tbuckley/cabot-search huggingface dataset:
Identification of novel upregulated microRNAs in the pathogenesis of gastric cancer by the use of open access databases and bioinformatics tools.
Authors: Ignacio Alberto Wichmann, Rocio Artigas, Alejandra Alarcon, Wilda Olivares, Nicole Roldan, Jacqueline Fry, Paulina Cerda, Alejandro Corvalan
Journal: Journal of Clinical Oncology (2015)

15 Background: Gastric cancer (GC) is the third leading cause of cancer death worldwide. Chronic infection by H.pylori and EBV is related to the multistep cascade of GC. This cascade hypothesizes that a specific sequence of lesions leads to GC. Epigenetic processes, such as DNA methylation or miRNAs, are new players in the pathogenesis of GC. We aim to identify novel upregulated microRNAs associated with the multistep cascade through the use of open access databases and bioinformatics tools. Methods: We selected 3 GEO DataSets with human miRNA expression levels in paired tumor and non-tumor samples from gastric cancer patients. The largest library, GSE 23739 (40 matched T/N samples) was used as a "discovery dataset”. Only miRNAs upregulated &gt;1.2 fold T over N were considered. Upregulated miRNAs were further validated in two independent datasets: i) GSE28700 (22 fresh-frozen paired T and N samples) and ii) GSE54397 (16 formalin-fixed T and N samples) and confirmed with TCGA Stomach Adenocarcinoma (STAD) data (doi:10.1038/nature13480). Finally, upregulated miRNAs were analyzed by Diana Tools miRPath, for associated oncogenic pathways and target genes. Results: From the discovery dataset GSE 23739 we identified 231 upregulated miRNAs between 40 matched T/N samples. Only 12 of these candidates were found in both validation datasets GSE28700 and GSE54397. Only three of these miRNAs were undescribed in GC: miRNAs-505, -552 and -592. TCGA STAD data confirmed our results. Analysis in miRPath revealed association with three oncogenic pathways PI3K-AKT, TGFβ and Erbβ; as well as genes relevant in oncogenesis: MAP2K1, RPS6KB1, TGFA, SMAD3, IGF1, LAMC1, IFNAR1, ITGB6, PIK3CA, PPP2R2D, EIF4E, BRCA1, FOXO3 and CREB3L3. Conclusions: The use of open access databases and bioinformatics tools enabled us to identify three novel upregulated microRNAs with oncogenic potential in GC. The analysis of these miRNAs revealed associated oncogenic pathways and target genes. These findings need to be further inquired in an experimental manner in order to assess the potential role of these miRNAs in the multistep cascade of GC.
Adherence to guidelines for adjuvant chemotherapy (AC) use in stage II colon cancer (CC).
Authors: Winson Y. Cheung, Howard John Lim, Daniel John Renouf, Ryan Woods, Caroline Speers
Journal: Journal of Clinical Oncology (2012)

169 Background: Treatment guidelines suggest that AC may be considered inpatients (pts) with "high risk" stage II CC, defined by the presence of &gt;/=1 poor prognostic features, such as obstruction or perforation, T4 stage, &lt;12 lymph nodes retrieved, positive resection margins, and lymphovascular or perineural invasion. However, survival benefits associated with AC use in high risk pts remain largely unproven. Therefore, current recommendations are primarily driven by consensus rather than by evidence. Our aims were to examine population-based concordance with current guidelines for AC use in stage II CC and to explore the relationship between AC use and survival in high- vs. low-risk pts. Methods: All pts diagnosed with stage II CC in British Columbia from 1999 to 2008 and evaluated at 1 of 5 regional cancer centers were reviewed. Kaplan-Meier and Cox regression methods were used to correlate high- vs. low-risk status as well as receipt of AC with relapse-free (RFS), disease specific (DSS), and overall survival (OS). Results: We identified 