tbuckley/cabot-search huggingface dataset:
Patients with metastatic castration-resistant prostate cancer (mCRPC) are primary resistant (PR) to the new agent (NA)-based second line: Clinical outcomes and prognostic factors of subsequent treatment with another NA.
Authors: Orazio Caffo, Emilio Bria, Ugo De Giorgi, Marcello Tucci, Elisa Biasco, Lucia Fratino, Sabrina Rossetti, Roberto Iacovelli, Franco Morelli, Alessandro D'Angelo, Enrico Campadelli, Francesco Verderame, Nicolo Borsellino, Donata Sartori, Annalisa Guida, Riccardo Ricotta, Sandro Barni, Francesca Maines, Isabella Sperduti, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2017)

e585 Background: Several NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] changed the prognosis of mCRPC pts being able to significantly prolong their overall survival (OS) after docetaxel failure. Unfortunately, a quote of pts experiences an early progression (within 3 mos) during the second line treatment and it is unclear if a clinical benefit may result from a subsequent treatment with another NA. The present study is aimed to assess the clinical outcomes and prognostic factors of subsequent NA treatment in those pts PR to the second line NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. For the purpose of the present analysis we consider as PR pts who progressed within 3 months from the start of the NA second line. Cox regression analysis was used to assess the independent prognostic value of a series of third-line baseline covariates, in terms of progression free survival (PFS) and OS. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. The NA-based second line consisted of AA (261 pts), CABA (151), and ENZ (64): we identified 55 PR pts (AA 24 – CABA 24 – ENZ 7). All pts received a subsequent NA-based third line: 22 received AA, 25 CABA, and 8 ENZ. Compared to no-PR pts, PR pts showed a lower biochemical response rate (12.2% vs 31.6%; p = 0.005), but no significant differences in terms of objective response rate (17.1% vs 15.2%), PFS (median 3.5 vs 4.7 mos), and OS (median 9.4 vs 12.9 mos). Considering the PR population, at the multivariate analysis , lactate dehydrogenase and PSA were independent prognostic factors for PFS in third line, while hemoglobin, PSA, administration of one NA in fourth line and lactate dehydrogenase were independent prognostic factors for OS. Conclusions: In our experience, NA-based third line is active also in mCRPC PR population and some factors may help in selecting patients with higher probability of achieving a disease control.
A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes.
Authors: Qiao Li, Binghe Xu, Qing LI, Pin Zhang, Peng Yuan, Jiayu Wang, Fei Ma, Yang Luo, Ying Fan, Ruigang Cai
Journal: Journal of Clinical Oncology (2015)

e12077 Background: Triple-negative breast cancer (TNBC) is a huge clinical challenge with limited choices of treatment. DNA damage agents such as platinum have been proved effective in TNBC. Besides, significant synergistic cytotoxicity of cisplatin and capecitabine has been demonstrated by in vitro and in vivo studies. Furthermore, the combination of cisplatin and capecitabine (XP) was proved effective and well tolerated in multiple advanced solid tumors. However, whether combination of XP is a suitable choice for treatment of metastatic TNBC is unknown. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of XP regimen in metastatic TNBC patients pretreated with anthracyclines and taxanes. Methods: Patients with metastatic TNBC who had anthracyclines and taxanes as prior therapy were treated with capecitabine 2000 mg/m2 P.O. on day 1 through 14 plus cisplatin 75mg/m2 iv. on day 1 of a 21-day cycle for a maximum of 6 cycles, followed by capecitabine maintenance therapy. The primary end point was ORR and the secondary end points included PFS, OS and safety. Results: Thirty-three consecutive women diagnosed with stage IV TNBC were enrolled. Median age at enrollment was 47 (range: 25-71). A majority of patients (57.6%) had 2 or more metastatic sites, and 69.7% of patients had visceral involvement. A total of 148 cycles was given, with a median of 5 cycles (Range 2-6) per patient. ORR was 63.6%. Median PFS was 6.0 (95%CI: 3.1-8.9) months in the entire population and 9.0 (95%CI: 3.4-14.6) months in responding patients. One-year survival rate was 68% (95%CI: 57.6-77.4) in all enrolled patients and 95% (95%CI: 90.1-99.9) in responding patients. Most adverse events were mild and manageable, with neutropenia and nausea/vomiting as most common toxicities. Grade 3/4 toxicities included leukopenia (10, 30.3%), neutropenia (10, 30.3%), anemia (2, 6.1%), thrombocytopenia (1, 3.0%), nausea/vomiting (3, 9.1%), hand-foot syndrome (1, 3.0%), and sensory neuropathy (1, 3.0%). Conclusions: Capecitabine plus cisplatin demonstrated a clear activity and an acceptable safety profile in metastatic TNBC patients pretreated with anthracyclines and taxanes. Clinical trial information: NCT01928680.
Survival after cardiac arrest is best in specialist cardiac centres, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Patients who experience a cardiac arrest have a better chance of survival if they are taken immediately to a specialist heart centre rather than the nearest general hospital, regardless of distance, a Danish study published in the European Heart Journal has found.1

