tbuckley/cabot-search huggingface dataset:
Driving improvement in oncofertility.
Authors: Shelby Darland, Jennifer N. Eichmeyer, Kelli Christiaens, Kallie Penchansky, Michele Betts, Dan Sayam Zuckerman, Thomas M. Beck
Journal: Journal of Clinical Oncology (2013)

183 Background: In 2006 the American Society of Clinical Oncology (ASCO) recommended that oncologists discuss infertility as a result of cancer treatment with patients of reproductive age and provide referrals to specialists as needed. Despite these guidelines the majority of cancer centers are not in compliance. Mountain States Tumor Institute (MSTI) piloted a process to improve quality of oncofertility preservation (OP) through identification, documentation, and referral to reproductive specialists. Methods: A physician survey in 2010 indicated that perceived barriers to OP discussion were a lack of accessible materials as well as oversight on the part of the provider. Random chart audits of the Quality Oncology Practice Initiative (QOPI) measures (infertility risks discussed prior to treatment and fertility preservation options discussed/referral to a specialist) occurred biannually at that time. To increase awareness of the data chart audits and reporting shifted to quarterly and included all patients that met OP criteria. Additionally, a committee was formed in 2011 to develop patient/provider packets, collaborate with the local reproductive specialists, and create an OP process. The committee established an OP algorithm involving support staff to flag patients of reproductive age at initial medical oncology consultation and utilizing genetic counselors (GC) and social workers (SW) to expedite and facilitate referrals to reproductive specialists. GC/SW were chosen due to sensitivity with psychosocial issues and to share the additional workload. The OP program was launched in October of 2012. Results: Baseline assessment in 2009 revealed MSTI was compliant 6% and 6%. Six months after program initiation the OP measures improved to 47% and 45% respectively. Notably March and April 2013 showed dramatic improvements with 100% and 75% compliance for both OP measures. Conclusions: It is well known that OP has been a challenge for many cancer centers. This multipronged approach is an example of a novel process implementation that demonstrated significant improvement with the QOPI oncofertility measures. Continued work is needed on improving physician documentation and consistency of OP patient identification.
The prostaglandine E2 transporting organic anion transporting polypeptide OATP4A1: A potential prognostic marker in colorectal cancer?
Authors: Veronika Buxhofer-Ausch, Christoph A. Ausch, Heike Bauer, Marina Mollik, Aida Larijani, Erika Bajna, Martin Svoboda, Enikoe Kallay, Angelika Reiner, Stephan Kriwanek, Christian Sebesta, Gerhard Hamilton, Robert Zeillinger, Theresia Thalhammer
Journal: Journal of Clinical Oncology (2013)

430 Background: Organic anions transporters (OATPs) are important for tumor progression and therapeutic response by regulating cellular levels of hormones, second messenger proteins and drugs. OATP4A1 is a transporter of pro-inflammatory prostaglandin E2 and may contribute to cancer progression. Data on the expression of OATP4A1 and its clinical impact in primary colorectal cancer (CRC) is rare. Our study was designed to proof the overexpression of OATP4A1 in primary CRC. Methods: Frozen samples from 20 unselected CRC patients (pat) and five CRC cell lines were analyzed for OATP4A1 mRNA expression by real time PCR (mean level normalized to the calibrator, MNE). Immunohistochemistry was performed on paraffin- embedded tumor sections from 50 CRC pat., UICC 0-II (25/50 with subsequent relapse). An automatic quantitative image analysis program was applied to quantify OATP4A1 expression. Expression and intensity was correlated with clinical parameters and relapses. Results: Significant (p&gt;0.05) higher levels of OATP4A1 mRNA were observed in 20 cancer samples as compared to adjacent non-cancerous tissue (2.44 vs. 0.46 MNE). The highest expression (9.85 MNE) was observed in a well-differentiated tumor sample. Similar high levels were observed in the COGA1A cell line, expression in the other cell lines ranged between 1.83 and 0.28 MNE. Immunoreactive staining for OATP4A1 was located in the membrane and occasionally in the cytosol of tumor cells, it was exclusively membrane located in the adjacent non-cancerous epithelial cells. The staining intensity was significantly higher in cancer cells compared to non-cancerous areas (1528±326 vs.376±218) while staining of stroma cells was only occasionally detectable. Surprisingly, the highest OATP4A1 levels were observed in immune cells (2839±381 vs.298±56). Data on the clinical impact of OATP4A1 in the early stage CRC pat. will be presented at the meeting. Conclusions: The profound expression of OATP4A1 in CRC cells and in the inflammatory infiltrates supports its implication on cancer progression. Suitability of OATP4A1 as a potential prognostic marker has to be established on a larger patient collective.
Immunohistochemical evaluation of aldose reductase expression in collecting duct carcinoma for differential diagnosis from other renal malignancy.
Authors: Yasuhiro Hashimoto, Hayato Yamamoto, Akiko Okamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Takuya Koie, Chikara Ohyama, Hiromitsu Mimata
Journal: Journal of Clinical Oncology (2014)