1,697 stage II CC pts: 1,236 (73%) high risk and 461 (27%) low risk among whom only 363 (29%) and 61 (13%) received AC, respectively. Individuals with high risk features who received guideline-concordant AC were younger (median 62 vs. 72 years, p&lt;0.001) and had better performance status (ECOG 0/1 47% vs. 34%, p=0.02). In the high-risk group, AC was associated with improved 5-year OS, but not with RFS or DSS. After adjusting for confounders, an OS advantage from AC persisted for high-risk pts (HR 0.67, 95 CI 0.52-0.86, p=0.002), but no significant RFS or DSS benefits were seen (HR 0.76, 95 CI 0.58-0.99, p=0.05 and HR 0.75, 95 CI 0.55-1.02, p=0.11, respectively). Subgroup analyses showed that only individuals with T4 lesions had improved RFS (HR 0.63, 95 CI 0.42-0.95, p=0.03), DSS (HR 0.59, 95 CI 0.37-0.93, p=0.02), and OS (HR 0.50, 95 CI 0.33-0.77, p=0.002). Conclusions: In this population-based cohort of stage II CC patients, less than one-third of high risk patients received guideline-concordant AC. Consistent survival benefits were only seen in those with T4 lesions, suggesting a very limited role for AC. Guidelines that are mainly consensus-driven and associated with minimal survival benefits have poor uptake.
Association of hospital readmission following cystectomy with omission of postoperative chemotherapy in patients with urothelial carcinoma of the bladder.
Authors: Marc C. Smaldone, Robert G. Uzzo, Alexander Kutikov, Elizabeth Handorf, Yu-Ning Wong, Katrina Armstrong, Justin E. Bekelman
Journal: Journal of Clinical Oncology (2013)

254 Background: Hypothesizing that complications after radical cystectomy requiring hospital re-admission may preclude subsequent systemic treatment, our objective was to test the association between readmission within 30 days of surgery and receipt of post-operative chemotherapy in Medicare beneficiaries. Methods: Using 1995-2007 linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, all patients undergoing cystectomy for pathologic stage III-IV urothelial carcinoma were identified. Univariate and multivariate logistic regression analyses were used to test the association between hospital readmission within 30 days and receipt of post-operative chemotherapy (defined ≤9 months from surgery) adjusting for demographic, clinical, hospital, and procedural characteristics. Results: We identified 4,034 patients undergoing radical cystectomy for urothelial carcinoma, of which 1,498 met final inclusion criteria (mean age 75.9±6.3 years, 62.7% male). 563 patients (37.6%) were readmitted within 30 days of surgery (7.5% with ≥2 readmissions). Postoperative chemotherapy was administered in 26.1% of candidates who were readmitted, compared to 35.4% who were not readmitted following surgery (p&lt;0.001). Following adjustment, the odds of receiving chemotherapy were 30% less in patients readmitted to the hospital (OR 0.70 [CI 0.53-0.92]) when compared to patients who were not readmitted. Stratified by number of readmissions, the odds of receiving chemotherapy in patients with 1 and ≥2 readmissions were 26% (OR 0.74 [CI 0.56-0.99]) and 54% (OR 0.46 [CI 0.27-0.79]) less when compared to patients not readmitted. Use of a more restrictive 6 month post operative chemotherapy definition did not significantly impact our findings (OR 0.66 [CI 0.47-0.93]). Conclusions: In a cohort of Medicare beneficiaries undergoing cystectomy, hospital readmission within 30 days is associated with omission of post-operative chemotherapy in patients with Stage III-IV urothelial carcinoma. These data inform treatment planning decisions and strengthen the argument supporting chemotherapy utilization in the neoadjuvant setting.
Does the number of surgical excisions before delivering intraoperative radiotherapy (IORT) affect skin toxicity?
