tbuckley/cabot-search huggingface dataset:
Phase I/II study of stereotactic ablative radiotherapy including regional lymph node irradiation for patients with high-risk prostate cancer (SATURN): Early results.
Authors: Hima Bindu Musunuru, Laura D'Alimonte, Melanie Davidson, Ling Ho, Patrick Cheung, Danny Vesprini, Stanley K. Liu, William Chu, Hans T. Chung, Ananth Ravi, Andrea Deabreu, Zeeba Bhounr, Liying Zhang, Kristina Commissso, Andrew Loblaw
Journal: Journal of Clinical Oncology (2016)

264 Background: Dose escalation using five-fraction stereotactic ablative radiotherapy (SABR) is gaining popularity in the treatment of prostate cancer. This has not been extensively tested in the context of pelvic radiation for high-risk groups. The objectives of study are to report early toxicity and quality of life outcomes in patients following 5-fraction prostate and pelvic radiation. Methods: A phase I/II study was performed where high-risk prostate cancer patients (T3a-3b or Gleason score ≥ 8 or PSA &gt; 20ng/ml) received 40Gy to prostate and 25Gy to pelvis and seminal vesicles in 5 weekly fractions, on a gantry-based platform. A 3mm planning target volume margin to the prostate and a 6mm margin to the lymph nodes was applied. Image guidance was performed using gold seed fiducials and cone beam computerized tomography. Androgen deprivation therapy (ADT) was used for 12-18 months. Common Terminology Criteria for Adverse Events version 3.0 was used to assess toxicities at 3- and 6-months. Quality of life data (QOL) was captured using EPIC questionnaire. A minimally clinically important change (MCIC) definition was triggered if the EPIC QOL score decreases &gt; 0.5 SD, where SD is the standard deviation of baseline scores. Results: Thirty patients completed the planned treatment with a median follow up of 11.9 months (IQR 8.3, 13.0). The following toxicities were observed: grade 2 genitourinary (GU): 50% at 3 months and 34.5% at 6 months; grade 2 gastrointestinal (GI): 3.3% at 3months and 6.9% at 6 months. No ≥ grade 3 toxicities were observed. Mean (95% Confidence Interval) EPIC urinary QOL scores were 86.6 (81.9-91.3), 87.1(81.4-92.6) and 86.1(80.2-92.0) at baseline, 3 months and 6 months and the bowel scores were 94.1(91.3-97.0), 93.2(89.1-97.2) and 93.2(89.5-96.8), respectively. Proportion of patients experiencing MCIC at 3 months and 6 months were 27.8% and 31.8% for urinary domain, 23.5% and 28.6% for bowel domain; respectively. Conclusions: This gantry-based novel fractionation schedule incorporating pelvic radiation for high-risk prostate cancer in combination with ADT is feasible and well tolerated in the acute setting. Clinical trial information: NCT 01953055.
Prognostic value of flare-up phenomenon after discontinuation of sunitinib (SU) or pazopanib (PA) in metastatic renal cell carcinoma (mRCC).
