tbuckley/cabot-search huggingface dataset:
Temporal trends in colorectal cancer screening (CRCS).
Authors: Siddhartha Das, Leo Chen, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

356 Background: The rate of CRCS continues to be suboptimal. Our study objectives were to characterize temporal trends in CRCS in general and within specific subpopulations and identify clinical and system factors that pose barriers to CRCS. Methods: Data from respondents aged ≥50 years who were classified as average risk (no personal or family history of colorectal cancer) from the 2001 to 2009 California Health Interview Survey were analyzed. Up-to-date CRCS was defined as having had a sigmoidoscopy or colonoscopy within the past 10 years. Using multivariate regression analyses that adjusted for confounders, rates of CRCS over consecutive periods of 2 calendar years were determined. Stratified analyses that explored for effect modification based on gender, ethnicity, smoking history, educational attainment, income level, health insurance status, and urban vs. rural residence were conducted. Results: A total of 126,873 screening-eligible respondents was included: median age was 63 years (range 50-85); 50,303 (46%) were men, and 95,534 (63%) were white. In the entire cohort, only 73,589 (55%) reported up-to-date CRCS. Over time, there was a significant trend towards increased CRCS, ranging from 48% in 2001 to 61% in 2009 (p&lt;0.01). After adjusting for confounding variables, this trend persisted with higher odds of up-to-date CRCS in more recent years (see Table). Specific characteristics were associated with decreased likelihood of CRCS: women (OR 0.63), low education (OR 0.72), poor income (OR 0.84), no insurance (OR 0.44), and rural residence (OR 0.93) (p&lt;0.01 for all). Temporal increases in CRCS were most prominent in particular groups, such as women (OR 3.55 in 2009 vs. 2001) and the uninsured (OR 11.48 in 2009 vs. 2001) (p&lt;0.01 for both). Conclusions: Although CRCS improved over time, there is still room for significant improvement. Temporal increases in CRCS were most substantial among women and the uninsured. Interventions used to improve CRCS in these groups should be harnessed and implemented within other minorities to enhance screening. [Table: see text]
Is laparoscopy still needed for staging resectable pancreatic cancer?
Authors: Peter Michael Santoro, Raafat Z. Abdel-Misih, Nicholas J. Petrelli, Joseph J. Bennett
Journal: Journal of Clinical Oncology (2012)

168 Background: Imaging for pancreatic cancer has demonstrated increased accuracy in staging patients before resection. Many propose diagnostic laparoscopy is therefore unnecessary before laparotomy and resection. Pancreatic cancer still has a high incidence of peritoneal and liver metastases that may be radiographically occult. Our hypothesis is that laparoscopy is still necessary to detect occult disease and avoid non-curative laparotomy in cases of peri-pancreatic malignancy. Methods: Patient data were collected at a large, academic community-based tertiary care center with a specialized pancreatic team. Retrospective chart review was performed for patients surgically treated for peri-pancreatic neoplasms between the years 2005-2011. Patients with adenocarcinoma were the focus of this study. All patients had triple phase CT imaging for staging and to assess resectability. Patients who had laparoscopy (group 1) were identified and compared to those who did not (group 2). Results: Two hundred and two patients from 2005-2011 with pancreatic neoplasms were identified as radiographically resectable. Of these, 107 had pancreatic adenocarcinoma (53%). In the first group, 80 patients underwent diagnostic laparoscopy (75%) and metastatic disease was identified in 8 cases (10%). Laparotomy for resection was performed for the remaining 72 patients and 6 were found to have metastatic disease that was missed during laparoscopy. The overall prevalence of metastatic disease in this group was 17.5%. In the second group, 27 patients underwent laparotomy without laparoscopy. Four of these patients(15%) were found to have metastatic disease. The sensitivity of laparoscopy to detect radiographically occult metastases was 70%. Laparoscopy still missed 43% (6/14) of patients ultimately found to have metastatic disease in this group. Conclusions: Occult metastases were still found in 15%-17.5% of patients despite modern CT scan imaging. Even though laparoscopy missed some metastases when compared to laparotomy, our results show that 10% of patients were spared an unnecessary laparotomy. Laparoscopy should still play a role in staging patients with radiographically resectable pancreatic cancer.
A Correction to the Research Article Titled: “Engineering a Prostate-Specific Membrane Antigen–Activated Tumor Endothelial Cell Prodrug for Cancer Therapy” by S. R. Denmeade, A. M. Mhaka, D. Marc Rosen, W. N. Brennen, S. Dalrymple, I. Dach, C. Olesen, B. Gurel, A. M. De Marzo, G. Wilding, M. A. Carducci, C. A. Dionne, J. V. Møller, P. Nissen, S. B. Christensen, J. T. Isaacs
Journal: Science Translational Medicine (2012)
Changes in VEGF-A-serum levels after DEBIRI-TACE in patients with liver metastases of chemorefractory colorectal cancer.
Authors: Stefan Pluntke, Sven Dyrda, Amena Malik, Hansjochen Wilke, Michael Stahl, Jens-Albrecht Koch
Journal: Journal of Clinical Oncology (2012)

