tbuckley/cabot-search huggingface dataset:
Frequency of BRCA mutations and co-occurring alterations in prostate cancer.
Authors: Charles E. Myers, Rebecca Feldman, Brian L. Abbott, Sandeep K. Reddy, Michael Castro
Journal: Journal of Clinical Oncology (2016)

289 Background: Evidence is building for the utility of PARP (oral poly (ADP-ribose) polymerase) inhibitors in BRCA-mutated patients, across solid tumors. We examined the presence of somatic BRCA mutations (detected in tumor), in a population of prostate cancer patients. Comparisons between BRCA-mutated and BRCA-wildtype patients were made to determine potential combination strategies. Methods: 85 advanced prostate cancer patients were included in the study and tested centrally at a CLIA laboratory (Caris Life Sciences, Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (C/FISH). Results: Average age of BRCA-mutated patients was 58, compared to 62 in the non-BRCA-mutated cohort. Metastatic (Stage IV) disease was present in 67% in both cohorts (8/12; 49/73). BRCA2 mutations were more frequent (12%; 10/85) than BRCA1 (2%; 2/85). Of the BRCA-mutated patients, 5 variants are classified as having pathogenic effect; the rest consisted of variants of unknown clinical significance. Concurrent mutations in BRCA1 and BRCA2 were found in 17% (2/12) of patients. One patient harbored multiple BRCA mutations (n = 4, c.7977-1G &gt; C, I2068fs, K2077Q, T2337I). Regarding co-occurring alterations, 36% (4/11) and 0% (0/11) exhibited PD1 + TILs and PD-L1+ tumor expression. Amongst theranostic markers tested by IHC, TOPO1 and TUBB3 were differentially expressed in BRCA-mutated vs. BRCA-wildtype groups: 91% (10/11) vs. 59% (41/69); p = 0.04 and 64% (7/11) and 23% (16/70); p = 0.0099. Co-occurring variants detected by NGS, included high rates of TP53: 42% (5/12) compared to BRCA- wildtype (30% 21/71), not significant. Of 3 patients that included expanded NGS analysis (600 genes), each harbored ≥ 39 mutations. Conclusions: The frequency of somatic BRCA mutations observed in prostate cancer, together, with preliminary clinical evidence for the efficacy of targeted therapies for these patients; highlight the potential role of a new class of agents for advanced prostate cancer.
Comparison of real-world acute care interventions (ACI) in patients (pts) with advanced non-small cell lung cancer (adv NSCLC) treated with chemotherapy versus targeted therapies.
Authors: Janna Radtchenko, Beata Korytowsky, Menaka Bhor, Ken Tuell, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2016)

37 Background: This analysis compared the frequency of ACI for any cause (emergency room [ER] visits, hospitalizations, and readmissions) to better understand the burden of treatment in adv NSCLC pts treated with chemotherapy (chemo) vs targeted therapy (TT). Methods: Using Inovalon’s MORE 2 Registry claims data, adv NSCLC pts treated with antineoplastics identified by ICD-9 codes from July 2013-2014 were selected. Inclusion: pts &gt;18 y who received first-line (1L) systemic therapy within 6 mo of diagnosis. Exclusion: pts with small cell lung cancer or secondary malignancies and pts in clinical trials. TT was defined as erlotinib, ceritinib, afatinib, crizotinib, ramucirumab, or bevacizumab monotherapy. Analysis included frequency distributions, chi-square, and t-tests. Results: Of 5319 pts included, 1304 (25%) received 1821 total lines of TT. Overall, median age was 66 y, 48% were male, 56% were on Medicare, and 41% received ≥ 2 L of therapy. Mean Charlson Comorbidity Index (CCI) was 2.2 (lower in pts on TT [2.1 vs. 2.2, P&lt;.0001]). Pts on TT were older, more likely to be female, and less likely to have Medicare (Table). Overall, 45% of pts were hospitalized, of whom 50% were readmitted (43% while on the same line); 62% of pts had an ER visit, of whom 62% were readmitted (56% while on the same line). Pts on TT were less likely to be hospitalized, have ER visits, and be readmitted (hospital or ER). Conclusions: Pts with adv NSCLC had considerable ACI. Readmission was common for both hospitalizations and ER visits, with many pts readmitted while on the same line. Pts on TT had fewer ACI and readmissions vs pts on chemo; however, nearly half of pts in this study required hospitalization, highlighting the need for novel therapies with improved safety and efficacy. [Table: see text]
Circulating tumor cell (CTC) enumeration in patients with metastatic neuroendocrine prostate cancer (NEPC) and castration-resistant prostate cancer (CRPC).
Authors: Gurveen Kaur, Beerinder Singh, Himisha Beltran, Naveed Hassan Akhtar, David M. Nanus, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2014)

