tbuckley/cabot-search huggingface dataset:
Administration of high-dose chemotherapy (HDCT) with stem-cell support in patients (pts) with advanced germ cell tumors (GCT) 40 years of age or older: A retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) database.
Authors: Andrea Necchi, Giovanni Rosti, Manuela Badoglio, Patrizia Giannatempo, Daniele Raggi, Simona Secondino, Francesco Lanza, Paolo Pedrazzoli
Journal: Journal of Clinical Oncology (2017)

415 Background: The administration of HDCT in GCT pts ≥ 40 years may raise concerns, owing to the limited data on safety outcomes. Yet HDCT strategy may be the optimal one to achieve a cure in many cases. Consequently, understanding more on the outcomes of these pts and on safety of HDCT delivery has relevant clinical impact. Methods: Criteria for patient selection consisted of: GCT diagnosis, male gender, age ≥ 40 at the time of first HDCT course. Summary statistics were used to describe patient characteristics and outcomes. Probabilities for overall survival (OS) and transplant-related mortality (TRM) were calculated using the Kaplan-Meier method. TRM was defined as mortality from any cause other than disease progression within 100 days of HDCT. Results: From 11/1981 to 12/2015, 1,179 pts aged ≥ 40 have been registered, from 236 centers, in the EBMT database after having received single (n = 578) or multiple (n = 601) HDCT courses. Age distribution was: 917 pts 40-49, 236 pts 50-59, 26 pts 60-71. 56 had extragonadal GCT. Bone marrow was used as stem cell source in 85 pts (7.2%). Median follow-up was 38.6 months. Overall 74 TR deaths were found. Significant decrease of TRM was observed during the decades: 1981-1990 (8.3%), 1991-2000 (6.8%), 2001-2015 (4,1%, p = 0.024). Focusing on 2001-2015 period, no differences were found according to age: 40-49y (n = 673): 4.7%, 50-59y (n = 174): 1.8%, 60-71y (n = 23): 4,3% (p = 0.419). TRM for HD-carboplatin-etoposide regimen only (all pts &gt; 1990) was as follows: 40-49y (n = 289): 2.9%, 50-71y (n = 90): 1.1% (p = 0.713). 2-y OS was consistent across all age subgroups. Causes of death were: infection/sepsis (46/74, 62.2%), organ failure (11/74, 14.9%), and cardiac toxicity (8/10.8%), other (9 pts). The retrospective nature of the data is a major limitation. Conclusions: The administration of HD-carboplatin-etoposide in GCT pts ≥ 40 and ≥ 50 years is feasible and is supported by adequate safety data. Collecting additional information on non-severe long-term sequelae is needed. These results may add important information to improve patient counselling.
Changes in prostate cancer presentation for radiation oncology care after USPSTF recommendations, 2007-2013.
Authors: Kevin W. Su, James B. Yu, Timothy Shafman, Suzanne B. Evans, Roy H. Decker, Arie Dosoretz, Daniel E. Dosoretz, Rudi Ross, Sharon Salenius, Steven E. Finkelstein, Jane Hall, Pamela R. Soulos, Cary Philip Gross
Journal: Journal of Clinical Oncology (2015)

e16070 Background: In 2008, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific-antigen based screening for prostate cancer in men age > 75, and in 2012 recommended against screening in all men. It is unknown whether these guidelines have changed the number or risk profile of patients presenting to radiation oncology care. Methods: We conducted a retrospective study of patients who presented with localized prostate cancer in 2007-2013 to a network of radiation oncology clinics in southwest Florida. In the area, the provider network (21st Century Oncology) supplies nearly all radiation oncology services. We assessed trends in total patient volume and determined the risk distribution of a random sample of patients, using risk groups defined by the National Comprehensive Cancer Network. We applied this risk distribution to the total patient volume to estimate the number of patients presenting in each risk group. Results: The number of patients presenting with prostate cancer decreased from 1,860 to 1,209. The estimated number of low and intermediate risk patients decreased significantly, from 858 to 354 and 657 to 506, respectively. There was no significant change in high risk or metastatic disease. Similar trends held in all age groups, except intermediate-risk disease decreased significantly only for men > 75 years. Conclusions: The USPSTF guidelines may have decreased the number of patients presenting with prostate cancer for radiation oncology care, particularly those with low risk disease, without a short term increase in the incidence of higher risk disease. Future research should assess the longer-term impact of these guidelines nationally. Estimated number and risk distribution of patients presenting to radiation oncology [95% CI]. Risk All patients > 75 years < 75 years 2007 2013 2007 2013 2007 2013 Low 858 354 275 84 610 293 [779,939] [307, 405] [234, 317] [64, 108] [539, 679] [248, 342] Intermediate 657 506 250 165 403 345 [583, 736] [454, 560] [210, 292] [139, 192] [339, 473] [298, 394] High 323 312 151 146 154 138 [267, 389] [267, 361] [119, 189] [122, 173] [112, 208] [105, 178] Metastatic 22 37 14 13 4 24 [10, 48] [23, 61] [6, 32] [6, 26] [1, 31] [12, 48] Total 1,860 1,209 689 408 1,171 801
Pegylated liposomal doxorubicin and platinum in patients with advanced ovarian cancer in late relapse (&gt;6 months)
Authors: L. Wei, C. Chen, C. Huang, S. Chien, Y. Huang, W. Cheng, C. Hsieh
Journal: Journal of Clinical Oncology (2006)

