tbuckley/cabot-search huggingface dataset:
Intermittent abiraterone-acetate administration protocol and prognosis prediction for castrate-resistant prostate cancer.
Authors: Jason David Morken, Chad Cherington, Alan H. Bryce, Yang Kuang
Journal: Journal of Clinical Oncology (2016)

353 Background: One mechanism leading to castrate-resistant prostate cancer (CRPC) is upregulation of CYP17. Abiraterone acetate (AA) inhibits CYP17 and continuous AA administration (CAAA) is one the most common and effective CRPC treatments. Mathematical models can be potentially powerful clinical tools for optimizing treatment strategies and eliminating guess work. Here, we introduce a new model which builds on our previous work (Morken JD, Packer A, Everett RA, Nagy JD, Kuang Y. Mechanisms of resistance to intermittent androgen deprivation therapy identified in prostate cancer patients by novel computational method. Cancer Res 2014;74:2673-83.) and may be capable of predicting how patients will respond to CAAA and intermittent AA administration (IAAA). We are currently proposing a personalized IAAA protocol on the basis of these results. Methods: In this ongoing retrospective study, we use PSA data from patients whom underwent CAAA to validate the accuracy of our model of tumor growth and evolution. The PSA output is driven by dynamics of three cell populations—castration-sensitive (CS), castration-resistant abiraterone-sensitive (CSAS), and castration-sensitive abiraterone-resistant (CSAR) cells. We fit the model output to PSA data to find parameter values which minimize normalized mean squared error (NMSE). Once parameters are obtained, we ran simulations employing various IAAA protocols. Results: The model’s PSA dynamics are highly accurate. NMSE is very low across patients ranging from 0.0001-0.0085. Conclusions: Our results suggest that there exists an IAAA protocol for each patient that, at worst, yields the same time to tumor progression as CAAA, yet improves quality of life and reduces cost. In nearly 20% of patients, IAAA appears to delay tumor progression over CAAA. The model is accurate at predicting how patients will respond to CAAA and IAAA for patients whose PSA is regularly monitored. Near-future work aims to personalize IAAA protocol based on patient pre CRPC PSA dynamics and to identify a protocol which delays progression for most patients.
Distribution and histopathology of colorectal polyps in the Asian population in the United States.
Authors: Samarth Patel, Raghav Bansal, Divyangkumar Gandhi, Loveleen Sidhu, Aron Walfish, Ishita Rajnish
Journal: Journal of Clinical Oncology (2014)

436 Background: Limited data exists for colorectal polyps in Asian population in U.S. Advanced polyps are considered as a high risk for CRC and require close surveillance. The aim of the study was to evaluate and compare the characteristics of polyps based on patient demographics, anatomic distribution, size, and histopathology in the Asian population living in one of the most heavily populated and diverse communities in U.S. Methods: We conducted a retrospective, single center chart review study of all asymptomatic Asian patients who underwent screening colonoscopy at a New York City hospital from Jan 2006 to Dec 2010. The patients without polyps were excluded from the study. Based on histopathology and size, polyps were divided into 2 groups: advanced and non-advanced. Results: Of the total 1,300 patients, 311 were found to have colon polyps. Mean age of the study population was 60.8 years (range 50-82). There were 173 males and 138 females, with male to female ratio 1.3:1. In gender analysis, 61% of the advanced polyps were found in males, however, the difference was not statistically significant (p = 0.255). 41% of patients had right sided polyps, 49% had left sided polyps, and 10% had bilateral polyps. Analysis showed significant increase in the proportion of patients with advanced polyps on left side (65%, p &lt; 0.05). Large size (≥ 1 cm) of the polyp correlated with advanced nature of the polyp (p &lt; 0.0001). On pathology review of the patients with polyps, 191 had non-advanced tubular adenoma, 38 had advanced tubular adenoma, 33 had hyperplastic polyp, 35 had villous/tubulovillous, and 13 had high grade dysplasia/colorectal cancer. Only 43 out of 86 patients (49%) with advanced polyps had follow-up colonoscopy. Conclusions: Polyps located on the left side were independently associated with advanced nature of polyp. Our results also revealed that large size polyps (≥ 1 cm) were strongly associated with being advanced in nature.Vigilant approach of the left side and large lesions should be exercised during screening colonoscopy in Asian Americans. Failure of the patients to follow up could be secondary to poor access to health care, language barrier, or health care beliefs. Efforts should be made to ensure adequate follow-up for surveillance colonoscopy.
The effect of beta-blocker treatment in patients with cutaneous melanoma.
Authors: V. De Giorgi, M. Grazzini, S. Gandini, S. Benemei, T. Lotti, N. Marchionni, S. Rossari, A. Gori, P. Geppetti
Journal: Journal of Clinical Oncology (2011)

