tbuckley/cabot-search huggingface dataset:
Use of <i>KRAS</i> codon 13 mutations to predict response to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma.
Authors: Marjun Philip Duldulao, Wendy Lee, Zhenbin Chen, Wenyan Li, Rebecca A. Nelson, Joseph Kim, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2012)

453 Background: The predictive role of KRAS mutation in therapeutic management of metastatic colorectal cancer has been much investigated. However, the association between KRAS mutations and rectal cancer response to neoadjuvant chemoradiation therapy (CRT) remains unclear. Our objectives were to determine the incidence of KRAS mutations in patients with rectal cancer and identify potential correlations with response to CRT. Methods: Patients with Stage II-III rectal cancer (n=148) from a multicenter prospective clinical trial were assessed. DNA was extracted from pretreatment tumor biopsies; and genotyping of KRAS was completed by PCR and direct sequencing. All patients underwent pre-operative CRT followed by surgery; and treatment response was evaluated by a pathologist. Surgical specimens without evidence of residual disease were deemed to have a pathologic complete response (pCR). Results: Overall, 60 of 148 (40.5%) patients had KRAS mutation. Breakdown of the different KRAS mutations revealed that 40 (66.7%) mutations occurred in codon 12, 12 (20.0%) in codon 13, 5 (8.3%) in codon 61, and 3 (5.0%) in other locations. When examining the relationship between KRAS and CRT response, we observed that detection of any KRAS mutation was associated with a decreased rate of pCR compared to wild-type KRAS (13.3% vs. 33.0%, respectively; p=0.007). More specifically, patients with KRAS codon 13 mutations did not respond to CRT compared to non-codon 13 mutations (p=0.037). In contrast, the detection of codon 12 or codon 61 mutations was not associated with response to CRT ( Table ). Conclusions: Patients with KRAS mutation have lower response rates to CRT compared to patients with wild-type KRAS. However, our results indicate that this association does not apply to all KRAS mutations, rather to KRAS codon 13 mutation alone. Thus, these data are the first to show that patients with KRAS codon 13 mutations may not derive pCR from neoadjuvant CRT. [Table: see text]
Androgen Receptor Modulation Optimized for Response in Splice Variant (ARMOR3-SV): Randomized, open-label, multicenter, controlled study of galeterone versus enzalutamide (enz) in men expressing AR-V7 splice variant (SV), metastatic castrate resistant prostate cancer (mCRPC).
Authors: Jennifer Roberts, Reena Dhillon, Daniel T. Dransfield, Khalid Kevin Mamlouk, Karen J. Ferrante
Journal: Journal of Clinical Oncology (2015)

259 Background: Recent data showed that mCRPC patients (pts) with the androgen receptor (AR) SV AR-V7, a truncated form of the AR that lacks the ligand-binding domain and remains a constitutively active transcription factor, had worse clinical outcomes than patients without AR-V7 (Antonarakis et al, NEJM 2014; Efstathiou et al, ASCO 2014; Bambury et al, ESMO 2014). Galeterone, a small molecule, disrupts AR signaling via selective inhibition of CYP17 lyase, competitively inhibits androgen binding to AR, and degrades AR protein. In preclinical models, it demonstrated activity against many AR aberrations, including AR-V7, AR v567es , AR-T878A, and AR-F876L. Given the encouraging results in pts with AR C-terminal loss in the phase 2 ARMOR2 trial (Taplin et al, ESMO 2014), further research is warranted. Methods: ARMOR3-SV is a global, phase 3, randomized, open-label, multicenter, controlled study of galeterone vs enz in men expressing AR-V7 SV–mCRPC. Among other enrollment criteria, eligible pts must have the AR-V7 splice variant, be on GnRH therapy or have had a bilateral orchiectomy with testosterone &lt;50 ng/dL. Approximately &lt;170 pts will be randomized to receive once-daily oral therapy with galeterone 2550 mg or enz 160 mg. The primary endpoint is radiographic progression-free survival. Secondary endpoints include overall survival, time to cytotoxic therapy, and skeletal related events. Pts will be followed until radiographic disease progression as assessed by an independent, blinded radiologic review. Post-progression anticancer interventions will be collected and pts will be followed until death or study termination. Results: Because AR-V7 status must be determined for enrollment, the availability of a validated, accurate, rapid, quantitative, and universally applicable assay performed in a central CLIA-certified laboratory is critical to the trial. Conclusions: Choice of assay to identify and select mCRPC pts harboring AR-V7 is key to enrollment strategy for ARMOR3-SV. The study is expected begin in the first half of 2015.
Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation
Authors: Bertrand Calippe, Sebastien Augustin, Fanny Beguier, Hugo Charles-Messance, Lucie Poupel, Jean-Baptiste Conart, Shulong J. Hu, Sophie Lavalette, Alexandre Fauvet, Julie Rayes, Olivier Levy, William Raoul, Catherine Fitting, Thomas Denèfle, Matthew C. Pickering, Claire Harris, Sylvie Jorieux, Patrick M. Sullivan, José-Alain Sahel, Philippe Karoyan, Przemyslaw Sapieha, Xavier Guillonneau, Emmanuel L. Gautier, Florian Sennlaub
Journal: Immunity (2017)
The impact of clinical trial evidence and sociodemographic factors on institutional practice patterns for stage I testicular cancer.
Authors: Gautum Agarwal, Oscar Valderamma, Sabine Nguyen, Adam Luchey, Julio Pow-Sang, Philippe E. Spiess, Michael Adam Poch, Wade Jeffers Sexton
Journal: Journal of Clinical Oncology (2014)

