tbuckley/cabot-search huggingface dataset:
Phase I study of isotype-selective histone deacetylase (HDAC) inhibitor MGCD0103 given as three-times weekly oral dose in patients (pts) with advanced solid tumors
Authors: M. Carducci, L. L. Siu, R. Sullivan, M. Maclean, A. Kalita, E. X. Chen, R. Pili, R. E. Martell, J. Besterman, G. K. Reid
Journal: Journal of Clinical Oncology (2006)

3007 Background: MGCD0103 is a novel isotype-selective inhibitor of human HDACs. Deacetylation of histones by HDACs is postulated to inactivate tumor suppressor genes leading to neoplastic transformation. Inhibition of these enzymes might restore normal growth control. Methods: A phase I trial of MGCD0103, given as a three-times weekly oral dose 2 out of every 3 weeks, has been performed in pts with advanced solid tumors. Main endpoints are safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) assessments of HDAC activity and histone acetylation status in buffy coat white cells. Results: Five dose levels have been evaluated (mg/m 2 ): 12.5, 20, 27, 36, and 45. As of January, 2006, 28 pts have been enrolled with the following demographics: M:F = 18:10; median age (range) = 60 (29–75); ECOG 0:1:2 = 9:13:1 (n = 23); primary tumor sites: colorectal (8), renal (5), lung (4), others (11); prior chemotherapy, radiotherapy, immunotherapy were given to 22, 12 and 2 pts, respectively (n=23). A total of 62 cycles have been administered, with median = 2 and range=1–7 cycles. MGCD0103 has been well tolerated; most common AEs (23 pts): grade 1–3 fatigue (91% of pts), grade 1–2 nausea and vomiting (70 and 48%), anorexia (26%), constipation (39%). Disease stabilization &gt; 2 cycles has been observed in 3 renal cell cancer pts (4, 6, and 7 cycles) and 1 colorectal cancer pt (4 cycles). Preliminary PK analyses demonstrated intra-pt PK variability, however co-administration of acidic carbonated beverage (protocol amendment) appears to reduce variability without altering average Cmax or AUC (0–24) comparing Day 1 with Day 14. There was little accumulation or decrease in concentrations with extended dosing, and t1/2 was dose-independent at 7.7–11.3 hr. (±0.6–1.6). PD data reveal dose-dependent maximal inhibition of HDAC activity in patients co-administered an acidic beverage. Conclusions: At doses evaluated MGCD0103 appears tolerated and exhibits favourable PK and PD. [Table: see text]
Coexpression of HER3 as a predictor of survival in HER2-positve breast cancer patients.
Authors: Rupert Bartsch, Anna Sophie Berghoff, Zsuzsanna Bago-Horvath, Matthias Preusser, Guenther G. Steger, Margareta Rudas, Peter Birner, Christoph Zielinski
Journal: Journal of Clinical Oncology (2013)

611 Background: Improved understanding of the pathobiology of the metastatic cascade as well as the identification of new prognostic markers may lead the path to the development of novel targeted agents in breast cancer patients (BC pts). Recently, HER3-expression was postulated as independent risk factor for metastatic spread. Methods: Pts of different BC subtypes (luminal, HER2-amplified, triple-negative) with metastatic disease were identified from a breast cancer data base. Tissue of the primary tumor was retrieved from the local pathology institute. Immunohistochemical staining of estrogen-receptor, progesterone-receptor, and HER2 and HER3 was performed. In HER2 equivocal cases, subsequent FISH analysis was performed. Results: Specimens of 110 pts (36/110 luminal, 35/110 HER2-amplified, 40/110 triple-negative) were available for this analysis. 23/110 (21%) specimens showed strong, complete, membranous staining for HER3 of at least 10% of all tumor cells. HER2/HER3 co-expression was observed in 12/110 (11%) specimens. HER3 showed a statistically significant association with HER2-expression (p=0.02; Chi square test). No correlation was observed for HER3-expression and overall survival (OS), incidence of brain metastases, or time to diagnosis of brain metastases in the entire patient cohort (p&gt;0.05; log rank). In the HER2-amplified subgroup, however, HER3-expression was significantly associated with shorter OS (median 30 vs. 63 months; p=0.02; log rank test) and remained significant when entered into a multivariate model (p=0.02; Cox regression). Conclusions: HER2/HER3 co-expression is significantly associated with impaired OS in pts with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or inhibition of HER2/HER3 hetero-dimerization could improve prognosis of this patient population.
Adrenalectomy for low-tumor-burden metastatic lung cancer: Results of a single institution experience.
Authors: José María López-Picazo, Patricia Martin-Romano, Leyre Zubiri Oteiza, Alfonso Gurpide, Ignacio Gil-Bazo, Jose Luis Perez-Gracia, Juan Pablo Fusco, Marta Moreno-Jiménez, Omar Esteban Carranza, Salvador Martin-Algarra
Journal: Journal of Clinical Oncology (2013)

e19114 Background: Adrenal gland is a common site of metastasis in lung cancer. Adrenal metastasis (AM) can occur at the time of diagnosis (synchronous AM) or later (metachronous AM). When an AM appears as an isolated site of dissemination it is considered a good-prognosis metastatic disease. Nevertheless few data are available about the prognosis and the optimal management of these patients. Methods: Retrospective analysis of the historical series of adrenalectomies in patients treated of lung cancer at our institution. Results: From April 2002 to April 2011, 30 patients (27m/3f) diagnosed of AM of lung cancer (16 non-squamous, 8 squamous, 6 small-cell; 21 metachronous AM, 9 synchronous AM) were treated with adrenalectomy (26 laparoscopic, 4 open surgery). Median age was 55 years old (range: 42-71). Median size of the AM was 35 mm (range: 12-140). There were no severe complications of surgery in any patient. All the patients had received radical treatment for the primary tumour and for other metatatic sites (8 patients brain metastases, 3 patients other sites) before adrenalectomy. Median overall survival (OS) and disease-free survival from adrenalectomy for the entire group were 44 (95% CI: 10-78) and 15 (95%CI: 7,6-22.3) months respectively. We found an statistical trend (p=0.087) of better OS from adrenalectomy for patients with non-squamous histology compared with squamous histology: 57 (95%CI: 38.4-75.6) and 21 (18.3-23.8) months respectively. The percentage of alive patients at 2 and 5 years was 59.1% and 36% respectively. Conclusions: These results add new data about the prognosis of patients with adrenal metastases into the context of low-tumor-burden metastatic lung cancer. Adrenalectomy is a tolerable procedure which plays a role in the management of these patients.
Thymic epithelial tumors at University Federico II of Naples: A 30-year experience.
Authors: Carlo Buonerba, Piera Federico, Filomena Calabrese, Margaret Ottaviano, Lucia Nappi, Pasquale Rescigno, Elide Matano, Giuseppe Di Lorenzo, Vincenzo Damiano, Giovannella Palmieri
Journal: Journal of Clinical Oncology (2013)

7603 Background: According to the 2004 WHO classification, thymic epithelial tumors (TETs) comprise different histologies, including thymomas, thymic carcinoma, typical and atypical carcinoids. Histology classification of TETs has a dramatic impact on the prognosis and therapeutic strategy. We here review all TETs treated at our Institution over the past 30 years. Methods: Eligible patients had a pathologically confirmed TET and had at least one access at our Institution. Relevant demographic and clinical data were retrieved. An exploratory analysis was conducted using a step-wise model in patients with completely resected tumors to seek for factors predictive of recurrence after radical surgery. Results: One hundred and three patients with TETs were included in this retrospective analysis. Forty-three were female, sixty were male. Median age was 43 years (range 32-58). Forty-three patients had myasthenia gravis. Four had a thymic neuroendrocrine tumor, 19 had a thymic carcinoma, while the remaining had a thymoma. Forty-seven patients were alive at the time of analysis. Median overall survival was 5.85 years (range, 2.58-9.9). In the whole sample population, seventy-six patients had a completely resected tumor with clear pathological margins. In this sub-group of 76 patients (median age: 46, 35-55; 30 females, 46 males), 12 had a thymic carcinoma and 30 patients recurred after radical surgery. At multivariate analysis, which included age, sex, adjuvant chemotherapy, adjuvant radiotherapy, maximum tumor diameter, presence of myasthenia gravis and stage, the only factor significantly predictive of recurrence was tumor histology (odds ratio: 3,8182, 95% CI: 1,03 to 14,1; p = 0.04). Conclusions: We showed that patients with thymic carcinomas are at increased risk of recurrence after radical surgery independently on adjuvant chemotherapy/radiotherapy treatment. Additional therapeutic options are required in the adjuvant setting of completely resected thymic carcinomas.
Radiofrequency ablation (RFA) of breast cancer: A multicenter retrospective analysis.
Authors: Toshikazu Ito, Shoji Oura, Naohito Yamamoto, Shinji Nagamine, Masato Takahashi, Hirokazu Tanino, Noboru Yamamichi, Mitsuharu Earashi, Hiroyoshi Doihara, Shigeru Imoto, Shoshu Mitsuyama, Hiroshi Sonoo, Kohei Akazawa
Journal: Journal of Clinical Oncology (2012)

1119 Background: Local ablative therapy of breast cancer represents the next frontier in the minimally invasive breast-conservation treatment. We performed a retrospective study of ultrasound-guided percutaneous radiofrequency ablation (RFA) of breast cancers to determine safety and complication related to this treatment. Methods: Four hundred and ninety-seven patients with core biopsy proven breast carcinoma in 10 institutions of non-surgical ablaton study group underwent RFA without surgical excision were enrolled in this study. Results: Mean patient age was 54 years (range 22 - 92 years). Mean tumor size was 1.6 cm. Four hundred and twenty-five tumors ( 86 %) were ≤ 2 cm. The median follow-up period was 50 months (range 3 – 92 months). The mean required for ablation was 19 minutes (range, 4- 72 minutes), and the average temperature of the tumor after ablation was 91 degrees Celsius. The local recurrence rate after RFA was higher in tumors of negative estrogen receptor (8 of 78, 10%) than in tumors of positive estrogen receptor (17 of 437, 4%; p&lt;0.05), and was higher in tumors of positive HER2/neu than in tumors of negative HER2/neu (14.9% vs. 3.2%; p&lt;0.01). The local recurrence rate after RFA was higher in tumors of positive node than in tumors of negative node (9.8% vs. 3.6%), and was higher in tumors without irradiation than in tumors with irradiation (18.2% vs. 3.2%; p&lt;0.001). The local recurrence rate after RFA was higher in tumors of &gt; 2 cm (13 of 72, 18%) than in tumors of ≤ 2 cm (11 of 425, 3%; p&lt;0.001). RFA-relating adverse events were observed in 17 patients of local pain, 14 patients of skin burn and 4 patients of retraction of nipple. Conclusions: RFA is considered to be a safe and promising minimally invasive treatment of small breast cancer ≤ 2 cm in diameter. Further studies are necessary to optimize the technique and evaluate its future role as local therapy for breast cancer.
Mimics of gastrointestinal stromal tumors (GISTs): Implications for diagnosis and management—The Cambridge GIST Study Group (CGSG) experience.
Authors: Han Hsi Wong, Rajani Chengal, Richard Hardwick, Gail Horan, Helen Hatcher, Helena Margaret Earl, Stephanie Pursglove, Venkata Ramesh Bulusu
Journal: Journal of Clinical Oncology (2013)

e21503 Background: Historically, GISTs were often misdiagnosed as other tumours. However, with the increasing awareness of GISTs, one needs to be careful in confirming the diagnosis since other tumours can simulate GISTs on endoscopy/imaging/histology. We report our 8 year experience of GIST mimics from the CGSG database. Methods: 250 cases discussed in the specialist multidisciplinary meeting from 2004 – 2012 were reviewed. Tumours initially suspected to be GISTs but turned out to be other tumours were included in this analysis. Patient demographics, endoscopic, imaging and histological features were analysed in 41 GIST mimics. Central review by specialist histopathologist was undertaken with immunohistochemical and molecular analysis to differentiate these tumours from GISTs. Results: GIST mimics N= 41. Median age 56 years (range 11 – 82 years), male:female ratio 1:1. Median size 8 cm (range 1.9 – 30 cm). Site of origin of tumours: stomach 34%, oesophagus/junction 15%, mesentery 12%, small bowel 10%, colon 5%, retroperitoneum 5%, pancreas 5%, liver 2% and indeterminate site of origin 12%. Suspicion of GIST was raised from imaging (46%), endoscopy (41%) and histology (39%). The histological subtypes of GIST mimics are summarised in the Table. Conclusions: Many benign and malignant tumours do mimic GISTs on imaging/endoscopy or histology. The diagnosis of GISTs should be made by a specialist multidisciplinary team with experience in imaging and histopathology. Distinguishing GISTs from their mimics is of critical importance both for prognosis and management. [Table: see text]
Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development program (phase I trials) at Institut Gustave Roussy.
Authors: Myriam Kossai, Boris Duchemann, Caroline Caramella, Celine Boutros, Christophe Massard, Philippe Vielh, Anas Gazzah, Rastislav Bahleda, Eric Angevin, Antoine Hollebecque, Jean-Charles Soria, Benjamin Besse
Journal: Journal of Clinical Oncology (2013)

7604 Background: Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options, particularly in advanced stages and/or in thymic carcinomas (TC). The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients (pts) with a refractory TEN enrolled in Phase I trials. Methods: We reviewed retrospectively pts with advanced pretreated TEN enrolled in Phase I trials at the Institut Gustave Roussy (SITEP) between 1994 and 2012. Toxicities were reported and scored according to NCI CTCAE version 3.0. Efficacy was assessed using RECIST version 1.1. Results: Twenty-two treated pts were enrolled (14 with TC, 8 with thymomas). The median number of prior systemic therapies was 2 (1-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatment received were mTOR inhibitor (mTORi) in 4 of pts, antiangiogenic agents (AA) in 11 pts, and other targeted therapies in 7 pts. The median follow-up time was 22.1 months (range, 1.25-77.79 months). Autoimmune associated disease (AID) was reported in 6 pts. 18% had grade III/IV toxicity, 54% grade I/II toxicity and no toxic death was reported. AID exacerbated in one patient. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 pts had stable disease (median 6.6 months) and 2 had a progressive disease. Objective response rate (ORR) was 42%, 25.0% for thymoma and 21.4% for TC. The median overall survival was 54.5 months (95% CI 25-75.50 months), 54.5 for thymoma and 62 for TC. The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59 months), 5.2 for thymoma and 6.9 for TC. Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies. Conclusions: Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response. Novel targeted therapies might be tested setting in a biology-oriented approach rather than a stochastical one. We are currently offering a molecular profiling in our patients (MOSCATO trial NCT01566019) for a better selection of appropriate Phase I trial.
Telenutrition in oncology: A novel model of care in a geographically diverse network.
Authors: Michele Leigh Szafranski, Beth York, Tara Eaton, Wendy G. Brick, Chasse Margot Bailey-Dorton
Journal: Journal of Clinical Oncology (2017)

43 Background: Telehealth is growing as a way for qualified providers to reach patients closer to home. Dietitians have been using telephone counseling to support cancer patients for years, but recently consults via videoconference have emerged to better duplicate in office, face-to-face service. Telenutritionallows Registered Dietitians (RDs)who are also Certified Oncology Specialists in Nutrition (CSOs) to provide patients consults at their regular medical oncologist’s office. As part of its goal to provide expert care to oncology patients in regional settings, genetics counselors, social workers, and Palliative Care providers at Levine Cancer Institute (LCI) are currently using a telehealth model to provide services traditionally available only in metro areas. Methods: RDs located within the LCI Network receive consults from regional sites in NC based on established criteria. LCI RDs use Vidyo to teleconference between LCI locations to meet with patients, caregivers, and the healthcare team to establish an appropriate plan of care. Appointments are scheduled directly on the virtual schedule by the referring office. Consents are signed and scanned into the chart. Assessment is completed using the same protocol and policy as face-to-face consults, and follow up can conducted via teleconference or phone, based on patient preference and the clinical judgement of the RD. Patient satisfaction surveys are completed at the end of each telenutritionsession and sent to the RD. Results: LCI initially started telenutritionwith one regional site in 2014, completing 3 consults with one RD housed at its main location. In 2015, three additional sites were added, as well as an additional RD housed regionally, and 22 consults were completed. 22 consults have been completed year to date in 2016. Conclusions: Early feedback from patients and providers suggest telenutrition may be an effective method to deliver quality nutritional interventions to patients in the comfort of their regular oncology office. Formal study is needed to explore patient barriers to care, reimbursement for services, expense of equipment, and feasibility of program expansion.
Real-world outcomes in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving second-line (2L) chemotherapy (CT) vs alternative androgen receptor-targeted agents (ARTA) after lack of response to first-line (1L) ARTA in US community oncology practices.
Authors: William K. Oh, Wendy Y. Cheng, Raymond Miao, Francis Vekeman, Marjolaine Gauthier-Loiselle, Mei Sheng Duh, Edward Drea, Ted P. Szatrowski
Journal: Journal of Clinical Oncology (2017)

214 Background: The relationship between treatment sequence and mCRPC outcomes is unclear. This retrospective study assessed if 2L CT vs alternative ARTA is associated with improved outcomes in pts with lack of response to 1L ARTA in the US community oncology setting. Methods: Using Altos electronic medical records, we identified 345 mCRPC pts with lack of response to 1L ARTA (abiraterone or enzalutamide) who received 2L docetaxel or cabazitaxel (CT cohort N = 147), or alternative ARTA (ARTA cohort N = 198) from May 2011 to Oct 2014. Outcomes were evaluated from start of 2L therapy and compared for 2L CT vs ARTA cohorts using one-sided tests. Prostate-specific antigen (PSA) response ( ≥ 50% reduction) and overall survival (OS) were assessed using logistic and Cox proportional hazard regression models adjusted for year, age, metastases, opioid use, ECOG performance score, PSA, hemoglobin (Hb), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and albumin (Alb) levels. Results: At start of 2L therapy, pts receiving CT vs ARTA were younger (median age, 74 vs 79 yr) and had a worse prognosis: higher mean PSA (439 vs 231 ng/mL), LDH (344 vs 234 U/L) and ALP (241 vs 166 U/L), lower mean Hb (11 vs 12 g/dL), higher mean Halabi risk score (159 vs 137; JCO 2014:32;671–7), increased opioid use (42 vs 22%), and more pts had Alb &lt; lower limit of normal (LLN; 25 vs 15%); all p &lt; 0.01. More pts in the CT vs ARTA cohort had a PSA response (adjusted odds ratio = 2.27, p = 0.005) and there was a non-statistically significant trend toward improved OS for 2L CT vs ARTA (adjusted hazard ratio [aHR] = 0.81, p = 0.148). Among pts with poor prognostic features, those in the CT cohort had significantly improved OS (Halabi intermediate–high risk score: aHR = 0.55 p = 0.009; Hb &lt; 11 g/dL: aHR = 0.41 p = 0.002; LDH &gt; upper limit of normal: aHR = 0.18 p = 0.014; Alb &lt; LLN: aHR = 0.42 p = 0.020), compared with those in the ARTA cohort. Conclusions: Treatment with 2L CT, vs 2L ARTA, may be more suitable for pts with a lack of response to 1L ARTA, particularly in pts with a poor prognosis. Funding: Sanofi Genzyme.
Increase in sensory sensitivity around, but not in the central part of, the hyperkeratotic papule in lichen amyloidosis
Authors: T. Andoh, T. Shimizu
Journal: British Journal of Dermatology (2017)

Lichen amyloidosis (LA) is an itchy skin disorder characterized by amyloid deposits in the superficial dermis. Pruritus is the presenting symptom in 90% of LA patients.1 However, the underlying mechanisms and mediators of pruritus in LA remain unclear.

One LA patient complained of severe pruritus in the hyperkeratotic papules, especially around the papule.

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Impact of major vascular resection on short- and long-term outcomes in patients with intrahepatic cholangiocarcinoma.
Authors: Bradley Reames, Timothy M. Pawlik, Aslam Ejaz, Hugo Marques, Luca Aldrighetti, Shishir Kumar Maithel, Todd W. Bauer, Feng Shen, George A. Poultsides, J. Wallis Marsh, Irinel Popescu, Charbel Sandroussi, T Clark
Journal: Journal of Clinical Oncology (2017)

275 Background: Major vascular (IVC or portal vein) resection for Intrahepatic Cholangiocarcinoma (ICC) has traditionally been considered a relative contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing liver surgery with major vascular resection using a multi-institutional database. Methods: 1,087 ICC patients who underwent liver resection between 1990-2016 were identified from 13 participating institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative outcomes and long-term overall survival. Results: Of 1,087 patients who underwent resection, 128(11.8%) also underwent major vascular resection [21(16.4%)IVC resections, 98(76.6%)PV resections, 9(7.0%)combined resections]. One hundred eighty-seven(17.2%) patients received neoadjuvant therapy. Most patients underwent a major hepatectomy involving ≥ 3 liver segments(n = 664,61.1%). On final pathology, the majority of patients had T1(40.4%) or T2(35.5%) tumors; 194(17.8%) had lymph node metastasis. Patients undergoing major vascular resection had more advanced T3/T4 tumors [44(34.4%) vs. 137(14.3%) without resection;P &lt; 0.001]. Of note, major vascular resection was not associated with the risk of any complication (OR .680,95%CI 0.32-1.45) or major complication (OR 0.69,95%CI 0.35-1.33); post-operative mortality was also comparable between groups (OR 1.06, 95%CI 0.32-3.48). In addition, median recurrence-free (14.0 months vs.14.7 months, HR.737,95%CI .49-1.10) and overall (33.4 months vs.40.2 months, HR .709,95%CI.36-1.40) survival were similar among patients who did and did not undergo major vascular resection, respectively(both P &gt; 0.05). Conclusions: Among patients with ICC, major vascular resection was not associated with increased peri-operative morbidity or mortality at major centers. Long-term outcomes following resection of ICC requiring vascular resection were also comparable to outcomes following resection of tumors without vascular involvement. Concurrent major vascular resection should be considered in appropriately selected ICC patients.