8524 Background: Preclinical investigation supports the hypothesis that beta-adrenergic activation plays a detrimental role in cancer, including melanoma, and that beta-blockers reduce the pro-tumorigenic effects of such activation. We explored the hypothesis that the use of beta-blockers may protect against melanoma (MM) progression, at any stage. Methods: We investigated whether the use of beta-blockers, for concomitant diseases, is associated with a reduced risk of disease progression and mortality in patients with a diagnosis of MM. To test this hypothesis, we retrospectively reviewed the clinical records database of patients who had received a histological diagnosis of MM between 1993 and 2009 at the Dermatology Department of the Florence University. Patients were considered treated (treated group) if they reported that they use or have used β-blockers for 1 year or more, whereas untreated patients (untreated group) were those who reported to have never used β-blockers or to have used them for less than 1 year. Results: We analyzed 741 melanoma patients included in the database: 245 (33%) were “in situ” and 112 (15%) were thick melanoma (>1 mm). The treated group consisted of 79 patients (11%), and the untreated group consisted of the remaining 662 patients. The median duration of β-blocker use in the treated group was 5 years (range: 1-31 years). After a median follow-up time of 4.2 years, 55 (8.3 %) of the patients in the untreated group showed disease progression, whereas progression was observed only in 2 (2.5 %) of the patients in the treated group. After adjusting for age, Breslow thickness and ulceration, the Cox model indicated that treatment with β-blockers and its duration reduced the risk of recurrence of the disease (P=0.0001 and P=0.0004, respectively): for each year of use we found a 33% (95%CI: 17% to 48%) reduction in the risk of recurrence. A similar trend was observed also for overall mortality (P=0.005 and P=0.01, for ever use and years of use, respectively): for each year of use we found a 38% (95%CI: 10% to 57%) reduction in the risk of death. Conclusions: The present data suggests that exposure to β-blockers for more than one year is associated with a reduced risk of progression of MM.
Clinical experience of docetaxel in combination with prednisolone and zoledronic acid for hormone-refractory prostate cancer (HRPC): A Bangladesh perspective.
Authors: E. Hoque, S. Karim, M. D. S. Reza, T. U. Ahmed, R. A. Adnan
Journal: Journal of Clinical Oncology (2011)

e15049 Background:The patients with prostate cancer initially respond to androgen ablation therapy but most patients ultimately develop a hormone-refractory state. Most of the patients in our country present HRPC with bone metastasis. Earlier patients were treated with Mitoxantrone plus Prednisolone. Zoledronic acid was used for symptomatic relief of pain and increases the QoL. Docetaxel showed good response in case of HRPC. We conducted a study to evaluate the efficacy and toxicity of docetaxel in combination with zoledronic acid plus prednisolone in pain and PSA control. Methods:A total number of thirty patients were randomly assigned to receive zoledronic acid 4 mg/m2 in q3w with prednisolone 5 mg twice daily in combination with docetaxel 75 mg/m2 in patients with hormone refractory prostate cancer (HRPC) at our institution between July 2007 and June 2009. The primary endpoint was to evaluate the response to pain and PSA level. Secondary endpoint included overall survival and QoL. Results:A total of 28 patients were evaluable for the study. 43% of the pts had predefined reductions in pain. 54% had at least a 50% decrease in the serum PSA level. The overall response rate was 48.4% (13 patients), with partial responses in 24.24% (7 patients). The median duration of response was 20.2 weeks. 32% had improvement in the QoL. Median survival was 18.4 months. Adverse events related to Docetaxel included alopecia (60.7%), anorexia (50.1%) and fatigue (32.5%). Grade 3/4 neutropenia occurred in 48.4% of patients. Conclusions:Earlier for bone Metastasis with HRPC, zoledronic acid, Mitoxantrone and prednisolone was the choice of treatment. But the result was not satisfactory. Combining docetaxel with zoledronic acid and prednisolone in Bangladeshi population has shown excellent response in case of pain and PSA reduction with tolerable toxicities. Though the survival rate was unchanged the combination of docetaxel with ZA and Prednisolone regimen is effective in reduction of pain and PSA level in Bangladeshi patient population.
Pharmacogenetic (PGx) analysis of toxicity after oxaliplatin (Ox), capecitabine (Cap), bevacizumab (Bev) and cetuximab (Cet) therapy for advanced colorectal cancer (ACC): First results from the Dutch Colorectal Cancer Group (DCCG)-CAIRO2 trial
Authors: J. Pander, J. Tol, H. Gelderblom, N. F. Antonini, R. J. van der Straaten, C. J. Punt, H. Guchelaar
Journal: Journal of Clinical Oncology (2008)

