tbuckley/cabot-search huggingface dataset:
Are patients with oligodendroglioma at higher risk for radiation neurotoxicity?
Authors: Haroon Ahmad, Sohil H. Patel, Joseph Donahue, M. Beatriz Lopes, Benjamin Purow, David Schiff, Camilo E. Fadul
Journal: Journal of Clinical Oncology (2019)

2061 Background: Symptomatic radiation neurotoxicity (RN), manifesting on MRI as focal necrosis and/or T2 signal abnormality, is a dreaded complication of radiation therapy (RT). While RT is standard of care for anaplastic gliomas, the long-term benefit vs risk profile in low-grade gliomas is not well defined. Patients with oligodendroglioma carry a better overall survival than those with astrocytoma. Anecdotally, they are more prone to experience RN than astrocytomas, as suggested by Acharya et al in 2017. We hypothesized that, independent of grade, oligodendrogliomas have a higher incidence of RN as compared to astrocytomas. Methods: We reviewed the records of 628 patients with WHO grade II and III gliomas from our institution. Study population comprised 326 patients with: standard fractionated RT, pathology confirmation by a neuropathologist, and follow up of at least 2 years after diagnosis. RN was defined as either histologically confirmed by pathology or requiring intervention for clinically presumed RN (bevacizumab or high-dose steroids.) A separate category included patients with dramatic cognitive decline with increased T2 signal abnormality, in the absence or tumor progression. Results: There were 131 patients with oligodendroglioma, based upon 1p/19q co-deletion (105 cases) or histology in the absence of molecular testing (26 cases). The remaining 195 patients had astrocytoma with intact 1p/19q, isocitrate dehydrogenase (IDH) wild-type, or diagnosed histologically absent molecular testing. The incidence of RN were 18.3% and 8.2% for oligodendroglioma and astrocytoma, respectively (p = 0.0063). An additional four patients with oligodendroglioma and two with astrocytoma had significant cognitive deterioration with increased T2 signal abnormality, without tumor progression. Conclusions: The greater than two-fold increase in RN incidence for oligodendrogliomas is significant and suggests patients with oligodendrogliomas may be more at risk to develop RN. Therefore, in patients with oligodendroglioma, the consideration of fractionated RT needs to be weighed against the increased potential for RN. Analysis of baseline imaging and patient characteristics variables that correlate with development of RN are ongoing and will be presented at the meeting.
Rectal admission of chemotherapeutic drugs in neoadjuvant treatment schemes of locally advanced rectal cancer.
Authors: Luiza Korytova
Journal: Journal of Clinical Oncology (2019)

e15168 Background: High incidence and steady rise of rectal cancer morbidity, unsatisfactory treatment results, amount of disabling surgery, high rate of local recurrents advocate for searching for new methods of combined treatment of locally advanced rectal cancer. Methods: We had suggested to rectally install sterile hydrogel material based on sodium alginate with incorporated 5-FU for radio modification purposes during neoadjuvant chemo radiotherapy. 39 patients with histologically confirmed diagnosis were included into our study. 19 patients received preoperative radiotherapy with summary dose of 50-56 Gy and systemic chemotherapy with fluorpirimidines and rectally admitted hydrogel material with incorporated 5-FU twice per day. Control group consisted of 20 patients who had similar treatment, excluding rectal hydrogel installations. Results: There was no increase in early radiotherapy complications noticed. Three study group patients had complete response, 16 had partial response (versus 1 CR, 15 PR, 3 stabilization and 1 progression in control group). This allowed reduction of surgical assistance volume in seven patients - sphincter-preserving operations were performed. Grade 3-4 pathomorphosis by Dworak’s scale was identified in 17 out of 19 patients (13 out of 20 in control group). Conclusions: Use of hydrogel material based on sodium alginate with incorporated 5-FU does not increase amount and intensity of radiation induced complications, allows to improve patients quality of life and treatment results.
Treatment sequencing of anti-PD-1/PD-L1 and carboplatin (carbo)-based chemotherapy (chemo) in cisplatin-ineligible patients (pts) with metastatic urothelial cancer (mUC).
Authors: Xiao X. Wei, Lillian Werner, Min Yuen Teo, Jonathan E. Rosenberg, Vadim S Koshkin, Petros Grivas, Bernadett Szabados, Laura Morrison, Lucia Carril, Daniel E. Castellano, Pedro Isaacsson Velho, Noah M. Hahn, Rana R. McKay, Daniele Raggi, Andrea Necchi, Ravindran Kanesvaran, Parissa Alerasool, Jacob Gaines, Joaquim Bellmunt, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