The findings support the establishment of a few high volume, invasive heart centres to which cardiac arrest patients should be transferred, the researchers said.

They used the Danish Cardiac Arrest Registry to identify 41 186 patients who had experienced a cardiac arrest out …
Hepatitis B reactivation risk in patients with solid tumors receiving single-agent capecitabine versus doxorubicin-based chemotherapy.
Authors: Winnie Hui Yee Ling, Angela Pang, Soo-Chin Lee
Journal: Journal of Clinical Oncology (2012)

1575 Background: Reactivation of hepatitis B virus (HBV) in cancer patients on chemotherapy is a challenge especially in Asia where HBV infection is endemic. Risk of HBV reactivation differs according to cancer type, chemotherapy regimen, and concomitant use of steroids. The United States Centre for Disease Control and Prevention recommends universal screening for chronic HBV infection for all patients before chemotherapy although screening for low-risk chemotherapy regimens may not be cost effective. Methods: We sought to assess and compare HBV reactivation risk and effectiveness of prophylactic anti-viral therapy in preventing HBV reactivation in patients receiving a ‘high-risk’ (doxorubicin-based) chemotherapy regimen for which prophylactic anti-viral therapy for hepatitis B carriers is generally accepted versus a ‘low-risk’ (single agent capecitabine) chemotherapy regimen for solid tumours at a tertiary cancer centre. The electronic medical records of eligible patients were reviewed between January 2007 and December 2010. Results: A total of 708 patients were identified, including 434 and 274 who received doxorubicin-based chemotherapy and single agent capecitabine respectively. HBV screening rate was 42.6% (51% for doxorubicin-based chemotherapy, 30% for single agent capecitabine, p&lt;0.0001). 15/302 (5%) screened patients were found to be hepatitis B carriers (6 on doxorubicin, 9 on capecitabine). Overall, 3/708 patients (0.4%) developed HBV reactivation (all from the unscreened doxorubicin group, 3/214 (1.4%) compared to 0/192 (0%) unscreened patients in the capecitabine group, p&lt;0.0001). All 15 identified hepatitis B carriers received prophylactic anti-viral therapy (14 received lamuvidine, 1 had entacavir) and none had HBV reactivation. Conclusions: Not all chemotherapy regimens are associated with risk of HBV reactivation. Routine hepatitis B screening and prophylaxis for low-risk chemotherapy regimens such as single agent capecitabine may add morbidity and may not be cost effective.
Nomogram to assess benefit of new over historical agents as salvage therapy for metastatic urothelial carcinoma (mUC) in non-randomized trials: Effect of atezolizumab on 12-month survival.
Authors: Gregory Russell Pond, Guru Sonpavde, Jonathan E. Rosenberg, Toni K. Choueiri, Joaquim Bellmunt, Ashley Marie Regazzi, Stephanie Anne Mullane, Andrea Necchi, Daniele Raggi, Jae-Lyun Lee, Soonil Lee, Joe Simpson, Christina Louise Derleth, Shih-Wen Lin, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2017)

