tbuckley/cabot-search huggingface dataset:
The prognostic significance of combined gleason scores and PSA values as indicators of age standardized relative five-year survival: An analysis of the SEER database 2004-2014.
Authors: Erika Correa, Mariola A. Vazquez Martinez, Chetan Jeurkar, Sufana Shikdar, Maneesh Rajiv Jain, David Lane Topolsky, Pamela A. Crilley, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2018)

e18753 Background: The most common cancer in American men is adenocarcinoma of the prostate. With an enormous prognostic heterogeneity, identifying prognostic markers in this patient population becomes increasingly important. Our objective was to assess the age standardized relative 5-year (yr) survival of patients with specific Gleason scores (GS) plus prostate-specific antigen (PSA) values as indicators of prognosis at the time of diagnosis. Methods: This was a population based study of patients with prostate cancer in the Surveillance, Epidemiology, and End Results (SEER) database 2004-2014. The cohorts were separated by PSA and GS ranges. The PSA values were divided into intervals of 20 and GS were divided into 5 -7 and 8-10. The age standardized relative survival rate is based on survival data for the general population of SEER. Results: There were a total of 168,768 prostate cancer patients. As shown in the table, all PSA/GS, excluding 0.2-20 ng/mL /GS 5-7 demonstrated a decrease in age standardized relative 5-yr survival rate. The most impressive decrease in 5-yr survival rate was seen in PSA > 98 ng/ml /GS 8-10. One limitation found was that not all prostate cases had associated Gleason scores; however trends were still discernible. Conclusions: At diagnosis, the age standardized relative survival rate decreases with rising PSA and GS. The sharpest declivity was demonstrated with PSA > 98 ng/ml and GS 8-10, with a > 50 % decrease in age standardized relative 5-yr survival rate. This emphasizes that the use of PSA and Gleason Scores individually have limitations but using both of these tools together may contribute to better survivorship care in these patients. We can also infer that extremely elevated PSA values and associated Gleason scores suggest metastatic disease. Accordingly, there may be an indication for more aggressive treatment in this high-risk population. PSA/GS % Survival 1 yr 5 yr 0.2-20/5-7 100.00 100.00 0.2-20/8-10 99.90 93.90 20.1-40/5-7 99.70 97.5 20.1-40/8-10 98.7 77.9 40.1-60/5-7 99.4 40.1-60/8-10 97 68.9 60.1-80/5-7 97.9 84.5 60.1-80/8-10 94.3 59.5 80.1-97.9/5-7 98.3 80.1-97.9/8-10 94 > 98/5-7 94.8 > 98/8-10 87.4 41.1
Assessing tumor heterogeneity using circulating tumor DNA to predict and monitor therapeutic response in metastatic breast cancer.
Authors: Fei Ma, Yanfang Guan, Zongbi Yi, Lianpeng Chang, Xuefeng Xia, Qiao Li, Shanshan Chen, Xin Yi, Ling Yang, Binghe Xu
Journal: Journal of Clinical Oncology (2017)

11543 Background: Within metastatic breast cancer (mBC), tumor heterogeneity limited efficacy and duration of response to treatment. In this study, circulating tumor DNA (ctDNA) was used to evaluate tumor heterogeneity as a prognostic factor and monitor therapeutic response in patients with mBC. Methods: We collected plasma samples from 37 HER2-positive mBC patients treated with pyrotinib. Target-capture deep sequencing was performed to detect somatic mutations in plasma ctDNA. Clonal population structures were identified based on variations from ctDNA using Bayesian cluster with PyClone. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population. Results: Mutations in TP53 and genes of PI3K/Akt/mTOR pathway were associated with drug resistance for pyrotinib. The result showed that patients with resistant mutations occurring as a truncal event, who receiving monotherapy of pyrotinib, presented worse therapeutic effect (HR, 4.52; P = 0.03). The median PFS of patients with versus without resistant mutations in trunk clonal population was 7.8 weeks (95% CI 7.4 to 26.8 weeks) versus 31.6 weeks (95% CI 15.7 to 60 weeks), respectively. Patients with high heterogeneity (clonal population ≥3) had a significantly worse PFS (HR, 2.79; 95% CI 1.23 to 6.34; P = 0.014). The median PFS among patients with high versus low heterogeneity was 30.0 weeks (95% CI 13.9 to 53.5 weeks) versus 60.0 weeks (95% CI 31.4 to 84 weeks), respectively. Longitudinal monitoring of 21 patients during treatment showed positive correlation between mTBI in ctDNA and tumor size evaluated by CT imaging (P &lt; 0.0001). Monitoring the mTBI in serial ctDNA increased sensitivity for prediction of progressive disease in 6 of 21 patients, with a mean time of 12.7 weeks earlier than using CT scan. ROC curve analysis showed an area under the curve value was 0.97 (p &lt; 0.0001). Conclusions: Assessing tumor heterogeneity in ctDNA provides genetic predictors of treatment outcome. Molecular tumor burden in ctDNA is a potential indicator of therapeutic response. These observations might be supplements for the current therapeutic response evaluation.