2574 Background: In the CAIRO2 study the addition of Cet to the combination Cap, Ox and Bev for patients with untreated ACC is investigated. The aim of this side study is to evaluate predictive PGx factors for toxicity for Cet and Cap in the EGFR/FCGR pathway and thymidylate synthase (TYMS) gene, respectively. Methods: Treatment was administered q3wk until progression: Ox 130 mg/m2 iv cycle 1–6, Cap 1,000 mg/m2 orally bid on day 1–14 (1,250 mg/m2 after 6 cycles) and Bev 7.5 mg/kg iv on day 1 (arm A) with the addition of Cet 400 mg/m2 iv on day 1 of cycle 1, thereafter weekly 250 mg/m2 (arm B). Toxicity (NCI-CTC v3) was evaluated in the first 400 patients. Cet and Cap related toxicities were evaluated and DNA was isolated from peripheral blood after informed consent. Genotype of FCGR2A His131Arg (n=259), FCGR3A Phe158Val (n=253), EGF 61A>G (n=217) and CCND1 870G>A (n=273) were analyzed with Taqman, EGFR CA-repeat (n=221; both alleles <20 vs. any allele >/=20 repeats) was analyzed with fragment analysis and TYMS 2/3C/3G (n=255) was analyzed with direct sequencing. Multivariate logistic regression was performed with gender, age, performance status, treatment arm and number of affected organs as confounders. Results: Germline DNA from 299 (arm A: 153; arm B: 146) eligible patients was available. The FCGR2A polymorphism was associated with grade 3–4 acneiform skin reaction and/or nail changes (ASR/NC) (P=0.037). Carriage of the FCGR2A-His allele (n=199/259) was associated with an increased risk of grade 3–4 ASR/NC (OR=3.85; 95%CI=1.02–14.29). The FCGR3A, EGF, CCND1 and EGFR polymorphisms were not associated with grade 3–4 ASR/NC. Non-carriage of the TYMS-3G allele (n=156/255) was associated with an increased risk of grade 2–4 hand-foot syndrome (HFS) (OR=1.82; 95%CI=1.03–3.23) but not with the risk of grade 3–4 diarrhea. Conclusions: These results indicate that the FCGR2A His131Arg and TYMS-3G polymorphisms may be useful markers for predicting ASR/NC after Cet treatment and HFS after Cap treatment, respectively. No significant financial relationships to disclose.
Spirituality, religiosity, spiritual pain, and quality of life among Latin American patients with advanced cancer (LAAdCa): A multicenter study.
Authors: Marvin Omar Delgado-Guay, Alejandra Palma, Eva Rossina Duarte, Monica Grez, Laura Tupper, Diane D Liu, Andrea Octavia Ferguson, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

