tbuckley/cabot-search huggingface dataset:
Rectal cancer and pathologic complete response after preoperative chemoradiotherapy: Romanian single-center experience.
Authors: Eduard-Alexandru Bonci, Valentin Ioan Bobeş, Timea Kirsch, Ştefan Ţîţu, Teodora-Irina Adam, Ioan-Cătălin Vlad, Alexandru Irimie, Alina Muntean, Patriciu Achimaş-Cadariu
Journal: Journal of Clinical Oncology (2019)

e15002 Background: Current guidelines recommend neoadjuvant chemoradiation followed by total mesorectal excision for patients with locally advanced rectal cancer (LARC). After neoadjuvant chemoradiation, some of these patients achieve a pathologic complete response (pCR) of the primary tumor (ypT0) and seem to have improved oncologic outcomes. In the last years, a "wait-and-watch"/active surveillance or less radical surgery was proposed for these patients. The aim of this study was to analyze the overall survival (OS), disease-free survival (DFS), various clinicopathological factors and treatment factors in patients with LARC and ypT0 treated in our institution. Methods: Patients with LARC who received neoadjuvant chemoradiotherapy and achieved ypT0 on the surgical specimen were included in the present study. Clinical, pathological and surgical data from 51 patients was retrospectively collected between 1 st of January 2012 and 31 st of December 2017. Kaplan-Meier method and multivariate analysis were used to investigate the role of various clinicopathological factors and treatment characteristics in modulating the outcome for the patients included in the present study. Results: The study group included 18 females and 33 males having a mean age (+/- standard deviation) of 61 years (+/- 11,48) and 59 years (+/- 12,04), respectively. After a median follow-up of 19 months, OS was 88,24% and DFS was 98,03%. Classic open surgery was performed in all patients, low anterior resection and Miles resection was performed in 36 and 15 patients, respectively. Adjuvant chemotherapy was administered to 5 patients. Nodal status was ypT0N0 in 50 patients, ypT0N1 in one patient. Two of the recorded factors, stenosis and circumferential resection margin (CRM), appeared to play a significant role in modifying OS. Conclusions: Most of the patients with LARC treated with neoadjuvant chemoradiation and radical surgery seem to have a favorable long-term outcome but the stenosis and the involvement of CRM appears to predict the postoperative OS. Further studies are needed to determine the role of other factors in predicting OS and DFS in patients with LARC and ypT0.
Evaluation of quality of life, satisfaction and cost of care in metastatic colorectal cancer patients receiving ambulatory chemotherapy.
Authors: Phichai Chansriwong, Suwannee Sirilerttrakul, Nopakan Wannakansophon, Patamaporn Tangteerakoon, Suluck Vongterapak, Manmana Jirajarus, Sineenuch Ckumdee, Ekaphop Sirachainan
Journal: Journal of Clinical Oncology (2019)

6536 Background: Colorectal cancer is an important health problems in Thailand; chemotherapy remains the most suitable treatment for metastatic patients. Chemotherapy treatment that was once delivered only in hospital environments is now administered at patient's home that helping patients to live normal lives during receiving chemotherapy. The chemotherapy regimens are based on a 48 hours 5-fluorouracil infusion combined that need patients to be hospitalized, consequence to decrease QOL and increase cost of treatment. Aims: Compares the QOL score, patients’ satisfaction and cost difference in treating ambulatory chemotherapy (AC) patients compared with inpatient treatment. Methods: An observational cohort which enrolled 156 patients at the Ramathibodi hospital from Dec 2015 to Nov 2016. AC administered by the central venous access device (CVAD). The regimen as FOLFOX or FOLFIRI, 5-FU were in the elastomeric infusion pump and administered at the patients’ home. Nurse coordinators followed up with the patients by phone. The FACT-G and FACT-C scale, patients’ satisfaction and cost of treatment questionnaire were collected at time of enrolment, 2 months and end of treatment. Results: 156 patients are enrolled that 111 patients treated with AC and 45 patients treated with inpatient. 134 returned the questionnaire (response rate 86%). Intention to treat analysis revealed significantly improved in social wellbeing and FACT-G (p &lt;0.001) in AC group. Significant higher administration, service and overall satisfaction score in AC group. The AC reduced cost about 483 US dollars per cycle of chemotherapy. Conclusions: Ambulatory chemotherapy helps colorectal cancer patients to live normal lives by administer treatment at patients' home and results to significantly improve in quality of life especially in social wellbeing and more satisfaction. Moreover, ambulatory chemotherapy reduced cost of chemotherapy treatment.
Safety and efficacy of a phase I/IIa trial (NCT03066947) of a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer.
Authors: William Williams, Jarrod P. Holmes, Saveri Bhattacharya, Carmen Calfa, Shaker R. Dakhil, Jason Jerome Lukas, Elizabeth Tan-Chiu, Daniel Adams, George Peoples, Markus Lacher, Charles L. Wiseman
Journal: Journal of Clinical Oncology (2019)