Authors: Charlotte Dai Kubicky, Cory Donovan, Brian S. Diggs, Arpana Naik, Carol Marquez, Susha Pillai, John T. Vetto, Rodney F. Pommier
Journal: Journal of Clinical Oncology (2013)

72 Background: The TARGIT-A trial allowed administration of IORT both pre- and post-pathology. The advantage of post-pathology is the ability to determine eligibility based on margins, pathologic tumor size and nodal status, prior to delivering radiation. However, it is unclear whether having more than one operation before IORT is associated with worse skin toxicity. In this study, we aimed to examine the relationship of the number of operations and skin toxicities in women receiving IORT. Methods: We conducted a retrospective analysis of 57 consecutive patients who underwent IORT from 2009-2013. All patients received 20 Gy in 1 fraction prescribed to the applicator surface using the Carl Zeiss Intrabeam System. Skin toxicities were determined using CTCAE 4.0 and RTOG criteria. In addition, infection, skin erythema, desquamation, symptomatic seroma, and necrosis were scored individually and used as outcome measures. Pearson’s Chi-squared test was used to assess the association of the number of operations and skin toxicities. A multivariate analysis was performed and included age, applicator size, max skin dose, number of operations, DM, HTN, BMI, co-morbidity, and depth from skin on mammogram as variables. Results: The median follow-up was 11 months (range 1-33). The median age and applicator size were 68 yrs (range 49-85) and 4 cm (range 2.5-5). 20 (35%) patients had 1 operation (lumpectomy, SLNB and Intrabeam all in 1 setting). 36 (63%) patients had 2 operations (initial surgery, followed by Intrabeam +/- margin re-excision). One (2%) patient had 3 operations (initial surgery, re-excision, followed by Intrabeam). On univariate analysis, the number of operations was associated with increased infection (p = 0.044), but not other skin toxicities. On multivariate analysis, the association was no longer significant (p = 0.97). Conclusions: Our study suggests that delivering IORT post-pathology was not associated with worse acute or late skin complications. Delivering IORT after the initial operation decreases the uncertainty of margin status and avoids the controversy of excising an irradiated positive margin and/or the need for additional whole breast radiation.
Differences between taxanes in time on therapy and associated discontinuation events in metastatic breast cancer: Results from a U.S. claims analysis.
Authors: Rex W. Force, Brooke A. Pugmire, Gary Binder, Cindy Duval, Deya Corzo, Stefan Gluck
Journal: Journal of Clinical Oncology (2013)

158 Background: Taxanes in metastatic breast cancer (mBC) have demonstrated clinical benefits but have different toxicity profiles. This study evaluated differences in time to discontinuation (D/C) between taxanes overall and by specific events associated with D/C (i.e., death, adverse events (AE), subsequent therapy). Methods: Women receiving &gt;1 dose of either paclitaxel (P), docetaxel (D), or nab-paclitaxel (nab-P) between 2006-2009 were identified by ICD-9 codes indicative of mBC from a commercial payer claims database. Logistic regression and Cox-proportional hazards models were used to compare rates of D/C and time to D/C, respectively. Control variables were age, use of prior or concurrent chemo, and comorbidity score. Drug D/C was defined as no taxane administration for 35 days. AE within 35-days after D/C were considered taxane-associated. Death or disenrollment from the insurance plan within 90 days and initiation of subsequent therapy within 60 days after D/C were considered temporally associated with D/C. Results: 4,503 pts with mBC were included (2,599 received D; 1,643 received P, and 261 received nab-P). The most common reason for D/C in all pts was AEs (37.8%), initiation of subsequent therapy (34.4%), and death or disenrollment (8.4%). A higher proportion of pts on D (29.4%) and P (17.5%) had D/C due to neutropenia vs nab-P (6.9%, p&lt;0.001 for both comparisons). A higher proportion of pts on nab-P (12.3%) continued on therapy until death/disenrollment vs D (8.9%, p 0.046) or P (7.1%, p 0.023). Similarly, a higher proportion of pts on nab-P (51.2%) initiated subsequent therapy at D/C of taxane vs D (31%) or P (37.3%; p&lt;0.01 for both comparisons). Median time to D/C was 85 days for each of D and P, and 127 days for nab-P (p&lt;0.05). Median time to D/C associated with AEs, neutropenia, death/disenrollment or subsequent therapy were significantly longer for nab-P compared with D or P (p&lt;0.05). Conclusions: Women treated for mBC stayed on nab-P therapy 50% longer than with other taxanes. This time on therapy advantage also indicated that pts on nab-P were less likely to D/C due to AEs, more likely to stay on therapy, and more likely to be candidates for subsequent therapies.