346 Background: Early surrogate endpoints of benefit in mUC phase 2 salvage therapy trials are necessary to identify promising drugs, particularly for checkpoint inhibitors where response and progression-free survival are inadequate. We developed a nomogram using prognostic variables from phase 2 trials of historical agents to estimate 12 month survival to which observed survival in single arm trials could be compared. Methods: Data were obtained from phase II trials of salvage therapy for mUC for survival and 5 prognostic factors: hemoglobin, performance status, liver metastasis, treatment-free interval and albumin. Patients (pts) were randomly allotted to discovery:validation (DIS:VAL) datasets in a 2:1 ratio. A nomogram was developed for estimating 12-month survival. Calibration plots were constructed in the VAL dataset by plotting estimated vs. observed 12-mo survival and data bootstrapped to assess performance. The nomogram was applied to external nonrandomized salvage therapy data: 1) retrospective pemetrexed data or 2) trials of atezolizumab: PCD4989g and IMvigor210. Results: Data were available from 340 pts receiving sunitinib (n = 77), everolimus (n = 45), docetaxel + vandetanib or placebo (n = 109), pazopanib (n = 42), paclitaxel (n = 36) and docetaxel (n = 31). Calibration and prognostic ability of the model was acceptable (c-index = 0.634, 95% CI = 0.596-0.652). Observed 12-month survival for pts on pemetrexed (n = 127, 23.5% [95% CI: 16.2%-31.7%]) were similar to nomogram-predicted survival (19% [95% CI: 16.5-21.5], P&gt; 0.05), while observed result with atezolizumab (n = 403, 39.0% [95% CI: 34.1-43.9]) exceeded predicted result (24.6% [95% CI: 23.4-25.8], P&lt; 0.001). Conclusions: Atezolizumab was associated with a significantly longer 12-mo survival compared to nomogram-predicted survival while pemetrexed was not. This nomogram incorporates baseline prognostic factors to provide expected 12-mo survival of phase 2 patient cohorts with which to compare observed survival, thereby providing a useful tool to quantify benefit in phase II studies while controlling for the impact of clinical variables.
Low-dose, short-course sunitinib may normalize tumor vasculature and improve tumor blood flow to enhance chemotherapy efficacy in breast cancers.
Authors: Soo-Chin Lee, Andrea LA Wong, Thian C Ng, Choon Hua Thng, Ting Ting Wang, Maricel Cordero Tiemsim, Eugene Ong, Tong San Koh, Dennis Cheong, Pei-Jye Voon, I Peng Thomas Soh, Ching-Wan Chan, Philip Iau, Chee Seng Tan, Angela Pang, Boon C. Goh
Journal: Journal of Clinical Oncology (2012)

