tbuckley/cabot-search huggingface dataset:
An open, multicenter, phase II clinical trial to evaluate efficacy and safety of S-1 split cisplatin in patients with advanced gastric cancer (AGC): HGCSG0702—Safety analysis.
Authors: Ichiro Iwanaga, Satoshi Yuki, Hiraku Fukushima, Atsushi Ishiguro, Takenori Takahata, Takuto Miyagishima, Mineo Kudo, Yasuko Uehata, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2013)

121 Background: From the results of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan. However, many facilities are forced hospitalization of hydration upon administration of high dose Cisplatin (60mg/m2). Therefore, in Hokkaido Gastrointestinal Cancer Study Group (HGCSG), to investigate the safety and efficacy, we conducted a multicenter phase II clinical trials of S-1 plus split cisplatin as a therapeutic strategy that can be administered in the outpatient. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40-60 mg depending on patients body surface area) was given orally, twice daily for 3 consecutive weeks, and 30 mg/m2 cisplatin was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and duration of hospitalization. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7. Median no. of cycles was 3. The most common non-hematological adverse events (AE) were anorexia (70%), nausea (60%), fatigue (60%) and diarrhea (48%) and hematological AE were anemia (88%), neutropenia (83%), leukocytopenia (68%) and thrombocytopenia (60%). The main grade 3-4 AE were neutropenia (40%), anemia (30%), anorexia (30%) and fatigue (15%). These AE were as expected. The median dose intensity of S-1 was 270mg/m2/week (relative dose intensity (RDI) 80%), and cisplatin was 10.1mg/m2/week (RDI 84%). These toxicities were tolerable and manageable. No treatment-related death was observed. Conclusions: We conclude that this S-1 plus split cisplatin regimen was well tolerated in the treatment of AGC, and most patients could be administered in the outpatient. We are planning the final efficacy analysis for February 2013.
Community oncology treatment patterns and clinical effectiveness in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed after docetaxel.
Authors: Arthur C. Houts, Daniel Hennessy, Mark S. Walker, Leonardo Nicacio, Stephen F. Thompson, Paul J. E. Miller, Bradley G. Somer
Journal: Journal of Clinical Oncology (2013)

118 Background: Cabazitaxel (C) and abiraterone (A) improve survival in mCRPC after progression on docetaxel (D). We examined whether mCRPC patients progressing on D received C and/or A, in which sequence, and how they compared with patients not receiving C or A. Methods: This retrospective study used medical records from the ACORN Data Warehouse. Eligible patients were: diagnosed with mCRPC, progressed after 1 st -line D, treated 2 nd -line with C (DC) or A (DA). Some went to 3 rd -line C or A (DCA, DAC). A random sample of comparable patients without A or C (DO) was included. Demographic and clinical characteristics were extracted. Cox regression analyses assessed PFS and OS by 2 nd -line group after D. Results: Screened out patients were: 60 with no progression on D; 41 absent records; 18 with another cancer. Table below shows patients by treatment sequence group. Age, PS, and PSA did not differ significantly. More patients appear to have received A after C (56.7%) than C after A (25.7%). In the 3-drug sequence groups, more patients received DCA in the 6-month period from April-October 2011 (n = 17/19) than in the 6-month period from June-December 2012 (n = 2/10), suggesting a drop-off in use of C immediately after D. Cox PFS treatment effect was not significant. Cox OS treatment effect was significant (DA vs DC, HR = 1.693 [95% CI: 1.066, 2.691], p = 0.0258). Conclusions: Patterns suggest comparable outcomes in PFS. Controlling for patient characteristics, OS may be longer in DC vs DA. Patients appear undertreated in third line with fewer receiving C after A than the opposite sequence. We hypothesize that DAC may not be as feasible as DCA. Reasons for underutilization of C are being examined. [Table: see text]
Differences in outcome between right- and left-sided colon cancer: A population based study.
Authors: Frits Aarts, Ignace de Hingh, Johannes HW de Wilt, Valery E. P. Lemmens, Rob H.A. Verhoeven
Journal: Journal of Clinical Oncology (2013)