483 Background: Collecting duct carcinoma (CDC) is a rare tumor but its recognition is important for the prediction of prognosis and decision making of the treatment. However, its diagnosis is challenging because of versatility of pathological features. We explored the possibility whether aldose reductase (AR), osmoregulatory protein and abundant in renal medulla, can be used as a marker for the pathologic diagnosis of CDC. Methods: We prepared anti-AR monoclonal antibodies, examined expression of AR protein in the human normal kidney. Immunohistochemical expressions of AR, 34bE12, a-methyl CoA racemase (AMACR) and expressions of lectins (Ulex europaeus agglutinin 1; UEA-1 and peanut agglutinin; PNA) were examined on normal kidney, 12 cases of CDC, 10 cases of papillary renal cell carcinoma (pRCC), and 10 cases of invasive urothelial carcinoma (iUC). Results: AR expression distributed preferentially in the renal medulla and not in the cortex, reflected by its high concentration in medulla (2.12 ±1.35 μg/mg) compared with cortex (0.13 ± 0.03 μg/mg). Immunohistochemically, AR was strongly positive in 9 of 12 CDC cases. AR was negative in cases of either iUC or pRCC. In contrast, although lectins were positive in all cases of CDC, they were also found in all types of malignancy. iUC was positive for 34bE12 in all cases but also so in some cases of CDC and pRCC. AMACR was positive for all the cases of pRCC but also positive for other tumors. Conclusions: Compared with other markers, AR may be a more specific and potentially useful marker for CDC. [Table: see text]
Laparoscopic intraoperative sentinel lymph node detection by technetium-99 hysteroscopically injected in endometrial cancer patients.
Authors: G. Favero
Journal: Journal of Clinical Oncology (2011)

5104 Background: Systematic lymphadenectomy in old, obese, and/or polymorbid patients with endometrial cancer is a challenging procedure. Sentinel lymph node (SN) biopsy can potentially reduce morbidity not jeopardizing oncologic safety. The goals of this prospective study are to determine the feasibility and accuracy of sentinel lymph node biopsy, in endometrial cancer patients, following hysteroscopic Technetium-99 (Tc-99) injection. Methods: From January 2008 till December 2009, 30 women with endometrial cancer were consecutively included into the study. We injected 20 mBq Tc-99 hysteroscopically beneath the tumor, at the beginning of surgery SN biopsy, pelvic, and paraaortic lymphadenectomy, laparoscopic-assisted hysterectomy and bilateral salpingo-oophorectomy were carried out through laparoscopy in 26 patients, or by laparotomy in 4 patients. Results: We detected SN in 25 women (82%). The total number of removed lymph nodes was 821, including 59 SN and among them, 35% (20) were located in the paraaortic level. Thirteen patients (52%) had SN only in the pelvic region, while nine patients (36%) had SN in both pelvic and paraaortic areas, and 3 patients (12%) had SN isolated at the paraaortic level. Nodal metastases were histologically confirmed in six patients (20%), and SN was identified in all these patients however being false negative in 2 out of 6 patients (33%) with a sensitivity of 67% (4 out of 6). Conclusions: We could demonstrate the feasibility and the safety of the intraoperative lymphatic mapping and SN biopsy using hysteroscopy for Tc-99 injection. The observed sensitivity was lower than expected, compromising its routine clinical use and the technique must be improved.
Association of time to adjuvant chemotherapy (TTAC) and overall survival among patients with rectal cancer treated with preoperative radiation.
Authors: Gillian Gresham, Caroline Speers, Ryan Woods, Winson Y. Cheung, Kimberly Schaff, Mayo Fung, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2013)

