tbuckley/cabot-search huggingface dataset:
Predictors of venous thromboembolism in patients with glioblastoma multiforme.
Authors: Shahzaib Nabi, Pushpinderdeep Kahlon, Farshid Bozorgnia, Adeel Arshad, Tom Mikkelsen, Vijaya Donthireddy
Journal: Journal of Clinical Oncology (2015)

e13022 Background: Patients with glioblastoma multiforme (GBM) have a high risk of developing venous thromboembolism (VTE). We conducted a single center retrospective review to study the impact of various clinical factors on the risk of developing VTE. Methods: A retrospective chart review was conducted to identify patients diagnosed with GBM between 2001-2011. A total of 1002 patients were identified. Cases (n = 162) were defined as patients who developed VTE after diagnosis of GBM. Controls (n = 840) were patients without a diagnosis of VTE after diagnosis of GBM. Data was reviewed for age, sex, race, length of stay after brain surgery/biopsy, total number of hospital admissions, Karnofsky Performance Status (KPS), bevacizumab use and bleeding episodes. Results: The median age for development of a VTE was 61.8 ± 11.4 years. Mean time to development of VTE after GBM surgery was 78.3 days. In the VTE group, 78% had a KPS of ≤ 70, whereas only 18% of the controls had a KPS ≤ 70. Average inpatient stay after surgery related to GBM was 6.3 days in the VTE group and 3.8 days in the controls (odds ratio [OR] 1.14, 95% CI 1.09-1.18, p < 0.001). Average number of hospital admissions from the time of GBM diagnosis was 5.3 vs 2.4 (OR 1.43, 95% CI 1.33-1.53, p < 0.001) in the VTE and control groups respectively. Multiple inpatient admissions (OR 1.43, 95% CI 1.33-1.53, p < 0.001) and longer hospital stays (OR 1.14, 95% CI 1.09-1.18, p < 0.001) were associated with a higher risk of VTE. Presence of VTE was also associated with more deaths (OR 4.53, 95% CI 3.01-6.80, p < 0.001). Patients receiving bevacizumab were more likely to develop VTE (OR 1.79, 95% CI 1.21-2.64, p = 0.004) and have a bleeding episode (OR 3.78, 95% CI 2.70-5.30, p < 0.001). Conclusions: The risk of developing a VTE is significantly higher in GBM patients with lower KPS scores, longer inpatient stays after GBM related surgery and those who require multiple hospital admissions. Bevacizumab use is related to a higher incidence of VTE and bleeds. Presence of VTE in patients with GBM worsens their outcomes. This study suggests that a more aggressive strategy for VTE prophylaxis could be considered in GBM patients with risk factors for VTE, but a prospective study is needed to assess such an approach.
Contemporary active surveillance rates for newly diagnosed prostate cancer patients in large community urology practices.
Authors: Jeremy B. Shelton, Philip Buffington, Alec S Koo, Neal D. Shore
Journal: Journal of Clinical Oncology (2015)