493 Background: Colon cancer is the second most frequent cause of cancer death, with an increasing incidence during the last decade. Recently, there is an increased interest in possible differences in outcome after surgery between right- and left-sided colon carcinoma (RCC and LCC). Methods: A population based study was performed in the south part of the Netherlands covering a region with more than 2 million inhabitants. Patients suffering from either RCC or LCC, excluding rectal cancer, were compared with regard to epidemiological, clinical and histological parameters as well as survival data. A Cox proportional hazard model was used to estimate the impact of different parameters on survival. Results: The data of 12,731 patients with colon cancer from January first 2000 and December 31 2010 were analyzed. Of these, 42% was RCC and 55% was LCC. In the remaining 3% of patients the location was not otherwise specified. In comparison with LCC, the majority of RCC patients were female (53% vs. 46%) and older (42% vs 34% &gt; 75 years). The majority of RCC (77%) and LCC (87%) was non-mucinous adenocarcinoma. In RCC, 18% of tumors were mucinous adenocarcinoma vs 10% in LCC, p&lt; 0.001. Well differentiated tumors were more common in LCC, 70% vs 58% in RCC Moderately and poorly differentiated tumors were more present in RCC compared to LCC (23% vs 13%, p&lt;0.0001). Stage I tumors were more common for LCC vs stage II-IV tumors in RCC, p&lt;0.0001. In RCC 1-9 lymph nodes were found in 37% vs 51% in LCC. In RCC 49% &gt;10 LN were found vs 34% in LCC. No difference was found between anatomical sites regarding tumor positive LN, nor in LN ratio. Synchronous distant metastases were present in 30% of RCC vs 25% in LCC. Median overall survival in RCC was 46 months vs 60 months in LCC, p&lt;0.0001. Survival differed between age groups and location and was worse for RCC with age 45-59 yrs: RCC vs LCC p&lt;0.0008, age 60-74 yrs: RCC vs LCC, p&lt;0.0006). Also, in T4 tumors, survival was worse for RCC, p&lt;0.007. Conclusions: Prognosis of colon carcinoma is correlated to anatomical distribution with a significantly worse prognosis for RCC patients. Since RCC is more common in people of older age and the incidence is increasing, these findings may have future implications for the planning of treatment strategies.
Impact of breast cancer diagnosis and treatment on sexual dysfunction.
Authors: Hadeel Assad, Gauri Badhwar, Sameeksha Bhama, Cynthia Vakhariya, Judie R. Goodman
Journal: Journal of Clinical Oncology (2014)

125 Background: Sexual dysfunction is a common and under acknowledged disorder in women with breast cancer. Sexual dysfunction in this scenario may be related to multiple factors: psychological distress due to diagnosis, physical decline due to treatment, change in hormonal milieu and/or poor body image. Methods: We assessed the changes in sexual activity after breast cancer diagnosis and treatment in 45 women using an anonymous questionnaire. Data was analyzed via descriptive statistics and paired sample t-test. Results: The age of women in our study ranged between 33-73 years with an average age of 51.6 years. Most of the subjects (89%) had completed chemotherapy and/or radiation therapy however 52% were still on hormonal treatment. Women who were more sexually active prior to breast cancer diagnosis were more likely to experience sexual dysfunction (p = 0.001). Overall, 45% of the women with breast cancer experienced a decline in their sexual health. A greater decline occurred after breast cancer treatment (chemotherapy and/or hormonal therapy) than after diagnosis (p &lt; 0.05). Fifty percent had a decrease in libido and sexual arousal, 40.5% had difficulty in reaching sexual orgasm, and 29% had dyspareunia. Sexual difficulties were addressed by the treating oncologist in 3 out of the 45 women. Conclusions: The data reveals that sexual dysfunction is prevalent in breast cancer survivors. Its onset in concomitance with the diagnosis of breast cancer reflects the psychosocial impact of such a diagnosis. The further decline in sexual health after treatment emphasizes the important adverse effects of chemotherapy and hormone therapy in terms of vaginal dryness, dysparunia and sexual well-being. Despite its prevalence, sexual dysfunction is not commonly addressed in women with breast cancer. [Table: see text]
Morbidity and mortality after colorectal cancer surgery in patients with cirrhosis: A critical review of the literature.
Authors: Tarek Boussaha, Jean François Cadranel, Allaoua Smail, Hortensia Lison, Armand Garioud, Elisabeth Carola, Sarah Naomie Dumont, Benoist Chibaudel, Thierry André, Yann Parc
Journal: Journal of Clinical Oncology (2014)