4541 Background: Anti-PD-1/PD-L1 agents and carbo-based chemo are therapy options in 1st-line (1L) setting for cisplatin-ineligible pts with mUC. However, optimal sequencing is unclear. Methods: We conducted a multicenter retrospective analysis of cisplatin-ineligible pts with mUC treated with 1L PD-1/PD-L1 monotherapy followed by carbo-based chemo (IO→Cb) or the reverse order (Cb→IO) without intervening systemic therapy. Perioperative cisplatin-based chemo was allowed if completed &gt; 1 year from 1L mUC therapy initiation. To assess association between overall survival (OS) and therapy sequence, a multivariate analysis (MVA) was performed from initiation of 2L therapy, adjusted for treatment sequence, time interval between initiation of 1L and 2L therapies, Hb ( &lt; 10 vs ≥10 g/dl), ECOG PS (0-1 vs 2-3), and metastatic site (LN/soft tissue only vs non-liver vs liver). Results: 146 pts (IO→Cb n = 43, Cb→IO n = 103) were evaluable with median age 72, 76% men, 78% ECOG PS 0-1, 17.8% with liver metastasis. Baseline factors were balanced except for higher proportion of men in IO→Cb group (91% vs 70%, p = 0.01). Median time interval between initiation of 1L and 2L therapy for IO→Cb and Cb→IO were 15.6mo (4.8-78.1) and 23.0mo (2.1-103.3), respectively. Response rates are summarized (Table). On MVA, treatment sequence was not associated with OS (HR 1.05, p = 0.85). Site of metastasis was the only factor significantly associated with OS (p = 0.002). Conclusions: In our retrospective analysis of cisplatin-ineligible pts with mUC regardless of PD-L1 expression, anti-PD-1/PD-L1 followed by carbo-based chemo or the reverse sequence appeared to confer comparable OS. The observed response rates and time interval between initiation of 1L and 2L therapy are likely contributed by pt selection, where all pts received 2L. Further investigation of the ‘PD-L1 high’ population is warranted, given higher response rates with anti-PD-1/PD-L1 vs ‘PD-L1 low’ population. Ongoing phase III trials will help inform optimal sequencing. [Table: see text]
Diagnostic value of cytokeratin-1, survivin and TG expression in circulating tumor cells in the differentiation of benign and malignant thyroid nodules.
Authors: Jie Liu, Siyuan Xu, Jinghua Luo, Yan Wang, Xia Liu, Rong Du, Yu Tang, Jianwei Wang, Nan Fang, Qixi Wu
Journal: Journal of Clinical Oncology (2019)

e17575 Background: Fine needle aspiration cytology (FNAB) has the advantages of minimal trauma, speed and accuracy, and is currently considered to be the most predictive screening technique before thyroid nodule surgery. However, there are several drawbacks to this method, including certain complications, a relatively high false negative rate, a low acceptance of invasive surgery among patients, and the fact that about 20% of the lesions cannot be clearly defined as benign or malignant. Blood-based noninvasive testing can be used to analyze circulating cancer cells (CTCs) for clinical testing. Here, we investigated the performance of CTCs in thyroid cancer screening. Methods: We established a multi-marker real-time quantitative PCR (CK-19/surviving/Tg) to detect and quantify CTCs in peripheral blood samples. 100 subjects who were diagnosed by ultrasound imaging as having thyroid nodules were enrolled. FNAB or surgical specimens were subjected to pathological tests to differentiate between the benign nodules and thyroid cancer. Meanwhile the CTCs in the blood were isolated and quantified by multi-marker qPCR. Results: Among 100 patients, 50 were diagnosed as Papillary Thyroid Carcinoma (PTC) by pathological test. The sensitivity of each single marker of CK19, Survivin and Tg were only 48%, 44%, and 50% respectively, with the specificity of 94%, 100% and 94%. However, the combination of these three markers results in the highest sensitivity and specificity of 86% and 90%. Thus, the combined marker could achieve the best diagnostic value. Conclusions: Compared with FNAB, CTC is minimally invasive. The performance of the multi-marker real-time quantitative PCR showed that CTC could be used as an adjunctive test after ultrasound evaluation. Our results indicated that CTCs have potential clinical value in the identification of benign and malignant thyroid nodules.
Chlamydia trachomatis samples testing falsely negative in the Aptima Combo 2 test in Finland, 2019
Authors: Kaisu Rantakokko-Jalava, Kati Hokynar, Niina Hieta, Anniina Keskitalo, Pia Jokela, Anna Muotiala, T. Sakari Jokiranta, Rutta Kuusela, Hannu Sarkkinen, Janne Aittoniemi, Tytti Vuorinen, Antti J Hakanen, Mirja Puolakkainen
Journal: Eurosurveillance (2019)