A phase II study of S-1 for the treatment of cytokine and/or tyrosine-kinase inhibitor (TKI) refractory metastatic renal cell carcinoma: Updated results.
Authors: Yoshihiko Tomita, Nobuo Shinohara, Atsushi Mizokami, Masato Fujisawa, Katsuyoshi Hashine, Masaharu Nishikido, Masayuki Nakagawa, Hideyuki Akaza, Taiji Tsukamoto, Seiji Naito
Journal: Journal of Clinical Oncology (2012)

393 Background: S-1 is an oral anticancer agent combining tegafur, a prodrug of 5-fluorouracil (5-FU), with 5-chloro-2,4-dihydroxypyridine and potassium oxonate. S-1 has shown efficacy for cytokine and/or tyrosine-kinase inhibitor (TKI) refractory metastatic renal-cell carcinoma (mRCC). We report the final results of a phase II study and evaluate 5-FU-related enzymes as a predictor of the response to S-1. Methods: 45 patients received S-1 at a dose of 40 mg/m 2 twice daily for 28 days, followed by 14 days of rest. The primary endpoint was the objective response rate (ORR). The secondary endpoints of progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Formalin-fixed, paraffin-embedded specimens obtained by radical nephrectomy were used for mRNA expression assay, performed by reverse-transcriptase polymerase chain reaction. Results: 45 patients including 6 were progressed after TKI were enrolled from April 2006. 24 patients received more than 5 cycles, and 2 continued to receive S-1 as of October 2011. Two (4.4%) of the 45 patients had complete responses to S-1, 9 (20.0%) had partial responses, and 28 (62.8%) had stable disease. The final PFS and OS were 9.2 and 42.8 months, respectively, and the PFS of TKI refractory patients was approximately two times of final PFS (18.0 months). The most common grade 3-4 adverse events according to CTCAE v.3.0 were similar to the previous report except for hemoglobin decreased and fatigue. On mRNA expression analysis, the expression level of thymidylate synthase correlated with ORR and PFS. On the other hand, OS did not differ significantly between patients with low expression and those with high expression of 5-FU-related enzymes. Conclusions: S-1 is effective and well tolerated in patients with cytokine and/or TKI refractory mRCC. Moreover, long-term treatment with S-1 is safe in mRCC patients enabling long-term disease control, especially in TKI refractory patients. Clinical trial with large number of TKI refractory patients is warranted to determine the efficacy of S-1.
Phase II trial of trabectedin (T) in heavily pretreated recurrent ovarian cancer (ROC) patients.
