tbuckley/cabot-search huggingface dataset:
High prevalence of <i>BRCA1/2</i> germline mutations in female breast cancer patients with triple-negative phenotype (TNBC) and family history.
Authors: C. Saura, G. Sáanchez-Ollé, N. Bosch, N. Gadea, M. Masas, A. Tenes, S. Gutierrez-Enríquez, O. Díez, J. Baselga, J. Balmañna
Journal: Journal of Clinical Oncology (2010)

1534 Background: Modulation of response to chemotherapy and prediction of efficacy to certain targeted therapies in TNBC is highly associated to BRCA1/2 mutations. We aimed to identify if TN phenotype in BC female patients added to family history is a useful predictor for detecting the presence of any of these mutations. Methods: We analyzed the mutation status of 227 consecutive unrelated female BC patients (probands) referred to our High Risk and Cancer Prevention Unit who had undergone full genetic testing of BRCA1/2 (direct sequencing and large rearrangements analysis). Univariate analyses were performed to compare the prevalence of mutations between TNBC and non-TNBC according to family history (breast/ovarian cancer in first/second degree relatives) and age at diagnosis (dichotomized at 50). A multivariate analysis was performed to identify predictors of finding a mutation. Results: Overall, 58/227 (26%) had a TNBC, 184 (81%) had a family history, and 190 (84%) were diagnosed before 50y. Twenty-one percent (47/227) of probands carried a mutation, 20 (9%) in BRCA1 and 27 (12%) in BRCA2. Among the 58 TNBC patients, 36% (21) carried a BRCA1/2 mutation (16 in BRCA1 and 5 in BRCA2). In contrast, only 15% (26/169) of the non-TNBC carried a mutation (p = 7*10-4). All TNBC patients with a BRCA1 mutation had a positive family history, while 2 out of 5 BRCA2 presented as early onset sporadic without family history. Multivariate analysis showed that both a TN phenotype and a positive family history were independent predictors of a BRCA1/2 mutation (OR 4.5 [95% CI 2.1-9.6] and 5.9 [95% CI 1.8-19.1], respectively). Conclusions: Prevalence of BRCA1/2 mutations was high among TNBC patients, especially when associated with a positive family history. BRCA2 mutations were also found in early onset sporadic TNBC patients. BRCA1/2 germline testing should be considered at the time of designing clinical trials for patients with TNBC. No significant financial relationships to disclose.
Patient-reported quality of life in men with TURP undergoing proton therapy for prostate cancer.
Authors: Derek Lee, Bradford S. Hoppe, Tamara L. Smith, Christopher G. Morris, Romaine Charles Nichols, Randal H. Henderson, William M. Mendenhall, Christopher R. Williams, Zuofeng Li, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2013)

220 Background: We report on quality of life (QOL) and early toxicity following proton therapy (PT) among men with prostate cancer who underwent transurethral resection of the prostate (TURP) prior to treatment. Methods: Between 2006 and 2010, 1,540 patients were treated definitively with PT for prostate cancer at UFPTI and enrolled on a prospective IRB-approved outcomes protocol. One hundred of the men had received a TURP before PT. Baseline comorbidities, medications, expanded prostate index composite (EPIC) score, international prostate symptom score (IPSS), and CTCAE vs.3 toxicity assessment were collected prospectively. The Kaplan-Meier product limit method was used to estimate freedom from toxicity. Results: Men who had TURP prior to PT had lower EPIC scores at baseline and at all followup points for urinary function, urinary incontinence, and urinary summary (Table). The TURP group also had lower EPIC bowel bother, bowel function, and bowel summary at baseline, 6-month, and 1-year followup. EPIC urinary bother, urinary irritation/obstruction, and subscales did not show a statistically significant difference at baseline, but they did show lower scores for the TURP group at variable follow-up time points. The IPSS scores among the TURP group did not show a statistical difference from the non-TURP group, except at the 6-month follow-up time point. Toxicity assessment showed that the 2-year and 3-year cumulative incidence of grade 3 GU toxicity rate in the pretreatment TURP group were 14% and 18%, respectively. Conclusions: Pretreatment TURP was associated with both a high incidence of physician-assessed toxicity and inferior patient-reported QOL scores both before and after PT treatment. Studies investigating QOL and toxicity after specific prostate cancer therapies should stratify patients by pretreatment TURP. Longer follow-up and further evaluation of risk factors for grade 3 GU toxicity among this cohort are needed. [Table: see text]
Universal screening for Lynch syndrome (LS) in colorectal cancer (CRC) and survival.
Authors: Sigurdis Haraldsdottir, Christina Sing-Ying Wu, Heather Hampel, Wendy Frankel, Xueliang Jeff Pan, Tanios S. Bekaii-Saab, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2014)