Authors: Roberto Iacovelli, Francesco Massari, Laurence Albiges, Bernard Escudier
Journal: Journal of Clinical Oncology (2014)

448 Background: SU and PA are VEGFR inhibitors, approved for the treatment of mRCC. Cessation of treatment has been reported to induce flare-up, with increased tumor growth rate (TGR). We aimed to investigate this phenomenon and its prognostic role in mRCC. Methods: Patients who discontinued first line SU or PA with available data about CT scans performed before (t -1 ), at the time of discontinuation (t 0 ) and after (t +1 ), were included in this analysis. TGR was evaluated as the difference between the sum of longest diameters (SLD) of the target lesions during the interval time between the CTs (TGR1=SLD 0 –SLD -1 /t 0 -t -1 and TGR2=SLD +1 -SLD 0 /t +1 -t 0 ) and expressed in cm/month. Flare-up was evaluated as the difference between the TGRs. Median overall survival was evaluated from t 0 (OS 0 ) to death by the Kaplan-Meier method and correlation with variables was evaluated with Cox model. Results: Sixty-three patients treated from Oct 2006 to Nov 2012 at the Institut Gustave Roussy were eligible. Median age was 57.1 y, 81% were males, 89% had SU and 11% PA. Heng prognostic groups were good in 33% and intermediate in 67% of the pts. Median OS 0 was 24.1 months (95%CI, 8.3 – 40.0). Major reasons for discontinuation were durable partial/complete response (16%), severe toxicity (22%) and progression of disease (62%). The median TGR1 and TGR2 were 0.2 and 0.7 cm/month, respectively (p=0.001), no correlation was found (p=0.33) and no differences were found between SU and PA in TGR1 (p=0.95) and TGR2 (p=0.53). Median flare-up was 0.5 cm/month (IQR: 0.1 – 1.2); in pts who discontinued for response, toxicity, or PD it was 0.1 (IQR: -0.2 – 0.6), 0.5 (IQR; 0.2 – 2.0) and 0.8 (0.1 – 1.7), respectively. At the univariate analysis flare-up was a prognostic factor for OS 0 (HR: 1.13, 95%CI: 1.02 – 1.24; p=0.018). When compared to Heng criteria in the multivariate analysis, it was confirmed to be an independent prognostic factor: each increase of 1 cm in flare-up increases the risk of death by 11% (HR: 1.11, 95%CI: 1.00 – 1.23; p=0.048). Conclusions: Flare-up is an independent prognostic factor present in patients affected by mRCC who discontinued SU or PA. This is independent by the reason for discontinuation and the type of therapy.
Mitoxantrone-based treatment in taxane-refractory advanced hormone refractory prostate cancer: A community-based retrospective analysis.
Authors: J. R. Ismail, B. Bystricky, E. Moylan, S. O'Reilly
Journal: Journal of Clinical Oncology (2010)

e15137 Background: Mitoxantrone and prednisolone (MP) is a reasonable choice as second-line therapy after failure of docetaxel-based chemotherapy in hormone refractory prostate cancer (HRPC) patients. Methods: Patients who received a taxane followed by Mitoxantrone between 2005 and 2009 were retrospectively selected through a pharmacy database search. 20 patients with progressive metastatic disease, ECOG performance status of 0-2 and adequate organ function were analysed. Mitoxantrone (12mg/m2) and prednisolone (5mg bid) were administered in 21 day cycles. PSA response is defined as >50% fall in PSA from baseline confirmed by a repeat PSA at least 4 or more weeks later. Progression is defined by objective disease progression or a PSA increase of more than 50% above nadir or 25 % above baseline. Results: At baseline, mean age was 72 years (range 49-81) and mean PSA was 504 ng/ml (range 12 – 2080). 10 patients had a Gleason Score (GS) of 6-7, 8 patients GS 8-9, and 2 unknown. The median number of prior hormonal therapies was two. All patients were on an LHRH agonist and 70 % of patients had received oral anti-androgen therapy, all of whom had undergone prior anti-androgen withdrawal. 19 patients received prior docetaxel and prednisolone as first line chemotherapy and 1 patient received paclitaxel/carboplatin with 45% (9/20) documented PSA responses in first line. Mean number of MP cycles administered was 4.5 (range 1-7). 16 patients were also on bisphosphonate therapy. 6 patients (30%) had documented symptom palliation and PSA response was documented in 4 of them (20%) with median time to PSA progression of 2.5 months (95% CI: 2.3- 2.7). Median overall survival (OS) from second line was 11.3 months (95% CI: 0-27) and median OS from first line was 21.7 months (95% CI: 12.4-31). Overall MP therapy was well tolerated. There was no significant treatment related toxicity. 2 patients died from other causes whilst on therapy. Conclusions: MP has modest anti-cancer activity in metastatic HRPC patients pre-treated with taxane-based chemotherapy. OS in this analysis approximates that of published data. No significant financial relationships to disclose.