372 Background: Contemporary management for patients with stage I testicular cancer (TC) continues to evolve. Survival is dependent upon staging, surveillance, and the treatment(s) rendered. We sought to determine whether treatment recommendations have been impacted by evidence gained from recent clinical trials and how sociodemographic factors might affect therapeutic decisions for patients with stage I pure seminoma (PS) and nonseminoma (NSGCT). Methods: We performed a single institution, institutional review board approved, retrospective review of patients evaluated for TC from 1999 to 2013. Chi-square and logistic regression analyses were performed between multiple variables including: type of treatment, specialty of the provider, year of treatment, insurance status, distance traveled to our hospital, and education level. Results: Four hundred forty patients were evaluated; of this group 121 patients had stage I TC. For NSGCT patients, living further than 50 miles from our center was associated with treatment (p=0.013). NSGCT patients who had completed an undergraduate education were more likely to undergo surveillance compared to those with a high school education (p&lt;0.01). If intervention was recommended, NSGCT patients evaluated prior to 2010 were more likely to undergo primary retroperitoneal lymph node dissection (RPLND) (p&lt;0.01). After 2010 these patients were more likely to have primary chemotherapy (PC) (p&lt;0.01). NSGCT patients evaluated by urologic oncologists had higher RPLND rates while patients evaluated by medical oncologists more often received PC (p&lt;0.01). The percentage of PS patients receiving external beam radiation decreased from 40% to 5% after 2010, while the rate of surveillance increased from 47% to 79% (p=0.016). For all stage I patients the presence of lymphovascular invasion was associated with treatment compared to surveillance (p&lt;0.001). Conclusions: The management of patients with stage I TC has changed significantly over the past decade. In our study, management recommendations have been shown to be dependent upon the specialty of the provider and other social factors such as distance from the hospital as well as education level, which suggests the possibility of bias during patient counseling.
Association of HER2/neu gene amplification and copy numbers of HER2/neu and chromosome 17 with tumor characteristics in resected colorectal cancer (CRC)
Authors: S. Sharif, R. Ramanathan, K. Cieply, E. Sasatomi, B. Elinoff, L. Liao, A. M. Krasinskas
Journal: Journal of Clinical Oncology (2005)