e16078 Background: The recommended management of incident localized prostate cancer has shifted recently with wide agreement that active surveillance (AS) is appropriate for a majority of men with lower risk disease. Similarly, shifts in accessibility to curative therapies, in conjunction with consolidation of community urology practices, have raised questions about contemporary management of incident prostate cancer in the community. We sought to describe this among a geographically diverse sample of community-based consolidated urology practices. Methods: We performed a retrospective chart abstraction in 8 large urology practices from 7 states analyzing initial treatment choices among men ≤75 years old diagnosed in 2013 and 2014 with lower and intermediate risk prostate cancer (per National Comprehensive Cancer Network (NCCN) criteria) and with ≥6 months follow-up. We performed univariate analysis and multinomial regression to evaluate the correlation of NCCN risk group, race, age, and urology practice on treatment choice. Results: Of 2,464 incident cases, 1401 met inclusion criteria and 252 (17.3%) had very low-, 526 (36.1%) low- and 623 (42.7%) intermediate risk disease. The mean age was 63.6; 72.3% were white, 12.37% black, 4.2% other and 10.3% unknown. Initial primary therapeutic decisions are shown in the table. In multivariate analysis, risk group (p<0.001), age (p<0.001) and urology practice (p<0.001) predicted choice of active surveillance, while race (p=0.43) did not. Surgery and radiation use was equal by risk groups, with a trend toward higher use of surgery among men with intermediate risk disease, of whom 44.6% received surgery and 32.2% received radiation (p<0.06). Conclusions: Community urologists appear to have rapidly adopted AS and appear to use surgery and radiation similarly. Primary therapy by NCCN risk group. Primary Therapy NCCN Risk Group Total n (%) Very Low n (%) Low n (%) Intermediate n (%) Active surveillance 177 (70.2) 206 (39.2) 48 (7.7) 431 (30.1) Surgery 28 (11.11) 147 (28.0) 278 (44.6) 453 (32.3) Radiation 30 (11.9) 125 (23.8) 207 (32.2) 362(25.8) No follow-up 12 (4.8) 34 (6.5) 53 (8.5) 99 (7.1) Other 5 (2.0) 14 (2.7) 37 (5.9) 56 (4.0) Total 252 526 623 1,401
Incidence of ipsilateral recurrence after open or thoracoscopic resection of colorectal lung metastases.
Authors: Nuria Prenafeta Claramunt, David Hwang, Gail Elizabeth Darling, Marc de Perrot, Andrew Pierre, Kazuhiro Yasufuku, Shaf Keshavjee, Thomas K. Waddell, Marcelo Cypel
Journal: Journal of Clinical Oncology (2015)

e14515 Background: There is still controversy whether full lung palpation is required for patients undergoing pulmonary metastasectomy. We aimed to compare pulmonary ipsilateral recurrence (IR) after video-assisted surgery (VATS) or thoracotomy using a propensity matching approach. Methods: A retrospective review of all patients undergoing surgery for colorectal cancer (CRC) lung metastases between 2003 and 2012 was performed. IR rate was compared between the two groups after adjusting for disease free interval (DFI), number of metastases and type of resection. A logistic regression was used to create a propensity score (PS) within either 0.1 or 0.2 SD (Standard Deviation). As a confirmation, a classification tree approach was performed to create PSs that were applied as weights to obtain an adjusted estimate of difference in IR rates. Results: 211 patients underwent surgery for CRC lung metastases. 75 (35.5%) were VATS and 136 (64.5%) were via thoracotomy. Before matching, 118 (55.9%) were males and 93 (44.1%) were females where the mean age at the time of metastases diagnosis was 61.1(50-72.3) years. In total, 19 (25.3%) presented IR in VATS, and 39 (28.7%) in open surgery. 5 year-overall survival was 53.1% (61.9%, VATS group and 49.2%, open group). After adjusting for the three variables mentioned above, we matched: 74 cases within 0.1SD of PS and 75 cases within 0.2SD of PS. Propensity matching increased the balance between groups (Table). The IR after matching was 25.3% in VATS group vs. 20.5% in thoracotomy group (p = 0.43). Results using the classification tree approach were similar; the difference in risk of IR was 0.2%(-19.3%-19.7%), p = 0.98. Conclusions: No significant difference was observed in the rates of IR. These results support the use of VATS in selected patients with lung metastases from CRC. Balances between open and VATS groups (0.2SD of PS). Variables (mean) VATS-unmatched OPEN-unmatched VATS-matched OPEN-matched DFI (months) 24.33 27.01 24.33 22.30 # of metastases 1.16 2.54 1.16 1.24 Wedge 0.91 0.52 0.91 0.92 Lobectomy 0.04 0.17 0.04 0.00 Segmentectomy 0.05 0.28 0.05 0.08
Translocated sarcomas: is molecular testing performed in adult sarcomas?
Authors: Matias Chacon, Constanza Perez de la Puente, Martin Angel, Julio Kaplan, Reinaldo D. Chacon
Journal: Journal of Clinical Oncology (2015)