246 Background: The associations between spirituality (S), religiosity (R), spiritual pain (SP), symptom, coping and quality of life (QOL) have not been well characterized in LAAdCa. The main purpose of this Multicenter study was to analyze these associations. Methods: We interviewed 325 LAAdCa at a Palliative Care clinic in Chile, Guatemala, and USA. They completed FICA (S/R assessment), ESAS–FS (including SP), PSWQ (Worry), B-COPE and B-R-COPE (coping), FACIT-sp-ex (Spiritual Well-being). Results: Median age 58 (range: 19-85), 60% women, 62% Catholic, 30% Christian not Catholics, and 2% with no religion. 97% of LAAdCa considered themselves spiritual and 89% religious, median 7(IQR: 5-10) and 7(5-9) respectively. Median Importance of S/R in life (score 0 = none, 10 = very important) was 10 (IQR:8-10). The frequency and associations among the importance of S/R and different items were: helps them to cope with their illness (98%, r = 0.73; p &lt; 0.0001), is a source of strength and comfort (99%, r = 0.79; p &lt; 0.0001), and has a positive effect in physical symptoms (81%, r = 0.40; p &lt; 0.0001), emotional symptoms (84%, r = 0.42, p &lt; 0.0001), and helps to their caregivers to cope with pts' illness (100%, r = 0.66, p &lt; 0.0001). 60% of LAAdCa reported that their S/R needs had not been supported by the medical team. 24% had received pastoral attention inside the hospital. 162/311 (52%) of LAAdCa reported spiritual pain (median 6; IQR: 5-8). Spiritual pain significantly correlated with worse pain (p = 0.02), fatigue (p = 0.0002), depression (p &lt; 0.0001), anxiety (p &lt; 0.0001), Financial distress (p &lt; 0.0001), worry (p &lt; 0.001), behavioral disengagement (p = 0.01), FACIT-sp-Ex (p = 0.0002), negative religious coping strategies (p &lt; 0.0001), caregiver’s SP (p = 0.02), caregiver’s depression (p &lt; 0.0001), caregiver’s anxiety (p = 0.0007), and worse caregiver’s QOL (p = 0.001). Conclusions: Majority of LAAdCa considered themselves spiritual and religious. S/R help to deal with their illness and correlates with less emotional distress, positive coping strategies and QOL. Still more than 50% LAAdCa reported SP and their S/R needs are not totally supported by the medical team. More research is needed.
Prostate cancer care in Canada: Informed decision-making, patterns of care, and treatment trends.
Authors: Kim Tran, Rami Rahal, Carolyn Sandoval, Geoff Porter, Sharon Fung, Cheryl Louzado, Julie Xu, Heather E. Bryant
Journal: Journal of Clinical Oncology (2016)

289 Background: Because treatment options for localized prostate cancer (PCa) have similar survival outcomes but varying side effects, it is important that patients are meaningfully involved in the decision-making process to ensure the chosen treatment aligns with their needs, wants and preferences. Here, we describe PCa patients’ experience with informed decision-making as well as treatment patterns and trends over time. Methods: Focus groups were conducted with 47 men treated for PCa across Canada to understand their cancer journey experience. Thematic analysis was conducted. A subset of this data on informed decision-making is described. Men (≥ 35 years) diagnosed with localized, low-risk PCa from 2011-2013 were identified using data from six provincial cancer registries. Treatment data were identified by linking hospital/cancer centre data with registry data. Descriptive statistics were generated to describe treatment patterns and trends. Results: Focus group participants expressed a desire to be involved in the treatment decision-making process. While many participants felt completely informed about the treatment choices available to them, others felt they had not been properly engaged in the treatment decision-making process. Some participants felt they had opted for surgery or radiation therapy (RT) without full knowledge of the trade-offs between potential benefits and side effects. Others felt they may have made different decisions about their care had they been more informed. From registry data, in 2013 surgery was the most common primary treatment for men with low-risk PCa ranging from 12.0% in New Brunswick to 41.7% in Nova Scotia. RT was the second most common ranging from 6.4% in New Brunswick to 18.3% in Saskatchewan. Varying majorities of men had no record of surgical or radiation treatment, a proxy for active surveillance. Treatment trends over time suggest an increase in the use of non-active treatment approaches from 60.7% in 2011 to 69.9% in 2013. Conclusions: System performance indicators yield useful information about oncology practice patterns and trends. This information is enhanced when combined with patient level information on how men felt about decision-making around their PCa care.
PCF chemotherapy combined with surgical treatment of advanced gastric cancer.
Authors: Cheng Xiangdong
Journal: Journal of Clinical Oncology (2013)