Inclusion of corrected calcium and creatinine levels in a novel nomogram for prediction of pathologically localized prostate cancer.
Authors: Okyaz Eminaga, Omran Alhamad, Udo Engelmann, Sebastian Wille, Axel Heidenreich
Journal: Journal of Clinical Oncology (2016)

140 Background: The role of routine parameters in the prediction of organ-confined Prostate Cancer (oPCa) remains unclear. Methods: We conducted a retrospective study of 246 patients with PCa diagnosed on biopsy, who underwent radical prostatectomy with extended lymph node dissection. None of these patients received a neoadjuvant therapy. Gleason score (xGLS), percent of positive cores involved by PCa (pCores), results of transrectal evaluation (TRUS, DRE), prostate volume (PVol), albumin-corrected Calcium (Ca), Hemoglobin (Hb), Creatinine (Crea), PSA, and age at RPE were considered. Postoperative variables including Gleason score (pGLS), TNM stages were evaluated. These patients were divided according to disease advancement into pathologically localized (pT2) and advanced PCa (pT3/4 or pN1). A L2 penalized regression model including all preoperative parameters was evaluated to design a nomogram for oPCa prediction. Furthermore, the internal validation of the nomogram was performed using bootstrapping and cross-validations. The precision and accuracy of the novel nomogram were evaluated by using AUC, F-Score, Brier-Score and the classification accuracy (CA). Results: The lowest probability for pathologically localized PCa was found in patients having the following features: PSA &gt; 20 ng/ml, detection of PCa in all cores, high Ca [1.21 fold over upper normal limit (ULN)] and Crea levels (2.27 fold over ULN), xGls &gt; 7 and normal PVol. A nomogram for oPCa was developed including the following parameter: Crea, Ca, PSA, xGls, PVol, TRUS, pCores. The sensitivity and the specificity of the nomogram for prediction of pathologically localized PCa were 92.2% and 35.9%, respectively. AUC of 0.811, CA of 80.1%, F-Score 0.879, a precision of 84.0%. and Brier-Score of 0.2599 were calculated. The predicted probability of the novel nomogram was associated with higher accuracy for prediction of oPCa compared to those of Partin table and Kattan nomogram. Conclusions: Serum creatinine and corrected calcium are indpendent predictors of oPCa. The novel nomogram can predict oPCa with high precision and accuracy. However, an external validation of the novel nomogram is needed.
Implementation of EMR and effects on health care delivery.
Authors: Leonardo Viana Nicacio, Nat Turner, Zach Weinberg, Dorothy Dulko, Geoffrey Calkins, Gil Shklarski
Journal: Journal of Clinical Oncology (2013)

250 Background: Electronic health records have potential to enhance health care safety and quality by enabling effective communication, Clinical Decision Support technology, and generation of structured data for analysis. Despite the fact that EHRs have been shown to improve health care processes, the rapid growth of technology used to support medical care has resulted in the creation of enormous volumes of data used to assess and manage healthcare delivery. Valuable data is often siloed in multiple IT systems or captured in free-text clinical notes and non-searchable documents (unstructured data) making it impossible to quickly develop and act on real-time longitudinal data. Methods: Flatiron (FI) operates a "big data" software platform that aggregates, cleans and structures deep clinical oncology data thus facilitating understanding of operational, clinical and financial analytics related to cancer care. The platform proposes to solve these fundamental data challenges, enabling a range of real-time quality measures. It is best understood as three related components: the first is the technical integration between FI and providers' IT and data systems. That integration serves as the plumbing through which data flows securely from the provider to FI. The second is FI’s structured database, which transforms raw clinical, operational, and billing data into clean, structured, longitudinal, real-time patient data. The third is the FI user interface portal, which is a web-based analytics tool that facilitates access to the continually updated structured database. Results: Over 10 institutions have partnered with FI to deploy the platform. The full integration of an institution can be achieved in 12 to 16 weeks with daily updates to the analytics after the initial phase. Over 15,000 patients are expected to be fully integrated in the next 3-6 months. Initial QOPI and other quality measures have been included and customizable dashboards linking charge databases with clinical outcomes have been created. Dashboards with quality metrics will be presented in the conference. Conclusions: Implementation of EMRs alone does not improve healthcare delivery. Data on colorectal cancer patients will be presented at the meeting.
