tbuckley/cabot-search huggingface dataset:
Proton therapy for prostate cancer: An analysis of rectal toxicity outcomes at University of Florida Proton Therapy Institute (UFPTI).
Authors: Rovel J. Colaco, Bradford S. Hoppe, Randal H. Henderson, Romaine Charles Nichols, Christopher G. Morris, Curtis Bryant, Zuofeng Li, William M. Mendenhall, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2014)

161 Background: We aimed to characterize gastrointestinal effects of proton therapy (PT) in patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients on investigational protocols (IP) versus outcome tracking protocols (OTP). Methods: 1,290 patients treated consecutively with PT between August 2006 and June 2010 were studied. Pre-existing potential risk factors for RB (hemorrhoids, diabetes, aspirin, other anticoagulants) were recorded. Common terminology criteria for adverse events (CTCAE version 4.0) were used to grade toxicity. Median follow up was 3.5 years. Results: The majority (94.6%) of Grade 2 or higher gastrointestinal toxicity (GR2+) events after PT were rectal bleeding. GR1 RB occurred in 390 (30.2%) of patients, including those requiring no prescription intervention (82.6%) and those placed on a vitamin A regimen (16.3%). GR2 RB occurred in 14.7% of patients, including patients requiring prescription rectal suppositories (9.5%), cautery (4.9%), or hyperbaric oxygen (0.3%). Grade 3 (GR3) occurred in 0.8% of patients, including those requiring transfusion (0.6%) or colostomy (0.1%). Multivariate analyses showed that pretreatment daily aspirin (p=0.03), other anticoagulation (p=0.001), and the volume of rectum exposed to radiation dose levels (V70) (&lt;.0001) were associated with an increased risk of Gr2+RB. Patients treated on investigational protocols (IP) had similar toxicity rates as those treated on an outcomes tracking protocol (OTP). Reduced rectal toxicity was noted in latter years of the study, which correlated with changes in treatment technique, pretreatment evaluation, and post-treatment supportive care regimens. Conclusions: PT was associated with low rates of GI toxicity, the most common toxicity being transient RB. GR2+RB is strongly associated with patient use of aspirin, other anti-coagulation and radiation dose volume parameters.
Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice
Authors: Pazit Beckerman, Jing Bi-Karchin, Ae Seo Deok Park, Chengxiang Qiu, Patrick D Dummer, Irfana Soomro, Carine M Boustany-Kari, Steven S Pullen, Jeffrey H Miner, Chien-An A Hu, Tibor Rohacs, Kazunori Inoue, Shuta Ishibe, Moin A Saleem, Matthew B Palmer, Ana Maria Cuervo, Jeffrey B Kopp, Katalin Susztak
Journal: Nature Medicine (2017)
Detection of circulating tumor cells: Prognostic and predictive role.
Authors: I. Turker, U. Uyeturk, O. Uysal Sonmez, K. Helvaci, B. Budakoglu, Ü. Yalçintas Arslan, O. Esbah, O. Bal, A. S. Ekinci, O. B. Oksuzoglu, N. Zengin
Journal: Journal of Clinical Oncology (2011)

e11002 Background: The effectiveness of CTC determination on progression free survival (PFS) and overall survival (OS) in early and advanced breast cancer as an adjunct to standard care of treatment was evaluated. Methods: Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital and gave informed consent to participate, were included in this prospective trial. Patients’ characteristics, treatment schedules and survival data were evaluated. Physical examination and routine radiological assessment were done regularly for the evaluation of response. CTC was detected by CellSearch method before and 9 to 12 weeks after the initiation of chemotherapy. Results: All patients were female. Median age was 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic groups, respectively. CTC was positive (≥5) in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients at anytime during chemotherapy in the metastatic group whereas CTC was positive in only one patient in early stage group before and at anytime during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p<0.001). OS was affected from multiple visceral metastatic sites (p=0.055) and higher grade (p=0.044) besides CTC positivity (log rank p<0.001). Radiological response of chemotherapy during chemotherapy cycles was also correlated with better survival (p<0.001). Conclusions: As a result, CTC positivity was confirmed as a prospective marker even in a small patient population, in this single center study. Measurement of CTC by CellSearch method in metastatic breast carcinoma may be an indicative of early risk of relapse or death and even as less as two times of measurement during the whole chemotherapy program may be enough to have a decision but this finding should be confirmed with prospective trials in larger study populations.
The loss of BAP1 protein expression in the first recurrence site of metastasis to predict prognosis.
Authors: Yuji Miura, Naoko Inoshita, Yukinori Ozaki, Yuko Tanabe, Koichi Suyama, Masaomi Ikeda, Toshikazu Okaneya, Toshimi Takano
Journal: Journal of Clinical Oncology (2016)