3592 Background: HER2/neu is an oncogene on chromosome (chr) 17 that encodes a type I tyrosine kinase growth factor receptor. In breast cancer, HER2/neu status, as assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), reliably identifies aggressive tumors and is routinely used for therapeutic decisions. In CRC, HER2/neu protein overexpression has been studied mostly by IHC, but its significance is still unclear. Our objective was to use FISH to compare various tumor characteristics with HER2/neu gene amplification and copy numbers of HER2/neu and chr 17 as possible markers for aggressive tumors. Methods: HER2/neu gene amplification (defined as a ratio of HER-2/neu to chr 17 centromere of >2), HER2/neu copy number (cutoff >4.37) and chr 17 copy number (cutoff >2.03) were assessed by FISH in 272 surgically resected colon cancers from 02/00 to 04/03. FISH results were correlated with these tumor characteristics: size, grade (1= well, 2=moderately and 3=poorly differentiated) and TNM stage. Statistical analysis was performed using Fisher’s exact test and Student’s t-test. Results: The mean patient age was 67 and 53% were female. Tumor characteristics: mean size, 4.8 cm; median histologic grade, 2 of 3; and most common stage, III (32%), followed by II (30%), I (23%) and IV (15%). HER2/neu gene amplification was detected in 55 of 272 (20%) tumors. The average HER2/neu and chr 17 copy numbers were 2.78 and 1.98, respectively. There was no statistically significant association between HER2/neu gene amplification, HER2/neu copy number or chr 17 copy number when compared to tumor size, grade or stage. Conclusions: Fifty-five out of 272 (20%) CRCs demonstrated HER2/neu gene amplification but no association was found with tumor size, grade or stage. In view of the 20% amplification rate, which approximates that seen in breast cancer, clinical trials with trastuzumab (Herceptin) appear worth pursuing. Correlation of HER2/neu expression with overall survival in these 272 patients is merited. To the best of our knowledge, ours is the largest reported series examining HER2/neu overexpression, HER2/neu and chr 17 copy numbers in CRC by FISH. No significant financial relationships to disclose.
Association of trimodality therapy (TMT) with rate of local-regional relapse and rare luminal-only relapse for patients with esophageal and esophagogastric junction (E-EGJ) cancer: Implications for the surveillance strategy.
Authors: Kazuki Sudo, Takashi Taketa, Arlene M. Correa, Maria-Claudia Campagna, Roopma Wadhwa, Mariela A. Blum, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Zhongxing X. Liao, David C. Rice, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

79 Background: For local-regional E-EGJ cancer patients, the preferred therapy is chemoradiation (CTRT) followed by surgery (TMT). Following TMT, esophagogastroduodenoscopy (EGD) and imaging studies are routinely performed but the literature lacks guidance for an evidence-based surveillance strategy. Methods: Between 2000 and 2010, 579 patients with local-regional E-EGJ cancer underwent TMT. We reviewed the patterns of relapse over time. Local-regional relapse was classified as regional or luminal-only. Overall survival was estimated by the Kaplan-Meier method. Results: For 579 patients, the median follow-up time was 57.4 months (95% confidence interval [CI]: 51.5-63.3 months). First relapses were as follows: 199 patients (34.4%) with distant metastases and 33 (5.7%) with local-regional relapse (of these only 10 [or 1.7% of 579] had a luminal-only relapse). 3 out of 33 patients underwent salvage surgery and survived &gt;2 years from relapse. Sixteen out of 33 patients received CTRT and only 4 survived &gt;2 years. Therefore, 7 (21% of patients with local-regional relapse or 1.2% of 579 patients) survived &gt;2 years. For the 33 patients with local-regional relapse, the median overall survival from relapse was 15.3 months (95% CI: 11.0-19.6). Conclusions: After TMT therapy, local-regional relapses are uncommon (&lt;6%) and luminal-only relapses are even rare (&lt;2%). 91% of local-regional relapses occur within 3 years of surgery. Only 7 (1.2% of 579) patients survived &gt; 2 years despite therapy. These data can contribute to an evidence-based surveillance strategy for E-EGJ cancer patients after TMT. Supported by UTMDACC and generous donors.
Usability and acceptance of novel personal health technology to support early palliative care for patients with cancer and caregivers.
Authors: Janice Bell, Sarah C. Reed, Katherine Kim, Victoria Ngo, Wendy Wait, Ester Apesoa-Varano, Joy Morgan, Robin L. Whitney, Emma Blackmon, Jill Joseph
Journal: Journal of Clinical Oncology (2016)