Since February 2019, over 160 Chlamydia trachomatis (CT) cases testing negative or equivocal by Aptima Combo 2 (AC2) but positive by Aptima CT test run with Panther instruments occurred in Finland. The AC2 test targets chlamydial 23S rRNA while the CT test targets 16S rRNA. Sequencing of 10 strains revealed a nucleotide substitution in 23S rRNA. The significance of this for the failure of the AC2 test to detect the variant is not yet known.
Evaluation of Economic and Clinical Outcomes Under Centers for Medicare &amp; Medicaid Services Mandatory Bundled Payments for Joint Replacements
Authors: Derek A. Haas, Xiaoran Zhang, Robert S. Kaplan, Zirui Song
Journal: JAMA Internal Medicine (2019)

In 2016, the Centers for Medicare & Medicaid Services (CMS) launched its first mandatory bundled payment program, the Comprehensive Care for Joint Replacement (CJR) model, by randomizing metropolitan statistical areas (MSAs) into the payment model.To evaluate changes in key economic and clinical outcomes associated with the CJR model.A retrospective, national, population-based analysis of Medicare fee-for-service beneficiaries undergoing lower extremity joint replacement was conducted using 100% Medicare Part A data and 5% Medicare Part B data. Within an intention-to-treat framework, a difference-in-differences approach was used to compare Medicare spending, quality of care, volume of episodes, and patient selection in episodes of lower extremity joint replacements in the first 2 years of the program between propensity score-matched CJR and non-CJR hospitals (episodes initiated from April 1, 2016, through December 31, 2017, with the latter completed by March 31, 2018). Lower extremity joint replacement episodes in MSAs randomly assigned to the CJR model were compared with those in MSAs not assigned to the CJR model.Random assignment of MSAs into the CJR model within prespecified strata.Spending and its components, quality of care, volume of episodes, and patient characteristics were the main outcomes.After propensity score matching, there were 157 828 primary lower extremity joint replacement cases across 684 hospitals in the CJR (treatment) group (101 641 [64.4%] women; mean [SD] age, 72.8 [8.9] years) and 180 594 cases across 726 hospitals in the non-CJR (control) group (115 580 women [64.0%] women; mean [SD] age, 72.6 [8.8] years). The CJR was associated with a decrease of $582 per episode in Medicare Part A spending, a 2.5% savings on claims (95% CI, -$873 to -$290; P < .001) driven by a 5.5% decline in 90-day postacute care spending, concentrated in skilled nursing facilities (-4.5% change from baseline; 95% CI, -$460 to -$26; P = .03) and inpatient rehabilitation facilities (-22.9% change from baseline; 95% CI,-$497 to -$176; P < .001). Estimated savings on claims, while consistent with changes in practice patterns, may not have exceeded the reconciliation payments to hospitals reported by CMS to date. No significant changes in hospital length of stay, readmissions, complications, 30- or 90-day mortality, volume of episodes, or patient characteristics relative to control were found.The CJR was associated with reduced Medicare Part A spending on claims over 2 years, largely through lower postacute spending. Mandatory bundled payments may serve as a useful model for policy efforts to change clinicians' and facilities' behavior without harming quality.
Chemotherapy-associated lipid changes in breast cancer patients: A retrospective analysis from a high-volume institution in China.
Authors: Tao He, Qing Lv, Yunhao Wu, Yuan Fan, Jie Chen
Journal: Journal of Clinical Oncology (2019)