599 Background: It is well known that the loss of BAP1 protein expression in primary site of clear cell type renal cell carcinoma (ccRCC) is prognostic marker. However, the existence of intratumoral heterogeneity in primary site of ccRCC makes it difficult to assess accurate prognosis. The aim of this study is to investigate the heterogeneity of BAP1 expression in metastatic sites and to evaluate the possibility as a prognostic marker. Methods: We collected samples of both primary and matched metastatic sites of the first recurrence in 41 metastatic ccRCC patients. Immunohistochemistry (IHC) for BAP1 and PBRM1 protein expression were performed on at least two tissue microarray (TMA) sections from primary site and at least one TMA sections from metastatic sites. We retrospectively analyzed the association of the IHC with clinical outcomes. Results: 41 primary and metastatic sites were available for this analysis. The most of metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression-positive, -negative and -heterogeneity in primary/metastatic sites were 29/29 (70.7/70.7%), 8/11 (19.5/26.8%) and 4/1 (9.8/2.4%), respectively. PBRM1 protein expression-positive, -negative and -heterogeneity in primary/metastatic site were 22/27 (53.7/65.9%), 9/11 (21.9/26.8%) and 10/3 (24.4/7.3%), respectively. The concordance between primary and metastatic site for BAP1 and PBRM1 protein expression was 82.9 and 63.4%, respectively. Median overall survival (OS) from the first recurrence of metastasis in patients with BAP1-positive and -negative in metastatic sites was 97 and 51 months, respectively (p = 0.0275). Median OS from the first recurrence of metastasis in patients with PBRM1-positive and -negative in metastatic sites was 82 and 58 months, respectively (p = 0.44). Conclusions: There is more intratumoral heterogeneity for BAP1 and PBRM1 in primary site than metastatic sites of ccRCC. The loss of BAP1 protein expression by IHC in metastatic sites predicts poor clinical outcome.
Neoadjuvant gemcitabine and carboplatin followed by immediate radical cystectomy for muscle-invasive bladder cancer patients ineligible for cisplatin-based chemotherapy: A propensity score-matched analysis.
Authors: Takuya Koie, Chikara Ohyama, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto
Journal: Journal of Clinical Oncology (2016)

375 Background: Standard neoadjuvant chemotherapy has not yet been established for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin (CDDP)-based chemotherapy. We conducted a propensity score analysis to evaluate the clinical significance of neoadjuvant gemcitabine and carboplatin (GCarbo) chemotherapy for CDDP-ineligible patients with MIBC. Methods: We enrolled 381 patients with MIBC, and retrospectively compared two cohorts of CDDP-ineligible patients with MIBC. The GCarbo cohort consisted of 63 patients, who received 2 courses of GCarbo consisting of 800 mg/m 2 gemcitabine on days 1, 8, and 15 and carboplatin with an area under the curve of 4 on day 2, prior to RC. The RC alone cohort consisted of 56 patients receiving RC without neoadjuvant or adjuvant chemotherapy. The endpoints were overall (OS), cancer-specific (CSS), and disease-free survival (DFS). The oncological outcomes were analyzed using log-rank test and multivariate Cox regression model. Results: Propensity score-matched analysis indicated 56 matched pairs from both groups. The 3-year OS rates were 77.9% for the GCarbo cohort and 50.7% for the RC alone cohort (P = 0.002). The 3-year CSS rates were 92.8% for the GCarbo cohort and 52.6% for RC alone group (P &lt; 0.001). The 3-year DFS rates were 80.6% for the GCarbo cohort and 48.1% for the RC alone cohort (P = 0.005). Multivariate analysis revealed that GCarbo was an extremely strong predictor of improved survival. Conclusions: Although the present study is non-randomized, neoadjuvant GCarbo chemotherapy followed by immediate RC significantly improved OS, CSS, and DFS in CDDP-ineligible MIBC patients.
Concomitant 3D-radiotherapy (3D-RT) with cisplatin (P) for advanced paranasal sinus carcinoma
Authors: S. Crvenkova, K. Valentina, S. Kraleva, I. Stojkovski
Journal: Journal of Clinical Oncology (2005)