73 Background: Little research has assessed whether and how technology can support early palliative care. Our team developed a HIPAA-compliant, cloud-based Personal Health Network (PHN) with a secure, online network of family, caregivers, clinicians and service providers designated by the patient; symptom reporting/management resources; and support for communication among network members via audio/video conferencing, messaging, and document sharing. This study examines PHN usability and acceptance, and identifies additional functions for early palliative care. Methods: Patients undergoing chemotherapy in a Comprehensive Cancer Center (n = 19) and their caregivers (n = 17) watched video demonstrations of the technology, participated in semi-structured interviews, and completed surveys measuring computer self-efficacy, PHN usability and acceptance. Results: Most participants were male with college education; mean age was 58 years. Most had a tablet or desktop computer (75%), a mobile phone (94%) and believed that technology improves the security of medication information (66%). At the same time, only 44% used email to contact healthcare providers and 30% used the internet to connect with others for support and information. Most reported the PHN was easy to learn and use and was an efficient and useful tool for patient-driven social networking, team communication, care coordination and symptom management. Participants suggested adapting the PHN to support spiritual and emotional needs and advance care planning. Common concerns included skepticism about receipt of timely responses from providers to symptom reports and the need for ongoing support for older adults with limited technology experience. Conclusions: These preliminary findings support adaption of the PHN to support palliative care components identified as important to patients and caregivers and further PHN usability and acceptance testing in larger, more diverse samples. The results also underscore the need for systems to support technology users, to clarify expectations of response time with patients and caregivers, and to assure these expectations can be met by healthcare providers.
A pilot trial of early specialty palliative care for patients with advanced pancreatic cancer: Challenges encountered and lessons learned.
Authors: Yael Schenker, Nathan Bahary, Rene Claxton, Julie Childers, Dio Kavalieratos, Linda King, Barry C. Lembersky, Seo Young Park, Greer A Tiver, Robert Arnold
Journal: Journal of Clinical Oncology (2016)

110 Background: Palliative care trials face implementation barriers. We describe challenges encountered in a pilot trial of early specialty palliative care for patients with pancreatic cancer. Methods: We conducted a mixed-methods pilot randomized controlled trial of early specialty physician-led palliative care in advanced pancreatic cancer. Recently diagnosed patients with borderline, locally-advanced, or metastatic pancreatic cancer and their caregivers (total N=60) were recruited from clinic at a comprehensive cancer center and randomized (2:1) to receive monthly specialty palliative care visits for 3 months in addition to standard oncology care vs. standard oncology care alone. Feasibility assessments included enrollment and intervention completion rates. Acceptability and perceived effectiveness were assessed via drop-out rates and semi-structured participant interviews. Results: The enrollment target was reached after 50 weeks, with a randomized: approached rate of 27%. Mean patient age was 63 (SD 11) and 50% were male. Mean caregiver age was 62 (SD 12), 47% were male, and 80% were the spouse or partner of a patient. 70% of participants in the intervention group completed at least one specialty palliative care visit and 15% completed 3 palliative care visits within the 3-month time period. Two patients and 3 caregivers withdrew, and 4 patients died prior to 3 months. Enrollment barriers included patients not planning to continue receiving care from a participating oncologist and feeling too overwhelmed at the time of diagnosis to consider research participation. In semi-structured interviews, patients and caregivers noted that long travel times to the cancer center, difficulty scheduling palliative care visits at a convenient time, and lengthy study assessments posed burdens. Oncologists and palliative care physicians recommended more in-person communication between clinicians and tailoring palliative care visit content and schedules to match patient needs. Conclusions: Future palliative care intervention trials must consider implementation challenges related to recruitment, retention, intervention fidelity, and participant burden. Clinical trial information: NCT01885884.
Pegylated liposomal doxorubicin and carboplatin (C-PLD) versus paclitaxel and carboplatin (C-P) in platinum-sensitive ovarian cancer (OC) patients (pts): Treatment at recurrence and overall survival (OS) final analysis from CALYPSO phase III GCIG trial.
Authors: C. Marth, J. Alexandre, L. C. Hanker, C. Brown, J. Kaern, M. Heywood, A. Bonaventura, I. B. Vergote, S. Pignata, A. Ferrero, V. Gebski, M. Gropp, T. Skeie-Jensen, C. Giede, P. A. Vasey, C. Schauer, N. Reed, G. Ferrandina, R. Fossati, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2011)