Cost saving analysis of reduced-dose versus standard-dose bevacizumab in recurrent glioblastoma.
Authors: Jack Patrick Gleeson, John Patrick Greene, William J Mullally, Claire Brady, Caitriona Goggin, Colum Dennehy, Derek Gerard Power, Bryan Hennessy, Oscar S. Breathnach, Richard Martin Bambury, Seamus O'Reilly, William Grogan, Dearbhaile Catherine Collins, Patrick G. Morris, Deirdre O'Mahony
Journal: Journal of Clinical Oncology (2018)

e18910 Background: FDA approval for bevacizumab (BEV) in progressive glioblastoma (GBM) was based on two phase II studies, both of which used a 10mg/kg every 2 weeks regimen. However, other studies have shown similar benefits and less toxicities at lower doses, thus the optimal dose regimen is yet to be established due to a lack of randomised trials. Reducing the dose of BEV would have substantial savings for institutional and government healthcare spending. We performed a drug cost analysis of differing doses of BEV in a national neuro-oncology center in Ireland. Methods: A retrospective review of the use of BEV in progressive GBM after first-line standard chemoradiotherapy with temozolomide was performed. Patient characteristics, outcomes and tolerability were evaluated. Two dosing schedules were utilized, standard dose BEV (10mg/kg) and reduced-dose BEV (5mg/kg) every 2 weeks, in 118 GBM patients (n = 69 vs 49, respectively). This analysis focused on cost savings. BEV drug costs per year were calculated for a normally distributed population with an average weight of 70kg using both a 10mg/kg and 5mg/kg dose regimen. Drug doses were dose banded, as per national guidelines. BEV cost was calculated factoring 100mg and 400mg BEV vials availability only. The annual cost of the two regimens were compared. Results: Overall survival (OS) analysis of the two dose regimens was similar, with median OS of 5.6 months (standard-dose cohort) and 5.5 months (reduced-dose cohort), p= 0.55. Reducing the dose from 10mg/Kg to 5mg/Kg for a 70kg adult with progressive GBM resulted in an average annual drug cost reduction of 44.18%, or a cost saving of €24,456.90 ($29,966.02, at current rates) per patient. Within our study population, if all standard-dose patients (n = 69) were treated with the reduced-dose BEV regimen there would have been a €534,167 ($654,045) cost saving total. Conclusions: Lowering the dose of BEV from standard 10mg/kg to 5mg/kg every 2 weeks for patients with progressive GBM could offer significant cost savings in Ireland if adopted, with similar overall survival. This justifies further study.
Multimodality treatment for esophageal cancer in Turkey: A single center experience.