5608 Background: To determine the benefit of concomitant 3D-RT with P on locoregional control in-patients (pts) with locally advanced paranasal sinus carcinoma. Methods: 6 pts with histopathologically proven carcinoma of the maxillary sinuses and residual macroscopic tumor were treated with combined P (30 mg/m2once per week(w)) and 3D-RT. All pts had undergone surgical reduction. The isocenric 3D technique consisted of several unwedged or wedged beams using 6-MV photon beams. The prescribed total dose at the isocenter was 66–70 Gy in fraction of 2 Gy. The clinical target volume (CTV) was determined according to the CT/MRI findings of the gross tumor volume (GTV). We were considered edges of the resections and regions with residual disease in which the GTV had invaded surround structures. In those regions in which the GTV was limited by intact bone, no margin was added in that direction. In the regions in which the GTV had invaded other paranasal sinuses the whole compartment was included in the CTV. In those regions in which the GTV had invaded the orbit or extended intracranially margin of 0.5–1 sm. was added to the GTV. A 3-mm expansion margin was applied to the CTV to obtain the planning target volume (PTV). All pts were closely followed with clinical examination and control MRI scans in intervals of 6 w and 3 months (m), then 6 m after therapy. Treatment related acute and late side effects ware assessed according to the Common Toxicity Criteria (CTC). Results: Median follow-up was 10 m. One pt developed locoregional recurrence 9 m after therapy. Actuarial locoreginal control rate was 83.33%, with locoregional recurrence of 16.67%. Most common acute side effects were skin erythema CTC Grade 1 in all pts and mucositis Grade 2 and 3. Mild xerostomia was persistent in all pts. Hematological toxicity was low with anemia Grade 1 in 2 pts and leucopenia grade 2 in 3 pts. Conclusions: Our preliminary data indicate that concomitant P and 3 D-RT is feasible and effective in pts with locally advanced paranasal carcinoma. Acute and late toxicity is moderate. Here, P has radiosensitisizing potential and 3D-RT brings opportunity for substantial decrease in the irradiated volume. No significant financial relationships to disclose.
Hepatitis B surveillance in adult chemotherapy patients.
Authors: Sarah Gordon, Jeffrey L. Berenberg, Tomas Ferguson, Jacqui D. Mitchell
Journal: Journal of Clinical Oncology (2013)

76 Background: The high prevalence of Hepatitis B virus (HBV) in the Hawaiian and Pacific Islander population and the death of two chemotherapy patients from reactivation led to a screening protocol to identify and treat chronic HBV. The goal of this quality improvement project was to assess the at risk population, compliance with screening between 2009 and 2011 and determine any necessary improvements. Methods: New intravenous chemotherapy patients are tested for Hepatitis B surface antigen (HBSAg), Hepatitis B core antibody (HBc), and Hepatitis B surface antibody (HBSAb) prior to initiation of chemotherapy. HBSAg positive patients receive Infectious Disease referral and treatment. HBc positive patients are monitored with serial hepatic function tests. We documented testing and if the patients were treated or followed with hepatic function tests. We reported all positive screening results (defined as HBsAg positive and HBc positive/HBsAb negative patients) and if the patients were treated or screened. We also characterized our patient population by race. Results: 329 patients received chemotherapy. HBsAg positive patients (5, 1.5%), were referred to Infectious Disease for treatment. The HBc positive patients (55) were followed with serial hepatic function tests for the duration of chemotherapy. 13 of these were HBsAb negative (4% of all patients). A total of 5.5% of all patients had a positive screening result as defined above. Overall compliance was 98%. 85% of individuals with a positive serology result self identified as either Asian or Pacific Islander. Conclusions: Reactivation of chronic HBV in individuals exposed to immunosuppressive treatments has a mortality rate of 4-41%. Expert societies do not agree regarding screening all patients. Hawaii has a higher prevalence of chronic hepatitis B (positive HBsAg) compared to the mainland US population (3.6% vs. 0.4% respectively). We screened 98% of intravenous chemotherapy patients. No patients developed evidence of reactivation. To improve upon our protocol we extended laboratory monitoring to three months following completion of chemotherapy and initiated vaccination for HBc positive HBsAb negative patients. We propose that screening at risk populations should be standard practice.
Metastasis free survival following salvage radiotherapy versus hormonal therapy alone in patients with biochemical recurrence after radical prostatectomy.
Authors: Jae-Sung Kim, Changhoon Song, Sung Kyu Hong, Seok-Soo Byun, Sang Eun Lee
Journal: Journal of Clinical Oncology (2016)