461 Background: Studies suggest that delayed adjuvant chemotherapy (AC) beyond 8 weeks is associated with inferior survival in early-stage colon cancer (CA). The optimal TTAC in rectal CA remains unclear. The objective of this study was to determine the prognostic effect of TTAC in stage II and III rectal CA treated with standard preoperative (op) chemoradiation. Methods: Patients with stage II/III rectal CA treated with pre-op chemoradiation, received post-op AC, and referred to the British Columbia Cancer Agency between 1999 and 2008 were included. Univariate and multivariate analyses were conducted using Kaplan Meier and Cox regression methods to evaluate the association between TTAC and outcomes. X-tiles cut-point analysis was performed to determine the optimal TTAC. Results: A total of 327 eligible patients were identified: median age 61 (range 22-85), 70% male, and 75% stage III. In terms post-op AC, 51% received 5-fluorouracil (5-FU), 32% received capecitabine, 12% received 5-FU and oxaliplatin, and 5% received other chemotherapy. Median TTAC was 7.0 weeks (wks) (range 1.6-33.3 wks). Cut-point analysis revealed the optimal TTAC to be 5.6 wks (HR: 0.42, 95%CI 0.22-0.82, p=0.0087). Initiation of AC within optimal TTAC (5.6 wks) and 6 wks from date of surgery (sx) was associated with a significant survival benefit while no significant effect was seen at 8 wks. TTAC of ≤ 6 wkswas found to be a significant prognostic factor in multivariate analysis (p=0.047) adjusted for ECOG, age, sex, stage, margin status, and grade. In stratified analysis by stage, patients with stage III disease benefited from AC (p=0.018) while those with stage II did not (p=0.71). Conclusions: In this study, the optimal TTAC was 6 weeks or less. Initiation of AC within this time frame was associated with improved OS. This is less than the optimal timeframe indicated in the literature for colon CA. [Table: see text]
Updated Results of a Phase I/II Trial of Autologous Peripheral Blood Progenitor Cell Transplantation with Velcade™ Maintenance as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma
Authors: Mickey Liao, R Malone, K Bartoni, B Habtemariam, Ronald Paquette, Sven de Vos, Mary C Territo, Gary Schiller
Journal: Blood (2008)
Use of iPad technology to determine cancer patient-reported preferences for and understanding of pharmacogenetic testing (PGT).
Authors: Petra Martin, Catherine Brown, Sinead Cuffe, Dan Pringle, Mary Mahler, Jodie Villeneuve, Chongya Niu, Rebecca Charow, Christine Lam, Ravi M. Shani, Henrique Hon, Memori Otsuka, Osvaldo Epsin-Garcia, Wei Xu, Shabbir Alibbhai, Jodie Jenkinson, Geoffrey Liu
Journal: Journal of Clinical Oncology (2012)

319 Background: PGT in oncology can be used to predict the efficacy and toxicity of a particular treatment in an individual. Previous work by our group has demonstrated that among cancer patients willing to undergo chemotherapy, &gt;98% wanted PGT testing if it could identify patients who would respond to chemo. However, in the original study using a paper questionnaire, 22% of patients did not understand the concept of PGT and its clinical implications. Therefore, we have devised a simpler, more visual questionnaire in electronic format using iPad technology and simple animations. We are assessing if patient understanding using this format is increased and also if patients prefer completing the survey with this novel technology. Methods: An interim analysis of a broad cross-section of cancer patients using an iPad was performed. PGT questions related to hypothetical efficacy, toxicity, time to test results, willingness to pay as well as understanding of PGT scenarios were assessed. Results: 135 cancer patients (87% adjuvant, 12% metastatic; 27% breast, 25% colon, 22% heme malignancy, 23% other) attending Princess Margaret Hosptial participated. 85% of patients accepted chemo that had a 5% absolute improvement in survival and &lt;10% chance of side effects. 94% of patients chose to have PGT if it could identify subsets of patients who would benefit from chemo. The median that patients were willing to pay for PGT was $250 (range $0-$5,000), however the median that patients felt was a reasonable price was $100 ($0-$5,000). 11% of patients admitted that they did not understand the concept of PGT and its clinical implications. Conclusions: Almost all patients who were willing to undergo chemo were also willing to accept PGT. Fewer patients in this study compared with our original paper directed questionnaire described themselves as lacking an understanding of PGT (11% versus 22% respectively), suggesting that survey administration on an iPad with a visual characterization of question scenarios improved understanding. Final data from over 300 patients will be analyzed in the fall, which would include data on patient attitudes on use of such technology for communication and decision making.
Effects of pretreatment, pharmacologic factors, and yoga intervention on CINV outcomes in breast cancer
Authors: R. M. Raghavendra, B. S. Ajaikumar, S. Patil, D. B. Ravi, R. N. Niti, K. S. Gopinath, S. B. Srinath
Journal: Journal of Clinical Oncology (2008)