93 Background: TACE with irinotecan-loaded drug-eluting beads has shown activity in colorectal liver metastases. Among the factors potentially interfering with its effectiveness is a hypothetical neo-angiogenic reaction due to ischemia. Methods: Patients with predominant liver metastases from CRC which were refractory to chemotherapy and documented tumor progression during or shortly after the last chemotherapy, were prospectively treated with irinotecan-loaded drug-eluting beads with a size of 100-300 µm. Therapy was applied by a temporary catheter placed in the liver arteries. Usually each lobe of the liver was according to the recommended DEBIRI treatment algorithm. Each treatment of one liver lobe was performed with 1 vial of the 100-300 µm DC-Beads loaded with 100 mg irinotecan. Blood samples to measure the VEGF serum levels were taken before TACE and at days 7, 14, and 21 after first treatment. Results: Complete blood samples were taken from 15 patients from 2/11 to 2/12. 60% of patients had an increase of the VEGF-A-Level with a median of 107 %, 40% of patients had a decrease of the VEGF-A-Level with a median of – 39% respectively. The relative decrease of the VEGF-A-Levels depends on a prior liver resection (p=0.05), and a significant decrease was found in patients with a prior bevacizumab therapy (p=0.025). A trend to an increase in VEGF-A-Levels was detected in patients with a low count of liver metastases (p=0.087). Conclusions: These findings show different behavior of the VEGF-A-levels after DEBIRI-TACE, suggesting that the occlusion of blood vessels and subsequent ischemia induces neo-angiogenesis due to these growth factors in a subset of 60% of the patients treated with a DEBIRI-TACE. We found a trend for a lower count of liver metastases, prior liver resection and a prior bevacizumab-therapy, respectively influencing the VEGF-A-Level-changes. The trend toward a decrease in patients with a prior bevacizumab therapy may be due to a neoangiogenesis-pathway other than VEGF-mediated. These first results could implicate that antiangiogenic drugs might be effective as an additive therapy to chemoembolization in a subset of patients, e.g., those with no prior bevacizumab therapy.
Correlation between patient-reported fatigue and hemoglobin (Hgb) levels in metastatic renal cell carcinoma (mRCC) patients (pts) receiving sunitinib (SU).
Authors: Mellar P. Davis, Ewa M. Matczak, Connie Chen, Beata Korytowsky, Helen Bhattacharyya, Xun Lin, Brian I. Rini
Journal: Journal of Clinical Oncology (2014)

418 Background: Low Hgb is linked with fatigue in cancer pts; however, the onset and severity of fatigue is multifactorial. The approved SU dosing schedule in mRCC is 4 weeks on treatment, 2 weeks off, and quality of life (QoL) when examined on day 28 is significantly worse than on day 1 of each cycle. The relationship between pt-reported fatigue and Hgb levels with SU in mRCC was investigated. Methods: Two randomized clinical trials of SU were combined to examine the pt-reported fatigue item from FKSI-15 which asks pts to indicate their level of fatigue on a 5-point Likert scale from 0=“not at all” to 4=“very much”. Data were collected at baseline (BL; cycle 1, day 1) and on days 28 and 42 of each 42-day cycle. For each visit, only pts who had data for both fatigue and Hgb at BL were included in the analysis. Results: 481 pts were included. Fatigue and Hgb levels at BL and over cycles 1–6 are shown in the table. Pts reported worse fatigue (higher score) at day 28 of each cycle than on day 42. Fatigue scores typically ranged from 1= “a little bit” to 2=“somewhat”. Changes in Hgb levels, however, were modest and opposite to fatigue changes i.e. were higher on day 28 of each cycle and lower on day 42. Findings were similar beyond cycle 6. Conclusions: Pts indicated less fatigue on day 42, after the 2-week break, than on day 28 of each cycle, consistent with previous overall QoL findings. Low Hgb is not associated with worse fatigue in mRCC pts receiving SU.This may be due to the multifactorial nature of fatigue. The ‘on’ and ‘off’ periods in intermittent dosing are important considerations of patients’ full experience of QoL. [Table: see text]
Docetaxel/cisplatin alternating with re-irradiation in recurrent head and neck cancer
Authors: T. Hehr, J. Classen, C. Belka, S. Welz, J. Schaefer, A. Koitschev, M. Bamberg, W. Budach
Journal: Journal of Clinical Oncology (2005)

5540 Purpose: Inoperable loco-regional recurrences of head and neck cancer in a previously irradiated volume (RH&N) represent a therapeutic dilemma. Chemotherapy alone has no curative potential, whereas re-irradiation and concurrent chemoradiation can salvage a small fraction of patients. Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy. Alternating chemoradiation enables one to give full-dose chemotherapy and radiotherapy. The latter maybe especially advantages for recurrent, potentially radiation resistant tumors. The feasibility and efficacy of an full-dose docetaxel containing alternating chemoradiation schedule was tested in two sequential trials. Patients and Methods: Thirty-nine patients (Karnofsky Performance score ≥ 70%) with histologically proven recurrent squamous cell cancer that occurred ≥ 6 months in a previously irradiated area (≥ 60 Gy) were considered unresectable and unsuitable for brachytherapy. Alternating chemoradiation consisted of three cycles of docetaxel 50 mg/m2 d1 and cisplatin 15 mg/m2 d2–5, q d22, and involved field radiotherapy 2.0 Gy QD d8–12, d15–19, d29–33, and d36–40 (patients 1 - 27 received 40.0 Gy total dose, patients 28 - 39 received 49.6 Gy total dose with concomittant boost). Dose reduction of docetaxel to 50 mg/m2 was necessary, because of hematological toxicity in the first 12 patients with docetaxel 60 mg/m2. Results: Alternating chemo-re-irradiation was applied as planned in 19 of 37 patients, with re-irradiation completed per protocol in 80%. Overall, patients received 80 % of the intended dose of docetaxel and 75% of cisplatin. Mucositis CTC °III occurred in 17%, leukopenia CTC ≥°III in 32%, and four early deaths were observed. Median follow up 18 months, median time to local progression and overall survival 10 months, respectively, 2-year survival rate 20%. Conclusions: Alternating chemo-re-irradiation in RH&N resulted in 80% overall response with acceptable toxicity. A significant minority of patients had durable tumor control with a chance of long-term survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
The effect of selective JAK2 inhibitor SAR302503 on tumorigenic STAT3 signaling in human prostate cancer in vivo.
Authors: Dayson Moreira, Sumanta Kumar Pal, Fangxian Sun, Marcin Kortylewski
Journal: Journal of Clinical Oncology (2014)

192 Background: STAT3 transcription factor is a critical mediator of signaling by IL-6, a cytokine promoting aggressive, castration-resistant prostate cancers (CPRCs). Importantly, STAT3 activation propagates from cancer cells to the tumor-associated immune cells, thereby generating immunosuppressive and proangiogenic tumor microenvironment. Janus kinase inhibitors provide an attractive method for disrupting IL-6/Jak/STAT3 signaling in both cancer and immune cells to amplify therapeutic effects. Methods: We tested the effect of selective Jak2 inhibitor, SAR302503, in xenotransplanted DU145 CPRCs and the tumor-associated myeloid immune cells in NSG mice. Results: Our initial results confirmed verified that oral gavage of 75 to 100 mg/kg SAR302503 results in dose-dependent inhibition of Jak2 phosphorylation in lysates from whole s.c. growing DU145 tumors within 18 h after treatment. Repeated daily treatment using SAR302503 (75 mg/kg) reduced phosphorylation of both Jak2 and STAT3, induced cancer cell death and significantly reduced growth of aggressive DU145 tumors. More detailed flow cytometric analysis revealed confirmed STAT3 inhibition in cancer cells and even greater extent in tumor-associated myeloid cells. SAR302503 did not reduce the total percentage of tumor-infiltrating myeloid cells. However, it promoted maturation of myeloid-derived suppressor cells. Conclusions: Our findings indicate that SAR302503 can potentially induce both direct and immune-mediated effects on castration-resistant prostate tumors. These preliminary results merit further studies in syngeneic tumor models that will assess whether Jak2/STAT3 inhibition can disrupt immunosuppressive and/or angiogenic functions of prostate cancer-associated myeloid cells. Further, these results may support clinical examination of SAR302503 either alone or in combination with other immunomodulatory therapies for metastatic CPRC.
Body mass index: A potential risk factor for breast cancer in minority patients.
Authors: V. Sharma, D. Patel, A. Abichandani, P. Saraf, A. J. Cohen
Journal: Journal of Clinical Oncology (2011)

1599 Background: Breast cancer (BC), the most common cancer among women in the United States, has many established risk factors including reproductive factors, hormone use, and obesity. Obesity has also been associated with a poorer prognosis. Serum estrogen levels are higher in obesity, and may influence the characteristics and development of BC. African-Americans (AA) have been found to have a poorer prognosis for undefined reasons. In previous studies linking obesity to BC prognosis, AA women have been under-represented. This study was undertaken to look at the association of body mass index (BMI), estrogen receptor (ER) status, and stage at diagnosis (dx) in minority patients (pts). Methods: A retrospective review of the tumor registry at an urban, tertiary care medical center identified 474 women with pathologically confirmed BC from 2005 to 2010. Clinical information at dx including race, age, family history, stage, height and weight, and menopausal status was obtained. The BMI (lb/in²) at dx was calculated and pts were categorized into four groups: obese (OB) (>30), over-weight (OW) (25-29.9), normal weight (NW) (18.5-24.9), and underweight (UW) (<18.5). Pathology was reviewed to confirm ER status. 60% (284/474) of pts had complete information and were evaluable. Results: Of the 284 pts, 71% were AA, 3% Asian, 5% Hispanic, 14% White Non-Hispanic, and 7% other. The age range was 28 to 96 years (mean 60 years). 80% of pts were post-menopausal. 41% had a family history of malignancy. Staging was as follows: 16%, DCIS, 22% stage I, 37% stage II, 18% stage III, and 7% stage IV. 70% were ER (+). 2% were UW. 20% were NW. 30% were OW. 48% were OB. Higher BMI pts were more likely to have ER (+) BC (p==0.044) (see table). There was statistically significant correlation between higher BMI and advanced stage in this cohort (p==0.050). Conclusions: The majority of BC pts in this cohort were AA and OW or OB. A higher BMI correlated with ER (+) status and advanced stage. The impact that obesity has on BC characteristics and prognosis is complicated as it is influenced by path-physiology, as well as psycho-social factors. Further studies including evaluation of weight control on BC in AA women is warranted. BMI No. of ER-positive pts No. of ER-negative pts OB 101 35 OW 59 25 NW 36 21 UW 2 5
Clinical activity of enzalutamide pre- and post-docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rosa Nadal, Zhe Zhang, Hitesh Raheja, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2014)

216 Background: Enzalutamide is an androgen receptor signaling inhibitor that is FDA-approved for post-docetaxel mCRPC patients. Overlapping mechanisms of action and clinical evidence for an interaction between taxanes and androgen-targeted therapies complicates optimal sequencing of taxanes and enzalutamide. We retrospectively evaluated the efficacy of enzalutamide pre- (preD) and post-docetaxel (postD) therapy. Methods: Men with mCRPC who received enzalutamide preD or postD were identified from a single institution database. We investigated factors influencing enzalutamide activity by using univariate and multivariable Cox regression models, with particular attention to whether or not prior docetaxel had been used. Outcome measures of interest were time-to-PSA-progression (TTPP) and progression-free-survival (PFS). Results: A total of 72 patients received enzalutamide at our institution: 22 were preD and 50 were postD. Median duration of enzalutamide therapy was 5.5 mo (range, 0.7–33.6 mo). In univariate Cox regression analysis, the following factors were predictive of TTPP: ECOG status (≥1 vs 0), number of metastases (&gt;5 vs 0-5), hemoglobin and albumin. Prior docetaxel treatment was associated with a trend towards shorter TTPP on enzalutamide (HR 0.54, 95%CI 0.27–1.10, P=0.09). The following factors were predictive of PFS in univariate analysis: ECOG status, number of metastases, hemoglobin and albumin. Prior docetaxel therapy was associated with a trend towards shorter PFS on enzalutamide (HR 0.57, 95%CI 0.29–1.13, P=0.10). Conclusions: These data suggest numerically inferior TTPP and PFS outcomes to enzalutamide in men previously treated with docetaxel compared to men who were docetaxel-naïve, although the small sample size precludes statistically significant results. This potentially supports the hypothesis of cross-resistance between enzalutamide and docetaxel.
Can molecular markers help predict outcome in pseudomyxoma peritonei?
Authors: M. S. Beg, J. Wang, S. A. Ahmad, X. Wang, O. O. Olowokure
Journal: Journal of Clinical Oncology (2011)

455 Background: Pseudomyxoma peritonei (PMP) is a rare malignancy characterized by mucinous ascites and peritoneal tumors. Cytoreductive surgery (CRS) with or without intraperitoneal hyperthermic perfusion (IPHP) is considered the mainstay of therapy, but prognosis is variable. Due to its rarity, data on molecular phenotype is lacking and the impact on outcome is unknown. The goal of our study is to correlate molecular markers with outcome in PMP. Methods: A retrospective analysis of cases treated at the University of Cincinnati was performed and tumors analyzed. Medical records were reviewed for clinical, demographic and outcome data. Immunohistochemical studies were performed on formalin fixed paraffin embedded tissue using antibodies to Ki-67, cyclin D, and EGFR. Tumor cells were microdissected from H&amp;E stained sections using laser capture microdissection and DNA was extracted. Exon 1 of K-ras gene was amplified by PCR and then directly sequenced. Data were analyzed using SPSS. Results: Of 22 patients (pts) included in this study 16 (73%) had an appendix primary and 6 (27%) colon. There were 12 females (55%) and 20 (90%) pts were white. Mean age was 53 (29-74) years. Most pts had prior surgery (18, 82%). Complete resection (&gt;99% of visible disease) was achieved in 15 (68%) pts while 17 pts (77%) underwent IPHP. Nine pts had known recurrence (41%) and median time to recurrence (TTR) was 21(+/- 0.398) months (mo). There was one confirmed death and median survival could not be calculated. K-ras mutation was seen in 13 (60%), cyclin-D1 in 9 (41%) and EGFR in 10 (45%) cases. High Ki-67 (&gt;51%) was seen in 8 cases. On univariate analysis median TTR was 15 and 43 mo for pts with high and low Ki-67 (p=0.1); 21 and 43 mo for K-ras positive and negative mutation (p=0.16), 43 and 15 mo for EGFR positive and negative tumors (p=0.6). TTR was 21 mo for cyclin D1 positive as well as negative. Conclusions: Pts with PMP who have undergone CRS and IPHP can have prolonged survival but relapses are common. Our study highlights the possible role of molecular markers such as EGFR and K-ras in tumorigenesis. A potential role in prognosis is being validated in a larger study. Future treatment strategies should incorporate molecular testing to enhance our understanding of PMP. No significant financial relationships to disclose.
Postchemotherapy retroperitoneal lymph node dissection for advanced germ cell tumors at a Japanese single high-volume center.
Authors: Terukazu Nakamura, Yasunori Kimura, Takashi Ueda, Yoshio Naya, Fumiya Hongo, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2013)

331 Background: Post chemotherapy lymph node dissection (PCRPLND) plays important role in the management of advanced germ cell tumors (GCTs). Guidelines recommend performing PCRPLND for advanced GCT with tumor marker normalization. The aim of this study is to assess efficacy and preserve antegrade ejaculation at Japanese single high volume center. Methods: One hundred and eleven patients who had PCRPLND at Kyoto Prefectural University of Medicine between June 1998 and August 2011 were studied. Five cases of desperation RPLND and 6 cases of laparoscopic RPLND were also included. Results: Median age was 30 years old (17-68y.o.). Seminoma was 11 cases and nonseminoma was 100 cases at primary site. Good, intermediate and poor prognosis group of International Germ Cell Cancer classification was 48, 35 and 20 cases, respectively. Seventy-four cases were treated after induction chemotherapy and 41 cases were done after salvage chemotherapy. median operation time was 590 min. and median blood loss was 1650ml. Nerve-sparing procedure were performed for 90 cases. Antegrade ejaculation was preserved in 83.5% of this cohort. Especially, antegrade ejaculation was preserved in 93.3% of the patients with bilateral nerve sparing. Necrosi/fibrosis, teratoma only and viable cancer were detected in 54.4%, 32.5% and 13.1%, respectively. Additional procedure such as nephrectomy was performed in 12 cases. Five-year overall survival was 95.1%. In the desperation group, only one case is alive without disease. Conclusions: The results of PCRPLND at high volume center could be satisfied and preservation of antegrade ejaculation could be obtained. On the other hand, indication of desperation RPLND had to be carefully considered.
The Zebrafish Provides Mechanistic Insights into the Role of Poly(A)-Specific Ribonuclease (PARN) in Hematopoietic Stem Cell (HSC) Homeostasis and Bone Marrow Failure
Authors: Adam P Deveau, Andrew J Coombs, Santhosh Dhanraj, Gretchen Wagner, Yigal Dror, Jason N. Berman
Journal: Blood (2015)