Authors: Umut Demirci, Fatma Bugdayci Basal, Ferit Aslan, Erkan Erdur, Ayse Demirci, Tahsin Ozatli, Berna Oksuzoglu
Journal: Journal of Clinical Oncology (2017)

e15507 Background: Esophagus cancer is an important cause of cancer-related deaths in Turkey as well as in the world. In our study, clinicopathological features and survival results of patients treated for esophageal cancer were presented. Methods: This study retrospectively reviewed esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients who were admitted to our center, between 2012 and 2016. Results: A total of 82 patients (56 males) with a median age of 56 years were evaluated. Seventy-one (87%) patients were diagnosed with SCC, 10 (12%) with ADC, 1 with adenosquamous carcinoma. All ADC patients were HER2 negative. The localization of tumors; lower third (55%), middle third (27%) and upper third (18%) of the esophagus. Prior to surgery, neoadjuvant chemoradiotherapy (CRT) was administered in 21 patients (26%); 10 of them receiving carboplatin and paclitaxel (CP), and 11 receiving cisplatin and 5-FU (CF). TNM classification of operated patients were as follows; Stage 1 (n = 5), stage 2 (n = 10), stage 3 (n = 8) and stage 4 (n = 1). Adjuvant chemotherapy (CF) was administered in the other 6 (7%) patients. Definitive CRT was given in 36 patients (44%), with CF being administered in 32 patients, and CP therapy in 4 patients. There were 19 patients (23%) with metastatic diagnosis and 13 of whom were treated with CF, and 4 with docetaxel-cisplatin-5FU combination. With median follow up of 21 months, median overall survival (OS) and time to progression (TTP) were 24 and 17 months, respectively. The median OS and TTP of patients with metastatic disease were 14 and th 9 months, respectively. The median OS and TTP of the patients who underwent surgery were 45 and 34 months, respectively. Conclusions: Our findings in this study regarding the rate of histology, the percentages of patients with metastatic vs. locally advanced disease, and survival rates were similar to the literature.
Phase II-study of sequential high-dose-chemotherapy with paclitaxel, ifosfamide, carboplatin, etoposide( P-ICE) in patients with relapsed or refractory germ cell tumors (GCT).
Authors: Thomas Kegel, Franziska Cygon, Fabian Maximilian Meinert, Khaled Hammad, Frank Steinbach, Florian Seseke, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2017)

4552 Background: High-dose chemotherapy (HD-CTx) is an active option for salvage chemotherapy in patients (pts) with refractory or relapsed GCT. All previous trials with HD-CTx used one or two cycles of high dose chemotherapy (CTx) including 2 or a maximum of 3 drugs. Another potentially more active option is the application of four sequential HD-CTx cycles (Schmoll et al, JCO 2003). Methods: We conducted a phase II trial of 1(-2) cycle(s) induction CTx with standard dose P-ICE (Paclitaxel 135mg/m² d1, Ifosfamide 1500mg/m² d1-3, Carboplatin 150mg/m² d1-3, Etoposide 150mg/m² d1-3), followed by 4 sequential cycles of HD-P-ICE (Paclitaxel 200mg/m² d1, Ifosfamide 3300mg/m² d1-3, Carboplatin 330mg/m² d1-3, Etoposide 330mg/m² d1-3). Eligibility criteria: relapse or progression under one or more induction CTx, ECOG PS (0-1), Creatinine-clearance &gt; 30ml/min, adaequate liver function, measurable tumor or at least marker-elevation. Results: 37 pts entered the trial and 33 are evaluable (4 pts never received HD-CTx due to lack of stem cells (3) or medical reasons (1)). Prior CTx:1 (N = 26), 2 (N = 4), 3 (N = 3); primary extragonadal: 6; seminoma/ non-seminoma 5/28; ECOG-PS: 0 (19), 1 (14). Response rate: CR/NED 17 (51.5%), CR/NED/PR-/SD- with marker normalization 21 (63.6%), PD 12 (36.4%). DFS of CR/NED: median 59 (8-105) months; RFS of all favourable responders 60 (8-105) months, PFS total 46 (2-105) months. OS for all pts. 51 (6-105) months, OS Favourable Responders: 65 (23 – 105), Nonfavourable Responders: 11 (6-27) months,. Toxicity was tolerable without treatment related death, with mainly grade 4 bone-marrow toxicity and grade 2 mucositis and/or diarrhea. Conclusions: Sequential HD-CTx with one cycle of SD-P-ICE and four cycles HD-CTx is feasible with acceptable toxicity and favourable efficacy. Sequential HD-CTx using the four most active drugs might be a potentially option for this pts-population due to good tolerability, applicability and interesting long-term outcome. Comparison of the standard approach with 1 to 3 sequential high dose cycles of Carboplatin/Etoposide is ongoing (TIGER-Trial). Clinical trial information: EUDRA-CT: 2006-006004-11.