415 Background: It has been argued that universal screening for LS should be performed on all patients (pts) diagnosed with CRC because screening LS pts and their relatives can detect early cancers and improve outcomes. This approach is being adopted by many comprehensive cancer centers around the country. The Ohio State University (OSU) began screening for deficient mismatch repair (dMMR) proteins by immunohistochemistry (IHC) on all CRC cases in 2006. This retrospective study aims to assess whether universal screening with IHC followed by conclusive testing (BRAF mutation in setting of MLH1 deficiency, and/or gene sequencing) affects pts survival. Methods: All CRC pts diagnosed at OSU from 3/2006-6/2012 with dMMR testing per IHC were included, and their charts were reviewed. Chi-square test was used to for categorical parameters, t-test was used for continuous variables, and the log-rank test for overall survival (OS) to compare the difference between pts with full conclusive testing vs those without full testing. Patients who expired within 4 weeks of diagnosis were excluded (n=10) from the OS analysis. Results: One hundred and twenty-two tumors (15.7% of 777 tumors tested) had dMMR by IHC during the study period. Fifty-one pts went on to have conclusive testing done; thirteen patients (25.5%) were diagnosed with LS, 29 patients (56.9%) had MLH1-hypermethylated tumors, and 9 patients (17.6%) were not found to have MMR mutations on gene sequencing. In an OS analysis, patients undergoing conclusive testing had significantly longer survival as compared to those with abnormal IHC without further testing (median OS not reached vs. 38 months, p=0.04). The difference was similar and remained marginally significant (p= 0.04-0.09) after correcting for age, stage and testing date using different models. Conclusions: Patients who had conclusive testing after initial abnormal universal screening with IHC had significantly longer OS compared to pts who had abnormal IHC without follow-up testing. It is possible that ascertainment bias and pts compliance influenced survival so larger prospective studies that document stage and treatment are needed to determine if increased surveillance in the setting of a LS diagnosis leads to better OS.
Patterns of recurrence by microsatellite instability in colorectal cancer.
Authors: Chang-gon Kim, Joong Bae Ahn, Minkyu Jung, Seung Hoon Beom, Joo Hoon Kim, Su Jin Heo, Ji Hyung Kim, Sang Joon Shin
Journal: Journal of Clinical Oncology (2016)

501 Background: Although colorectal cancer (CRC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CRC, patterns of recurrence has not been precisely investigated. We aim to explore patterns of recurrence and prognosis of CRC with MSI-H (high-frequency MSI) in comparison to MSI-L (low-frequency of MSI)/MSS. Methods: Patients with stage I-III colorectal cancer who received complete surgical resection were included using retrospective cohort of Yonsei Cancer Center. Patients were categorized to MSI status (MSI-H vs. MSS-L/MSS). Patterns of recurrence, disease free survival (DFS) and overall survival (time from diagnosis to death as OS1 and time from recurrence to death as OS2) between two groups were compared. Results: A total of 2944 patients were evaluated. Of all, 263 patients (8.9%) has MSI-H tumor. Patients with MSI-L/MSS tumor experienced more systemic recurrence events than patients with MSI-H tumor (13.1% vs. 4.6%). In patients who experienced recurrence, MSI-H tumor has tendency toward young age, proximal location and poorly differentiated histology. MSI-H tumor is more likely to recur as peritoneal metastasis (33.3% vs. 8.0%, p-value 0.002) and lymph node metastasis (25.0% vs. 7.7%, p-value 0.033). In contrast, MSI-L/MSS tumor is more likely to recur as lung metastasis (37.1% vs. 0.0%, p-value 0,008). There was no difference in DFS [hazard ratio (HR) = 0.753, p-value 0.241] and OS1 [HR = 1.486, p-value 0.203]. However, OS2 was marginally inferior in MSI-H tumor [HR = 1.779, p-value 0.064]. Conclusions: Patterns of recurrence in MSI-H CRC is different from that of MSI-L/MSS and modification of surveillance strategy in MSI-H CRC should be considered. In addition, prognosis of recurred MSI-H CRC is not superior than MSI-L/MSS and prognostic value of MSI in this circumstance should be evaluated using larger sample size.
Efficacy of panitumumab (pmab) vs. cetuximab (cmab) in patients (pts) with wild-type (WT) <i>KRAS</i> exon 2 metastatic colorectal cancer (mCRC) treated with prior bevacizumab (bev): Results from ASPECCT.
Authors: Marc Peeters, Tae Won Kim, Jin Li, Stefano Cascinu, Paul Ruff, Attili Venkatasatya Suresh, Anne Thomas, Sergei Tjulandin, Xuesong Guan, Tien Hoang, Yong Jiang Hei, Timothy Jay Price
Journal: Journal of Clinical Oncology (2016)