Cell-free DNA as a prognostic marker for response to taxan-based chemotherapy in patients with prostate cancer (CaP).
Authors: Alexandra Kienel, Daniel Porres, Charlotte Piper, Thomas van Erps, Axel Heidenreich, David J. K. P. Pfister
Journal: Journal of Clinical Oncology (2013)

228 Background: PSA is of limited value for predicting response to chemotherapy in castration resistant CaP patients. Nevertheless there is no better biological marker to control therapy response. cfDNA showed significant results in prostae cancer diagnostics and predicting recurrence after radical prostatectomy. We analyzed for the first time the role of cfDNA in castration resistant CaP predicting response to chemotherapy. Methods: We analyzed cfDNA isolated from an EDTA blood sample from 58 patients taken before initiating a first or second-line taxan based chemotherapy. 54 (93,1%), 8 (13,8%) and 3 (5.1%) of the patients had bone, lymph node or parenchymatous metastases respectively. Patients were selected according to PSA response after at least 3 cycles of chemotherapy to 30% (A), 50% (B) and 80% (C) decrease under chemotherapy. The concentration of cfDNA at the beginning of the therapy was correlated to PSA resonse at the end of the treatment. Results: Mean PSA and cfDNA concentration at therapy initiation was 391 (0,1-2663)ng/ml and 32,5 (8,93-136,63)ng/ml. In group A there was a trend of higher cfDNA concentration in the patients not achieving a PSA decrease of at least 30% (24,6ng/ml versus 35.5ng/ml) not reaching statistical significance (p=0,078). Conclusions: Patients with PSA decrease of less than 30% and PSA progression under chemotherapy have the poorest outcome. cfDNA is easy to investigate and is probably of importance to distinguish patients profiting from chemotherapy in a palliative setting. These data should be validated in a larger patient cohort.
A pilot study of FOLFOX with or without radiation in treating patients with locally advanced rectal cancer.
Authors: Y. Deng, Y. Cai, J. Xiao, J. Ling, L. Fang, M. Huang, J. Peng, D. Ren, P. Lan, J. Wang
Journal: Journal of Clinical Oncology (2011)

e14147 Background: Preoperative 5FU-based chemo plus radiation therapy is standard for patients (pts) with locally advanced rectal cancer (RC). We conducted a pilot feasibility trial of adding the third generation drug oxaliplatin to the standard treatment to see whether the treatment outcome can be improved and the place of RT can be replaced. Methods: Pts with clinical stage II-III resectable RC were treated with 4 cycles of FOLFOX (CT) or 5 cycles of FOLFOX with radiation (2Gy/fraction, total 46Gy, CRT). Pts then were re-imaged and had repeat colonoscopy with MRI to assess the primary tumor response. Those with progressive disease in FOLFOX group were to be referred for pre-op 5FU plus RT, followed by surgery, and those with clinical regression/stable disease were to have surgery without pre-op RT. Post-op 5FU plus RT was planned for any pts who did not have an R0 resection. 7-8 cycles of FOLFOX were recommended in Post-op chemo. The primary endpoint was the objective response rate. Secondary outcomes were the pathologic CR rate, the 3-year disease free survival and local recurrence (LR) rate. Results: Of 51 pts were accrued since April 2007, 25 have completed pre-op RCT, 26 who have completed pre-op CT, 7 of 25 RCT pts (28%) had a path CR, however no pts with CT had path CR, the difference was significant. ORR was 92%, 80.8% and disease control rate (DCR) 96%, 96.2% respectively, there was no difference between the two groups. The quality of life was better and the in-hospital time was shorter the CT alone group. Local and distant recurrence rate data are immature. But so far, no recurrence was found in the CT group, which indicated the potential benefit of CT alone in the adjuvant setting. Conclusions: Preliminary results of this pilot trial depicts that preoperative FOLFOX alone without RT achieves a high rate of DCR. And FOLFOX with RT achieves a high rate of CR. Further phase III trials are warranted.