e12528 Background: Sarcomas represent about 1% of malignant tumors. They might be classified as sarcomas without or with specific molecular alterations. On the latter group specific translocations are present mainly but not in the 100% of these tumors. Regularly translocations are studied in pediatric population. There is no data about this subject in adult Latin American patients (pts). Specific translocations may potentially enlighten areas such as diagnosis and specific treatment, as well as prognostic and predictive factors. Methods: Retrospective institutional sarcoma data base analysis was performed (period 1994 – 2014). Potentially translocated sarcomas (PTS), including small blue round cell morphology sarcomas with > 75% specific translocations incidence, were studied: Ewing Sarcoma-PNET (ES-PNET), desmoplastic small round cell tumor (DSRCT) and rhabdomyosarcoma (RS) in adult population. Results: 62 pts with PTS were identified. Male 63%, median age 25 years (r: 17–78). Histology: 34 (55%) ES-PNET, 24 (39%) RS and 4 (6.5%) DSRCT. Primary site: soft tissue 73%. Most frequent primary site in ES-PNET: lower limb, thoracic wall and paravertebral on a third of pts; RS: paratesticular 5 pts; DSRCT: intraabdominal on every case. Metastatic disease at diagnosis: 25 (40%) pts. Primary treatment: multimodality strategy 40 (64.5%), surgery 11 (18%), chemotherapy 9 (14.5%), surgery + radiotherapy 2 (3%). Polichemotherapy with alternate regimen: 26 (42%). Response to multimodality: 17 (44%) complete, 16 (41%) partial, progression disease in 6 pts. Median DFS: 41 months (IC95% 27,847 - 54,122). Relapse: local site 29%, distant site 32%. Median OS: 5.7 years (IC95% 3,838 - 7,566); compared to other histologies ES-PNET pts had longer OS (p 0.011) as well as those treated with multimodality strategy (p 0,009). Specific translocations were studied in 4 (6%) pts; 1 of them presented no molecular specific alterations. Conclusions: In this retrospective study in an adult population of pts with PTS, the specific translocations were studied only in 6%. Additionally the mayor benefit in primary treatment for PTS was observed with multimodality strategy. Cooperative groups for further molecular studies should be encouraged with pediatric oncologists.
A systematic review showing the lack of diagnostic criteria and tools developed for lower‐limb cellulitis
Authors: M. Patel, S.I. Lee, R.K. Akyea, D. Grindlay, N. Francis, N.J. Levell, P. Smart, J. Kai, K.S. Thomas
Journal: British Journal of Dermatology (2019)

Cellulitis can be a difficult diagnosis to make. Furthermore, 31% of patients admitted from the emergency department with suspected lower-limb cellulitis have been misdiagnosed, with incorrect treatment potentially resulting in avoidable hospital admission and the prescription of unnecessary antibiotics.
Masitinib plus irinotecan for second line treatment of esophagogastric adenocarcinoma: An open label phase Ib/II trial.
Authors: Aziz Zaanan, Jaafar Bennouna, Sandrine Hiret, Jean-Yves Douillard, Olivier Bouche, David Tougeron, Thierry Lecomte, Céline Lepère, Colin Mansfield, Alain Moussy, Patrice Dubreuil, Olivier Hermine, Julien Taieb
Journal: Journal of Clinical Oncology (2015)

4027 Background: Masitinib (MAS) is a selective c-Kit inhibitor that efficiently inhibits mast cell function. In vitro studies have shown that MAS could enhance efficacy of 5-fluorouracil (5-FU) and irinotecan (IRI) for treatment of gastric cancer cell lines. Methods: Patients (pts) with measurable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction were eligible to receive MAS (6 mg/kg/day) in combination with 5-FU (400 mg/m2 bolus then 2400 mg/m2, 46h/2w), or IRI (350 mg/m²/3w), or FOLFIRI, after progression to platinum based first line chemotherapy. The phase I study evaluated safety with
Percutaneous endoscopic gastrostomy tube placement in veterans treated with concurrent chemotherapy and radiation for head and neck cancer.
Authors: Evan Michael Mariash, Mark A. Klein
Journal: Journal of Clinical Oncology (2015)