113 Background: Local advanced gastric cancer that could not receive R0 resection or gastric cancer with distant metastasis usually received palliative chemotherapy or entered into a number of clinical trials, and surgery usually roled as a symptomatic treatment. This study is to investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of these patients. Methods: From July 2008 to February 2011, 72 cases of local advanced gastric cancer that cannot be treated with R0 resection (T4N2~3M0) or gastric cancer with single organ metastases (M1) were prospectively analysed. Patients received 2-4 cycles of PCF chemotherapy (PTX 150mg/m 2 , d1, CDDP 25mg/m 2 , d1-3, CF 250 mg/m 2 , d1-3,5-FU 750 mg/m 2 , d1-3, repeated every 3 weeks), then the primary and metastatic tumor were treated with cytoreductive surgery: mainly treated with radical resection of gastric tumor, combined with D3 and D4 lymph node dissection, pancreaticoduodenal resection, colon resection, ovariectomy, peritoneal resection, liver resection, and tumor radio frequency, followed with another 2-4 cycles of PCF chemotherapy. The treatment completion rate, patients’ tolerance, and overall survival (OS) time were analyzed. Results: 50 patients (69.4%) accomplished chemotherapy and surgical resection as planned. 42 cases had R0 resection (58.3%). The postoperative complication rate was 6.0%. Grade 3/4 toxic effects included bone marrow suppression (30.6%) and gastrointestinal reaction (40.3%), the overall response rate (CR+PR) was 72.2%. Survival analysis: the median survival time was 23.5 months. 1-year and 2-year survival rate was 67.0% and 47.0%. The OS of patients with surgical resection was much longer than that of the non-surgery group. (30.2 vs. 8.9 months) (p &lt;0.01). The OS of local advanced group was 30.3 months, and was significantly longer than 17.6 months of the distant metastasis group (p &lt;0.01); however, it had no significant difference compared to 28.2 months of the distant metastasis group with R0 resection. Conclusions: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for patients with local advanced gastric cancer or gastric cancer with single organ metastasis.
In vitro efficacy of MAGMAS inhibition in prostate cancer.
Authors: Benjamin C. Powers, Bhaskar Das, Boumediene Bouzahzah, Peter J. Van Veldhuizen, Emma Borrego-Diaz Reyes
Journal: Journal of Clinical Oncology (2014)

281 Background: Prostate cancer is the second most common cancer worldwide in males. The initial treatment in advanced cases is medical or surgical castration. The outlook declines when prostate cancer advances independently, despite the aforementioned castration. Within the last ten years, a handful of new agents have proven effective in this castration-resistant phase, but finding more effective, novel ways of treating advanced prostate cancer is warranted. MAGMAS (mitochondria-associated, granulocyte-macrophage colony stimulating factor (GM-CSF) signaling molecule) is a protein ubiquitously expressed in eukaryotic cells that plays a key role in embryonal development in a variety of species. Overexpression of MAGMAS has anti-apoptotic effects, as GM-CSF is a growth factor essential for survival, proliferation and differentiation of cells. MAGMAS and GM-CSF receptor levels have been shown to be overexpressed in prostate cancer, but do not correlate with pathological grade or clinical stage. The purpose of our study was to evaluate the efficacy of a MAGMAS inhibitor, synthesized by Dr Bhaskar Das, in androgen-dependent and androgen-independent prostate cancer cell lines, as well as in a normal prostate cell line as another control. Methods: The different cell lines were treated with MAGMAS inhibitor at various concentrations in vitro. For analysis, we used MTT Cell Proliferation assay at 24 and 48 hours, per manufacturer’s protocol. We tested MAGMAS inhibitor effect on apoptosis/necrosis, cell migration and microtubule destabilization as well. Results: After prostate cancer cell lines were treated with MAGMAS inhibitor in vitro, cell proliferation and migration decreased, apoptosis and necrosis were induced, and microtubules were destabilized, all showing more impressive results in the androgen-independent cells. MAGMAS inhibition did not affect cell proliferation in the normal prostate cells. Conclusions: In vitro studies show MAGMAS inhibition proves efficacious in both androgen-dependent and androgen-independent prostate cancer cell lines. This will be evaluated further in a xenograft mouse model.