608 Background: Cirrhotic patients with localized colorectal cancer are potential candidates for tumor resection. The aim of this review was to evaluate the morbi-mortality after colorectal surgery. Methods: Comprehensive search was conducted using PUBMED, EMBASE, and the COCHRANE Library. Prospective and retrospective studies were selected. The study population included cirrhotic patients who underwent colorectal resection for non-metastatic colorectal cancer and patients with benign and other malignant disease. The postoperative morbi-mortality and independent risk factors were analysed. Results: Eight studies were identified. Among these, four studies compared the risk of colorectal surgery in patients with and without liver cirrhosis. The number of patients varied from 41 to 6,120. The severity of cirrhosis in most of the studies was classified with the Child-Pugh score. Class B and C were observed in 20% to 60% of the patients. Sepsis represented the main postoperative complication and occurred in 48% to 77% of patients. Mortality varied according to the Child-Pugh score, ranging from 11% to 41%, and was significantly higher for patients with cirrhosis in Child-Pugh Class C. Urgent surgical procedure had a negative impact on prognosis. The average length of hospital stay ranged from 9 to 18 days. Cirrhosis was associated with a 2-3 time and a 4-10 time increased risk of postoperative mortality in the absence and presence of portal hypertension, respectively compared with non-cirrhotic patients. The independent risk factors for postoperative morbidity and mortality were encephalopathy, ascites, low haemoglobin, prolonged prothrombin time, elevated bilirubin, hypoalbuminemia, postoperative infection, total colectomy, elective or non-elective surgery, the presence of co-morbidities and MELD score ≥ 15. Conclusions: Colorectal cancer surgery is associated with an increased risk of postoperative morbidity and mortality in cirrhosis patients. Studies evaluating exclusively the operative risk for colorectal cancer surgery in this patient’s population are rare. Prospective controlled trials to optimize the perioperative management of those patients are needed.
Who dies from prostate cancer in a Western country? A multicenter analysis.
Authors: Yohann Loriot, Jean-Christophe Eymard, Laurence Albiges, Christophe Massard, Anna Patrikidou, Ecaterina Ileana, Mario Di Palma, Alberto Bossi, Pierre Blanchard, Bernard Escudier, Karim Fizazi
Journal: Journal of Clinical Oncology (2013)

211 Background: In the last 30 years, a major shift in initial staging has occurred for men with prostate cancer (CaP) in many Western countries, with the incidence of detectable metastases at diagnosis decreasing from more than half the cases in the 1970s to currently less than 10%. Still, prostate cancer is the second killing neoplasm in men. We used two prospective databases of patients with castration-resistant prostate cancer (CRPC) to describe the natural history of metastatic CRPC in the modern era. Methods: The outcome of 190 men with CaP treated for metastatic disease from 2007-2011 was studied. Characteristics of patients who died from CaP were analyzed. Results: After a median follow-up of 6.8 years, 112 patients had died from CaP and 109 were assessable for presence of metastasis at initial diagnosis. Of these 109 pts, 53 (49%) had detectable metastasis at diagnosis: 43 pts (81%), 6 pts (11%) and 17 pts (32%) had bone, visceral; and lymph nodes metastases, respectively. Overall, 10 pts (19%) had more than one metastatic site. Median time to CRPC was 16 months (range: 3-122 months) and median overall survival was 5 years (CI 95%: 4.6 – 6.6 years) for these pts with detectable metastasis at diagnosis. Among patients with localized CaP at diagnosis (n=56; 51%), 23 pts (41%) had T stage ≥ 3, 23 pts (41%) had a Gleason score ≥ 8. Their median PSA was 15 ng/ml (4-400). Overall, 39 pts (70%) were classified as having a high-risk CaP. 13 patients (23%) dying from CaP had an initial Gleason score ≤ 6. The median overall survival was 7 years (CI 95%: 6.1 – 9.1 years). Conclusions: In the modern era, approximately half of the patients eventually dying from CaP had detectable metastases at diagnosis. The paradigm of patients progressing from localized disease to metastatic disease and eventually death is represented only in the other half. Further efforts should be made to conduct clinical trials in patients with newly diagnosed metastatic prostate cancer.
High throughput sequencing technology (Sequenom) as a tool to detect SNPs in human metastatic colorectal cancer (mCRC) and cell lines.
Authors: J. B. Nayak, R. Maitra, A. Basu-Mallick, A. Sood, J. Mariadason, D. M. Reynolds, S. Goel
Journal: Journal of Clinical Oncology (2011)

