tbuckley/cabot-search huggingface dataset:
KRAS mutant circulating free DNA (cfDNA) and circulating tumor cell (CTC) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer.
Authors: Carmen Guillén Ponce, Julie Earl, Sandra Garcia Nieto, Jose Carlos Martinez-Avila, Jose Montans, Alfonso Sanjuanbenito, Mercedes Rodríguez Garrote, Eduardo Lisa, Elena MendÃÂa, Eduardo Lobo, Nuria Malats, Alfredo Carrato
Journal: Journal of Clinical Oncology (2015)

e15252 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to treat with the poorest prognosis as patients often present with late stage disease. The key to improving prognosis may lie in early detection of the disease. There are no reliable markers to check for microscopic metastatic or residual disease before or after surgery. KRAS mutations are found in approximately 95% of PDAC primary tumors. Minimally invasive tumor markers such as circulating free DNA (cfDNA) is a promising predictive marker in solid tumors. Methods: This is a pilot study of KRAS mutation detection in cfDNA , as a novel minimally invasive biomarker in PDAC, compared with Circulating Tumor Cell (CTC) detection. The total DNA content in plasma was estimated by quantification of RNaseP gene copy number. The 3 most common KRAS mutations found in PDAC (G12D, G12V and G12R) were detected in cfDNA by digital PCR. CTC were detected using the CellSearch System. Results: The concentration of cfDNA increased with disease stage. KRAS mutant cfDNA was detected in (8/31) 26% of patients of all stages, this included 3 patients with a localised resectable disease and the remaining patients had advanced disease. The presence of mutant KRAS in plasma correlated strongly with Overall Survival (OS), 60 days (95% CI:19-317) for mutation positive vs 772 days for mutation negative (95% CI:416-1127). CTC were detected in 20% of patients, the majority of which had metastatic disease. The presence of CTC also correlated significantly with OS, 88 days (95% CI: 27-206) CTC positive vs 393 days CTC negative (95% CI: 284-501). Conclusions: . KRAS mutant cfDNA detection out performed CellSearch CTC detection as a promising marker for the management of patients with PDAC as KRAS mutant DNA was found in all stages. The presence of tumor cfDNA in plasma may indicate disseminated or residual disease in these patients and thus may aid the clinicians to devise more adequate treatment plans for this devastating disease. This may also be used as an early detection marker as tumoral cfDNA may be detected several weeks before lesions are visible by standard imaging techniques.
SWOG 0421: Prognostic and predictive value of bone metabolism biomarkers (BMB) in castration resistant prostate cancer (CRPC) patients (pts) with skeletal metastases treated with docetaxel (DOC) with or without atrasentan (ATR).
Authors: Primo Lara, Benjamin Ely, David I. Quinn, Catherine M. Tangen, Erik Gertz, Philip C. Mack, Przemyslaw Twardowski, Nicholas J. Vogelzang, Maha Hussain, Ian Murchie Thompson, Marta Van Loan
Journal: Journal of Clinical Oncology (2012)

4547 Background: S0421, a phase III study of DOC +/- the endothelin antagonist ATR in CRPC pts with bone metastases, showed no overall survival (OS) benefit for DOC+ATR. While BMB may have a prognostic role in CRPC, their predictive role vis a vis bone-targeted therapy such as ATR is unknown. We prospectively assessed pre-treatment serum BMB from S0421 pts to validate their prognostic and predictive value. Methods: BMB for resorption (N-telopeptide, NTX and Pyridinoline, PYD) and formation (C-terminal collagen propeptide, CICP and bone alkaline phosphatase, BAP) were assayed [Quidel (PYD, CICP, BAP) and Wampole (NTX)]. Cox regression models for OS based on BMB adjusted for clinical