9599 Background: Several factors can confound the benefits of yoga intervention on Chemotherapy Induced Nausea and Vomiting (CINV) outcomes in breast cancer patients receiving moderately emetogenic chemotherapy. We have shown earlier that this yoga program was useful in reducing CINV in patients receiving moderately emetogenic chemotherapy. This study evaluated the effect of yoga intervention on CINV outcomes controlling for both non pharmacological and pharmacological confounders. Methods: Sixty-two subjects were randomly allocated to receive yoga (n=28) or control (supportive therapy intervention) (n=34) during the course of their chemotherapy. Both the groups had similar socio demographic and medical characteristics. During the course of their chemotherapy, intervention consisted of supervised and home practice of yoga sessions lasting for 60 minutes daily while the control group was imparted supportive therapy and coping preparation sessions. Primary outcome measure was Morrow Assessment of Nausea and Emesis (MANE) assessed after 4th cycle of chemotherapy. We used multiple hierarchical regression models to test the contribution of pre-treatment non pharmacological factors, pharmacological factors and intervention on CINV outcomes. Results: Pretreatment non pharmacological factors (lower age, menopausal status) and pharmacological factors (anxiolytic administration) are important predictors for determining CINV outcomes. However, yoga intervention significantly predicted much of the variance for post chemotherapy nausea frequency (13.4%), intensity (17.7%) and anticipatory nausea intensity (13.7%) when controlled for these correlates. Conclusions: The results suggest a possible use for yoga intervention with conventional antiemetics in managing chemotherapy related nausea. No significant financial relationships to disclose.
Association of bevacizumab-free interval with efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer.
Authors: Azusa Komori, Hiroya Taniguchi, Yukiya Narita, Shiori Uegaki, Sohhei Nitta, Kazuhisa Yamaguchi, Motoo Nomura, Shigenori Kadowaki, Daisuke Takahari, Takashi Ura, Masashi Andoh, Kei Muro
Journal: Journal of Clinical Oncology (2014)

610 Background: Both bevacizumab (Bev) and anti-EGFR agents are sequentially used for metastatic colorectal cancer (mCRC). Some basic studies reported the interaction between Bev and anti-EGFR agents in vivo. Therefore we hypothesized the shorter Bev-free interval may lead to poor outcome of anti-EGFR therapy. The aim of this study is to examine the association of the interval between last Bev administration and initial anti-EGFR agents with efficacy of anti-EGFR therapy. Methods: We retrospectively reviewed consecutive mCRC patients who underwent combination therapy of anti-EGFR agents and irinotecan after failure of fluoropyrimidines, oxaliplatin, irinotecan, and Bev at a single institution. We divided patients in two groups (group A: the interval between Bev and anti-EGFR agents &lt;6M, group B: ≥6M). Results: A total of 114 patients constituted the cohort of analysis. The median age was 63; 78 (68%) patients were male. Most patients (N=100, 88%) were treated with cetuximab, and 14 patients were panitumumab. Seventy-four patients were group A and 40 patients group B, respectively. There was no significant difference in patient characteristics. Response rate was 24.7% in group A, and 50.0% in group B (p=0.0072). The patients in group B have significantly longer progression free survival (4.2 vs. 6.6 M, HR 0.65, 95% CI 0.43- 0.98, p=0.042) and longer overall survival (11.6 vs. 14.3 M, HR 0.62, 95% CI 0.39- 0.97, p=0.038). Conclusions: The short interval (&lt;6M) between last Bev and anti-EGFR agents may interfere with the efficacy of anti-EGFR therapy.
Various clinical outcomes in patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma undergoing trimodality therapy: Prognostic implications.
Authors: Akihiro Suzuki, Lianchun Xiao, Takashi Taketa, Kazuki Sudo, Mariela A. Blum, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Wayne Lewis Hofstetter, Stephen Swisher, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