204 Background: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer. Circulating tumor cell (CTC) counts as measured by CellSearch are prognostic for large groups with metastatic prostate cancer (PC), but are not well described in NEPC. Methods: With institutional review board approval, we retrospectively identified patients with metastatic PC and available CTC enumeration (CellSearch methodology) and compared counts/7.5 mL blood and overall survival (OS), measured from the first recorded CTC count until death or last follow up. Entry criteria for clinical trials were used to define NEPC, including histology (small cell/neuroendocrine carcinoma or adenocarcinoma with more than 50% NE staining), serum chromogranin greater than 5x ULN and/or neuron specific enolase greater than 2x ULN, and/or predominant liver/brain metastases with lack of prostate-specific antigen [Beltran ASCO 2013, clinicaltrials.gov NCT01799278 ]. Frequency of detectable and unfavorable counts was tabulated and OS was compared across groups. Results: Sixty one patients were identified: 21 NEPC with median age 73.7 and 40 patients with castration-resistant prostate cancer (CRPC) with median age 73.9 over contemporary time periods 2009 to 2012. Median OS for the entire group was 22.6 months (mo), with a trend for shorter OS in NEPC (20.7 mo) than CRPC (22.7 mo), p=0.11. 47.6% of NEPC and 55% of CRPC had detectable CTC counts (p=0.58); 38.1% of NEPC and 40.0% of CRPC had greater than or equal to five CTCs (p=0.89). CTC counts of 0 to 4 versus greater than or equal to five were prognostic for both groups: NEPC with 0 to 4 CTCs had median OS of 22.6 versus 6.6 mo for CTCs greater than or equal to 5 (p&lt;0.001) and CRPC with 0 to 4 CTCs median OS not reached (mean 40.6 mo) versus 11.2 mo for those with greater than or equal to five CTCs (p&lt;0.001). Conclusions: Patients with NEPC have similar frequency of detectable and elevated CTC counts by CellSearch methodology as compared to an overall CRPC population. CTC counts are prognostic for both groups.
APRN Palliative Care Externship: Potential impact on oncology nursing palliative care delivery.
Authors: Constance Dahlin, Patrick J. Coyne, Brian Cassel
Journal: Journal of Clinical Oncology (2015)

149 Background: Understanding primary palliative care is essential for advanced practice nurses, no matter where they practice. Limitations resulting from the variability of APRN state practice acts, financial considerations, and expenses, challenge post-graduate education for APRNs. With the shortage of health care providers, it is necessary to consider innovative programs to offer this education. Although there are many palliative educational opportunities, there are few abilities to translate the education into practice. Few are focused on the APRN, particularly for community and rural practice where many oncology patients are located and receive care. Methods: The APRN Externship selected 48 externs who completed the week long course. Topics includes pain and symptom assessment and management; fostering communication skills; building understanding of community resources such as hospice, palliative care, and home care; incorporating palliative care into an oncology practice, introducing concepts of business and finance in palliative care; and developing of safe practice with policy, procedure, and guideline development with a focus on rural providers. Externs complete pre course and post course testing along with completing goals to improve patient care. Results: Through an IRB approved process, utilizing both quantitative and qualitative evaluation, we followed the effect of the externship on externs. Externs performed both pre-course as well as 1 month and 6 month post-course testing. They also completed a report on achievement of clinical goals to improve patient care delivery. Conclusions: APRN Palliative Externs reported positive effects from the externship experience to clinical practice. The qualitative and quantitative data has demonstrated sustained effect towards improving palliative care within advanced practice nursing. The APRN palliative externship model could serve as a model to promote better palliative care education for oncology APRNs thereby improving palliative care delivery within oncology nursing.
Patient retention and costs associated with a pancreatic multidisciplinary clinic.
Authors: Shereef M. Elnahal, Aaron Tyler Wild, Timothy M. Pawlik, Hao Wang, Deann Gavney, Tammy Snyder, Barbara A. Biedrzycki, Elizabeth M. Jaffee, Terry Langbaum, Elliott K. Fishman, Ralph H. Hruban, Daniel A. Laheru, Amy Hacker-Prietz, Richard D. Schulick, Martin Makary, Barish H. Edil, Christopher Lee Wolfgang, Joseph M. Herman
Journal: Journal of Clinical Oncology (2012)