variables were developed. An adjusted Cox model was fit with main effects and BMB x Treatment interaction to assess predictive value of ATR on OS. Results: Of 1,038 pts, 855 (82%) submitted baseline serum: 778 (91%) were usable and analyzable. Pt characteristics: median age = 69 years; PS 0-1 = 91%, Bisphosphonate use = 61%; Gleason &gt;7 = 56%; median PSA = 68; and bone mets only = 45%. BMB values (median; range): NTX (14 nM; 9.3-23.9), BAP (64.7 u/L; 35-164), CICP (9.5 ng/mL; 6.5-17.4), and PYD (2.8 nmol/L; 2.2-3.9). Table below shows prognostic role of BMB. Pts with very high BMB (upper 25 %ile, n=47) not only have poor prognosis (HR = 4.3, p&lt;0.001) but have OS benefit from ATR (HR=0.34, median OS = 13.6 vs. 6.7 months; interaction p=0.002**). Conclusions: S0421 validates the strong independent OS prognostic value of BMB in CRPC. Very high BMB levels appear to be significantly predictive of OS benefit with ATR. Further study of endothelin antagonists in CRPC should focus on this high-risk pt subset. (5R01-CA120469) [Table: see text]
Is the primary tumor location (PTL) associated with differential gene expression profiles in patients with metastatic colorectal cancer (mCRC)? Analysis of the FIRE1-trial.
Authors: Lien D. Le, Ulrich Robert Mansmann, Andreas Jung, Thomas Kirchner, Reinhold Schäfer, Daniel Neureiter, Julian Walter Holch, Volker Heinemann, Sebastian Stintzing
Journal: Journal of Clinical Oncology (2017)

598 Background: Site-differential molecular characteristics of PTL as well as its influence on overall survival have been reported. In our study, we investigated the association of PTL with gene- and pathway-wise RNA expression as well as its representation in RAS mutational status subgroups. Methods: The phase-III-trial FIRE-1 compared the efficacy of FuFIRI and mIROX in patients with mCRC. Formalin-fixed, paraffin-embedded pretreatment samples from 166 FIRE-I patients were collected. The splenic flexure was used for differentiation between left colon cancer (LC) and right colon cancer (RC). RAS mutated PTs (RAS mut ) had PCR confirmed mutations in KRAS gene (Exon 2, 3, or 4) or in NRAS gene (Exon 2, 3, or 4). RNA expression profiling used the nCounter(R) PanCancer Pathways Panel including DNA damage control and TGF-β. We also studied a set of selected genes (Aprataxin, AREG, CD3EAP, CES1, CES2, CMPK1, DPD, DUT, ERCC1, ERCC5, EREG, FGF2, GSTP1, KLC3, MTHFR, PPP1R13L, RCC1, TOPO1, TP, TS, and UGT1A1). The gene-wise analyses used Limma and the permutated t-test with appropriate multiple testing adjustment. Holistic pathway investigation used GlobalAncova and the global tests. RAS mutation status and its correlation with tumor side were included as factors in both analyses. Additionally, gene- and pathway-wise analyses were performed in RAS mut and RAS WT subgroups. Results: A total of 83 (50%) of 166 patients had any RAS mutation. A total of 28 (17%) patients had PTs on the right side and 13 of those (46%) were RAS mut . The top ten differentially expressed genes between LC and RC are MMP9, ERCC3, MAP3K1, RRAS2, SOCS3, RB1, TGFβ1, LEFTY1, NKD1, and CDC25B (unadjusted p-values &lt; 0.005). Potential enrichment in the DNA damage control pathway was found (p = 0.008). The RAS subgroup analyses showed a non-overlapping top ten list. Side specific effects may exist for the TGF-β pathway and the selected gene set in RAS WT patients. Conclusions: No strong association between PTL and gene expression showed up in mCRC tumors nor RAS subgroups. Potentially differential gene expression may exist for specific genes, two pathways and our selected gene set.
Primary hypertension to predict progression-free survival of target therapy in patients with metastatic renal cell carcinoma.