e12039 Background: Cytotoxic treatment may cause alterations in serum lipid of breast cancer patients but it remains controversial yet. The aim of this study is to investigate status of serum lipid pre- and post-chemotherapy as well as to compare lipid level alterations between different chemotherapy modalities. Methods: We retrospectively identified 1934 consecutive female patients who were surgically treated and pathologically diagnosed as breast cancer from February 2009 to December 2016 in a single institution. Results: There were 483(24.97%), 484(25.03%), 467(24.15%) and 500(25.85%) patients received AC-T, EC-T, TC and FEC chemotherapy regiment respectively. For the entire cohort, the levels of TG, TC and LDL were significant elevated in patients who received chemotherapy ( p＜ 0.01) while no significant difference was observed for HDL between pre- and post-chemotherapy. With chemotherapy regimens stratification, there were statistical significances with respect to TG, TC, HDL and LDL in AC-T, TC and FEC group between pre- and post-chemotherapy respectively ( p ＜0.05). Breast cancer patients with AC-T chemotherapy regimen increased TG value was higher than that of EC-T, TC, FEC regimens ( p ＜0.001) in premenopausal group. Moreover, utilizing of FEC regimen was associated with a significantly increased lipid level of HDL compared with the remaining regimens for both premenopausal and postmenopausal patients. Conclusions: Breast cancer patients receiving chemotherapy may carry a high risk of dyslipidemia. Therefore, regular lipid monitoring is very necessary for those breast cancer patients who receiving chemotherapy postoperatively.
Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?
Authors: Daniele Fanale, Lorena Incorvaia, Gaetana Rinaldi, Lidia Terruso, Giuseppe Badalamenti, Alessandra Cucinella, Mirna Swayden, Daniel Olive, Lidia Rita Corsini, Aurelia Guarini, Valerio Gristina, Luisa Castellana, Marco Bono, Viviana Bazan, Ignazio Ugo Carreca, Stefania Gori, Juan Iovanna, Antonio Russo
Journal: Journal of Clinical Oncology (2019)

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasma PD-1 levels were analyzed in 28 patients with metastatic melanoma using a specific ELISA assay. The characterization of TILs in tumor tissue was performed by immunohistochemistry. Statistical analysis was assessed using t-Student and ANOVA tests. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Results: 16 out of 28 patients showed the presence of TILs in primary tumor, 10 of which brisk and 6 nonbrisk. The plasma PD-1 levels were analyzed in relation to the presence/absence of TILs (p = 0.022), brisk TILs versus nonbrisk/absent TILs (p = 0.014), and brisk vs nonbrisk vs absent TILs (p = 0.032). In particular, low plasma PD-1 levels have been shown to be associated with brisk TILs in primary melanoma, intermediate values with nonbrisk TILs, and high expression with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant association between the plasma PD-1 expression levels and overall survival (OS) depending on the absence or presence of TILs (brisk/nonbrisk), however the median survival of patients having brisk TILs was five months higher than other 2 groups of patients with absent and nonbrisk TILs, respectively. Conclusions: This work highlights, for the first time, the potential ability of using the plasma PD-1 levels to predict prognosis also in patients with metastatic melanoma at diagnosis for which it is not possible to identify the primary tumor.
A phase II study of abemaciclib in patients (pts) with brain metastases (BM) secondary to HR+, HER2- metastatic breast cancer (MBC).
Authors: Carey K. Anders, Emilie Le Rhun, Thomas Denis Bachelot, Denise A. Yardley, Ahmad Awada, Pier Franco Conte, Peter Kabos, Melissa Bear, Zhengyu Yang, Yanyun Chen, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2019)