519 Background: The phase 3 ASPECCT trial of pts with chemorefractory WT KRAS exon 2 mCRC demonstrated that pmab was noninferior to cmab for overall survival (OS). A previous subgroup analysis of hazard ratios (HRs) suggested that pts who had received prior bev (any line, at any point before study start) in the pmab arm may have had better outcomes vs pts in the cmab arm (Price, 2014). Methods: Pts were randomized 1:1 to receive pmab or cmab. The subset of pts who had received prior bev were analyzed based on the final analysis of ASPECCT. Results: 999 pts were randomized and treated: 499 pmab and 500 cmab. The prior bev subset included 126 pts in the pmab arm (25%) and 132 pts in the cmab arm (26%). Pts in the pmab arm had longer median OS and progression-free survival (PFS) and higher objective response rates (ORR) compared with pts in the cmab arm. Results are shown (table). After adjustment for baseline covariates including ECOG performance status, number of metastatic sites, and baseline LDH, OS HR was 0.65 (95%CI=0.49-0.85) with pmab vs cmab in pts who had received prior bev. Pts in the pmab and cmab arms who did not receive prior bev had similar OS, PFS, and ORR. Post-progression antitumor therapy was similar between the pmab (47%) and cmab arms (52%) in pts who received prior bev. Conclusions: In ASPECCT, pts with WT KRASexon 2 mCRC who received prior bev-containing regimens may have derived greater benefit with pmab versus cmab monotherapy. Clinical trial information: NCT01001377. [Table: see text]
A phase III study for prevention of delayed nausea: A University of Rochester CCOP study of 1,021 patients receiving chemotherapy.
Authors: G. R. Morrow, J. A. Roscoe, C. Heckler, S. R. Dakhil, J. L. Wade, J. P. Kuebler, S. G. Mohile, L. J. Peppone, M. C. Janelsins
Journal: Journal of Clinical Oncology (2011)

9012 Background: Despite the widespread use of first generation serotonin receptor antagonists, dexamethasone (DEX) and a variety of other antiemetic medications, delayed nausea has continued to occur with nearly twice the frequency as acute nausea after treatment with highly (e.g. cisplatin [CIS]) and moderate-to-highly (e.g. doxorubicin [DOX], epirubicin [EPI]) emetogenic chemotherapy agents. Methods: We conducted a double-blind randomized clinical trial to evaluate the efficacy of four regimens for controlling delayed nausea: Arm 1:Palonosetron (PAL) + DEX on Day 1 and Compazine (COM) on Days 2and3; Arm 2: Granisetron (GRA) + DEX (Day 1) and COM (Days 2and3); Arm 3: Aprepitant (APR) + PAL + DEX (Day 1), and APR + DEX (Days 2and3); Arm 4: PAL + DEX (Day 1), and COM + DEX (Days 2and3). Eligibility included a diagnosis of cancer, chemotherapy naïve, scheduled to receive chemotherapy (any dose or schedule) with CIS, carboplatin, oxaliplatin, DOX or EPI without concurrent radiotherapy or interferon treatment. The primary endpoint was average nausea rating on a 1 (no nausea) to 7 (extremely nauseated) scale over morning, afternoon, evening and night for Days 2and3. Primary objectives were: (1) Arm 1 vs. Arm 4: Does addition of DEX enhance the Arm 1 regimen? (2) Arm 1 vs. Arm 2: Is PAL more effective than GRA in the Arm 1 regimen? (3) Arm 3 vs. Arm 4: Is the recommended guideline (Arm 3) the most effective regimen? Objectives 1-3 were evaluated with ANOVA with a 0.017 two-tailed significance level. Results: N=254, 254, 260 and 253 subjects were accrued to Arms 1-4, respectively. Means (95% CI) for Arms 1-4 were 1.87 (1.71, 2.02), 1.88 (1.72, 2.05), 1.65 (1.50,1.80), 1.68 (1.53, 1.82), respectively. Mean differences (95% CI) were: (1) Arm 1 – Arm 4: 0.19 (-0.02, 0.41), P=0.013. (2) Arm 1 – Arm 2: -0.01 (-0.23, 0.20), P=0.727. (3) Arm 3 – Arm 4: -0.03 (-0.24, 0.19), P=0.583. Conclusions: Addition of DEX to the Arm 1 regimen slightly improved delayed nausea. PAL and GRA in the Arm 1 regimen have similar effects. Arms 3 and 4 are the most effective regimens. The beneficial effect of adding APR was the same as adding COM. More effective regimens for controlling delayed nausea are needed. Supported by NCI grant CA37420.
Collecting tissue for research purposes: A survey of 16 institutions in the Translational Breast Cancer Research Consortium (TBCRC).
Authors: E. S. Frank, R. T. Burns, N. E. Carbine, L. Cargen, C. Chauhan, D. K. Cline, R. Kleban, S. A. Mertz, A. H. Meyn, J. Perlmutter, C. A. Rufenbarger, M. L. Smith, P. A. Spears, L. V. Vincent, A. C. Wolff
Journal: Journal of Clinical Oncology (2011)