96 Background: Multidisciplinary clinics (MDC) are a burgeoning method of administering timely and comprehensive oncologic care. The continuity of care achievable with MDCs, in addition to their costs, are not well-described. We compared retention rates and charges for MDC patients to patients with individual referrals at the same academic center. Methods: The geographic origins of 482 MDC patients and 3,766 non-MDC patients, all referred for pancreatic cancer treatment between 2008-2010, were defined as “local,” “adjacent states,” and “non-adjacent states.” Proportions of patients in each group who presented initially and subsequently returned were compared using chi-squared tests. Multivariate adjustment was performed for disease stage and other clinical risk factors. Gross charges per patient were determined using billing data. Results: Overall, the MDC retained a higher percentage of patients for subsequent treatment than the non-MDC group (60.8% vs. 53.6%; p=0.003), as well as all three individual regions. Multivariate adjustment results are not yet available, but will be at the time of the meeting. Mean charges per patient were 11% higher for the non-MDC group. Conclusions: The MDC achieved higher patient retention, suggesting improved continuity of care. Total charges were higher for the non-MDC group, suggesting that MDCs may be more cost-effective. [Table: see text] [Table: see text]
Second-line therapy of KRAS-mutated (KRASm) metastatic colorectal cancer (CRC) with the MEK inihibitor selumetinib ([SEL], AZ6244, ARRY-142886) in combination with irinotecan (IRI): An AGICC study.
Authors: Howard S. Hochster, Wells A. Messersmith, Bert H. O'Neil, Susan G. Groshen, Deirdre Jill Cohen, Crystal Shereen Denlinger, Philip Jordan Gold, S. Gail Eckhardt, Gershon Y. Locker, Patricia Ames, Marti McKinley, Lawrence P. Leichman
Journal: Journal of Clinical Oncology (2013)

380 Background: 2 nd -line therapy of KRASm CRC is limited; targeting downstream signal transduction enzymes is rational here. Use of the MEK inhibitor SEL is supported by preclinical and clinical evidence. We designed a dose-finding/phase II study of IRI plus SEL in KRASm CRC. Methods: Eligibility included: KRASm or BRAFm CRC with measurable disease progressing after 1st-line therapy with an oxalipatin-based chemo + bevacizumab regimen, PS 0-1, acceptable organ function. Patients were treated with IRI 180 mg/m2 iv q2w and SEL 50-75 mg po bid. First 3 patients of run-in portion were treated with SEL 50 mg and if no DLTs, next 3-6 patients at 75 mg po bid. If no DLTs, then phase II dose of SEL 75 mg po bid would be used. Primary endpoint was RECIST 1.0, investigator determined response rate (RR). As compared to the historical RR of 4% (and median PFS 2.5 mos) for 2 nd -line FOLFIRI (Tournigand), with alpha 0.10 &amp; beta 0.90, a sample size of 45 would have the power to detect improvement in RR to 15%, and 79% power to demonstrate improved med PFS to 4.0 mos. Early stopping would occur for responses of 0 of 20 patients. Results: 32 patients were entered and treated. Median age was 54 (40-71) yrs, 18 were male and 22 Caucasian, all KRASm. The first 3 tolerated SEL 50 mg bid without SAE and the remaining 29 were treated at 75 bid. Median number of cycles on study was 3.5 and median TTP approximately 4.0 months. Observed grade 3 AEs included: diarrhea 3, fatigue 2, neutropenia 2, and 1 each PLTS, enteritis, GI bleed, rash; one grade 4 ANC. Grade 2 AEs: diarrhea 12, rash 8 pts. Best response (investigator reported) included 3 (9%) confirmed PR and 15 (47%) SD [including 2 unconfirmed PR] of 32 entered. Six patients were on study for &gt; 6 months (6, 6, 8, 9, 12.5, 14.5 months). The study was terminated early due to non-protocol considerations. These data are not yet verified. Conclusions: Despite early termination, the higher RR and PFS noted for 32 patients with KRASm CRC treated with IRI and SEL as 2 nd -line therapy of CRC (and treated for up to 14.5 months), are promising compared with historical controls. The strategy of MEK inhibition in KRAS mutated CRC should be explored further. Clinical trial information: NCT01116271.
Impact of radiotherapy (RT) in patients (pts) affected by locally advanced prostate cancer (LAPC) undergoing hormone treatment (HT): Meta-analysis of randomized trials (RCTs).
Authors: V. Vaccaro, E. Bria, F. Cuppone, M. Milella, E. Ruggeri, I. Sperduti, P. Pinnaro, D. Giannarelli, F. Cognetti, P. Carlini
Journal: Journal of Clinical Oncology (2011)