130 Background: To describe metastasis-free survival (MFS) in patients with biochemical recurrence following radical prostatectomy (RP), and to define clinical prognostic factors for metastasis. Methods: From our institutional database, 1,408 patients underwent primary RP between 2005 and 2011. Of these, 267 patients who had biochemical recurrence (two consecutive PSA ≥ 0.2 ng/mL) and had post-biochemical recurrence follow-up greater than 12 months were used as the study cohort. As an initial management for biochemical recurrence, salvage radiotherapy (SRT) combined with or without androgen deprivation therapy (ADT) was administered to 186 patients, while 33 patients received salvage ADT alone. Remaining 48 patients had been observed without any treatments. We estimated MFS using the Kaplan–Meier method, and investigated factors influencing the risk of metastasis using Cox proportional hazards regression. Results: Median follow-up after RP was 6.0 years, and after biochemical recurrence was 4.2 years. At last follow-up, 28 of 267 patients (10.5%) had developed metastasis, while 5-year MFS rate was 88.6%. No one developed metastasis in patients under observation. SRT resulted in an improved 5-year MFS rate (89.3% vs. 76.7%; p =0.022) compared with salvage ADT alone. This inferiority of salvage ADT alone compared with salvage SRT was marginally significant in the multivariate analysis (hazard ratio [HR] 2.24; 95% confidence interval [CI] 0.93–5.36; p = 0.071). Gleason score ≥8 (HR 4.10; 95% CI 1.77–9.51; p = 0.001) and seminal vesicle invasion (HR 2.37; 95% CI 1.06–5.30; p = 0.036) were significantly associated with MFS in the multivariate analysis. Conclusions: In patients undergoing prostatectomy, MFS after biochemical recurrence is variable and is most strongly influenced by Gleason score and seminal vesicle invasion. These parameters serve to stratify patients into different risk groups with respect to metastatic progression. Salvage ADT alone should be used with caution with select patients.
Novel definition of BCG failure to enhance recruitment into clinical trials.
Authors: Daniel Levi Willis, Eugene K. Lee, Rian J. Dickstein, Roosevelt Anderson, Shanna M. Pretzsch, Graciela M. Nogueras-Gonzalez, H. Barton Grossman, Colin P.N. Dinney, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2013)

246 Background: Designing clinical trials after BCG failure can be problematic without a reasonable control arm. Thus, there is a need for early identification of BCG failure relevant to clinical trial design which allows one arm to continue on BCG. Here we present a definition of BCG failure based on FISH profile at 6th week of induction BCG that would facilitate such trials. Methods: The definition presented is based on findings from our IRB-approved, prospective clinical trial where Urovysion FISH assays were performed serially during the normal course of BCG therapy (SWOG protocol) at various time points (pre-BCG, 6 weeks, 3 and 6 mo.). Herein we incorporated the FISH analysis at 6 weeks in patients with a negative 3 month cystoscopy and correlated the result with recurrence and progression rates at 24 months. A novel definition of BCG failure was proposed by focusing the analysis on 84 patients with high grade disease (cTa: 33, cT1: 44, cTis 7). The 6 week FISH was selected as this would allow the control arm to proceed with BCG maintenance in a timely fashion, taking into account the time required for obtaining FISH results, registration of patients, and randomization. Results: Of the 36 patients with a positive FISH at 6 weeks (and no tumor at 3 months), 17 recurred (PPV = 47%) and 11 progressed (PPV = 31%), while among those with a negative FISH, 5 recurred (NPV = 90%) and 4 progressed (NPV = 92%) (p&lt;0.001). Kaplan Meier estimates of recurrence free survival with a positive 6 week FISH were 67% and 52%, and for progression free survival were 75% and 52%, at 1 and 2 years respectively. Therefore, if patients with a positive 6 week FISH (and negative 3 month cystoscopy) were considered as "molecular" BCG failures, a prospective clinical trial with 101 patients in the control (i.e. BCG maintenance) and experimental arms to detect a 20% difference in recurrence rates (α=0.05) with 80% power. Conclusions: Using the FISH status of patients at the 6 week interval on BCG therapy would allow a clinical trial design that incorporates one arm with continued BCG therapy, while enriching for events of interest, namely recurrence and progression. This would allow meaningful comparisons while negating any ethical concerns regarding a lack of “standard treatment” in BCG failure studies.
The cancer vaccine therapy using DCs derived from iPS cells (iPSDCs) expressing TAA gene.
Authors: Hiromitsu Iwamoto, Toshiyasu Ojima, Junya Kitadani, Hiroaki Tabata, Keiji Hayata, Masahiro Katsuda, Motoki Miyazawa, Masaki Nakamura, Mikihito Nakamori, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