1017 Background: Abemaciclib is a selective CDK4 &amp; 6 inhibitor approved to treat HR+, HER2- MBC pts on a continuous dosing schedule as monotherapy or in combination with endocrine therapy (ET). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma. Methods: JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt cohorts with BM secondary to HR+ MBC, non-small cell lung cancer, or melanoma. Here, we report on HR+, HER2- MBC pts. Eligible pts had ≥1 new or not previously irradiated measurable BM ≥10mm or a progressive previously irradiated BM. Pts receiving ET at the time of enrollment were permitted to continue the same ET provided that extracranial (EC) disease was stable ≥3 months and the CNS progression occurred on the ET. Abemaciclib was orally administered 200mg BID. Primary endpoint was objective intracranial response rate (OIRR; [CR+PR]) based on Neuro-Oncology BM response assessment criteria (RANO-BM). Secondary endpoints included intracranial clinical benefit rate, PFS, and safety. Results: 58 HR+, HER2- MBC pts were enrolled and 52 pts were evaluable. Pts had a median of 4 prior systemic therapies, 75% of pts had prior chemotherapies (0-6, median of 2), and 71% of pts had prior ET (0-4, median of 1), in the metastatic setting. 50% of pts had prior whole brain radiotherapy, 39% stereotactic radiosurgery, and 8% surgical resection of BM. Median time from radiation to study enrollment was 9.4 months. Out of the 52 evaluable patients, 3 pts had a confirmed intracranial response (6% OIRR), and 38% of pts showed a decrease in the sum of their intracranial target lesions. Intracranial clinical benefit rate (CR+PR+SD persisting for ≥ 6 months) was 25%. Median PFS was 4.4 months (95% CI, 2.6-5.5). Safety and tolerability were similar to previous reports for abemaciclib. Conclusions: Abemaciclib demonstrated intracranial clinical benefit in heavily pretreated HR+, HER2- MBC pts with BM in this study. Further evaluations are ongoing to identify ABC patients with BM who might benefit most from abemaciclib. Clinical trial information: NCT02308020.
The prognostic role of the androgen receptor in patients with triple-negative early breast cancers and primary surgery.
Authors: Lynn Jongen, Giuseppe Floris, Hans Wildiers, Frank Claessens, Luna De Sutter, Romaric Croes, Jan Decloedt, Annouschka Laenen, Jan Ardui, Kevin Punie, Patrick Berteloot, Ignace Vergote, Patrick Neven
Journal: Journal of Clinical Oncology (2019)

e12042 Background: The prognostic value of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is debated and might be partially masked by the use of adjuvant chemotherapy, which might benefit AR-negative TNBC more than AR-positive cases. We compared the prognostic value of AR in a case control study of consecutive women with TNBC treated or not with adjuvant chemotherapy (ACT). Methods: We retrospectively studied AR expression by immunohistochemistry in all consecutive patients with a secondary metastatic TNBC treated in UZ-Leuven between 2000 and 2009. The control group were cases of TNBC never developing secondary metastatic disease during a long follow-up period matched 1:1 for age and tumor grade. Relations between demographics and clinical pathological features and AR protein expression were studied, including stromal tumor infiltrating lymphocytes (sTILs). Secondary metastatic disease connections with AR protein expression was assessed using the Akaike information criterion; time-to metastasis (TTM) was studied using a linear model with and without ACT correcting for lymph node involvement. We explored whether results differed by AR protein expression levels (0%, 1-34%, ≥34% of tumor cells) and body-mass index (BMI) comparing normal ( &lt; 25kg/m2) with overweight/obese patients BMI. Results: We included 139 patients (69 metastatic and 70 non-metastatic; median age 51.0 years); median follow-up for both groups was 8 years. AR protein expression level ≥ 1% was observed in 25% (n = 34) and ACT was given in 73% (n = 101). AR-positive as compared to AR-negative TNBC patients were older (p = 0.04). Results based on multivariable models including lymph node status and ACT as confounders showed that AR-negative cases have a higher metastasis risk compared to AR-positive patients (3.015 odds ratio (95% CI 1.199-7.582), p = 0.02); this difference was more significant in ACT-naive patients (10.823 odds ratio (95% CI 1.897-61.740), p = 0.007). ACT-treated patients had the best outcome if AR was low (1≤ and &lt; 34%) followed by those with a normal weight and an AR-negative high sTIL TNBC. Conclusions: The AR is prognostic in TNBC and this is clearer in non-ACT treated patients with a TNBC. Our results might suggest that if ACT is given, only the AR-positive TNBC with low AR-expression do well.