e17090 Background: Patients with head and neck cancer are at risk of nutritional compromise. Percutaneous endoscopic gastrostomy (PEG) tubes are used to provide head and neck cancer patients nutrition; however, there is no consensus as to the most appropriate time to place a PEG tube. Our hypothesis is that patients who receive PEG tubes prophylactically will have less weight loss and nutritional compromise compared to patients with reactively placed PEG tubes or no PEG tubes. Methods: Patients with head and neck cancer treated with concurrent chemotherapy and radiation at the Minneapolis VA Medical Center from 2009 to 2013 were identified. Seventy-three patients were identified and stratified into 3 groups: those who did not receive a PEG tube, those who received a PEG tube prophylactically, and those that received a PEG tube in a reactive manner. Data was obtained retrospectively for clinical variables at specified times and analyzed. Results: The median age was 62. Fifty-one patients had stage IV disease. The most common primary site of disease was the oropharynx (34 patients). Sixteen patients had no PEG tube placed, 57 patients had a PEG tube placed prophylactically, and 19 tubes were placed reactively. There were no significant differences between groups in baseline characteristics. The mean decline in weight for patients at 6 weeks was 24.4 pounds in patients not receiving a PEG tube, 15.0 pounds in patients receiving a prophylactic PEG tube, and 20.6 pounds in patients receiving a PEG tube reactively (p = 0.03). Albumin levels did not differ significantly between groups. At a mean follow-up of 2.1 years, overall survival was 68.8%, 79.0%, and 100% in the respective groups (no PEG tube, prophylactic, reactive, p = 0.041). There were 48 infections in patients with prophylactic PEG tubes placed, 7 in those with a reactive PEG tube, and 3 in those without a PEG tube (p = 0.008). Conclusions: PEG tubes are associated with less weight loss in head and neck cancer patients receiving concurrent chemotherapy and radiation, but albumin levels do not differ significantly. A prospective study of PEG tube placement in the Veteran head and neck cancer population is needed to evaluate this common practice.
Abstract MP37: Estimating Sodium Intake Using Timed Urine Collections From a Controlled Feeding Study
Authors: Andrea J Lobene, Claire J Macdonald-Clarke, Berdine R Martin, Linda D McCabe, George P McCabe, Connie M Weaver
Journal: Circulation (2019)

Introduction: Hypertension is a major risk factor for CVD affecting 34% of American adults. High sodium (Na) intake is identified as a modifiable risk factor for high blood pressure, but our ability to assess Na intake is poor. The gold standard is to measure Na excretion in a 24h urine collection, but this is burdensome. An alternative method is to predict 24h Na excretion from a spot urine sample. However, we do not know how well predicted 24h Na excretion reflects intake, the true outcome of interest, or the ideal time to collect a spot urine sample. These gaps can only be filled using a controlled feeding study in which intake is known and timing of urine collections is controlled. Hypothesis: We hypothesized that, with currently available equations, 24h Na excretion predicted from spot urine samples will not accurately reflect intake. Methods: This is a secondary analysis of a randomized, multi-phase, crossover, full-feeding trial in healthy adults ( n = 39, aged 29.7 ± 11.2 y). Data from the two control phases were used in which dietary intake and testing conditions were identical. Participants ate three meals in a clinic setting and spot urine samples were collected every 2 hours as part of a 24h collection. Urine samples were analyzed for sodium, potassium, and creatinine. The INTERSALT equations were used to predict 24h Na excretion from each of the 9 spot urine samples collected. Predicted 24h Na excretion values were compared with observed 24h excretion and known dietary intake using repeated measures ANOVA. Intra-class correlations for each timed spot urine sample were calculated to determine the variability in average spot urine Na excretion between the two control phases. Results: Predicted 24h Na excretion using the spot urines at hour 10, 12, overnight, and early morning collection were not significantly different from observed 24h Na excretion (all p ≥ 0.21). However, predicted 24h Na excretion underestimates observed 24h Na excretion by about &gt;600 mg. Importantly, all predicted 24h excretions as well as observed 24h excretion were significantly lower than intake by &gt;1000 mg (all p &lt; 0.001). Intraclass correlations were significant at hour 0, 2, 8, 12, and evening/overnight (all p &lt; 0.05), suggesting low day-to-day variability in Na excretion at these times. Conclusions: Regardless of time of spot urine collection, predicted 24h Na excretion is lower than Na intake, suggesting currently-available equations do not provide adequate estimates of Na intake. The next step is to develop equations to accurately predict Na intake from a controlled feeding study model using spot urine samples collected at a time when Na excretion is consistent from day to day. These improved equations could be used to implement effective dietary interventions to reduce blood pressure and CVD risk.
Exploratory study of prognostic factors in mCRPC patients who administered enzalutamide focusing on early PSA decline and PSA kinetics at PSA progression: Results of retrospective multicenter study.
Authors: Yoshiyuki Miyazawa, Nobuaki Shimizu, Yutaka Takezawa, Toshiyuki Nakamura, Takeshi Miyao, Hiroshi Nakayama, Sota Kurihara, Takahiro Syuto, Masashi Nomura, Yoshitaka Sekine, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki
Journal: Journal of Clinical Oncology (2019)