Authors: Zhi Hong Chi, Li Li Mao, Lu Si, Chuan Liang Cui, Xi Nan Sheng, Si Ming Li, Bi Xia Tang, Jun Guo
Journal: Journal of Clinical Oncology (2012)

e15052 Background: Primary Hypertension(PH) was identified as a risk factor for RCC(renal cell carcinoma) in previous studies, only one report showed history of hypertension predicted better survival in RCC patients. In recent years, treatment related hypertension (TRH) was found to be associated with clinical outcome of targeted therapy. However, little is known about whether primary hypertension had an effect on survival of mRCC patients treated with targeted therapy. The objective of this study was to investigate the effects of primary hypertension on treatment outcome in patients treated with targeted therapy for metastatic RCC (mRCC). Methods: We conducted follow-up on a cohort of consecutiave mRCC cases treated with sunitinib or sorafenib in our center. Baseline characters were recorded such as age, gender, blood pressure, stage, et al. All the patients were followed up for progression free survival (PFS), overall survival (OS), objective response rate(RR). Results: We studied a cohort of 77 cases, 58(24.7%) pts were male, 18(23.4%) pts were 65 years or older, and 47 (61%) pts received sunitinib. 28 pts(36.4%) had a history of PH and 19 pts (24.7%) developed TRH, which was more common in PH pts than pts with normal blood pressure(p=0.003). With a median follow-up time of 24 months (range: 1.5-36.2 months), 60 pts developed disease progression and 34 pts died. Patients with primary hypertension demonstrated longer median PFS than those with normal baseline blood pressure (14.0m vs 9.5m, 95%CI: 8.0-10.9m) (p=0.01). In multivariable analysis, primary hypertension was independent predictors of PFS (HR =0.51, 95% CI; 0.27-0.98). No significant differences were found between clinical outcomes and other factors such as gender, age. Conclusions: Data from this study suggested that primary hypertension may be an independent predictor of longer PFS in mRCC pts treated with targeted agents.
Metastatic melanoma presenting during childhood: NCI Pediatric Oncology Branch experience.
Authors: Melinda S. Merchant, Donna B Bernstein, Cindy Delbrook, Matthew Wright, Crystal Mackall
Journal: Journal of Clinical Oncology (2014)

10075 Background: Childhood melanoma is rare with an incidence of ~300 cases/yr in the United States. Stage IV disease is detected in 1-10% of reported pediatric melanomas. The treatment of this chemoresistant disease in pediatric patients can be quite challenging, even with access to recently approved therapies for melanoma. Limited numbers have made it difficult to determine if the presentation and characteristics of pediatric metastatic melanoma are similar to the disease seen in adults. Methods: In a retrospective chart review, we identified sixteen pediatric patients with metastatic melanoma who were referred to the Pediatric Oncology Branch. Molecular status of tumors was determined by CLIA certified tests. Patient overall survival data was collected while patients were treated with ongoing immunotherapy protocols or with treatment using approved agents. Results: A total of 16 patients aged 2-21yo were evaluated from January 2009 to January 2014. Fifteen patients had cutaneous melanoma and one teen had mucosal melanoma. Eleven patients (68%) had a head and neck primary, including 8 patients with the scalp identified as the primary site. One teenager presented with widely metastatic disease from an unknown primary. In addition to common sites of metastases in lymph node, liver, and lung, pediatric patients also developed brain metastases (n=8 patients) and ocular metastases (n=1 patient). Five of the 12 tumors (42%) tested at diagnosis were found to harbor the BRAF V600E mutation. An NRAS mutation was identified in two melanomas. No ckit mutations were identified. Despite multiple treatment strategies, all patients experienced progressive or relapsed disease. The median survival of this cohort was 6 months following diagnosis of metastatic melanoma. Conclusions: Metastatic melanoma in the pediatric population is an aggressive disease with widespread pattern of metastasis. Head and neck primaries had a higher incidence in this series than has been identified in pediatric or adult melanoma of all stages. It is unclear if this increase is due to delayed detection or differences in biology. Further advances in pediatric melanoma will be aided by in-depth genomic analysis and collaborative study of these rare cases.
Heart rate variability (HRV) training for symptom control in cancer survivors.
Authors: Mark Allen O'Rourke, Sherry Stokes, Franco Regina, Kerri Susko, William Hendry, Annie Anderson, Jameson Sofge, Jay Ginsberg, James Burch
Journal: Journal of Clinical Oncology (2017)

148 Background: Late effects of cancer and its treatment include pain, fatigue, stress, and depression, all mediated by autonomic dysfunction. Heart Rate Variability (HRV) coherence is an established measure of optimal autonomic function. HRV coherence is achieved when the heart beat-to-beat intervals increase and decrease with respiration in a smooth rhythm. High coherence is associated with improved mood, cognition, executive function, and optimal pulmonary gas exchange. Cancer survivors have lower HRV than controls. Low HRV has been associated with early mortality, inflammation, and other adverse intermediary outcomes. HRV biofeedback (HRV-B) training improves HRV coherence, restores autonomic health, and reduces the above symptoms. HRV-B is non-pharmacologic, inexpensive, and self-maintained. This report describes a feasibility study of HRV-B in symptomatic cancer survivors. Methods: In a randomized, waitlist-controlled clinical trial, 179 were screened, 35 enrolled and 31 completed the protocol. Participants in the intervention arm received weekly HRV-B training up to six weeks. Outcome measures assessed at baseline (pre) and after week six (post) included HRV coherence plus the Brief Pain Inventory (BPI), Multi-Dimensional Fatigue Inventory (MFI), Perceived Stress Scale (PSS) and Beck Depression Inventory II (BDI-II). Data analyzed using linear-mixed models for repeated measures (SAS Proc Mixed). Results: Conclusions: Delivering HRV Biofeedback training to cancer survivors is feasible in a clinical setting. This study provides preliminary evidence that HRV-B training for cancer survivors improves HRV and reduces pain, fatigue, stress, and depression. HRV-B training has potential for symptom control in cancer survivors. Controlled, multisite studies are indicated.[Table: see text]
Outcomes of UCB (unrelated cord blood) transplantation are equivalent to matched-sibling hematopoietic stem cell transplantation (HSCT) in children with high-risk acute lymphocytic leukemia (ALL)
Authors: D. A. Jacobsohn, B. Hewlett, R. Seshadri, M. Ranalli, R. Duerst, M. Kletzel
Journal: Journal of Clinical Oncology (2004)

8563 Background: HSCT is commonly used for pediatric ALL patients with early relapse or other high-risk features. Given the lack of matched-sibling donors and multiple advantages of UCB as a stem cell source (less GVHD, rapid availability), we compared the outcomes of high-risk pediatric ALL patients that underwent HSCT at Children's Memorial Hospital (since 1992) with UCB (4–5/6 HLA match) or HLA-matched sibling transplant (6/6 HLA match). Methods: Patients included: ALL CR2 patients who relapsed <36 mos from diagnosis and ALL CR1 patients with at least 1 high-risk feature (unfavorable karyotype, poor response to induction, age<1 yr, WBC>100,000 at diagnosis). 25% of CR1 patients in both groups had 2 or more high-risk features. Cytoreduction, which was the same in both groups, consisted of TBI 150cGy × 8 (d-9 to-6), VP-16 1g/m2 over 24hr (d-5 to-4), and cyclophosphamide 60 mg/kg/day (d-4 to-2). GVHD prophylaxis: CSA, short-course MTX, and for UCB ATG d +1, +3, +5, +7. Three of the matched-sibling grafts were T-cell depleted. Results: There were 23 matched-sibling (20 BM/3 PBSC) and 26 UCB recipients. Both groups had equivalent high-risk factors. Engraftment took longer in UCB recipients. 100d TRM and GVHD rates were equal in both groups. 3 yr EFS was 60% in both groups. Age, gender, degree of HLA-matching (for UCB), and acute/chronic GVHD did not affect EFS. Conclusions: In pediatric patients with high-risk ALL being considered for HSCT, outcome of matched-sibling HSCT and UCB transplant is equivalent with regards to TRM, GVHD, and EFS. UCB should be considered an equivalent stem cell source to use in this group when a HLA-matched sibling is not available. No significant financial relationships to disclose.