e15038 Background: The addition of HT to RT significantly decreases recurrences and mortality of pts affected by LAPC eligible for exclusive RT. However, the value of adding RT to HT alone is still controversial. To address this issue, a literature-based meta-analysis was conducted. Methods: Hazard Ratios (HR) with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from papers or presentation. Differences in cancer-specific survival (CSS) and overall survival (OS) were explored. CSS- and OS-death rates, absolute differences (AD) with 95% CIs, and the number of pts needed to treat (NNT) for one to benefit were calculated. Testing for heterogeneity was performed as well. Results: Three trials (2,343 pts) were gathered. Data were available for 2 RCTs (2,080 pts) for CSS and OS; patient population ranged from 263 to 1,205 pts. Results are shown in the table. CSS death rate was 8.5% (95% CI 6.7, 10.1%) in the RT-HT arm, and 16.1% (95% CI 13.9, 18.3%) in the HT arm; OS death rate was 23.0% (95% CI 20.41 25.5%) in the RT-HT arm, and 29.5% (95% CI 26.7, 32.2%) in the HT arm. Conclusions: RT remains the treatment cornerstone for pts affected by LAPC, and cannot be excluded; pts receiving exclusive HT experience significantly worse CSS and OS. HT should be considered in addition to RT. Outcome HR (95% CI) P value Het. (p) AD (%) NNT CSS 0.51 (0.39, 0.66) <0.0001 0.33 7.6 13 OS 0.72 (0.61, 0.87) <0.0001 0.49 6.5 15-16
The relationship between systemic inflammation-based prognostic scores and body composition analysis in colorectal cancer patients.
Authors: Euan Douglas, Colin H. Richards, Campbell S. D. Roxburgh, Paul G. Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2014)

407 Background: Weight loss in cancer is increasingly recognised as part of syndrome associated with chronic activation of the systemic inflammatory response (McMillan DC, 2009). The aim of the present study was to examine the relationship between systemic inflammation based prognostic scores (SIBPS) and CT measured parameters of body composition in patients with primary operable colorectal cancer (CRC). Methods: 303 patients with primary operable CRC who underwent resection with curative intent (2003-2012) were studied. Image analysis of CT scans was used to measure total fat index (cm 2 /m 2 ), subcutaneous fat index (cm 2 /m 2 ), visceral fat index (cm 2 /m 2 ) and skeletal muscle index (cm 2 /m 2 ). SIBPS included the Glasgow Prognostic Score (mGPS), Neutrophil: Lymphocyte ratio (NLR), Platelet: Lymphocyte Ratio (PLR), Prognostic Index (PI), and Prognostic Nutritional Index (PNI). Results: In all patients there was a significant association between lower BMI and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p=0.028 and p&lt;0.001), NLR (p=0.004 and p=0.002), and PNI (p=0.001 and p=0.022). In male patients there was a significant association between lower BMI, total fat mass and skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p= 0.027, p=0.048 and p=0.001), NLR (p=0.002, p=0.034 and p=0.003), and PNI (p=0.003, p&lt;0.001 and p0.048). In female patients total body fat was associated with the PLR (p=0.001) and PNI (p=0.009) but only the mGPS (p=0.007) and the PI (p=0.013) were associated with reduced skeletal muscle. Conclusions: The present study highlights a consistent association between lower BMI and skeletal muscle mass and the presence of a systemic inflammatory response. These results are consistent with the hypothesis that chronic activation of the systemic inflammatory response results in the loss of lean tissue and that ultimately compromises survival in patients with CRC. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223-6.
A phase III, open-label, randomized comparison of AS1413 (amonafide L-malate) plus cytarabine with daunorubicin plus cytarabine in secondary acute myeloid leukemia (ACCEDE).
Authors: R. M. Stone, S. L. Allen, A. Pigneux, R. K. Stuart, M. Wetzler, D. Rizzieri, H. P. Erba, L. E. Damon, J. H. Jang, M. S. Tallman, K. Warzocha, T. Masszi, M. A. Sekeres, E. Miklos, H. Horst, D. L. D. Selleslag, S. R. Solomon, P. Venugopal, A. S. Lundberg, B. L. Powell
Journal: Journal of Clinical Oncology (2011)