292 Background: Recent studies have shown that an early PSA response to AR-targeting agents in mCRPC is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA Velocity while monitoring oncologic outcomes and survival in Japanese patients. Methods: A total of 241 patients with mCRPC treated with ENZ were analyzed. Patients’ median age is 75±7.9 (range 53-93). The patients pre-docetaxel settings were 171 cases (71 %), post-docetaxel settings were 70 cases (29 %). The PSA-PFS and OS were assessed according to PCWG2 criteria. This study was approved by the institutional review board of Gunma University Hospital (No.1595). Results: A case where PSA did not decline at all was defined as Primary Resistance (PR). A case in which PSA once declined after treatment but then progressed was defined as Acquired Resistance (AR). Those in which PSA remained low after treatment were defined as Good Response (GR). We observed 77 PR cases (31.9 %), 125 AR cases (51.9 %) and 39 GR cases (16.2 %).PSA-PFS and OS pre-docetaxel were significantly increased as compared to patients’ post-docetaxcel (PSA-PFS; 47.0 wks vs. 13.4 wks p &lt; 0.001, OS; Not Yet Reached vs. 80.7 wks p &lt; 0.001). Multivariate analysis of prognostic factors, including the PSA response at 4 weeks, was performed using a Cox regression analysis. The PS (0 or 1-2), Hb (≧11.4 or &lt; 11.4), time to CRPC(≧12 m or &lt; 12 m), docetaxel treatment history (none or done) and a PSA decrease of 50% at 4 weeks were all significant factors for the prediction of OS (all variables, p &lt; 0.05). In cases of acquired resistance (n = 125), a multivariate analysis using PSA kinetics factors such as PSADT and PSA Velocity (ng/mL/month) at PSA progression, Hb, time to CRPC(≧12 m or &lt; 12 m), PSADT (≧2 months or &lt; 2 months) and PSA Velocity ( &lt; 20 ng/mL/month or≧20 ng/mL/month), were all factors predicting OS following PSA progression (p &lt; 0.05). Conclusions: Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostication factor for mCRPC patients.
Blood alcohol level in patients treated with gemcitabine and taxanes.
Authors: Elias Assaf, Muriel Verlinde-Carvalho, Hassan Daher, Anne Hulin, Elodie Faye, Benoit Rousseau, Isabelle Baumgaertner, Marie Chaubet-Houdu, Charlotte Joly, Carolina Saldana, Amina Taleb, Alain Astier, Muriel Paul, Christophe Tournigand
Journal: Journal of Clinical Oncology (2015)