Multimodality salvage therapy for anal cancer failing standard chemoradiation
Authors: Y. N. You, D. W. Larson, E. J. Dozois, H. Nelson, E. Antpack Filho, K. Klein, R. C. Miller
Journal: Journal of Clinical Oncology (2009)

e15635 Background: Most squamous cell carcinomas of the anal canal (SCC) respond to chemoradiation, but effective therapy for locally-invasive(T4) or recurrent disease that fails standard chemoradiation and/or salvage abdominoperineal resection (APR) has not been clearly delineated. A multimodality approach including chemoradiation, extended pelvic resection and intraoperative radiation therapy (IORT) was assessed for survival impact and treatment morbidity.morbidities. Methods: A prospective registry including 26 patients with locally-invasive or recurrent disease treated between 1993 and 2007 was reviewed. Primary endpoint was overall survival (OS), obtained from prospectively collected patient questionnaires and medical record review, and analyzed by the Kaplan-Meier method. Short (60-day postoperative) and long-term (median followup: 1.6 years; 5.3 years among survivors) complications were assessed. Results: Patients (median age: 51 years) presented with (1) locally-invasive disease that persisted despite initial standard chemoradiation (n=10, 39%), (2) disease that recurred after initial standard chemoradiation (n=10, 39%; median 1.7 years to recurrence), or (3) re-recurrence after a salvage APR (n=6, 23%; median 1.3 years since APR). All patients received chemotherapy and external beam radiation preoperatively, and 19% received additional postoperative chemoradiation. Gross pelvic disease was completely resected in all (R0 in 73%; R1 in 27%). IORT (750–3250cGy) was delivered at single (92%) or two sites (8%). Median overall survival (OS) was 1.7 years. Five-year OS were: 50%, 10%, and 22% for patients with locally-invasive, recurrent, and re-recurrent disease respectively. Short-term complications predominantly related to the perineal wound. Fifteen patients reported long-term complications (&gt;grade3): bowel obstruction in 8 (1 requiring operation), perineal wound fistula/non-healing in 9, leg paresthesia in 5, hydronephrosis in 3. Conclusions: For select patients with locally-persistent or recurrent SCC who fail standard primary treatment, a multimodality approach involving chemoradiation, extended pelvic resection and IORT offers a chance for improved survival. No significant financial relationships to disclose.
Effects of acute graft-versus-host-disease on physical and psychological functioning following hematopoietic stem cell transplantation.