A retrospective study of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of gastric cancer with synchronous peritoneal metastasis.
Authors: Bin Xiong, Zhiqiang Zhu, Xiaobin Lin, Min Sun, Dongxu Wang
Journal: Journal of Clinical Oncology (2018)

e16007 Background: Gastric cancer with synchronous peritoneal metastasis (GCSPM) is considered as an advanced disease. Prognostic-related factors in GCSPM treated by Cytroreductive surgery (CRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) remain unclear. Methods: Data from 67 patients treated for GCSPM in China single center (Zhongnan Hospital of Wuhan University) from January 2013 to October 2016 were collected. All of them were underwent CRS+HIPEC. The primary endpoints were median survival time (MST), 1-, 2-, and 3-year survival rate; secondary endpoints were prognosis-related factors. Extension of PC was assessed by the Peritoneal Cancer Index (PCI). To assess prognostic factors, the log rank test was used for identification of the difference between curves. To assess the confounding factors involved in CRS+HIPEC treated GCSPM, a Cox proportional hazards regression model was used. Multivariate models and sensitivity analyses were also performed. Results: The median survival time (MST) was 24.3 months with 95% confidence interval (CI) 19.2-29.4 months. The 1-, 2-, 3-year survival rates were 85.1%, 50.5%, and 27.5%, respectively. Sixty patients underwent complete cytoreductive surgery (CC0). Seven patients had CC1 confirmed residual tumor on pathology. Twenty-six patients had preoperative chemotherapy, and all patients had postoperative chemotherapy. Univariate analysis revealed five significant parameters that may affect the overall survival : absence of ascites, differentiated tumor, N stage < 2, PCI < 9, and ≥ 6 postoperative chemotherapy cycles. Multivariate cox regression analysis demonstrated three parameters with notable effects: N stage < 2, PCI < 9, and ≥ 6 postoperative chemotherapy cycles. Conclusions: Tumor N stage, PCI score, postoperative chemotherapy cycles were independent prognostic factors in GCSPM treated by CRS+HIPEC. Tumor N stage < 2, PCI < 9, postoperative chemotherapy cycles ≥ 6 indicates better prognosis in patients with GCSPM. CRS+HIPEC with adjuvant systematic postoperative chemotherapy may improve overall survival in GCSPM.
Outcomes in patients with myelofibrosis and RBC-transfusion dependence in the phase III PERSIST-1 study of pacritinib vs. best available therapy.