Authors: D. Lorusso, P. Malaguti, V. Masciullo, S. Mainenti, A. di Legge, M. Ludovisi, A. Pesce, F. Mascilini, E. Fusco, G. Scambia
Journal: Journal of Clinical Oncology (2011)

5060 Background: T is a minor groove DNA-binder with cytotoxic activity in ROC patients (pts). Methods: A phase II study on T 1,300 μg/m² 3-hour infusion q 21 days was conducted in heavily pre-treated ROC. All patients had measurable disease; overall response rate (ORR) was measured by RECIST criteria as primary end point. T was reduced to 1,100 μg/m² in case of recurrent grade 3-4 toxicity. Systemic antiemetic and liver toxicity prophylaxis was done. A 2-stage Simon design was adopted and second stage of accrual was to be opened if at least 3 responses were observed among the first 18 enrolled patients. Results: 44 ROC entered into the study between January and November 2010. 26 pts (59%) were platinum-sensitive (PS) and 18 (41%) platinum-resistant (PR). Median previous chemotherapy lines were 4 (60% of pts received T as 4th, 36% as 5th and 18% as 6th line of treatment). A total of 212 courses (median 5, range 2-8) were delivered. Dose reduction was necessary in 22/44 (50%) of pts and 17% of courses were delayed. The main hematological adverse events (per pts) were Grade 3-4: anemia 18%, leucopenia 32%, neutropenia 32% and thrombocytopenia 14%. Most frequent non-haematological toxicities were Grade 3: nausea 14%, asthenia 50%, transaminases elevations 31%. Three pts reported drug related cardiac toxicity (7%): 2 pts presented myocardial infarction with full recovery and 1 patient died of acute arrhythmia.. All three pts were highly pretreated with anthracyclines. Cardiac safety needs close control in this type of patients. Conclusions: T is an active drug in heavily pre-treated ROC. Safety profile does not appear different with respect to what is registered in less pre-treated pts. Platinum resistant (%) Platinum sensitive (%) Overall (%) N patients 18 (41) 26 (59) 44 CR – – – PR 0/18 6/26 (23) 6/44 (14) SD 6/18 (33) 10/26 (38) 16/44 (36) PFS 5.3 m (1.5-9.5) 6.8 m (2.7-10.2+) 6.8 m (1.5-10.2+) OS 7.2 m (1.7-9.5) 9.3 m (3.5-10.2+) 8.5 m (1.7-10.2+) Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PFS, progression-free survival; OS, overall survival; m, months.
Cancer patient experience: A pilot survey in Japan.
Authors: Izumi Kamiya, Ayako Okuyama, Kayoko Katayama, Natsumi Yamashita, Keizo Akuta, Shigeko Yamamoto, Toshihiko Ikegami, Masato Fushiki, Chikako Yamaki, Fumihiko Wakao, Takahiro Higashi, Tomoko Takayama
Journal: Journal of Clinical Oncology (2014)

260 Background: Patient-reported experiences of cancer care are an important outcome of cancer control programs. To establish a nation-wide system to monitor progress in cancer control policies, we piloted a patient experience survey to six hospitals in Japan. Methods: We conducted a self-administered questionnaire survey to a total of 1,804 adult cancer patients receiving cancer treatment in six hospitals (three cancer centers, two general hospitals, and one academic institution) from July 2013 to Mar 2014. Patients were asked to answer 94 questions covering eight dimensions of cancer experience: 1) decision-making, 2) care coordination, 3) patient education, 4) pain control, 5) emotional support, 6) family support, 7) access to care, and 8) care continuity. Results: Eighty percent of the patients reported that their treatment preferences were respected in the decision-making process, but a large proportion of patients (60%) also noted that they preferred to have their treatment decisions made for them by their physicians. Many (32%) expressed difficulty in communicating their questions and concerns to their physicians at the time of diagnosis. Only one fifth of patients were informed at the time of diagnosis that they can seek for a second opinion from other providers. Average patient-reported wait time to surgery was 30 days, which was considered to be long by a third of the patients. Eighty percent of patients felt that their care was well-coordinated by a multidisciplinary team, while % also felt that they received adequate emotional support from their medical staff. Relatively small proportion of outpatients (77%) felt that they had access to medical staff when they had medical questions, compared to nearly all patients in an inpatient setting. Only 65% of inpatients and 40% of outpatients felt that they had received best available pain control during their care. Less than half of the patients were able to communicate their preferred place of care after discharge with their healthcare provider. Conclusions: Patient-reported experiences of cancer care are an important outcome measure of cancer policy performance. This pilot study served to reveal some of the important on in future nationwide surveys.
Association of BCR-ABL mutation testing in patients with CML with likelihood of improvement in subsequent BCR-ABL test results.
Authors: Carol Smyth, Jason M. Bhan, Ajitpal Singh Dhaliwal, Tatiana Sorokina, Niyati Parikh, Jason S. Levitz, Jerald P. Radich
Journal: Journal of Clinical Oncology (2015)

e18074 Background: Mutational analysis is important in management of patients with CML. We compared BCR-ABL test results in patients who were tested for mutation after showing poor response to treatment vs. those who were not tested, to determine if mutation testing is associated with improved treatment response. Methods: We studied data from 40,000 CML patients in the Medivo Lab Value Exchange Database who were tested for BCR-ABL between 2011- 2014, and identified 6,247 instances where CML patients demonstrated a + slope in test results (defined: any subsequent test result > previous test result). We used + slope as a proxy for poor treatment response. The average time difference between two consecutive tests was 123 days. We found 183 instances (3%) where patients were tested for BCR-ABL mutation soon after showing poor treatment response, and 6,064 instances (97%) where patients were not tested. Logistic regression was used to assess whether patients who were tested for mutation were more likely to show improvement in later BCR-ABL test results than patients who were not tested. Results: Out of 183 instances where patients were tested for mutation, in 149 instances, patients showed improvement (81%) and in 34 instances, patients showed no improvement (19%). Out of 6,064 instances where patients were not tested for mutation, in 4,504 instances, patients showed improvement (74%) and in 1,560 instances, patients showed no improvement (26%). Logistic regression analysis showed that testing for BCR-ABL mutation was associated with a higher likelihood (52%) of subsequent improvement in BCR-ABL test values than not being tested for mutation, a statistically significant result (OR = 1.52, p = 0.03). Conclusions: Our results support mutation testing in patients with CML showing poor response to treatment. Further analyses are needed to confirm that patient tested for mutation are more likely to have changes in therapy and potentially better patient outcomes. Further analyses will also look at treatment choices, duration of treatment, and time to achieve MMR in these patient populations.
Oncologic outcome of lateral pelvic lymph node metastasis in locally advanced rectal cancer.
Authors: HyungJin Kim, Gun Kim, Ri Na Yoo, Bong-Hyeon Kye, Hyeon-Min Cho
Journal: Journal of Clinical Oncology (2016)

661 Background: Lateral pelvic lymph node (LPLN) metastasis is a major cause of recurrence in patients with rectal cancer. This study investigates the oncologic outcome based on LPLN status after neoadjuvant chemoradiotherapy (nCRT). Methods: Between January 2009 and February 2013, 141 patients with rectal cancer received nCRT followed by curative radical surgery in our hospital. 16 patients were identified with LPLN before nCRT. These patients were categorized to two groups according to nCRT response evidenced by post-nCRT imaging studies with 5mm criteria. Group 1 included 7 patients who showed disappearance of LPLN after nCRT. Group 2 consisted of the patients identified with LPLN after nCRT. Results: The mean follow-up period was 35.6 ± 12.8 months. The mean overall survival (OS) period and 3-year OS rate for the patient with LPLN before nCRT was 56.0 ± 2.6 months and 93.3%, respectively. The mean relapse free survival period and 3-year RFS rate for the patient with LPLN before nCRT was 32.6 ± 5.7 months and 47.1%, respectively. The risk factors associated with RFS were ypN stage (P = 0.031), tumor location (P = 0.002), and postoperative CEA level (P = 0.022). Comparing RFS between Group 1 and 2, Group 1 tended to demonstrate longer RFS (P = 0.058). Analyzing oncologic outcome of two groups compared to the cohort population, group 1 showed similar oncologic outcome with ypTNM stage II. Group 2 demonstrated a tendency of worse oncologic outcome than ypTNM stage III (Group 1 vs. ypII P = 0.761 and Group 2 vs. ypIII P = 0.135). Conclusions: Preoperative LPLN status after nCRT seems to influence oncologic outcome in rectal cancer patient. If patients with LPLN metastasis before nCRT exhibit persistent LPLN metastasis after nCRT, they may require additional treatment.