e14083 Background: Designing individualized therapy in colorectal cancer is critical for disease management and necessitates fast and accurate identification of mutations and SNPs. Analyzing multiple mutations using the gold standard direct Sanger sequencing is a time consuming and laborious process. Here we compared the efficacy of pyrosequencing and high throughput sequenom technology to the direct sequencing. The ability to analyze multiple samples for several hotspots plexed together provides two fold advantage of the sequenom technology. Methods: DNA was isolated from a panel of 22 colon cancer cell lines as published previously (Cancer Res 68: 1953-61, 2008) and 116 cancer specimens from 76 patients with mCRC. The DNA was then subject to PCR and sequenced. For the sequenom, while 34 hotspots were selected, we were able to test for 31 SNPs in 4 multiplexes. Results: Direct sequencing was performed on 4 genes at 12 hotspots or data gathered from the cosmic database. Pyrosequencing was performed on 3 genes at 9 hotspots. Sequenom multiplexing was performed on 31 hotspots in 19 genes in 4 multiplexes. Data on the cell lines are currently being reported. We were able to make
In Silico Design of Optimal Dissolution Kinetics of Fe‐Doped ZnO Nanoparticles Results in Cancer‐Specific Toxicity in a Preclinical Rodent Model
Authors: Bella B. Manshian, Suman Pokhrel, Uwe Himmelreich, Kaido Tämm, Lauri Sikk, Alberto Fernández, Robert Rallo, Tarmo Tamm, Lutz Mädler, Stefaan J. Soenen
Journal: Advanced Healthcare Materials (2017)

Cancer cells have unique but widely varying characteristics that have proven them difficult to be treated by classical therapeutics and calls for novel and selective treatment options. Nanomaterials (NMs) have been shown to display biological effects as a function of their chemical composition, and the extent and exact nature of these effects can vary between different biological environments. Here, ZnO NMs are doped with increasing levels of Fe, which allows to finely tune their dissolution rate resulting in significant differences in their biological behavior on cancer or normal cells. Based on in silico analysis, 2% Fe‐doped ZnO NMs are found to be optimal to cause selective cancer cell death, which is confirmed in both cultured cells and syngeneic tumor models, where they also reduce metastasis formation. These results show that upon tuning NM chemical composition, NMs can be designed as a targeted selective anticancer therapy.
Parkinson Sac Domain Mutation in Synaptojanin 1 Impairs Clathrin Uncoating at Synapses and Triggers Dystrophic Changes in Dopaminergic Axons
Authors: Mian Cao, Yumei Wu, Ghazaleh Ashrafi, Amber J. McCartney, Heather Wheeler, Eric A. Bushong, Daniela Boassa, Mark H. Ellisman, Timothy A. Ryan, Pietro De Camilli
Journal: Neuron (2017)
Is salvage focal cryotherapy curative treatment for patients with localized recurrent prostate cancer?
Authors: Aaron Katz, Kaitlin E. Kosinski, Courtney Berg
Journal: Journal of Clinical Oncology (2016)

26 Background: The salvage therapy options for patients with recurrent unilateral prostate cancer after primary radiation, or cryotherapy, are limited. Salvage focal cryotherapy is becoming a more popular treatment option as it has shown success in its disease-free survival rates. Salvage focal cryotherapy enables patients to delay or negate the use of hormone therapy, which has many unfavorable adverse effects. The aim of this study is to report on the curative success of salvage focal cryotherapy in patients with recurrent unilateral prostate cancer. Methods: We identified patients who underwent salvage focal cryotherapy at Winthrop University Hospital between February 2011 and August 2015. Age at the time of treatment, follow-up time, nadir PSA levels, and follow-up treatments were assessed. Results: From 2011 to 2015, 88 patients underwent salvage focal cryoablation. Of these patients, 14 (15.9%) required another therapy treatment after salvage focal cryoablation. Hormone therapy was a necessary treatment for 9 patients. Only 6 patients (6.8%) went on to hormone therapy due to an MRI finding of a local, nodal, or distant relapses. Three (3.4%) patients went on to hormone therapy due to a rise in PSA. Conclusions: Focal salvage therapy is associated with very low risk of clinical and radiographic progression of cancer. In our patients with radiation recurrent cancer, we were able to prevent or delay the use of hormone therapy in the majority of these men. [Table: see text]
The role of the electrocardiogram (ECG) in phase I drug development in patients with cancer: The University of Texas M. D. Anderson Cancer Center experience with 8,966 ECGs.
Authors: H. Veasey Rodrigues, A. Naing, D. S. Hong, G. S. Falchook, S. Fu, J. J. Wheler, A. M. Tsimberidou, S. L. Moulder, F. Janku, S. Wen, S. N. Fessahaye, E. C. Golden, D. I. Westerhold, M. Ewer, R. Kurzrock
Journal: Journal of Clinical Oncology (2011)