Authors: Claire N. Harrison, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Andrew Perkins, Jiri Mayer, Peter Ganly, Harry C. Schouten, Patrizia Tosi, Charles Michael Farber, Pierre Zachee, Christof Scheid, James P. Dean, Huafeng Zhou, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Jyoti Nangalia, Adam Mead, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2016)

7066 Background: Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R and currently being investigated in patients with hematologic malignancies. The phase III PERSIST-1 study evaluated outcomes at week 24 with pacritinib (PAC) vs. best available therapy (BAT) in patients with intermediate- to high-risk myelofibrosis. Patients were not excluded on the basis of baseline platelet or hemoglobin levels. This analysis evaluates outcomes at week 60 in patients with red blood cell-transfusion dependence (RBC-TD) at baseline. Methods: Eligible patients (N = 327) were randomized 2:1 to receive PAC (400 mg once daily) or BAT (any physician-selected therapy excluding JAK2 inhibitors) until disease progression (PD) or unacceptable toxicity. At week 24 or PD, BAT-treated patients could crossover to receive PAC. Endpoints included spleen volume reduction (SVR) ≥ 35%, ≥ 50% reduction in total symptom score (TSS) from baseline to week 24, and achievement of RBC transfusion independence (RBC-TI) by Gale criteria defined as no RBC transfusions for at least 90 days. TSS was assessed through week 48. Results: At baseline, 50 patients were RBC-TD (n = 35 [PAC], n = 15 [BAT]). During the study, 9 (25.7% [PAC]) vs. 0% (BAT) became RBC-TI. Among PAC-treated patients remaining RBC-TD at week 24, 11 (65%) were MF3 by reticulin/collagen fibrosis staging. Through week 60, 1 of 3 (33%) PAC-treated patients with RBC-TI at week 24 achieved SVR ≥ 35% vs. 5 of 17 (29%) PAC-treated patients who had remained RBC-TD. The median reduction in spleen volume was 28% in patients with RBC-TI at week 24 vs. 27% in patients remaining RBC-TD. At week 48, the median percent reduction from baseline in TSS was 45% for patients with RBC-TI at week 24 vs. 15% for patients remaining RBC-TD. Moreover, 1 of 3 (33%) RBC-TI patients and 3 of 7 (43%) RBC-TD patients had ≥ 50% TSS reduction. Conclusions: Treatment with PAC improved transfusion, spleen volume, and TSS outcomes in patients with intermediate to high-risk myelofibrosis and baseline RBC-TD. Clinical trial information: NCT01773187.
In Defense of “Denial”: Difficulty Knowing When Beliefs Are Unrealistic and Whether Unrealistic Beliefs Are Bad
Authors: J. S. Blumenthal-Barby, Peter A. Ubel
Journal: The American Journal of Bioethics (2018)

Bioethicists often draw sharp distinctions between hope and states like denial, self-deception, and unrealistic optimism. But what, exactly, is the difference between hope and its more suspect cousins? One common way of drawing the distinction focuses on accuracy of belief about the desired outcome: Hope, though perhaps sometimes misplaced, does not involve inaccuracy in the way that these other states do. Because inaccurate beliefs are thought to compromise informed decision making, bioethicists have considered these states to be ones where intervention is needed either to correct the person's mental state or to persuade the person to behave differently, or even to deny the person certain options (e.g., another round of chemotherapy). In this article, we argue that it is difficult to determine whether a patient is really in denial, self-deceived, or unrealistically optimistic. Moreover, even when we are confident that beliefs are unrealistic, they are not always as harmful as critics contend. As a result, we need to be more permissive in our approach to patients who we believe are unrealistically optimistic, in denial, or self-deceived-that is, unless patients significantly misunderstand their situation and thus make decisions that are clearly bad for them (especially in light of their own values and goals), we should not intervene by trying to change their mental states or persuade them to behave differently, or by paternalistically denying them certain options (e.g., a risky procedure).
Modified dose-dense taxotere cisplatin fluorouracil regimen (mTCF-dd) in a large cohort of patients (pts) with metastatic or locally advanced non-squamous gastroesophageal cancer (GEC).