Ovarian immature teratoma: Can all patients be salvaged at recurrence?
Authors: D. Vicus, M. Beiner, S. Klachook, B. A. Clarke, L. W. Le, S. Laframboise, H. Mackay
Journal: Journal of Clinical Oncology (2011)

e15520 Background: Ovarian immature teratoma is rare, accounting for less than 1% of all ovarian cancers therefore data is limited. The aim of this study was to evaluate clinicopathologic characteristics, treatment outcome and reproductive function in women diagnosed with an ovarian immature teratoma at a single institution over 35 years. Methods: Thirty-four women with ovarian immature teratoma stage IA to IIIA were identified and included in this study. Patients were treated at one institution; Princess Margaret Hospital, Toronto, Canada between 1970 and 2005. Results: Median age at diagnosis was 25.0yrs (range: 9.8 – 60.2 yrs). 27 (79%) presented with stage IA disease, 5 (15%) with stage IC, 1 (3%) with stage 2B, and 1 (3%) with stage 3A disease. 13 (38%) of the tumors were grade 1, 12 (35%) grade 2, and 9 (27%) grade 3. Initial management was surgical for all patients: 22 (65%) unilateral oophorectomy, 7 (20%) cystectomy only, and (15%) bilateral oophorectomy (4 with hysterectomy). 15 (44%) patients received adjuvant therapy; 2/13 (15%) patients with grade 1 tumors, 5/12 (42%) with grade 2 tumors and 8/9 (89%) with grade 3 tumors. After a median follow-up of 4.8 years (range 0.2-24.3 years) 4 (12%) recurrences occurred (two grade 2 and two grade 3 tumours), all within 22 months of the primary diagnosis. Three of the four patients died of their disease. The 2-year progression free survival is 87.1%. Three patients later presented with growing (mature) teratoma syndrome, they were all treated successfully with surgery. Eleven patients reported an attempt to conceive post treatment resulting in 11 pregnancies in 6 women (3 post chemotherapy). Conclusions: The majority of patients diagnosed with an immature teratoma are cured of their disease. However, women with grade 2 or 3 tumours have a significant chance of recurrent disease within two years of diagnosis that can be fatal.
Catheter-Based Renal Denervation Exacerbates Blood Pressure Fall During Hemorrhage
Authors: Reetu R. Singh, Varsha Sajeesh, Lindsea C. Booth, Zoe McArdle, Clive N. May, Geoffrey A. Head, Karen M. Moritz, Markus P. Schlaich, Kate M. Denton
Journal: Journal of the American College of Cardiology (2017)
Microsatellite instability to predict the efficacy of adjuvant chemotherapy for stage II colon cancer.