10615 Background: In order to understand the pathogenesis of breast cancer, many institutions are routinely requesting patients to donate tissue for current or future research. However, little is known about established processes for collecting tissue specimens for research studies. Methods: The Patient Advocate Working Group of the TBCRC, a collaborative group of 16 US academic breast cancer programs, conducted a two-part study to learn how patients are approached for tissue/biospecimen banking in its sites. Advocates from each institution contacted the appropriate person at each site to complete the surveys, explain their purposes, and ensure completion of the 2 online surveys (40 questions). Questions covered current practices, identified best practices, and recommended areas of improvement. One survey focused on the processes and staff involved in obtaining consent, the other focused on the information obtained from the consent form. Results: 16 invitations to respond were sent out and 12 sites completed the surveys. In all, a median of 80% (range, 20-100%) of patients were approached to obtain consent for tissue/biospecimen banking with an average patient refusal rate of 20%. 40% of the institutions limited the number of times a patient could be approached for consent and 20% of the institutions reported an annual goal for obtaining consents. 1 institution offered courses on interviewing skills, cultural or sensitivity training. The entire consent form was reviewed with patients about 80% of the time over an average of 20 minutes (range, 5-60). Only 1 TBCRC institution collected data from patients on their experience with consenting. Consent form differences included length (2-13 pages), permission for future contact (70%), permission to draw blood (65%) and donation of tissue without linkage to clinical data (43%). Conclusions: Development of patient educational materials on biospecimen donation, specialized training for staff, and a systematic approach to obtaining patient feedback may lead to a better patient experience and possibly a higher consent rate. Simplified consent forms that provide patients with necessary information for informed decision-making are needed.
Evidence-based recommendations on the management of extrahepatic manifestations of chronic hepatitis C virus infection
Authors: Manuel Ramos-Casals, Anna Linda Zignego, Clodoveo Ferri, Pilar Brito-Zerón, Soledad Retamozo, Milvia Casato, Peter Lamprecht, Alessandra Mangia, David Saadoun, Athanasios G. Tzioufas, Zobair M. Younossi, Patrice Cacoub
Journal: Journal of Hepatology (2017)
Perceptions of palliative care among hematologic malignancy specialists: A mixed-methods study.
Authors: Thomas William LeBlanc, Jonathan David O'Donnell, Megan Crowley-Makota, Daniel Paul Dohan, Michael W. Rabow, Cardinale B. Smith, Douglas B White, Greer A Tiver, Robert Arnold, Yael Schenker
Journal: Journal of Clinical Oncology (2014)

9 Background: Patients with hematologic malignancies have unmet palliative care needs but are less likely to receive specialist palliative care services than patients with solid tumors. This difference is poorly understood. Methods: Multisite, mixed-methods study to understand and contrast perceptions of palliative care among hematologic oncologists and solid tumor oncologists. Between February and October 2012, oncologists at 3 academic medical centers with well-established palliative care services completed surveys assessing referral practices and in-depth, semi-structured interviews about their views of palliative care. We compared referral patterns using standard statistical methods. We then analyzed qualitative interview data using constant comparative methods to explore reasons for observed differences. Results: Among 66 interviewees, 23 oncologists cared exclusively for patients with hematologic malignancies, and 43 treated only patients with solid tumors. Seven of 23 hematologic oncologists (30%) reported never referring a patient to palliative care; all solid tumor oncologists had previously referred (p&lt;0.001). In qualitative analyses, most hematologic oncologists viewed palliative care as end-of-life care, while most solid tumor oncologists viewed palliative care as a subspecialty that could assist with complex cases and/or offload burden in a busy clinic. Solid tumor oncologists emphasized practical barriers to palliative care referral, such as appointment availability and reimbursement issues. Hematologic oncologists emphasized philosophical concerns about palliative care referrals, including different treatment goals, responsiveness to chemotherapy, and a preference to control palliative aspects of patient care. Conclusions: Most hematologic oncologists view palliative care as end-of-life care, while solid tumor oncologists more often view palliative care as a subspecialty for co-managing complex patients. Efforts to integrate palliative care into hematologic malignancy practices will require solutions that address unique barriers to palliative care referral experienced by hematologic oncologists.
Can contrast-enhanced MRI using gadoxetate disodium (EOVIST) replace triphasic CT to derive future liver remnant?
Authors: Viet H. Le, Steven D. Trocha, Wesley B. Jones, Michael A. Devane, Brian McKinley
Journal: Journal of Clinical Oncology (2015)

