tbuckley/cabot-search huggingface dataset:
Genetic testing decisions of breast cancer patients: Results from the iCanCare study.
Authors: Reshma Jagsi, Allison W. Kurian, Kent A. Griffith, Ann S. Hamilton, Kevin C. Ward, Sarah T. Hawley, Monica Morrow, Steven J. Katz
Journal: Journal of Clinical Oncology (2015)

1541 Background: Breast cancer pts at high risk for pathologic genetic mutations should consider testing. Even those without elevated risk may have concerns about genetic predisposition. Little is known about cancer pts’ decisions to undergo genetic testing as access to multiple gene panels and rising awareness transforms the decision-making context. Methods: We surveyed a population-based sample of early-stage breast cancer pts diagnosed in 2013-14, identified by 2 SEER registries (Los Angeles and Georgia), about experiences with genetic testing after diagnosis. Surveys were completed about 6 months after dx. A “high risk” subgroup was determined based on age, family history, and ancestry, and receptor status. We evaluated patterns of receipt of counseling and correlates of testing in a preliminary sample (response rate 68%). Results: Among 2,051 pts analyzed, 728 (35%) were “high risk.” Most high risk pts (67%) and half (50%) of others desired testing. Most high risk pts (63%) and 38% of others spoke to a physician or other health care professional about testing. Overall, 23% reported formal genetic counseling (34% of high risk pts, 18% of others), and 28% received testing (46% of high risk pts, 19% of others). On multivariable analysis, test receipt was more common in pts with high risk, invasive vs in situ disease, and higher education. Among high risk pts, non-receipt of testing was associated with in situ vs. invasive disease (OR 1.8, p = .02), no family hx of breast cancer(OR 2.4, p = < .001), older age (OR 1.9 for +5-yrs, p < .001), lower education (OR 1.6, p = .05), and Medicaid insurance (OR 2.0 vs private, p = .03). Of 362 high risk pts who did not get tested, 54% indicated their doctor didn’t recommend it, 10% didn’t want it, and 12% said it was too expensive. Conclusions: Most newly diagnosed breast cancer pts desire genetic testing, but many do not discuss it with providers. Most high risk pts do not report formal genetic counseling; a substantial number report no discussion of genetic risk at all. Test receipt is reassuringly correlated with risk but also with SES. Providers must ensure that breast cancer patients with interest in genetic risk have adequate discussion, especially as access to more expansive testing soars. Funding: P01-CA-163233.
Integrating Research With Clinical Practice
Authors: Adrian F. Hernandez, Robert A. Harrington, Christopher J. O'Donnell
Journal: JAMA Cardiology (2017)

Robert Scragg, MBBS, PhD; Alistair W. Stewart, BSc; Debbie Waayer, MEd; Carlene M. M. Lawes, MBChB, PhD; Les Toop, MBChB, MD; John Sluyter, PhD; Judy Murphy, RN; Kay-Tee Khaw, MBBChir, MSc; Carlos A. Camargo Jr, MD, DrPH
Effects of fosaprepitant (Fosa) administered as single dose versus two doses, on nausea/vomiting (N/V) in patients receiving multiday chemotherapy (CT) with a highly emetogenic regimen of doxorubicin and ifosafamide (AI): Randomized cross-over study.
Authors: Saroj Vadhan-Raj, Xiao Zhou, Dejka M. Araujo, Neeta Somaiah, Anthony Paul Conley, Vinod Ravi, Mary Daniel, Robert S. Benjamin, Shreyaskumar Patel
Journal: Journal of Clinical Oncology (2014)

9616 Background: AI is multi-day regimen of highly emetogenic chemotherapy, with high incidence of delayed N/V. Fosa, NK1 receptor antagonist (RA), administered IV as single dose (FDA-approved), with 5HT3RA and dexamethasone has improved the control of emesis. However, delayed N/V still remains problematic. Purpose of the study was to examine the effects of fosa administered IV on day 1 vs days 1 and 4 on N/V and the effect on ifosfamide (Ifex) and its active metabolites, due to potential drug interactions via CYP450. Methods: Sarcoma pts, planned to receive AI, were randomized 1:1 to Arm A (single- dose Fosa on day 1) or Arm B (2-doses, on days 1 and 4). Within each arm, patients were randomized to Group-1: Fosa in cycle-1 (C-1) and no Fosa in cycle-2 (C-2), and group-2: no Fosa in C-1 and Fosa in C-2. Blood samples were drawn for levels of Ifex/metabolites to be analyzed at the end of study. All pts could receive 2 doses of Fosa during cycles 3-6. Pts were monitored for N/V with daily symptom diary and FLIE (functional living index -- emesis) score (days 1, 5 and 10). Results: Of 47 pts, 40 eligible pts were randomized. There were 13 men and 27 women, with median age of 45 years (range, 19-65) and KPS of 90 (80-100). At present, 34 pts have completed 2 CT cycles. As shown below, Fosa administered as 2 doses resulted in significantly better control of delayed N/V as compared to single-dose or the control cycle. Furthermore, in cycle-3 the higher CR rate for N/V was maintained with 2 doses. Treatment with Fosa (one or two doses) was well tolerated with no enhanced neurological toxicity. Conclusions: The results of this study showed for the first time that Fosa administered as 2 doses is well tolerated and more effective in the control of delayed N/V than single dose or no Fosa with 5HT3RA + Dexa in pts receiving multi-day CT. Clinical trial information: NCT01490060.Complete response (CR*) in C-1 and C-2. Study groups No. of pts Day 1 N (%) Days 2-5 N (%) Days 1-10 N (%) Single-dose 18 13 (72) 2 (11) 2 (11) Two-doses 16 10 (63) 8 (50) 6 (38) Control (no Fosa) 34 27 (79) 6 (18) 4 (12) P value ** 0.44 0.015 0.06 * CR: No emetic episodes and no rescue medications. ** Chi-square test.
Phase II study of single agent gemcitabine in patients with hormone refractory prostate cancer (HRPC)
Authors: S. Nilsson, M. Holmberg, G. Ljung, D. Pettersson-Skjold, R. Blom, A. Ullén, R. Westberg, I. Nilsson, B. Lennernas
Journal: Journal of Clinical Oncology (2004)

4705 Background: Gemcitabine is effective in several solid tumor forms but only limited data have been reported in HRPC. Methods: The primary objective was to study the median time to treatment failure (TTF). Other objectives were to investigate symptom control, toxicity and survival. The eligibility criteria comprise presence of bone metastases, increasing PSA and performance status (WHO) ≤ 2. Gemcitabine was given as single agent therapy in a dose of 1250 mg/m2 on day 1+8 of a 3-week cycle. The dose was reduced to 1000 mg/m2 in case of WHO grade 2–3 hematologic toxicity or grade 3–4 non-hematologic toxicity. Treatment was given until objective tumor progression was documented, increasing PSA at two consecutive measurements, unacceptable toxicity or patients wish to withdraw from further treatment. Bone scan was done at base-line and during treatment at intervals according to praxis of the participating institutions. Chest X-ray and abdominal CT were done at base-line and if found positive every 9th week during treatment. Hematology, laboratory and PSA tests were done at base-line and before every new treatment cycle. A symptom questioner was completed by the patient at base-line and before every new treatment cycle. Results: 50 patients have received study treatment and are considered evaluable for TTF and toxicity. The median TTF is 2,7 (0.0–7.8) months with 14 events being censored. The median survival time is 14.7 (0.3–30.7) months with 23 events being censored. CR were noted in two measurable sites (lymph node and liver) in two patients. According to the patient self ratings, symptoms were held at the base-line level during therapy except fatigue which slightly increased over time. The median PSA value leveled out during therapy. One patient experiencing grade 4 thrombocytopenia and 2 patients grade 3 leucopenia. Subjective toxicity has been mild. Conclusion: Single agent gemcitabine seems to be an reasonably good option when symptom control is the main purpose for further therapy. No significant financial relationships to disclose.
Prognostic value of decrease on blood lymphocytes in breast cancer patients undergoing primary chemotherapy
Authors: A. Vicente, E. García-Martínez, E. Gonzalez-Billalabeitia, M. Zafra, C. Castilla-Llorente, T. García-García, J. Macías, E. García-Garre, V. Vicente, F. Ayala de la Peña
Journal: Journal of Clinical Oncology (2009)

e11537 Background: There is evidence about chemotherapy creating a better tumor control by inmune system. Neoadjuvant treatment is an excellent situation to study tumor behaviour. The aim of this study is to determine whether decreases on blood lymphocytes (BL) absolute number have a prognostic significance on women with breast cancer receiving primary chemotherapy (PC). Methods: A retrospective analysis was performed of 105 breast cancer patients who underwent PC. Doxorubicin (60mg/m 2 q3w) - Cyclophosphamide (600mg/m 2 q3w) x4c followed docetaxel (100 mg/m 2 q3w) x4c was PC regimen in 73,4%. We collected data on BL before the first cycle of PC (basal BL), just before second doxorubicin- cyclophosphamide (AC) cycle (BLa), and three weeks from the end of PC (BLb). The median decrease (MD) in blood lymphocytes has been calculated: MDa = BLa - basal BL; MDb = BLb - basal BL. Results: Of 105 patients with breast cancer 16,2% were clinical stage IIA, 19% IIB, 30,5% IIIA, 14,3% IIIB, 15,2% IIIC. The mean age was 50 years. The complete pathologic response (pCR) rate was 14,9% in primary tumor, and 37,9% in axillary nodes. The median follow up is 25 months (mo). Overall survival: (OS) 25,3 mo (range 4 - 89.3). Disease-free survival: (DFS) 21,8 mo (range 5 - 80.3). The median decrease on blood lymphocytes is MDa=300 10 6 /L(2400, -1000), MDb=700 10 6 /L(3900, -400). A decrease on BL just before second AC cycle (&gt; MDa=300 10 6 /L) is correlated with worse DFS, in univariant and multivariant analysis (HR =4.022; 95% CI:1.105–14.63; p 0.035 at first; HR=5.36; 95% CI:1.1–25.82; p 0.037 at former). Patients with BL decrease three weeks after finishing PC (&gt;MDb=700 10 6 /L) have worse DFS in univariant as multivariant analysis (HR=5.9 95% CI:1.2–27.5; p0.022 at first; HR=9.7 95% CI:1.11- 85.07; p 0.04 at former). We have not found significant differences in OS. Conclusions: A decrease on blood lymphocyte number in women with breast cancer undergoing primary chemotherapy is correlated with worse DFS. No significant financial relationships to disclose.
Phase II, two-stage, two-arm, PIK3CA mutation stratified trial of MK-2206 in recurrent endometrial cancer (EC).
Authors: Andrea P. Myers, Russell Broaddus, Vicky Makker, Panagiotis A. Konstantinopoulos, Ronny Drapkin, Neil S. Horowitz, Joyce Liu, Paul Van Hummelen, Funda Meric-Bernstam, Michael J. Birrer, L. Austin Doyle, Robert L. Coleman, Carol Aghajanian, Gordon B. Mills, Lewis Cantley, Ursula A Matulonis, Shannon Neville Westin
Journal: Journal of Clinical Oncology (2013)

5524 Background: EC has high rates of PI3K pathway alteration including PTEN mutation (50%) or IHC loss (&gt;50%), PIK3CA mutation (25-40%) and PIK3R1 (20%) mutation. MK-2206 is an allosteric inhibitor of AKT, an effector kinase of PI3K signals. We hypothesized that pts whose tumors harbored PIK3CA mutations would be more likely to benefit from MK-2206 than those without PIK3CA mutation. Methods: Pts had recurrent or advanced EC; all histologies except MMMT were eligible. Up to 2 prior chemo lines were permitted; excluding prior treatment with PI3K/MTOR inhibitors. The first 19 pts were treated with MK-2206 200mg QW; due to initial skin toxicity rates, the starting dose was amended to 135mg QW. Co-primary endpoints were objective response and 6 mo PFS. The first 37 pts were stratified retrospectively. PIK3CA MT included R88Q, K111N, E110K, E418K, C420R, E453K, E542K/V,E545K, Q546R, H701P, M1043V, H1047R/L/Y changes. Independent Simon 2-stage tests were planned within PIK3CA MT and WT stratum: for MT, n1=15 and n2=10 pts would allow discrimination of RR&lt;5% and 6moPFS&lt;10% versus RR&gt;25% or 6moPFS&gt;35%; for WT, n1=31 and n2=24 pts would discriminate RR&lt;5% and 6moPFS&lt;10% versus RR&gt;20% or 6moPFS&gt;25%. Results: 37 pts were enrolled (1 ineligible) before accrual was stopped as timely CLIA-compliant prospective mutation analysis was not feasible. By PIK3CA mutation analysis, 9 pts were MT: 1 pt had both PR and 6moPFS. 27 pts were WT: 1 pt had PR and 3 pts had 6moPFS. 2 pts with 6moPFS were treated at 200mg; 2 pts with 6moPFS were treated at 135mg. Each group had 1 PR. The most common toxicity was grade 3 rash (19%). Grade 3 and 4 toxicities occurred in 50% and 8% of pts. Exploratory analysis of histology found all pts with 6moPFS were classified as serous (4 of 8) as compared to all other histologies (0 of 28, p=.001). Targeted exome sequencing and copy number analysis of the PI3K pathway and PTEN IHC are underway. Associative studies will be reported. Conclusions: There is limited single agent activity of MK-2206 in both PIK3CA MT and PIK3CA WT EC populations. Activity was detected in pts with serous histology tumors and warrants further study. Clinical trial information: NCT01307631. [Table: see text]
Chemoradiation without cisplatin in the radical treatment of carcinoma of the oesophagus
Authors: S. S. Baluch, J. S. Tobias
Journal: Journal of Clinical Oncology (2004)

4261 Background: Chemoradiation therapy is increasingly employed as radical treatment for locally advanced oesophageal cancer, capable of achieving cure and competing with surgery as a realistic alternative choice. However, the reported severe and life threatening complication rates, RTOG grade 3/4, using concurrent cisplatin and 5-FU are 20% and 44% respectively (1). We report here the outcome of patients treated with chemoradiation at the Middlesex Hospital, London, UK between 1998 and December 2002.The efficacy and tolerance data of a non-platinum containing chemotherapy regimen is presented. Methods: 43 patients with locally advanced cancer were treated between January 1998 and December 2002. 38 patients were evaluable. (28 male, 10 female, age range 38–86, median 70 years). All were staged by CT criteria. All were WHO PS 2 or better. 23 had squamous cell carcinoma while 15 had adenocarcinoma. All were M0; tumour stages were T4N1 (n=5), T4N0 (n=1), T3N1 (n=25), T3N0 (n=5), T2N1 (n=2). CT planned radiotherapy fields were used, to a dose of 50–60 Gy in 2Gy daily fractions. Chemotherapy consisted of 5-FU 1000mg/m2 as 24hour infusion (D1–4 and D29–32). Single-dose Mitomycin-C 12mg/m2 was given on D1. Results: 1year survival was 58%, three years19% and 4 years 12 %. Two of 8 patients at 5 years are alive.These figures are comparable to results with cisplatin-based chemotherapy e.g. RTOG 85–01 (1). None of the patients required PEG insertion. Only 6% developed G3 neutropenia. 20% patients developed oesophageal stricture and one patient developed grade 2 pneumonitis. Conclusions: MMC and 5-FU chemotherapy is a safe and well tolerated regimen, even in elderly patients, for concurrent chemoradiation of locally advanced oesophageal carcinoma. There is no need for routine PEG insertions for nutritional support as the resulting radiation mucositis is far less intense than with cisplatin-based regimens. Ref 1. Herskovic A et al New Engl J Med 1992; 326: 1593–98. No significant financial relationships to disclose.
Phase I safety and tolerability of once daily oral afatinib (A) in combination with docetaxel (D) in patients (pts) with relapsed or refractory advanced solid tumors.
Authors: Helene Senellart, Jaafar Bennouna, Nicolas Isambert, Helene De-Montserrat, Patrick J. Squiban, Inga Tschoepe, Jean-Pierre Delord
Journal: Journal of Clinical Oncology (2012)

e13010 Background: A is an orally bioavailable, irreversible, ErbB Family Blocker. This open label, Phase I, dose escalation trial investigated the safety, tolerability, and PK of A, in two parallel dose cohort expansion parts, in combination with either gemcitabine (Part A) or D (Part B) in patients with relapsed or refractory solid tumors. Preliminary results from Part B are presented here. Methods: Eligible pts (confirmed diagnosis of advanced solid tumors, ECOG PS 0–1) received once daily, oral dosing of A in combination with D, given iv on Day 1 of every 3 week cycle. Dosing of A started on Day 2 of Cycle 1. Primary objective was to establish the maximum tolerated dose (MTD) based on the occurrence of dose limiting toxicities (DLT) observed in Cycle 1. Dose escalation was performed with cohorts of 3–6 pts using a 3+3 design. Initial starting dose level was A 30 mg/day and D 60 mg /m², escalating up to A 50 mg/day and D 75 mg/m² until the MTD was reached, and followed by a PK expansion cohort of 12 pts at the MTD level. Incidence and severity of AEs were recorded. Results: To date, 21 pts have been treated with A (30–50 mg/day) and D (60–75 mg/m 2 ), with baseline characteristics: mean age (55.4 years), women (42.9%) and number of prior chemotherapies (≤2: 57%; &gt;2: 43%). Fourteen pts received 2–4 cycles of treatment and five patients received 4 or more cycles. In Cycle 1, DLT was experienced by one out of six pts receiving 30 mg afatinib + 60 mg/m² docetaxel (Grade 3 diarrhea). No DLT was observed during the subsequent dose levels up to A 50 mg/day and D 75 mg/m². AEs observed in most pts were diarrhea (76.2%) and asthenia (66.7%). Conclusions: In pts with relapsed or refractory advanced solid tumors, the combination of A and D is well tolerated. AEs were manageable and the MTD was not reached in the tested dose range up to A 50 mg/day and D 75 mg/m². Considering the potential for diarrhea and rash during later cycles, the recommended dose for the expansion cohort was A 40 mg/day in combination with D 75 mg/m². Enrollment is ongoing (nine pts to date) and additional safety data and preliminary evidence of activity are anticipated to be available at the time of presentation.
The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso‐occlusive crises
Authors: Edward Gomperts, John D. Belcher, Leo E. Otterbein, Thomas D. Coates, John Wood, Brett E. Skolnick, Howard Levy, Gregory M. Vercellotti
Journal: American Journal of Hematology (2017)

Abstract Sickle Cell Disease (SCD) is a painful, lifelong hemoglobinopathy inherited as a missense point mutation in the hemoglobin (Hb) beta‐globin gene. This disease has significant impact on quality of life and mortality, thus a substantial medical need exists to reduce the vaso‐occlusive crises which underlie the pathophysiology of the disease. The concept that a gaseous molecule may exert biological function has been well known for over one hundred years. Carbon monoxide (CO), although studied in SCD for over 50 years, has recently emerged as a powerful cytoprotective biological response modifier capable of regulating a host of physiologic and therapeutic processes that, at low concentrations, exerts key physiological functions in various models of tissue inflammation and injury. CO is physiologically generated by the metabolism of heme by the heme oxygenase enzymes and is measurable in blood. A substantial amount of preclinical and clinical data with CO have been generated, which provide compelling support for CO as a potential therapeutic in a number of pathological conditions. Data underlying the therapeutic mechanisms of CO, including in SCD, have been generated by a plethora of in vitro and preclinical studies including multiple SCD mouse models. These data show CO to have key signaling impacts on a host of metallo‐enzymes as well as key modulating genes that in sum, result in significant anti‐inflammatory, anti‐oxidant and anti‐apoptotic effects as well as vasodilation and anti‐adhesion of cells to the endothelium resulting in preservation of vascular flow. CO may also have a role as an anti‐polymerization HbS agent. In addition, considerable scientific data in the non‐SCD literature provide evidence for a beneficial impact of CO on cerebrovascular complications, suggesting that in SCD, CO could potentially limit these highly problematic neurologic outcomes. Research is needed and hopefully forthcoming, to carefully elucidate the safety and benefits of this potential therapy across the age spectrum of patients impacted by the host of pathophysiological complications of this devastating disease.
Breast conserving surgery and re-excision rates: A single-institution’s experience.
Authors: Esther Dubrovsky, Jennifer Chun, Shira Schwartz, Amber Guth, Deborah M. Axelrod, Freya Ruth Schnabel
Journal: Journal of Clinical Oncology (2017)

181 Background: Quality measures (QM) in breast surgery vary among organizations world-wide. Although the rate of breast conserving surgery is an accepted QM, the incorporation of a standard for re-excision rates (RER) remains controversial. RER clearly has an impact on cost and efficiency of care. The purpose of this study is to look at techniques that can reduce burden to the patient and the healthcare system by decreasing RER. Methods: Our institutional Breast Cancer Database was queried to identify all patients from 2010-2016 who underwent lumpectomy for Stage 0-III breast cancer by three high-volume breast surgeons. We analyzed the RER based on method of detection, localization technique, use of circumferential cavity shave margins, and use of device MarginProbe (DUNE Medical Devices). Results: Of 1420 women, the overall RER was 22% (312/1420). The RER was not decreased by addition of pre-operative MRI. Localization techniques were used for all non-palpable tumors and did not affect RER. The use of shave margins decreased RER from 28% to 17% (p&lt;0.0001). The use of MarginProbe decreased RER from 24 to 11% (p&lt;0.0001). Conclusions: Adjunctive use of circumferential cavity shave margins or directed margin excision with the MarginProbe during breast-conserving surgery decreased the RER to less than 20%. The burden of each additional surgery in financial cost, missed work, child care, and transportation can be significant. Rate of re-operation in Breast Surgery should be considered strongly within the quality efforts of any institution. [Table: see text]
Acute:chronic training loads in tennis: which metrics should we monitor?
Authors: Jason D Vescovi
Journal: British Journal of Sports Medicine (2017)

Recently, Pluim and Drew1 provided tips for managing loads to help reduce injury risk in tennis. A central premise was the importance for assessing the acute:chronic loads—a concept to understand that the rate of change towards high weekly loads is more problematic (ie, increases injury risk) than simply performing high loads. In general, activities performed by athletes can be viewed as stress (ie, external loads like running distances or the number of accelerations/decelerations performed) and strain (ie, internal loads like heart rate, blood lactate). Thus, metrics from several domains are necessary to comprehensively quantify training and competition loads; however, there is a paucity of literature describing these indicators for tennis across the developmental spectrum. This knowledge gap limits the ability to identify which key metrics should be targeted within a systematic monitoring plan and subsequently used to track the acute:chronic loads in tennis, thus enabling the development of strategies to reduce injury risk.

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