2545 Background: Cardiac sequelae resulting from oncologic drug use are an important consideration in early cancer drug development. Recently, the focus on cardiac monitoring has increased substantially. Prolongation of the QT interval (QTc) by non-cardiac drugs is the most common cause of drug development delays, non-approvals and, in diseases other than cancer, post-marketing withdrawals by the US Food and Drug Administration. Methods: We analyzed 8,966 electrocardiograms (ECGs) performed on 598 consecutive patients with cancer who were enrolled in 22 Phase I clinical trials starting on January 1, 2006 in the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center. Results: Thirty-three ECGs (0.36 % of the total ECGs, 95%CI: 0.3% - 0.5%) from 8 patients (1.3%, 95%CI:0.7% - 2.6%) showed QTc intervals above the upper limit of normal after starting treatment. In 3 of these ECGs (2 patients) the QTc were prolonged at baseline. All QTc prolongations were deemed clinically insignificant and drug was continued without adverse sequelae. Two of 598 patients (0.33%) experienced cardiac serious adverse events (myocardial infarction (MI) and atrial flutter with hypotension (attributable to metastatic tumor to the heart)); five patients demonstrated an asymptomatic drop in ejection fraction without associated ECG findings. The patient with MI presented with dyspnea on day 2 of study, and was diagnosed on a clinical, not protocol-dictated ECGs base (non-ST elevated MI). Conclusions: Frequent monitoring with serial ECGs did not provide clinically significant information.
Changes in circulating tumor cells (CTC) and markers of inflammation after sipuleucel-T treatment.
Authors: Mehmet Hepgur, Tanya B. Dorff, Jie Cai, Jacek K. Pinski, Mary Reed, Michael Luther, Betty Chan, David I. Quinn
Journal: Journal of Clinical Oncology (2013)

40 Background: Sipuleucel-T (SipT) prolongs survival of men with metastatic castrate-resistant prostate cancer (CRPC). We prospectively collected CTC, LDH, and inflammatory markers as part of an audit to investigate changes after SipT treatment compared to baseline. Methods: Men with CRPC had blood drawn routinely before and after SipT treatment. CTC were run using Veridex assay. LDH, C-reactive protein (CRP) and β2-microglobulin (β2m) were measured in a reference lab. Wilcoxon Signed Rank Test was used to compare pre- and post-treatment (median 3.5 weeks after final infusion) levels. Results: 61 men received SipT at USC from June 2010 to July 2012 and were included in the analysis. Median pre-SipT PSA level was 24.9 and 47% had Gleason 8-9; 20% had received chemotherapy. 18 men had detectable CTCs pre SipT (range 1-170). CTC count declined in 7 men, increased in 6 men, and stayed stable in 2 men (3 inevaluable); in 3 cases the change crossed men over from unfavorable ( &gt;5) to favorable count. PSA declines were noted in 10 men (16.4%) ranging from -0.5% to 99%. Change in CTC and PSA was discordant in 4 cases of 13. When CTC stayed stable PSA increased in 5 and decreased in 5 cases. Median CRP was 0.5 pre and 0.23 post SipT (p=0.025) and β2m was 1.74 pre and 2.01 post (p=0.02). Increased CRP was correlated with decreased CTC (r=0.7, p=0.003 Spearman test) but β2m changes were not (r=0.45, p=0.08 Spearman) and there was no correlation between changes in the inflammation markers and PSA decline. LDH did not change significantly. The relationship between infusion reaction, eosinophilia and inflammatory markers will be presented. Conclusions: We found that CTC counts can decline after SipT treatment, including conversion from unfavorable to favorable range, and can change independently of PSA. Correlation of CTCs with outcomes in a prospective study is warranted to explore this as a potential biomarker. [Table: see text]