e15053 Background: Preoperative chemoradiation (trimodality therapy) has the strongest evidence in trimodality-eligible patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma. Pathological complete response (pathCR) and clinical complete response (clinCR) are independent prognostic factors. We hypothesized that pathCR is associated with best prognosis. Methods: Patients with E-GEJ adenocarcinoma undergoing trimodality therapy were identified from the prospectively maintained database at our institution. The Log rank test, univariate and multivariate Cox proportional hazards regression analysis were applied for the survival analysis. Variables with p value &lt; 0.15 in the univariate analysis were included in the multivariate analysis, the backward selection procedure was used for the model selection. Variables with P value &lt; 0.05 were considered statistically significant. Results: For 314 esophageal cancer patients, the median follow-up time was 44.0 months (95% CI; 34.2-50.9). 107 of 314 patients died at this analysis. 80 patients (25.5%) had a pathCR. 160 patients (51.0%) had a clinCR prior to surgery but did not have pathCR. The remaining 74 (23.6%) had &lt;pathCR and &lt;clinCR. Median OS were: not achieved in pathCR patients, 82.8 months (95% CI; 63.9, NA) in clinCR patients and 27. 6 months (95% CI; 19.4, NA) &lt;pathCR/&lt;clinCR (p&lt;0.001). The median recurrence-free survival (RFS) were: 79.6 months (95% CI; 37.4, NA) in pathCR patients, 67.4 months (95% CI; 31.8, NA) in clinCR patients and 13.5 months (95% CI; 10.4, 21.4) in &lt;pathCR/&lt;clinCR (p&lt;0.001). In multivariate analysis, no lymph node metastasis (p&lt;0.001), not poorly differentiated adenocarcinoma (p=0.002) and pathCR (p=0.02), and cCR (p&lt;0.001) were independent prognosticators of OS and RFS. Conclusions: pathCR and clinCR are associated with a better survival ourtcome compared to patients without pathCR/clinCRand may be helpful in devising new therapeutic and surveillance strategies.
No Risk of Arterial or Venous Thrombosis in Monoclonal Gammopathy of Undetermined Significance: Results from a Population-Based Study
Authors: Ebba K Lindqvist, Sigrún H. Lund, Rene Costello, Debra Burton, Neha S Korde, Sham Mailankody, Vilmundur Gudnason, Gudny Eiriksdottir, Leonore Launer, Tamara B Harris, Malin Hultcrantz, Ola Landgren, Sigurdur Y Kristinsson, Magnus Bjorkholm
Journal: Blood (2015)
Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01).
Authors: Andrea Necchi, Daniele Raggi, Patrizia Giannatempo, Giuseppina Calareso, Elena Togliardi, Nicola Nicolai, Flavio Crippa, Luigi Mariani, Roberto Salvioni
Journal: Journal of Clinical Oncology (2016)

481 Background: Therapeutic options for pts with chemoresistant GCT are limited and prognosis is poor. Pazopanib (PZP) is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: Pazotest-01 enrolled pts who were given PZP 800 mg/day orally until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based regimens, including high-dose chemotherapy (HDCT). Baseline serum tumor markers (STM), a computed tomography and a FDG-PET were repeated after 4 wks of PZP and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-month PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, an increase in tumour size, or the appearance of new lesions. An enrolment of 43 pts was planned from a single center (NCT01743482). Results: From 05/2013 to 07/2015, 32 pts were enrolled (27 [84.4%] with nonseminoma, including 5 [15.6%] with malignant transformation, and 5 seminomas). 5 (15.6%) had primary mediastinal nonseminoma (PMNSGCT). 3 had failed two prior regimens, 15 (46.9%) three, and 14 (43.7%) &gt; 3 regimens, including HDCT in 15 (46.9%). 20 (62.5%) had liver, bone, or brain metastases. 29 pts had elevated STM: 18 of them (62.1%) had a STM decline (mean: -53.5%). 1 PR, 19 SD (64.5% clinical benefit) and 12 PD were obtained according to RECIST v1.1. 8 pts (25%) had a densitometric and 10 (29%) a metabolic partial response. The kinetics of response was predictable in all pts: best response was seen within 4wks of starting PZP, neither PR nor STM decline occurred &gt; 4wks. Median follow up was 15.7 months. Median PFS was 2.73 months, 3-month PFS was 28% (95%CI: 13.3-44.8). 4 pts (12.5%) were progression-free at &gt; 5 months FUP (including 1 PMNSGCT). Median OS was 4.9 months. 4 cases (12.5%) of G3 AST/ALT increase, and 1 case of G3 diarrhea and vomiting each have been observed. 7 pts (21.9%) had G2 asthenia. Conclusions: PZP is endowed with potent anti-tumor activity in extensively pretreated patients with GCT. PZP was well tolerated, and the combination with paclitaxel is a rational next step to improve the response duration. The primary endpoint is pending confirmation in the full sample-size, and mature results will be presented. Clinical trial information: NCT01743482.