Authors: Mackenzie L Erdmann, Mark Juckett, Walter L. Longo, Christopher L. Coe, Hollis Moore, Peiman Hematti, Erin S. Costanzo
Journal: Journal of Clinical Oncology (2014)

7038 Background: Acute graft-versus-host-disease (aGVHD) is a significant early complication of allogeneic hematopoietic stem cell transplantation (HSCT). Little is known about the effects of aGVHD on quality of life, and no prior studies have examined psychological effects. We compared physical and psychological functioning of HSCT survivors who developed aGVHD to those who did not. Methods: Adults with hematologic malignancies were enrolled in this prospective, longitudinal study prior to allogeneic HSCT. Those alive without recurrence at 6 months post-HSCT (N=108) were included in the analyses. Participants completed well-validated self-report measures of physical functioning (fatigue, pain, sleep, physical and functional well-being) and psychological functioning (depression, anxiety, psychological well-being) pre-HSCT and 3 and 6 months post-HSCT. Those diagnosed with mild (grade 1-2) and severe (grade 3-4) aGVHD were compared to those with no aGVHD on all measures after controlling for pre-HSCT measures, age, HSCT regimen, and chronic GVHD. Results: 52 participants were diagnosed with mild (n=39) or severe (n=13) aGVHD. By 3 and 6 months post-HSCT, there were no significant differences between those with and without a history of aGVHD on physical functioning measures. There were significant differences in anxiety at 3 and 6 months post-HSCT (F(2, 103)=3.19; p=.049; F(2, 98)=4.99; p=.011). There was also a trend toward a difference in the psychological well-being measure of personal strength at 6 months (F(2, 97)=2.86; p=.070). Follow-up comparisons showed that those with a history of severe aGVHD reported significantly greater anxiety but also a greater sense of personal strength as compared to those with mild or no aGVHD (pvalues<.05). Conclusions: Findings indicate that HSCT survivors who developed aGVHD, even severe cases, were doing as well as those without aGVHD on all indices of physical functioning and most indices of psychological functioning by 3 and 6 months post-HSCT. However, the experience of severe aGVHD appeared to affect select aspects of psychological functioning, conferring greater anxiety but also an enhanced sense of personal strength.
A phase III comparative study of nivolumab (anti-PD-1; BMS-963558; ONO-4538) versus docetaxel in patients (pts) with previously treated advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC).
Authors: Scott N. Gettinger, Julie R. Brahmer, Naiyer A. Rizvi, Neal Ready, Laura Quan Man Chow, Scott J. Antonia, Marc E. Buyse, Jacek Jassem, Friedrich Graf Finckenstein, Lucio Crinò, Thomas James Lynch
Journal: Journal of Clinical Oncology (2013)

TPS8121 Background: Lung cancer is the leading cause of cancer mortality globally. Non-squamous NSCLC represents up to 75% of NSCLC cases with most pts diagnosed with advanced disease, which progresses rapidly following failure of 1 st -line platinum-based doublet (Pt-doublet) chemotherapy. Benefit from current therapies has reached a plateau with median overall survival (OS) for late stage NSCLC pts of 10-12 months. Standard 2 nd -line therapy (single-agent chemotherapy; eg. docetaxel) results in OS of 8 months. Expression of programmed death-1 (PD-1), an immune checkpoint receptor that negatively regulates T-cell activation, is associated with poor prognosis in NSCLC. Nivolumab, a PD-1 receptor blocking antibody, prevents activation of PD-1 by its known ligands, PD-L1 and PD-L2, and demonstrated durable antitumor activity in NSCLC pts in a phase 1 study (Topalian ST, et al. N Engl J Med 2012). We present a phase III study comparing OS benefit of nivolumab vs docetaxel in pts with metastatic/recurrent non-squamous NSCLC. Methods: In this study, 574 pts will be randomized 1:1 to receive nivolumab 3 mg/kg IV q 2 weeks (wks) or docetaxel 75 mg/m 2 q 3 wks until disease progression or unacceptable toxicity. Pts will include those having progressed during/after Pt-doublet ± bevacizumab (bev) for advanced disease as well as pts with EGFR-mutant or ALK-rearranged NSCLC who have progressed following treatment with a tyrosine kinase inhibitor (TKI) and a Pt-doublet ± bev. Prior maintenance therapy with erlotinib, pemetrexed and/or bev is allowed. Pts will be stratified by prior use of maintenance therapy and receipt of 1 vs 2 (Pt doublet and TKI) prior lines of therapy. Response will be assessed (modified RECIST 1.1) at 9 wks following treatment initiation and every 6 wks thereafter until disease progression. The primary objective is to compare the OS of nivolumab vs docetaxel treated pts. Secondary objectives include comparison of objective response rates, progression-free survival and disease related symptom progression, and evaluation of clinical benefit of nivolumab vs docetaxel in PD-L1+ vs PD-L1- tumor subgroups. Clinical trial information: NCT01673867.