15035 Background: Platinum and doxorubicin have different mechanisms of action, show no cross-resistance, and their toxicities do not overlap. Because pegylated liposomaI doxorubicin (Lipo-Dox was manufactured by TTY Biopharm Company Ltd. in Taiwan) appears to be a promising form of delivering doxorubicin with decrease of some of the most problematic toxicities, a combination with platinum should be assessed. Methods: An open-label, non-comparative, single center phase II clinical trial. Eligible patients must have histologically proven advance ovarian cancer with two-dimensioned measurable disease or evaluable disease (defined as CA-125 ≥ 40 U/ml), who have been treated with one or two previous platinum- and taxane-based regimen. All patients will hospitalize for 24 hours for treatment. The dose of platinum is fixed (cisplatin at 75 mg/m 2 or carboplatin at AUC=5) on D1 and the initial dose of pegylated liposomaI doxorubicin (Lipo-Dox) is 35 mg/m 2 on D2 at a 4-week interval. Results: Twenty patients were enrolled from July 2002 to January 2004 and follow up until June 2004. All eligible patients are assessable for response and toxicity. The overall response rate was 80%. Of the 20 patients eligible for response evaluation, 10 (50%) patients had a complete response, 6 (30%) had partial response, 3 (15%) were with stable disease, and 1 (5%) showed progressive disease. An overall response (OR) was achieved in 80% of patients. In patients achieving an OR based on WHO criteria, median CA125 levels declined from 142 U/ml (range, 13–3670 U/ml) during the baseline to 26.5 U/ml (range, 5–375 U/ml) during the last cycle. Median time to response was 65 days (range, 12–188 days). Median duration of response was 471 days (range 146–1085 days). Furthermore, the median time to progression was 481 days (range, 138–1136 days). The main toxicity was myelosuppression, with grade 3 and 4 neutropenia in 3 patients, anemia in 4 patients, and leukopenia in 2 patients. Conclusions: Based on effectiveness and toxicity advantages, the combination of pegylated liposomaI doxorubicin (Lipo-Dox) and platinum should be considered in patients with advanced ovarian cancer in late relapse. No significant financial relationships to disclose.
Diabetes and Aging: Unique Considerations and Goals of Care
Authors: Rita R. Kalyani, Sherita H. Golden, William T. Cefalu
Journal: Diabetes Care (2017)

Diabetes in older adults is a growing public health burden. The unprecedented aging of the world's population is a major contributor to the diabetes epidemic, and older adults represent one of the fastest growing segments of the diabetes population. Of impending concern is that these numbers are projected to grow dramatically over the next few decades (1,2). Almost one-third of U.S. adults over the age of 65 years have diabetes. Approximately half of those are undiagnosed, and an additional one-third of older adults have prediabetes (3). Persons with diabetes today are living much longer compared with those in the past. We also recognize that management of older adults with diabetes is clearly more complicated given the observation that they commonly have multiple coexisting medical conditions that can impact clinical management. While rates of diabetes-related complications have declined overall in the general population, the incidence rates of macrovascular complications such as acute myocardial infarction and stroke continue to be the highest in older age-groups. These individuals also have the highest rate of diabetes-related end-stage renal disease (4).