5052 Background: CALYPSO is a large international randomized phase III trial comparing C-PLD and C-P in pts with OC in late relapse. Results of the progression-free survival (PFS), the primary endpoint, suggest a benefit in pts treated with C-PLD with a hazard ratio (HR) of 0.82 (P =.005). Overall severe non-hematologic toxicity (36.8% v 28.4%; P < .01) - including alopecia, neurotoxicity and carboplatin hypersensitivity leading to early discontinuation (15% v 6%; P < .001) - occurred more frequently in the C-P arm. Methods: From 04/05 to 10/07, 976 eligible pts were randomized to either C-P (carboplatin AUC 5 iv d1 + paclitaxel [P] 175 mg/m2 3h iv d1, q3w) or C-PLD (Carboplatin + PLD 30 mg/m2 iv d1 q4w) for at least 6 cycles. It was explored whether the treatment effect on PFS recently observed in CALYPSO was maintained after further treatment. OS of pts was analysed. Results: Median follow-up is 40 months (mo). 832 pts (86%) have progressed after CALYPSO treatment (C-PLD or C-P). At time of first progression following CALYPSO, median platinum-free interval (C-PLD:5.2, C-P: 5.5 mo) and percentage of pts receiving platinum-based treatment (C-PLD: 27% , C-P: 26%) were similar in both arms. Pts initially treated with C-PLD had significantly less risk of 2nd treatment failure compared with those initially receiving C-P, with a HR of 0.83 (95% CI: 0.73,0.96, p=0.01). There was a significant imbalance in the cross-over rate of PLD and paclitaxel between both arms (from C-PLD to P: 34%, from C-P to PLD: 57%). Median OS of the global population (n=621 events) was 31.5 mo with a HR of 0.987 (P = 0.87) for C-PLD compared to C-P. Conclusions: In pts with OC in late relapse, the benefit in disease control of C-PLD over C-P was maintained at 1st treatment following CALYPSO relapse. OS was similar in both arms while cross-over treatment rate was superior in the C-P arm.
Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial
Authors: B. Besse, J. Mazières, L. Ribassin-Majed, F. Barlesi, J. Bennouna, R. Gervais, L. Moreau, H. Berard, D. Debieuvre, O. Molinier, D. Moro-Sibilot, P.J. Souquet, S. Jacquot, L. Petit, H. Lena, J.P. Pignon, B. Lacas, F. Morin, B. Milleron, G. Zalcman, J.C. Soria
Journal: Annals of Oncology (2017)
Minimal Residual Disease Monitoring by Four Color Flow Cytometry before Second Induction Is an Independent Prognostic Factor in Childhood Acute Myeloid Leukemia - AML-BFM MRD Study Group.
Authors: Claudia Langebrake, Michael Dworzak, Ondrej Hrusak, Ester Mejstrikova, Frank Griesinger, Martin Zimmermann, Ursula Creutzig, Dirk Reinhardt
Journal: Blood (2005)
Demethylating drugs as novel analgesics for cancer pain.
Authors: C. T. Viet, Y. Ye, B. L. Schmidt
Journal: Journal of Clinical Oncology (2011)

e13531 Background: Cancer pain is a major public health problem for which little progress has been made. Effective treatment could result from targeting undiscovered mechanisms of cancer pain. DNA methylation is common in carcinogenesis, but has no known role in pain. We recently showed that methylation is a novel mechanism mediating pain in cancer patients. Reversal of methylation by demethylating drugs could therefore serve as novel therapy for cancer pain. Objective: To determine the analgesic potential of demethylating drugs zebularine and decitabine on cancer pain in a mouse model. Methods: A mouse cancer model was created by inoculating HSC-3, an oral squamous cell carcinoma cell line, into the right hindpaw of BALB/c mice. Mice were divided into the 4 groups: 1) zebularine-only treatment, 2) decitabine-only treatment, 3) combination treatment of both drugs, and 4) control sham treatment. Zebularine was administered in drinking water, given ad libitum starting post-inoculation day (PID) 4. Decitabine was given as a single dose of 2mg/kg weight by an osmotic pump. Mechanical allodynia (pain), assessed by paw withdrawal, was measured at baseline and at intervals up to PID 21. ANOVA and Holm Sidak statistical tests were used. Molecular analysis of tumors was performed. Results: Mice developed visible tumors by PID 4. Mechanical allodynia increased significantly from baseline, indicating increased pain. Zebularine-only treatment decreased cancer pain to baseline levels (p<0.05) by PID 15. Combination treatment of decitabine and zebularine resulted in an even more profound decrease in pain by PID 7 (p<0.05). Methylation quantification of tumors showed that treated mice had demethylation of the OPRM1 gene, which codes for the mu-opioid receptor that binds opiates, compared to control mice. The resultant increase in mu-opioid receptor expression also stimulated secretion of beta-endorphin, an endogenous opioid, in the cancer microenvironment. Conclusions: In this study we demonstrate a novel mechanism of cancer pain and the use of demethylating drugs to treat cancer pain. Demethylating drugs act through an endogenous analgesic mechanism, which is potentially more effective than the exogenous analgesics currently used.