263 Background: Calculating future liver remnant volume (FLRV) is important in planning treatment of hepatic neoplasm. CE-MRI gadoxetate disodium (Eovist) has been shown to yield more information than 3p-CT, often narrowing the differential of hepatic neoplasms. The purpose of this study is to compare FLRV calculated from CE-MRI to those from 3p-CT. Methods: We performed a retrospective review of 28 patients with liver tumors evaluated with both 3p-CT and CE-MRI prior to treatment. Three-dimensional reconstructions were computed by manual tracing technique. 3p-CT is considered the gold standard. Results: The calculated total hepatic mean volumes for 3p-CT was 1,588 cm 3 and 1,916 cm 3 for CE-MRI, with spearman correlation (ρ) of 0.91 (p &lt;0.01). The total volume difference was 327 cm 3 (p &lt;0.01). The right hepatic lobe volume was 1,028 cm 3 (3p-CT) and 1,283 cm for (CE-MRI) (ρ 0.83, p &lt;0.01). The left hepatic volume was 525 cm 3 (3p-CT) and 638 cm 3 (CE-MRI), (ρ 0.79, p &lt;0.01). The difference in calculated volume for the right liver is 254 cm 3 , p &lt;0.01 (3.23%, p 0.008) and 94 cm 3 , p 0.07 (2.09%, p 0.045) for the left liver. Conclusions: Our data demonstrated a strong and positive correlation between 3p-CT and CE-MRI. When the 30% FLRV cutoff used, there is variability in 5 out of 28 patients (17.8%). Our data suggest that patients with FLRV calculated by CE-MRI that are near the resectability cutoff or those with abnormally large calculated FLRV should undergo 3p-CT for verification. Future studies are needed to further validate CE-MRI ability to calculate FLRV.
Comparative effectiveness of FOLFIRINOX (FOL) versus gemcitabine and nab-paclitaxel (GNP) for the first-line treatment of metastatic pancreatic cancer.
Authors: Wei-Han Cheng, Sarmad Sadeghi, Heinz-Josef Lenz, Joel W Hay, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2016)

306 Background: ACCORD-11 and IMPaCT established the efficacy of combination chemotherapy with FOL and GNP in metastatic pancreatic cancer (mPC). These two regimens have different administration schedule and toxicity profile. In this study we compare the effectiveness and costs of the two regimens including the costs of toxicities and supportive medications from a societal perspective. Methods: A Markov model was developed to simulate a cohort of mPC patients to estimate the cost per life-year gained (LYG) and per quality-adjusted life-year (QALY) for treatment with FOL and GNP. The model has three states: stable disease, progressive disease, and death. The cohorts were modeled over a 3-year time horizon in a one-month cycle length. Efficacy data were obtained from respective trials. Drug acquisition costs were extracted from Veteran Affairs Federal Supply Schedules. Other costs including visits, tests, and procedures were derived from the Medicare physician-fee-schedule. Literature was reviewed to estimate the adverse event costs and the utility scores for each health state. One-way sensitivity analyses were performed to determine the robustness of the model to changes in key parameters. Results: The model projected a life expectancy of 9 months and 7 months for FOL and GNP, respectively. FOL group showed a higher QALY than GNP group (0.51 vs. 0.40). Although the drug acquisition costs were significantly lower in FOL compared with GNP, FOL yielded a slightly higher cost after 3-years period ($55,944 vs. $56,628). FOL treatment incurred an incremental cost of $1,334 per additional life-month ($16,012 per life-year) and an incremental cost of $30,870 per QALY gained. The median overall survival and progression-free survival point estimate greatly influenced model results based on the results of sensitivity analysis. Conclusions: Compared with GNP, FOL showed a slightly higher cost but higher life expectancy and QALY as a first-line treatment in mPC. Given that the toxicity profile account for a significant portion of cost for FOL providing best supportive care and management of side effects can significantly impact the overall costs of treatment.