6520 Background: Secondary acute myeloid leukemia (sAML; after antecedent histologically documented myelodysplastic syndrome or arising from prior chemo or radiation therapy for another cancer) responds poorly to current therapies and is often multidrug resistant; results with the current standard induction therapy of an anthracycline plus cytarabine are disappointing. Amonafide L-malate (AS1413) is a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades multidrug resistance mechanisms. The ACCEDE trial, one of the largest ever conducted in this subgroup of AML patients, was designed to assess the efficacy and safety of AS1413 plus cytarabine compared with standard remission induction therapy of daunorubicin plus cytarabine in sAML. Methods: In this phase III, multicenter, open-label, study, patients aged ≥ 18 years with newly diagnosed sAML were randomized to cytarabine 200 mg/m2 continuous IV infusion daily on days 1–7 plus either AS1413 600 mg/m2 IV over 4 hours daily on days 1–5 (Arm A) or daunorubicin 45 mg/m2 IV over 30 minutes daily on days 1–3 (Arm B). The primary endpoint was CR rate (± hematopoietic recovery). The planned sample size of 420 patients provided 89% power to detect a 15% difference at the p=0.05 level (two-tailed) between anticipated CR rates. Results: 564 pts were screened and 433 randomized; 216 to arm A, 217 to arm B. Disease etiology, cytogenetics and age were balanced between both arms. CR + CRi: 94/216 (43.5%) Arm A, 94/217 Arm B (43.3%); p=0.966. Thirty-day mortality was 20.4% in arm A, 12.4% in arm B. Serious Adverse Events were balanced between the two arms, and no event occurred in more than 6% of patients in either arm. Subgroup analyses are ongoing. Conclusions: The combination of amonafide and cytarabine does not provide a CR benefit over treatment with daunorubicin and cytarabine in patients with secondary AML. sAML patients should be considered for clinical trials or specific therapies based on molecular profiles.
The Austrian Fulvestrant Registry: Results from a prospective observation of fulvestrant in postmenopausal patients
Authors: R. Bartsch, B. Mlineritsch, M. Gnant, T. Niernberger, U. Pluschnig, R. Greil, M. Pober, P. Sevelda, J. Thaler, G. G. Steger
Journal: Journal of Clinical Oncology (2008)

1060 Background: Endocrine therapy is the preferred treatment in estrogen- and/or progesterone-receptor (ER/PgR) positive metastatic breast cancer (MBC). Fulvestrant (F) is a pure ER antagonist with similar efficacy as aromatase inhibitors. We present results from 58 Austrian centres that contributed patients (pts) to the Austrian fulvestrant registry. Methods: F was administered at the registered dose. For baseline evaluation, CT-scans of chest and abdomen, mammography, gynecologic examination, and bone scan were mandatory. Tumor assessment was performed every three months. Primary endpoint was time to progression (TTP); secondary endpoints were clinical benefit rate (CBR; CR+PR+SD ≥ 6 months), and toxicity. TTP was estimated with the Kaplan-Meier product limit method. A multivariate analysis (Cox regression model) was performed to identify factors significantly influencing TTP. Results: 350 consecutive pts, median age 66 years (y), range 35 - 92 y, were included. 36% had prior adjuvant chemotherapy (CT), and 64% adjuvant endocrine therapy; 42% had prior CT for MBC. 49% had visceral metastases; 13.4% HER2-positive disease; 45% were > 65 y. F was administered as 1st-line therapy in 92 pts (26.3%), 2nd-line 170 (48.6%), 3rd-line 67 (19.1%), and 4th-line in 21 pts (6%). Median TTP was 7 months, range 2 - 34 (95% CI 6.09–7.9). 2.3% experienced CR, 12.3% PR, and 46% SD ≥ 6 months, resulting in a CBR of 60.6%. 6.9% had SD < 6, and 32.6% had PD. In the multivariate analysis, longer TTP was significantly associated with 1st-line treatment and nonvisceral metastases; other variables (age, time to recurrence ≤ 1 y, prior CT, Her2-, PgR-status) had no influence. 1.4% experienced grade 3 joint pain, and 0.3% grade 3 hot flashes. Other toxicities (grade 1 and 2 only) consisted of nausea, headache, fatigue, weight gain, and depression. 16 pts developed mild local reactions. Conclusions: Results confirm previous data that F is an effective and well tolerated treatment option, even in elderly pts. TTP and response rates are superior to other trials, probably due to the large number of pts receiving F as 1st- or 2nd-line treatment. Activity of F seems to be independent of HER2- and PgR-status. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, AstraZeneca, Novartis, Pfizer, Roche, sanofi-aventis Amgen, AstraZeneca, Novartis AstraZeneca, Novartis, Roche, sanofi-aventis