Heterogeneity in the health status of older adults (ranging from robust and otherwise healthy individuals to those with frailty and multiple comorbid conditions) and the paucity of evidence from clinical trials represent a challenge to making generalized treatment recommendations for older adults. Although many more individuals with type 1 diabetes are living longer (5), type 2 diabetes remains the most common type in older age-groups. Furthermore, older adults with diabetes may either have elderly onset disease (diagnosed at age 65 years or older) or long-standing diabetes with onset in middle age or earlier years (6), adding to the complexity of managing diabetes in older adults. Consequently, the American Diabetes Association (ADA) organized a Consensus Development Conference on Diabetes and Older Adults …
Correlation of baseline clinical characteristics and laparoscopic extent of carcinomatosis of women with initially unresectable ovarian, tubal or peritoneal adenocarcinoma, in ANTHALYA study: A randomized, open-label, phase II study assessing the efficacy and the safety of bevacizumab in neoadjuvant.
Authors: Roman Rouzier, Sebastien Gouy, Frédéric Selle, Eric Lambaudie, Frederic Guyon, Virginie Fourchotte, Christophe Pomel, Pierre Emmanuel Colombo, Elsa Kalbacher, Sandrine Martin, Raffaele Fauvet, Philippe Follana, Anne Lesoin, Fabrice Lecuru, Violette Menguy, Youssef Ghazi, Elisabeth Chereau, Sarah Zohar, Paul H. Cottu, Florence Joly
Journal: Journal of Clinical Oncology (2015)

5538 Background: ANTHALYA study is a randomized non comparative clinical trial to evaluate the efficacy and safety of neoadjuvant chemotherapy associated with bevacizumab. It was a 2:1 randomization to receive carboplatin, paclitaxel with (experimental arm) or without (control arm) bevacizumab in the neoadjuvant setting. The extent of initial carcinomatosis is a major determinant of complete resection but is rarely well described. We report here the extent of carcinomatosis explored by laparoscopy of patients included in Anthalya and its correlation with baseline characteristics. Methods: Non-optimally resectable stage IIIC or IV ovarian cancer patients were eligible for this study. Disease extent was evaluated by a standardized form and the Fagotti score was calculated. Baseline clinical characteristics were compared to trials comparing primary debulking surgery and IDS. Results: This multicenter study was conducted in 15 centers: 205 patients have been screened and 95 patients were included. Median age was 63 years, ECOG performance status 0/1 was 92%, FIGO stage IIIc and IV was 70% and 30% respectively. Lesions assessed were larger than 5 cm in diameter in 63% of patients and larger than 10 cm in 28%. Median CA-125 was 1045 U/ml (over 500U/mL in 71% cases). Carcinomatosis explored by laparoscopy was present on diaphragmatic peritoneum and digestive tract in 96% patients and 89% patients, respectively. Fagotti score > = 8 was 46%. There were more stage IV patients with low Fagotti score than stage IIIC. There was a correlation between carcinomatosis extent and tumor size > 100mm. Baseline characteristics were balanced between arms and similar to previous neoadjuvant trials. Conclusions: ANTHALYA aims to determine the efficacy and safety of neoadjuvant bevacizumab. 46% of patients had high Fagotti score ( > = 8). The evaluation of the carcinomatosis by laparoscopy present in 99% of patients confirms advanced disease tumor. ANTHALYA tumor and patient characteristics were similar to previous neoadjuvant trials. Clinical trial information: NCT01739218.
High-dose chemotherapy (HDCT) for recurrent ovarian germ cell tumors (OGCT): Indiana University (IU) experience.
Authors: Natraj Reddy Ammakkanavar, Daniela Matei, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

5547 Background: OGCT are rare subtype of ovarian cancer, accounting for less than 5% of malignant ovarian cancer cases. First-line cisplatin combination chemotherapy has a 70-80% cure rate. There is very little data for salvage chemotherapy. The objective of this study was to determine the outcomes with HDCT in patients with recurrent OGCT treated at Indiana University (IU). This represents the largest reported data with HDCT in OGCT. Methods: We performed a retrospective review of 12 patients with diagnosis of recurrent OGCT who underwent HDCT at IU during 1990-2013. Demographics, disease variables, treatments and outcomes were analyzed. Results: Median age at the time of HDCT was 25 years (range: 14 - 39 years). 11 of 12 patients had yolk sac tumor (median AFP: 1021). 7 patients had platinum resistant disease. Median number of prior chemotherapy treatments were 2 (range: 1- 4). At the start of HDCT, median serum alpha-fetoprotein (AFP) level was 792 for all patients. 4 of 12 patients had liver metastasis. 10 of 12 patients received 2 courses of HDCT cycles, consisting of carboplatin at 700mg/m2/day and etoposide 750mg/m2/day for 3 consecutive days followed by autologous stem cell rescue in each treatment cycle. 7 patients achieved complete response (CR) including 4 who are continuously disease free at 4+ months, 15+ months, 10+ years and 22+ years. 3 of the 5 patients, who received HDCT as a first-line salvage therapy, are continuously disease free. Only 1 of the 7 patients, who received HDCT as a second-line salvage therapy or later, is continuously disease free. 3 of the 5 patients with platinum sensitive disease are disease free. Median overall survival was 11.5 months (range: 4 months - 22 years). Toxicities noted were as expected and reported with HDCT for testicular germ cell tumors (NEJM 2007; 357:340-348). No treatment related deaths were noted. Conclusions: Our data demonstrates that HDCT is an effective treatment for recurrent OGCT. Better outcomes were observed for first line salvage and platinum sensitive recurrences.
Phase II trial of the CDK4 inhibitor PD0332991 in CDK4-amplified liposarcoma.
Authors: Mark Andrew Dickson, Mary Louise Keohan, William D. Tap, Cristina Antonescu, Jonathan Landa, Li-Xuan Qin, Eric Gerard Dohrenwend, Dustin Rathbone, Yelena Ustoyev, Mercedes M Condy, Samuel Singer, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2012)