e17664 Background: Because of weak solubility in water, many cytotoxics are dissolved in ethanol. FDA recently raised alert noticing that patients could be intoxicated after their treatments. The main alcohol-containing chemotherapy drugs are gemcitabine (Gem), paclitaxel (Pac) and docetaxel (Doc). We explored prospectively blood alcohol levels in pts treated with Gem, Pac or Doc. Methods: Alcohol concentration was determined by peripheral blood sample before chemotherapy infusion (T0), at the end (T1) and 30 min later (T2) in three different prospective cohorts (Gem, Pac, Doc) in a single institution. Bioelectrical impedance analysis was performed to estimate fluid volume in order to calculate theoretical alcohol level. Clinical impact was evaluated through psychometric tests (Zazzo attention test, Stroop test) before and at the end of chemotherapy infusion. Results: 60 consecutive patients were included in our study (M/F 29/31) (Gem n = 21, Pac n = 19, Doc n = 21). Median age was 63.8 yrs (35-88). Median Gem infusion duration (ID) was 100 minutes. Median alcohol administration was 20.5 g (11.6-26). T0 alcohol concentration was 0 g/l, T1 0.32 g/l (0.1-0.65), T2 0.17g/l (0.1-0.4).Median Pac ID was 96 minutes. Median alcohol administration was 9.5 g (6.9-10.5). T0 alcohol concentration was 0 g/l, T1 0.1 g/l, T2 0.1 g/l. Median Doc ID was 90 minutes. Median alcohol administration was 2.8 g (1.8-4). T0 alcohol concentration was 0 g/l, T1 0.1 g/l, T2 0.1 g/l. Concerning Zazzo test, a significant decrease in attention abilities were shown after gemcitabine infusion, compared with taxanes (p = .001). Conclusions: Patients should be clearly informed concerning alcohol infusion during chemotherapy, and that abilities may be impaired. They should be monitored during 1 hour after gemcitabine infusion before leaving care unit.
Predictive PK/PD models for hematological toxicities to inform MTD determination and regimen selection for ADCs.
Authors: Santhosh Palani, Joanna C Masters, Xu Meng, Dawei Xuan
Journal: Journal of Clinical Oncology (2015)

2568 Background: Off-target hematological toxicities have primarily been dose-limiting for ADCs. Here, we present a PK/PD model framework where the incidences of hematological toxicities can be predicted across ADCs if they share the same linker/payload (LP), and can be predicted across regimens within an ADC. Having prior knowledge of the MTD can provide a safe and efficient dose-escalation design, reduce the number of patients receiving sub-efficacious doses and aid in regimen selection. Methods: A semi-mechanistic PK/PD model of neutropenia (NP) for SGN-35 was constructed using a previously established structural model. Published ADC thrombocytopenia (TCP) PK/PD models were also utilized. Results: Predicting across regimens:Due to the availability of the clinical data in multiple regimens for T-DM1 and SGN-35, models developed using data from Q3W regimen were utilized to predict the toxicity incidences of QW regimen. T-DM1 Q3W model predicted 10% grade 3+4 TCP in patients at QW MTD, matching with the clinically observed incidence of 11%. SGN-35 Q3W model predicted 19% grade 3+4 NP at QW MTD, which is consistent with the clinically observed incidence of 10%. Predicting across ADCs: Since SGN-35, CDX-011 and PSMA-ADCs share the same LP (vcMMAE), we utilized the SGN-35 model to predict incidences for CDX-011 and PSMA-ADC. SGN-35 Q3W model predicted 18% and 50% grade 3+4 NP incidences for the 1.9 mg/kg CDX-011 and 2.8 mg/kg PSMA-ADC, respectively, again in concordance with the observed incidences of 26% and 55%. Predicting across ADCs, regimens and populations: As CMC-544 and GO share the same LP (abCali), we predicted TCP incidences for GO in AML patients from the Q4W CMC-544 model developed with data from NHL patients. The model predicted grade 3+4 TCP incidence of 98% for GO regimen of 9 mg/m2 (2 doses, 14-days apart), which agrees with the observed incidence of 99%. Conclusions: Robust predictability of hematological toxicity is demonstrated across 5 ADC, 2 toxicities and 3 regimens. With prospective validation, the approach presented here can help construct a safe and efficient dose-escalation scheme, provide a projected MTD, and assist in optimal regimen selection for ADCs entering clinical development.