Authors: J. E. Kim, H. J. Kim, Y. S. Hong, J. Lee, M. Ryu, H. Chang, S. J. Jang, M. Kim, C. S. Yu, J. C. Kim, T. W. Kim
Journal: Journal of Clinical Oncology (2011)

3560 Background: MMR has been suggested, with controversy, as prognostic and predictive marker of adjuvant chemotherapy (aCT) in stage II colon cancer. The aim of this study was to evaluate association between MMR and survival in stage II colon cancer. Methods: Between January 2003 and December 2008, 860 patients (pts) with curatively resected stage II colon cancer were included. Deficient MMR (dMMR) was defined as tumors with MLH1 and/or MSH2 loss and others as proficient MMR (pMMR) by immunohistochemistry. Clinical risk (CR) factors were used for dividing pts into high or standard CR group. Competing risk analysis was performed to compensate death by other causes rather than recurrence. Results: Of 860 pts, 14.7% showed dMMR, 42.4% had ≥1 CR factor, 85.8% pts received aCT. Age and gender were balanced with MMR status and CR, while younger pts received more aCT (median age; 60 vs. 67.5 years, p=<0.0001). There was no difference in terms of recurrence rate (RR), disease-free survival (DFS) or overall survival (OS) according to either MMR status or CR group. Among CR factors, pT4 was the only prognostic factor associated with poor OS (p=0.021). aCT was associated with lower RR (p<0.0001), better DFS (p<0.0001) and OS (p<0.0001). By multivariate analysis, neither MMR nor CR was related to DFS or OS, while aCT was associated with better OS (HR=0.206 [0.116-0.369], p<0.0001). The estimated cumulative incidence of recurrence after considering competing risk was not affected by MMR, CR and aCT (Table). Conclusions: MMR status did not affect DFS and OS in pts with stage II colon cancer. Only pT4 among high CR factors did influence OS. Although aCT seemed to decrease RR and improve OS by conventional survival analysis, it was not associated with cumulative incidence of recurrence after adjusting competing risk. Multivariate competing risk analysis for DFS. HR 95% CI Age 0.974 0.629-1.510 Perforation or obstruction 1.516 0.835-2.750 Poorly differentiated type 0.61 0.179-2.080 Pathologic T4 1.691 0.697-4.100 Lymphovascular or perineural invasion 0.823 0.450-1.510 Number of sampled lymph nodes <12 0.744 0.405-1.370 pMMR 0.767 0.374-1.580 Adjuvant chemotherapy 0.648 0.357-1.180
Risk factors predicting recurrence in operated endometrial cancer.
Authors: S. Sukumaran, S. Subramaniam, S. Paramasivam, R. Woodman, C. Carter, G. Kichenadasse
Journal: Journal of Clinical Oncology (2011)

e15592 Background: Early stage endometrial cancers have a good prognosis. However, these are a heterogeneous group of patients with varying recurrence risk (RR). Methods: Retrospective analysis of patients, diagnosed and treated, with endometrial cancer at Flinders Medical Centre, South Australia, from 1 January 2000 until 31 December 2009. Demographic, clinical and pathologic factors were analyzed to determine association with RR. Results: A total of 152 women with a median age of 65 years were analysed. Surgery was the primary intervention in 146 patietns (96%). Optimal debulking status was achieved in 113 patients (74.3%). Endometriod adenocarcinoma was the most common histological subtype (67%). Other subtypes included adenocarcinoma (18.4%), papillary serous carcinoma (3.9%), carcinosarcoma (1.9%), mixed (4.6%) and other (3.9%). Fifty-eight patients had grade 1 tumour, 55 grade II and 36 grade III. Out of 103 patients who had their lymphovascular space invasion (LVSI) status assessed, 21 (20.4%) were positive while 82 (79.6%) were negative. Stages I, II, III & IV were constituted by 109, 10, 20 and 7 patients respectively. The numbers of patients with low, intermediate and high RR (as per stage and grade) were 114, 11 and 25 respectively. Forty-five patients (29.6%) received adjuvant treatment, which included external beam radiotherapy (26), brachy-therapy (10), chemotherapy (9) and medroxy-progesterone (2). At a median follow up of 33.6 months, 21 patients had evidence of disease recurrence. Recurrence was loco-regional in 11 patients and systemic in 10. On uni-variate Cox regression analysis, factors associated with increased RR included resection status, grade, LVSI, number of lymph nodes resected and risk category. LVSI status and risk category maintained their significance, as independent predictors of RR, in a multivariate model, when adjusted for age and adjuvant therapy. Adjuvant therapy did not seem to alter the RR. Conclusions: Our data confirmed the validity of risk stratification to assess the RR in operated endometrial cancer. Positive LVSI status also conferred an increased risk for recurrence. Further studies are required to determine the optimal role of adjuvant therapy, according to RR, in women with endometrial cancer.