10002 Background: CDK4 is amplified in approximately 90% of well-differentiated/de-differentiated liposarcomas (WD/DDLS). The selective CDK4/CDK6 inhibitor PD0332991 (PD) inhibits growth and induces senescence in liposarcoma cell lines and xenografts. In a phase I trial of PD, several patients with progressive WD/DDLS had prolonged stable disease for several years. To determine the safety and efficacy of PD, a phase II study was performed. Methods: Participants were patients with advanced WD/DDLS. Eligibility criteria were age≥18 years, measurable WD/DDLS (RECIST 1.1), documented progression on at least one systemic therapy directly before enrollment, CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥1+). Pts received oral PD 200mg daily for 14 consecutive days in 21-day cycles. The primary endpoint was progression-free survival (PFS) at 12 weeks. Based on historical data, a promising result was defined as a 12-week PFS of ≥40% and not promising as ≤20%. The sample size was up to 28 evaluable patients. If 9 patients were progression free at 12 weeks, then PD would be considered to have activity in WD/DDLS. Results: Of 44 patients screened (42/44 CDK4 amplified; 41/44 RB+), 29 were enrolled and 27 were evaluable for the primary endpoint. Median age was 65 (range 37-83); 52% were male; ECOG scores were 0 (69%) or 1 (31%), and the median number of prior regimens was 1 (range 1-5). PFS at 12 weeks was 70% (19/27 patients; 90% CI 56-100%), and thus the study significantly exceeded its primary endpoint. At the data cutoff, the median PFS was 18 weeks. Seven patients remain on study with stable disease at 18-48 weeks of followup. Grade 3 and 4 events included anemia (grade 3, 14%), thrombocytopenia (grade 3, 17%; grade 4, 14%), neutropenia (grade 3, 41%; grade 4, 7%) and febrile neutropenia (3%). Dose reductions were required in 24% of patients. Conclusions: Among patients with WD/DDLS with CDK4 amplification and RB expression who had actively progressing disease despite prior systemic therapy, treatment with the CDK4 inhibitor PD0332991 was associated with improved PFS. A randomized phase 3 trial is planned.
Patterns of tumor progression in a phase 3 study of bevacizumab (Bv) plus radiotherapy (RT) plus temozolomide (T) for newly diagnosed glioblastoma (GB).
Authors: Wolfgang Wick, Olivier L. Chinot, Warren P. Mason, Roger Henriksson, Frank Saran, Ryo Nishikawa, Cedric Revil, Yannick Kerloeguen, Timothy Francis Cloughesy
Journal: Journal of Clinical Oncology (2014)