768 Background: Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the initiation of anti-tumor immune responses. Many cancer patients have previously been treated by the cancer vaccine therapy using DCs worldwide. We have employed a study of a cancer vaccine therapy using genetically modified DCs expressing tumor-associated antigen (TAA) gene. Clinically DCs are generated from the peripheral blood monocytes of patients. Thus the number of monocytes and potential of them are limited, so they are serious obstacle. Recent studies have revealed that induced pluripotent stem (iPS) cells can be generated from murine fibroblasts. Furthermore, it has been reported that DCs can be successfully derived from murine iPS cells (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of naive DCs, then the above-mentioned problems may be solved. Methods: We have induced iPSDCs from murine iPS cells by 4 steps and examined the efficacy as APCs of iPSDCs compared with naive DCs. We also examined whether a vaccine therapy using genetically modified iPSDCs can induce strong therapeutic antitumor immunity compared with naive DCs. Next, we examined the therapeutic antitumor immunity of iPSDCs expressing CEA gene compared with that of naive DCs in pre-clinical study with CEA transgenic mice. Results: We have clarified that genetically modified iPSDCs have an equal efficacy as APCs and TAA-specific therapeutic antitumor immunity, equivalent to naive DCs. And we also have clarified that genetically modified iPSDCs expressing CEA gene have a TAA-specific therapeutic antitumor immunity. Conclusions: This vaccine strategy using genetically modified iPSDCs has an equal capacity with naive DCs in terms of a therapeutic efficacy. Now, we are engaging another pre-clinical study with human, in an effort to apply in a clinical setting.
Prognostic relevance of promoter methylation-associated loss of ID4 expression in glioblastoma multiforme.
Authors: M. Martini, T. Cenci, N. Montano, V. Cesarini, R. Pallini, L. M. Larocca
Journal: Journal of Clinical Oncology (2011)

2076 Background: Inhibitors of DNA binding/differentiation (ID1-4) are a family of helix-loop-helix transcription factor, highly expressed during embryogenesis and at lower levels in mature tissues. Expression of ID proteins have related to features of malignancies, including cellular transformation, angiogenesis and metastasis. ID4 plays an important role in neuronal stem cell differentiation and its deregulation has been implicated in glial neoplasia. Recent works have shown that hypermethylation of ID4 can determine the silencing of this protein in several human cancers. Methods: We analyzed the methylation status of ID4 by methylation-specific-PCR in 85 glioblastoma multiforme (GBM) cases and in 20 normal brain tissues. After surgical treatment, all GBMs were subjected to a cycle of radiotherapy (2 Gy per fraction, once a day, 5 days a week, 60 Gy total dose) with concomitant administration of temozolomide (75 mg per square meter of body surface area per day) for 7 days a week from the first to the last day of radiotherapy, followed by 5 cycles of adjuvant temozolomide (at 200 mg per square meter of body surface area on days 1 through 5) given at four-week intervals. Methylation status was confirmed by sequencing after subcloning and RNA and protein expression was assessed by real-time PCR and immunohistochemistry. The relationship between ID4 methylation and clinical outcome was investigated. Results: The promoter of ID4 was methylated in 17/85 GBMs. After subcloning, the methylation was confirmed by sequencing in over 95% of GpC dinucleotides. In methylated GBMs, ID4 mRNA expression was reduced by 5 folds as compared with unmethylated GBMs. A significant reduction of protein expression was detected in all hypermethylated cases. ID4 methylation was significantly associated with a favourable clinical outcome (p=0.0033). No significant differences were found between patients with and without ID4 methylation with respect to age, sex, p53 mutation, Ki67 labeling index and extent of surgical resection. Conclusions: Our data suggest that methylation of ID4 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment.