHC for tumor infiltration by CD8+ T cells. Results: G3/4 TrAEs included thrombocytopenia (55%), anemia (45%) and neutropenia (25%). There was no significant bleeding or febrile neutropenia. 16 pts had a objective tumor response assessment; 2 had an irCR, 1 an irPR, 10 had irSD. Eight remain on treatment, 2 for &gt; 1 year. ORR was 15%, the DCR was 65%. The mPFS was 3.9 months. AM0010 increased serum Th1 cytokines and reduced mediators of chronic inflammation IL-23 and IL-17 and the immunosuppressive cytokine TGFb. AM0010 increased the number and proliferation of PD1+ activated CD8+ T cells and induced de-novo oligoclonal expansion of T cell clones without affecting total lymphocyte counts. Conclusions: AM0010 with FOLFOX is well tolerated with moderate hematological toxicity in patients with PDAC. The observed immune activation including CD8+ T cell activation and prolonged objective responses are encouraging and will be explored in a phase 3 trial starting in 2016.
Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation
Authors: Jason P. Frazier, Jessica A. Bertout, William S. Kerwin, Alicia Moreno-Gonzalez, Joey R. Casalini, Marc O. Grenley, Emily Beirne, Kori L. Watts, Andy Keener, Derek J. Thirstrup, Ilona Tretyak, Sally H. Ditzler, Chelsea D. Tripp, Kevin Choy, Sarah Gillings, Megan N. Breit, Karri A. Meleo, Vanessa Rizzo, Chamisa L. Herrera, James A. Perry, Ravi K. Amaravadi, James M. Olson, Richard A. Klinghoffer
Journal: Cancer Research (2017)

Abstract The vision of a precision medicine–guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient's tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies. Cancer Res; 77(11); 2869–80. ©2017 AACR.
Impact of bone marrow fibrosis (BMF) at diagnosis in patients with multiple myeloma (MM).
Authors: Mohan Preet, Jinli Liu, Constantine A Axiotis, Albert S Braverman, Gurinder Singh Sidhu
Journal: Journal of Clinical Oncology (2013)

e19522 Background: BMF is known to occur in a minority of myeloma patients, but its incidence in American patients of African origin is not known. The impact of BMT on presenting clinical and laboratory findings, and its relationship to genetic variants has not been defined. Methods: Kings County Hospital is located in the East Flatbush section of Brooklyn, New York, where the population is mainly of African-Caribbean origin. Records and bone marrow specimens of myeloma patients who presented from 2000 through 2010 were reviewed. Degree of fibrosis was graded according to World Health Organization criteria: mild, moderate and severe. Results: Records of 113 patients were reviewed, 110 (97%) 97 of whom were African American or Caribbean; 62 (55%) were female and 51 (45%) male. Their ages ranged from 38 to 89 (median 65). Of the 27 patients with BMF (24%), 17 (63%) were female. Mild, moderate and severe BMF were present in 14 (52%), 7 (26%) and 6 (22%) patients respectively. Presentation calcium and creatinine levels were normal in all patients. Hemoglobin levels were similar (median 9.6 G/dl) in patients without BMF and in those with mild and moderate grades, the median level was 7.5 G/dl in those with severe BMF. Immunoglobulin G, A and D levels (67, 20 and 1) were similar in patients with and without BMF, but lambda light chain expression was greater in the BMF patients: 41 vs 24%. Cytogenetic data (CGD) was available in 46 patients; and abnormal in 10 (22%). All patients with abnormalities of chromosomal number were hyperdiploid. Of the 27 BMF patients CG data was available in 17, and was abnormal in 2 (12%). FISH results were normal in 23 of 25 patients, and in all of those with BMF. The fraction of the BMF and non BMF patients surviving after median follow up periods of 828 and 885 days were similar. Conclusions: BMF in this population was 24%, and severe in 5%. Female preponderance is a characteristic of MM patients of African origin, and was more marked in those with BMF. The BMF patients were characterized by more severe anemia and greater lambda light chain expression.
The association between American Indian/Alaska Native race and time to treatment initiation for nonmetastatic breast, colorectal, and lung cancer patients in Medicare.
Authors: Scott V. Adams, Andrea N. Burnett-Hartman, Aasthaa Bansal, Jean A. McDougall, Andrew Karnopp, Stacey Shiovitz, Scott David Ramsey
Journal: Journal of Clinical Oncology (2014)

6573 Background: Early initiation of treatment following a cancer diagnosis is associated with better patient outcomes. Therefore, we compared time to treatment initiation in American Indian/Alaska Native (AIAN) vs. non-Hispanic White (NHW) cancer patients, with the goal of identifying a modifiable factor to improve survival among AIAN cancer patients. Methods: We used Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims to identify new cases of colorectal, lung, or female breast cancer who were: 1) diagnosed from 2001-2007 with local or regional stage disease, 2) residing in a SEER catchment area, 3) enrolled in Medicare A and B at diagnosis, 4) ≥65 years old, and 5) AIAN or NHW. Cancer diagnosis date was obtained from SEER; the date of first surgical, chemotherapeutic, or radiation treatment was ascertained from Medicare claims. We used Cox regression models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the rate of treatment initiation during the 6 months following diagnosis between AIAN and NHW patients, stratified by cancer site and stage. Model covariates were age, sex, diagnosis year, marital status, rural residence, and pre-diagnosis Klabunde comorbidity score. Results: 146,877 NHW and 522 AIAN patients were diagnosed with local or regional breast, colorectal, or lung cancer over the study period. Compared to NHWs, AIANs were younger (mean age 75.0 vs. 76.2y), more likely to live in rural areas (37% vs. 22%), and had higher co-morbidity scores (mean Klabunde 0.43 vs. 0.36). The rate of treatment initiation during the 6 months following diagnosis was lower in AIAN compared to NHW patients diagnosed with breast (HR=0.85, CI: 0.72-0.99), colorectal (HR=0.74, CI: 0.63-0.87), or lung (HR=0.82, CI: 0.67-1.00) cancer. Conclusions: Our results suggest that despite equal Medicare insurance coverage, AIANs may experience delays in treatment initiation compared to otherwise similar NHWs. Decreasing the time to treatment initiation may improve survival rates for AIAN cancer patients, who currently have among the lowest five-year survival rates of any racial group.
Phase I/II study of weekly paclitaxel with or without MLN8237 (alisertib), an investigational aurora A kinase inhibitor, in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (OC), or breast cancer (BrC): Phase I results.
Authors: Gerald Steven Falchook, Barbara Ann Goff, Razelle Kurzrock, Heidi J. Gray, Lainie P. Martin, Robert L. Coleman, Hua Liu, Xiaofei Zhou, Ely Benaim, Russell Schilder
Journal: Journal of Clinical Oncology (2012)

5021 Background: Preclinical data indicate that inhibiting aurora A kinase (AAK), a key mitotic regulator, in OC can enhance the activity of taxane-based chemotherapy. This is the first clinical study to evaluate the AAK inhibitor MLN8237 (A) in combination with paclitaxel (P). Methods: Eligible women (aged ≥18 y) had previously treated, metastatic or locally recurrent OC or BrC. OC pts had previously received a platinum and taxane, and had disease recurrence within 12 mo of discontinuing platinum. Pts received IV P (D1, 8, 15) with oral A (enteric coated tablet, 3 d on, 4 d off, wkly for 3 wks) in 28-d cycles. Doses were escalated in a 3+3 schema. Phase I endpoints were safety, response by RECIST and CA125, and pharmacokinetics (PK). Results: 28 pts were treated at doses of P80 mg/m 2 + A10 mg BID (n=5), P80+A20 (n=6), P60+A20 (n=4), P60+A30 (n=6), P60+A40 (n=4) and P60+A50 (n=3). 25 pts had OC (20 ovarian, 4 primary peritoneal, 1 mullerian) and 3 BrC. Median age was 59 y (range 37–72). Pts received a median of 2.5 (1–16) and 2.5 cycles (1–15) of A and P, respectively. 11 pts are ongoing. 3 pts had DLTs: Gr 4 diarrhea (P80+A20), Gr 3 stomatitis (P80+A20) and Gr 4 neutropenia for &gt;7 d with fever (P60+A30). MTD has not yet been reached. 27 pts had ≥1 drug-related adverse event (AE); most common were neutropenia (n=18), anemia (n=13) and nausea (n=12). 21 pts had Gr ≥3 drug-related AEs; the most common was neutropenia (n=15). 5 pts had drug-related SAEs. No pts have died on study. Preliminary PK data (n=24) indicated fast absorption of A with a median T max of 3 hr. Geometric means of A AUC 0–12hr on D3 were 3740 nM*hr (CV: 22%), 7180 nM*hr (31%), 11,900 nM*hr (49%) and 15,100 nM*hr (72%) at 10, 20, 30 and 40 mg BID, respectively. A exposures increased approximately dose proportionally. Partial responses by RECIST (n=5) and/or CA125 (n=7) in 8 pts (29%; 7 OC, 1 BrC); 3 pts had stable disease ≥6 mo. Conclusions: Emerging data from this first combination study suggest that P+A is generally well tolerated and has antitumor activity in pts with OC/BrC. Dose-escalation is ongoing to determine the recommended phase II dose.
Psychosocial distress screening at a single urban community oncology center: Trends among Hispanic and Caucasian women with newly diagnosed breast cancer.
Authors: Gregory Joseph Britt, Rebecca C. Shay, Monica Rassmusen, Sandra Vannice, Jana M Bolduan Lomax
Journal: Journal of Clinical Oncology (2017)

198 Background: We aim to describe our psychosocial distress screening program with attention to our female breast cancer population and symptoms of anxiety and depression among English-speaking Caucasians and Spanish speaking Hispanics. Methods: We retrospectively examined the emotional distress scores of 170 women with newly diagnosed breast cancer at the Cancer Centers of Colorado at SCL Heath/Saint Joseph Hospital from January-December 2015. SCL Health IRB approval was obtained. Patients were provided a distress screening questionnaire (English or Spanish) at their initial visit. Data points included: gender, age, ethnicity, primary language, emotional distress (worry/nervousness or anxiety/fears and sadness/depression) and degree of distress (“thermometer” scale 0-10 or not at all, slightly, moderately, seriously or very seriously). The degree of distress measures were revised in August 2015 from a “thermometer” scale to a descriptive scale. Results: Of 170 women studied, there were 104 Caucasian, 49 Hispanic, and 17 other race/ethnicity (including Black, Asian, Native American, and Pacific Islander). 76 women (40 Caucasian, 31 Hispanic, 5 other) did not participate in filling out the questionnaire. Of the 94 patients responding, 68% were Caucasian (n=64), 19% Hispanic (n=18), and 13% other (n=12). With regard to symptoms, 55% of Caucasians (n=35), 44% of Hispanics (n=8), and 50% of other (n=6) reported anxiety. Moreover, 36% of Caucasians (n=23), 56% of Hispanics (n=10), and 33% of other (n=4) recorded sadness/depression. Among the descriptive scale scores from August-December 2015, Hispanics were the only group to record “seriously” or “very seriously” in regard to anxiety or sadness/depression. Conclusions: Our retrospective study of emotional distress screening demonstrated lower participation among Hispanics with breast cancer. Concerns of anxiety and depression were common among all groups, with a small number of Hispanics reporting the highest levels. Emotional distress screening is an important component of cancer care for women with breast cancer and barriers for non-English speaking Hispanic patients need to be examined.
Prognostic implications of gain of 1q in favorable histology Wilms tumor: A report from the Children’s Oncology Group.
Authors: Eric J. Gratias, Lawrence J Jennings, James Robert Anderson, Jeffrey Dome, Paul Edward Grundy, Elizabeth Perlman
Journal: Journal of Clinical Oncology (2013)

10014 Background: Wilms tumor is the most common childhood renal tumor. While the majority of patients with favorable histology Wilms Tumor (FHWT) have good outcomes, many patients still experience recurrence and death from disease. This study’s goal was to determine if chromosome 1q gain is associated with event-free (EFS) and overall survival (OS) in FHWT. Methods: Unilateral FHWT samples were obtained from patients enrolled on National Wilms Tumor Study-4 and Pediatric Oncology Group 9046, “A Molecular Genetic analysis of Wilms Tumor.” 1q gain, 1p loss, and 16q loss were determined using multiplex ligation-dependent probe amplification (MLPA). Results: The eight-year EFS was 87% (95% CI 82%, 91%) for the entire cohort of 212 patients. Tumors of 58/212 patients (27%) displayed 1q gain. A strong relationship between 1q gain and 1p/16q loss was observed. The eight-year EFS was 76% (95% CI 63%, 85%) for those with 1q gain and 93% (95% CI 87%, 96%) for those lacking 1q gain (p=0.0024). The eight-year OS was 89% (95% CI 78%, 95%) for those with 1q gain, and 98% (95% CI 94%, 99%) for those lacking 1q gain (p=0.0075). Gain of 1q did not correlate with disease stage (p=0.16). After stratification for stage, 1q gain was associated with a significant increase in the risk of failure (risk ratio estimate: 2.72, p=0.0089). Conclusions: Gain of 1q is associated with inferior EFS and OS in FHWT and may provide a new and valuable prognostic marker to stratify therapy for patients with FHWT. A confirmatory study is necessary before this biomarker is incorporated into risk stratification schema of future therapeutic studies.
Randomized, placebo-controlled, phase II study of dasatinib with standard chemo-radiotherapy for newly diagnosed glioblastoma (GBM), NCCTG N0877 (Alliance).
Authors: Nadia N. Laack, Evanthia Galanis, S. Keith Anderson, Clinton Leinweber, Jan C. Buckner, Caterina Giannini, Francois J. Geoffroy, Derek Richard Johnson, Glenn Jay Lesser, Kurt A. Jaeckle, Jann Nagina Sarkaria
Journal: Journal of Clinical Oncology (2015)

2013 Background: Dasatinib is a potent oral ATP competitive multi-targeted kinase inhibitor of multiple members of the Src kinase family known to be involved in gliomagenesis, tumor invasion, and radiosensitivity. N0877 is a phase I/randomized phase II trial evaluating the combination of dasatinib, radiation (RT) and temozolomide (TMZ) in newly diagnosed GBM. Methods: Following a 13 patient phase I dose escalation trial which established the MTD and phase II dose of dasatinib to be 150 mg PO daily when given with RT and TMZ, the randomized placebo-controlled phase II portion of the trial was initiated. The study followed a 2:1 randomization procedure with 85% power to detect a hazard ratio of 1.6 or higher in overall survival (OS) between the two arms and a type I error rate of 0.10. Dasatinib or placebo was given orally for 42 days, beginning with the first day of RT (total dose 60 Gy) and first dose of TMZ (75 mg/m2/d). Following a 24 - 42 day rest, patients then received 6 cycles (28 day cycles) of dasatinib or placebo (days 1-28) and TMZ (days 1-5). At the completion of 6 cycles of TMZ + dasatinib/placebo, patients continued on dasatinib/placebo only (28 day cycles) until progressive disease. Results: Data from 187 of 196 patients enrolled were available for analysis. Median follow-up was 12.6m for dasatinib (N = 133 pts), and 14m for placebo (N = 63 pts). There was no significant difference in PFS between dasatinib and placebo (6.7m vs 7.8m, respectively; HR 0.80 favoring placebo, 95% CI 0.57-1.1, p = 0.18) or OS (15.5m vs 20.6m; HR 0.71 favoring placebo, 95% CI 0.46-1.1, p = 0.12). Response rate (CR+PR) was 10.5% for dasatinib and 8.3% in placebo arm (p = 0.77). The overall incidence of grade 3 or higher hematologic toxicity was lower in the dasatinib arm (43.9% vs 68.8%, p = 0.0012) primarily due to lower rates of lymphopenia. Grade 3 or higher non-hematologic toxicities were similar between arms (53.8% vs 41.3%, p = 0.1384). Analysis by MGMT status will be forthcoming. Conclusions: The combination of the Src kinase inhibitor dasatinib with standard RT/TMZ did not improve the outcome of newly diagnosed GBM patients as compared to standard therapy alone. Clinical trial information: NCT00869401.
Loss of nuclear p27KIP1 (p27) expression as a predictor of lymph node spread in T1 breast cancer.
Authors: Huichung Tina Ling, Julia Anne Smith, Maryann Kwa, Asma Ali Dilawari, Joan Cangiarella, Judith D. Goldberg, Tsivia Hochman, Eleni Andreopoulou, Amber Azniv Guth, Daniel F. Roses, Silvia Formenti, Franco Muggia
Journal: Journal of Clinical Oncology (2012)

e11010 Background: We originally reported that p27 loss in T1a/b breast carcinomas was associated with lack of estrogen and progesterone (ER/PR) hormone receptors, but not in T1c node negative tumors (Mirchandani et al, Anticancer Research 2011). The current study explored the association of p27 expression with lymph node (N) status. Methods: 217 consecutive patients with T1 tumors were identified from 2001-2003. All patients underwent sentinel node biopsy (and complete lymphadenectomy when positive on frozen section): 111 were N0 and 106 were N+. Immunohistochemistry was performed for ER/PR, Her2, and nuclear p27 (low vs normal) and tumors were graded (well, moderate, and poorly differentiated). Analysis was conducted to define associations between standard variables and p27 expression among node positive and node negative tumor carriers (Table). Results: Low p27 expression was found in 21% of N0 and 36% of N+ T1 breast cancer patients (Chi-square=6.14, p-value=0.01). However from a series of multivariable analyses, only tumor size was significantly associated with node positivity. Conclusions: Poorly differentiated tumors, T1c tumors, and low p27 expression were associated with lymph node positivity, but only tumor size was significant in multivariable analysis. Contrary to our prior report, the relationship between low p27 and ER/PR- is strongest in the T1c subset (data not shown). Future studies will expand study cohorts to explore whether low p27 expression is a biomarker of poor outcome at 10 years in patients with T1 tumors treated with antiestrogens. [Table: see text]