2051^ Background: In the AVAglio study, Bv+RT/T prolonged PFS (co-primary endpoint) in pts with newly diagnosed GB v placebo (P)+RT/T. It has been suggested that antiangiogenic therapy may promote infiltrative tumors at PD, so patterns of tumor progression were prospectively assessed in AVAglio (exploratory endpoint). Methods: Randomizedpts (n=921) received: RT/T+Bv or P, 6 wks; 28-day break; maintenance T+Bv or P (x6); Bv or P until PD/unacceptable toxicity. PD was investigator (INV) assessed (adapted Macdonald criteria). Lesion patterns were retrospectively assessed by an independent review facility for each disease assessment (baseline [BL]/during treatment/at INV-assessed PD). Diffuse/infiltrative patterns were defined as extended hypersignal on T2/fluid-attenuated inversion recovery (FLAIR) sequences, and are reported in pts with pattern derived at BL and INV-assessed PD. Results: Most pts had similar tumor invasiveness at BL and PD (Table). Among pts with non-diffuse disease at BL (n=100 and 138), numerically more Bv- v P-treated pts changed to diffuse disease at PD; median OS for these pts was similar (17.4 v 15.0 mo for Bv+RT/T v P+RT/T, respectively; HR 0.85, 95% CI 0.51–1.42, p=0.5355), and comparable with the OS of the ITT population. In all pts who had BL non-diffuse tumors, median OS was 20.1 v 18.4 months (Bv+RT/T v P+RT/T, respectively; HR 0.76, 95% CI 0.59–0.98, p=0.0303). In all pts with BL diffuse tumors, median OS was 15.6 v 16.2 months (Bv+RT/T v P+RT/T, respectively; HR 0.99, 95% CI 0.82–1.19, p=0.8882). Conclusions: In this exploratory analysis, a change from BL non-diffuse disease to diffuse disease at PD did not affect OS; BL pattern of disease did, suggesting that tumor infiltration at diagnosis is an important prognostic factor. Also, in the subset of pts with newly diagnosed non-diffuse GB, there was an OS benefit from adding Bv to standard of care. Clinical trial information: NCT00943826. Tumor pattern, nPD/nBL Bv+RT/T P+RT/T BL PD n=299 n=333 Pts with no changes Nondiffuse Nondiffuse 64/100 (64.0%) 104/138 (75.4%) Diffuse Diffuse 197/199 (99.0%) 194/195 (99.5%) Pts with changes from BL Nondiffuse Diffuse 36/100 (36.0%) 34/138 (24.6%) Diffuse Nondiffuse 2/199 (1.0%) 1/195 (0.5%)
Use of the FoundationOne next-generation sequencing (NGS) assay to detect actionable alterations leading to clinical benefit of targeted therapies for relapsed and refractory breast cancer.
Authors: Jeffrey S. Ross, Massimo Cristofanilli, Sean Downing, Roman Yelensky, Doron Lipson, Geoff Otto, Gary A. Palmer, Siraj M. Ali, Vincent A. Miller, Phil Stephens
Journal: Journal of Clinical Oncology (2013)

1009 Background: Genomically-informed cancer therapy linking therapeutics targeting the molecular alterations driving the malignancy has the potential to transform the care of patients with metastatic breast cancer (MBC). Methods: DNA was isolated from 4 FFPE sections cut at 10 microns from 177 consecutive MBC that had relapsed after surgery, conventional hormonal/chemo and anti-HER2 targeted therapies received by our CLIA lab (Foundation Medicine). DNA sequencing was performed for 3,320 exons of 182 cancer-related genes to average depth of 1017X. Actionable Genomic alterations (GA) were defined as those linked to targeted anti-cancer therapies approved or being evaluated in active registered clinical trials. Results: Genomic profiles were generated from 169/177 (95%) BCs identifying 565 GA, averaging 3.34 GAs per tumor (range 0 to 10). 152 (90%) tumors harbored an actionable alteration mean 1.88 per tumor (range 0 to 6). In 124 (73%) tumors, ≥1.0 actionable GA was detected that would be missed by current “hotspot assays”. Notable GA involved PIK3CA (37%), ERBB2 (14%), FGFR1/2 (14%), PTEN (10%), MDM2 (7%), CCND1/CCNE1/CDK4 (7%), BRCA1 and BRCA2 (6% each) and ESR1 and EGFR (3% each). Of 23 ERBB2 GA, 74% were amplifications and 26% were mutation/gene fusion. The frequency of ERBB2 mutation/fusion was significantly enriched in CDH1 mutated ILC (~9% of total BC) with a frequency of 19.0% (4/21) compared to other histological types of BCs 1.4% (2/148) [p=0.002]. Significant clinical efficacy included patients with HER2 IHC/FISH negative tumors featuring HER2 and EGFR activating mutations benefitting from lapatinib/trastuzumab and erlotinib respectively. Conclusions: Comprehensive genomic profiling with a NGS assay identified actionable GAs in the majority of MBC patients including ERBB2 and EGFR mutations that initiated use of targeted therapies resulting in significant clinical benefit. These data provide a framework for the GAs expected in advanced BC and should facilitate the implementation of molecularly targeted trials supporting the efforts for a modern approach to precision medicine for the disease.