1064 Background: Small molecule VEGFR inhibitors (VEGFR-I) have failed to improve outcome with chemotherapy in most solid tumors. Continuous administration of a potent VEGFR-I may destroy vasculature and impede drug delivery; in contrast, low-dose, short-course VEGFR-I before chemotherapy may normalize tumor vasculature and enhance drug delivery. Methods: We conducted a phase Ib followed by phase II randomized study in patients with measurable primary breast tumors using low-dose sunitinib (Su) for 1 week prior to doxorubicin/cyclophosphamide (AC) and measured tumor blood flow with DCE-MRI and microvessel density and pericyte recoverage with CD31 and α-smooth muscle actin (SMA) staining on tumor biopsies, at baseline, after 1 week of Su, and 2 weeks after cycle 1 AC. Patients in phase Ib received 12.5-25mg Su prior to AC; in phase II, patients were randomized to AC+/-12.5mg Su. Results: 21 patients have been enrolled, including 3 patients on 25mg Su+AC, 11 on 12.5mg Su+AC, and 7 on AC alone. After 1 week of 25mg Su, 2/3 patients had reduced tumor blood flow on DCE-MRI indicating anti-angiogenic effects. After 1 week of 12.5mg Su, significant increase in tumor fractional plasma volume (Vp) occurred (+28%±28%, p=0.025) suggesting increased perfusion, followed by decrease 2 weeks after AC (-33%±26%,p=0.035) corresponding to mean tumor size change of -17±15%, while no significant Vp changes occurred with AC alone (p=0.823); CD31 expression reduced (20.7 vs 15.7, p=0.173) while SMA/CD31 double staining increased (2.45 vs 7.34, p=0.046) indicating lower microvessel density and normalization of residual vasculature, which was not seen with AC alone (CD31, p=0.434; CD31/SMA, p=0.605). The main toxicity of Su+AC and AC alone was febrile neutropenia (29% vs 43%). 14 patients had surgery with pathological complete response in 1/6 patients who received 12.5mg Su+AC. Conclusions: 25mg Su for 1 week can reduce tumor blood flow, suggesting that concomitant standard dose Su may compromise drug delivery. Low dose 12.5mg Su for 1 week is sufficient to normalize tumor vasculature and increase tumor fractional plasma volume, and may potentially improve drug delivery and treatment outcome.
An effort to examine the feasibility of whole exome and transcriptome sequencing in guiding personalized therapy for patients with non-small cell lung cancer.
Authors: Jianxing He, Xin Zhang, Wenhua Liang, Xiaofei Ye, Yong Hou, Shida Zhu, Kui Wu, Jian Wang, Jun Wang, Qiang Pan
Journal: Journal of Clinical Oncology (2014)

e19136 Background: Usefulness of the next-generation sequencing in clinical practice for cancer treatment is in early development. We sought to evaluate the feasibility of clinical application of whole exome sequencing (WES) or whole exome plus transcriptome sequencing (WETS) to provide guidance for personalized therapy. Methods: Tumor samples and clinical information of 15 patients who were diagnosed with non-small cell lung cancer (NSCLC) were collected. Sequencing and bioinformatics analysis were then performed by BGI-Shenzhen to detect the genomic alterations and changes in RNA expressions. Interpretation was performed base on systematic review of publications that report the relationship between specific genomic alterations/gene expression level and the sensitivity/toxicity of the anticancer drugs. All agents involved in the interpretation were classified by FDA approval status and, subsequently, NCCN recommendations for NSCLC or other cancers. Results: All patients were analyzed for WES with 10 patients available for WETS.EGFR and KRAS mutation status detected by WES were in complete agreement with those detected by routine methods. The WES/WETS reported the presence of resistance to a median number of 7 (range 3-12) optional regimens which were recommended by the latest NCCN guideline for NSCLC. Meanwhile, patients were shown to harbor sensitive alterations pointing at a median number of 6.5 (range 1-13) drugs that had not been indicated for NSCLC. Similarly, WES/WETS yielded generally consistent results but added new information in comparison with the immunohistological assessment of the expression of BRCA1, ERCC1, RRM1, TS, β-tubulin, VEGF-C, ERK2 and CD34 (available in 9 patients). Additionally, paired samples from primary and metastatic lesion which were present in four patients showed similar alteration profiles with slight differences. All information was stored for future update of interpretations. Conclusions: This is the first attempt to use WES/WETS to guide treatment for NSCLC. The idea is feasible. However, the reliability and true benefits of WES/WETS-guided treatment require further validation.
Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model
Authors: Deepansh Dalela, María Santiago-Jiménez, Kasra Yousefi, R. Jeffrey Karnes, Ashley E. Ross, Robert B. Den, Stephen J. Freedland, Edward M. Schaeffer, Adam P. Dicker, Mani Menon, Alberto Briganti, Elai Davicioni, Firas Abdollah
Journal: Journal of Clinical Oncology (2017)