Authors: Laura Toppo, Gianluca Tomasello, Wanda Liguigli, Silvia Lazzarelli, Giulia Tanzi, Michele Ghidini, Bruno Perrucci, Matteo Brighenti, Margherita Ratti, Stefano Panni, Maria Olga Giganti, Maddalena Donini, Massimo Rovatti, Giuseppe Maglietta, Valerio Ranieri, Roberto Grassia, Elena Iiritano, ELISA Iezzi, Caterina Caminiti, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2016)

e15552 Background: TCF is one of the most effective first-line option in metastatic GEC. We previously reported on the promising and high activity of mTCF-dd (Tomasello G et al: Gastric Cancer 2014 Oct;17(4):711-7). Aim of this study is to describe clinical outcomes, safety and studying potential clinical prognostic factors of this intensified regimen in a very large consecutive cohort of pts coming from a single center. Methods: 250 consecutive pts with measurable or evaluable GEC treated in the same institution were longitudinally followed. 136 were enrolled in 3 different CTs and 114 treated by routine clinical practice. Pts with PS 0-2 and adequate organ function from 2004 to 2015 received mTCF-dd: Docetaxel (50-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h c.i. d 1-2), plus Pegfilgrastim 6 mg d 3, q2w. Analysis was done accordint to ITT principle. Results: Median age 63 (range 25-81), M:F 140:51. Metastatic sites were: liver 38%, peritoneum 33.5%, bone 14%, lung 12%. A median of 4 cycles (range 1-8) per patient was administered: 15% required a dose reduction, 48% were treated without any delay. At a median follow up of 60 months, 192 pts were evaluable. We observed 6% CR, 52% PR, 14% SD, 13% PD and 13% NE, for an ORR of 59% (95% CI 52-66); DCR was 76%. Median OS was 11.1 months (95% CI 9.5-13.5). Most frequent grade 3/4 toxicities: neutropenia (26%), asthenia (31%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (13%), febrile neutropenia (11%). 18 pts (9%) became operable after mTCF-dd and underwent surgery. Finally, we identified 18 pts (9%) [12 metastatic, 6 locally advanced] with OS > 3 years and 7 (4%) still maintaining a response at the time of the current analysis. A further group of 21 pts with bone mets at diagnosis bearing a very poor prognosis (OS: 7.8 m 95% CI 3.8-10 ) was also found. Overall population data and a multivariate Cox model will be presented at the meeting Conclusions: mTCF-dd in GEC is an effective and feasible option. A careful monitoring of adverse events is recommended. A biomolecular analysis of long-term survivors is underway.
Pathologic complete response rate after neoadjuvant chemoradiation in patients with locally advanced rectal cancer affects survival in patients with prolonged radiation-surgery interval.
Authors: Benjamin Mitchell Motz, Patrick Daniel Lorimer, Danielle Boselli, I'sis N Perry, Joshua S. Hill, Jonathan C. Salo
Journal: Journal of Clinical Oncology (2017)

3608 Background: The current standard of care in locally advanced rectal cancer is neoadjuvant chemoradiation and R0 resection. An optimal radiation-surgery interval (RSI) has not been established. A small institutional dataset showed RSI &gt; 49 days improved pathologic complete response (pCR) rates and disease free survival. However, in a national dataset, RSI greater than 60 days was associated with increased rates of positive margins and impaired overall survival. Because pCR is associated with improved survival, we used a national database to evaluate the relationship between RSI, pCR and survival after neoadjuvant therapy for rectal cancer. Methods: The NCDB was queried for cases 2004-2013 of AJCC stage II or III rectal adenocarcinoma that underwent neoadjuvant radiation followed by radical resection. We excluded patients with missing and outlier RSI. pCR was defined as ypT0N0M0. Chi-square, univariate, multivariable Cox model, and Cochran-Armitage time trend analyses were performed. Results: 23475 patients were identified. 7901 (33.7%) had RSI ≥60 days. pCR occurred in 1766 (11.3%) of the &lt; 60 group and 1174 (14.9%) of the ≥60 group (p &lt; 0.001). RSI ≥60 days has increased over time, from 22.1% in 2004 to 45.4% in 2013 (p &lt; 0.001), as have pCR rates, from 8.4% in 2004 to 14.2% in 2013 (p &lt; 0.001). Multivariable Cox model of the total cohort showed that RSI ≥60 days (HR = 1.11, 95% CI = 1.04-1.19) and residual disease (HR = 2.04, 95% CI = 1.78-2.34) were associated with increased mortality. Subgroup analysis of patients with pCR showed RSI ≥60 days was not associated with worse survival (HR = 1.07, 95% CI = 0.82-1.41). However, analysis of patients with residual disease showed RSI ≥60 days was associated with worse survival (HR = 1.13, 95% CI = 1.06-1.21). Conclusions: In a large national database, RSI ≥60 days worsens survival in patients who have residual disease after neoadjuvant therapy for locally advanced rectal cancer, while there is no difference in those with pCR. Emphasis should be placed on identifying patients who are unlikely to have pCR and to prioritize resection in these patients within 60 days of completion of chemoradiation.