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P &lt; .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score &gt; 0.6 were independent predictors of CR (all P &lt; .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy.
Pulmonary functional map on V/Q SPECT and TGFβ1 during radiotherapy and post-treatment lung function in patients with non-small cell lung cancer
Authors: S. Yuan, K. A. Frey, M. D. Gross, N. Ramnath, R. K. Ten Haken, X. Cai, J. A. Hayman, F. Kong
Journal: Journal of Clinical Oncology (2009)

7543 Background: Current research focus on the TGFß1 and pulmonary perfusion (Q) SPECT pre or post-treatment to predict lung toxicity in patients with non-small-cell lung cancer (NSCLC). However, ventilation (V) is also important, while the change of V/Q SPECT map and TGFβ1 during radiotherapy (RT) maybe more predictive for the lung function post-treatment. Methods: Patients with stage I-III NSCLC undergoing radiation based treatment were included and V/Q SPECT-CT, circulating TGF ß1 and carbon monoxide diffusing capacity (DLCO), as the key parameter of pulmonary function test, were assessed pre-, during- and 3 months post-RT. Patients were treated with conformal radiation therapy of more than 60 Gy, with or without chemotherapy per standard of care based on their stage of disease. The defects of V/Q SPECT images were defined by semi-quantitive method. Results: Total 45 patients with stage I-III NSCLC undergoing radiation (&gt;60 Gy) were enrolled. All patients had functional defects (V, or Q or both) at or adjacent to the tumor and the V/Q defects were mismatched in 40%, 50% and 23% patients, pre-, during- and post-RT, respectively. After 45 Gy, the V and Q defects improved remarkably in 38.4% and 34.6% patients respectively, and the V scores were also improved significant during-RT (p&lt;0.01). The Q scores of ipsilateral lung and V score of both lungs during-RT were correlated with DLCO 3 months post-RT margin-significantly (p=0.07) and significantly (p=0.02). The TGFß1 level decreased significantly during-RT and TGFß1 ratios (over the pre-RT level) at 4- and 6-week during-RT correlated with DLCO 3 months post-RT significantly (p=0.05). Conclusions: The V/Q SPECT map and TGFß1 level change during RT, and these changes are predictive for the lung function post-treatment in patients with NSCLC. No significant financial relationships to disclose.
Magnetic Resonance Imaging in the Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension
Authors: Andrew J. Swift, Dave Capener, Chris Johns, Neil Hamilton, Alex Rothman, Charlie Elliot, Robin Condliffe, Athanasios Charalampopoulos, Smitha Rajaram, Allan Lawrie, Michael J. Campbell, Jim M. Wild, David G. Kiely
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH).Objectives: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH.Methods: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry.Measurements and Main Results: During the follow-up period of 42 (range, 17–142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P < 0.01): right ventricular end-systolic volume index adjusted for age and sex, and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year (sensitivity, 70 [95% confidence interval (CI), 53–83]; specificity, 62 [95% CI, 62–68]; positive predictive value [PPV], 24 [95% CI, 16–32]; negative predictive value [NPV], 92 [95% CI, 87–96]) and at 3 years (sensitivity, 77 [95% CI, 67–85]; specificity, 73 [95% CI, 66–85]; PPV, 56 [95% CI, 47–65]; and NPV, 87 [95% CI, 81–92]). The model was more accurate in patients with idiopathic PAH at 3 years (sensitivity, 89 [95% CI, 65–84]; specificity, 76 [95% CI, 65–84]; PPV, 60 [95% CI, 46–74]; and NPV, 94 [95% CI, 85–98]).Conclusions: MRI measurements reflecting right ventricular structure and stiffness of the proximal pulmonary vasculature are independent predictors of outcome in PAH. In combination with clinical data MRI has moderate prognostic accuracy in the evaluation of patients with PAH.