e14026 Background: SV-BR-1-GM is a GM-CSF transfected breast cancer cell line which expresses HLA class I &amp; II antigens and has functional antigen-presenting cell activity. Prior studies suggest that partial matching of the HLA type of the patient with SV-BR-1-GM may be predictive of tumor regression. Methods: Subjects received low-dose cyclophosphamide 2-3d prior to ID injection of irradiated SV-BR-1-GM (20 million cells divided into 4 sites) and interferon-α into the inoculation sites ~2 &amp; 4 days subsequently. Cycles were q2 weeks x 3 then q mo. Results: A total of 30 patients were screened and 23 inoculated (Table). The patients were heavily pretreated with a median of 4 prior chemo/biological therapy regimens. There were no serious or unexpected adverse events. Local injection-site irritation was the most common toxicity. Objective tumor regression was seen in 3 patients, all of whom matched SV-BR-1-GM at least at one HLA locus: one patient with regression or clearing of 20 lung metastases; one with reduction in cutaneous involvement of the breast from 80% to 30% and one with regression of a breast lesion. Another 3 patients had decreases in circulating cancer-associated macrophage-like cells (CAMLs), which has been shown to correlate with tumor stage. They also all matched at least at one HLA allele. Circulating tumor cells and circulating epithelial cells were present in low numbers and tended to parallel trends in CAMLs which were present in larger numbers. CAMLs in 21/23 patients stained positive for PD-L1. Patients with tumor regression had robust DTH responses to SV-BR-1-GM. Conclusions: SV-BR-1-GM in this regimen appears to be safe and well-tolerated and is associated with objective regression of metastatic breast cancer and/or with decreases in circulating cancer-associated cells in 6/23 (26%) or patients. HLA matching may be a predictor of response. Clinical trial information: NCT03066947. [Table: see text]
Transcriptome-based cancer type prediction for tumors of unknown origin.
Authors: Jack Michuda, Catherine Igartua, Tim Taxter, Joshua SK Bell, Raphael Pelossof, Kevin White
Journal: Journal of Clinical Oncology (2019)

3081 Background: Tumors of unknown origin occur in approximately 5% of newly diagnosed cancers and are difficult to treat without establishing the tissue type from which they derive. Establishing tumor origin guides standard of care treatment for several NCCN targeted therapy guidelines. Leveraging tissue specificity in gene expression profiles, classification models based on RNA expression offer a promising approach to identify the likely primary cancer site in tumors of unknown origin. Methods: In this study, we developed a transcriptome-based cancer type classifier trained on over 10,000 tissue samples annotated by pathologists and sequenced for RNA expression to identify conserved patterns of expression characteristic of 30 tumor types across primary and metastatic tissue sites. The classifier probabilistically ranks cancer of origin. Results: Overall, the accuracy of the most probable cancer prediction was 85%, 88% within primary tumors and 77% within metastatic tumors. The top three cancers types with the highest accuracy were colorectal (accuracy in metastatic: 93%, accuracy in primary tumors: 99%), breast (95%, 96%) and lung (87%, 94%). Classifier performance was lower in low-purity metastatic tumors where the surrounding normal tissue obscures the tumor transcriptional profile, though the classifier still achieves 71% accuracy on metastatic tumors with less than 50% purity. Conclusions: We present a novel method to probabilistically predict tumor type for cancers of unknown origin using RNA-Seq. Our method achieves robust classification that is applicable to primary and metastatic tumors and demonstrates the value of utilizing RNA-Seq to aid cancer diagnosis and treatment decisions.
Effect of RNA-binding protein MSI2 deficiency on progression in triple-negative breast cancer via stabilizing TP53INP1.
Authors: Ping Wei, Ming Li, Wentao Yang, Xiaoyan Zhou
Journal: Journal of Clinical Oncology (2019)

e12555 Background: The RNA-binding protein Musashi-2 (MSI2) has been implicated in the tumorigenesis and tumor progression of human cancers. This study investigated the clinical significance of MSI2 and the potential molecular mechanisms involved in triple-negative breast cancer (TNBC) progression. Methods: The Illumina sequencing platform was used to analyze the mRNA transcriptome in TNBC vs. normal tissues, while quantitative reverse transcription–polymerase chain reaction and immunohistochemistry validated MSI2 expression in breast cancer tissues and the effects of MSI2 on TNBC cells were assayed in vitro and in viv o. RNA immunoprecipitation (RIP) DNA and RNA sequencing was performed to identify the potential MSI2-targeted mRNAs. RIP and luciferase analyses were used to confirm the mRNA targets of MSI2. Results: MSI2 expression was significantly downregulated in TNBC vs. normal tissues and was associated with a poor overall survival of patients. MSI2 overexpression in vitro and in vivo inhibited TNBC cell proliferation and invasion as well as the extracellular signal-regulated kinase 1/2 (ERK1/2) activity. Molecularly, MSI2 expression promoted the stability of TP53INP1 mRNA by its interaction with the TP53INP1 mRNA 3ʹ-untranslated region. Furthermore, knockdown of TP53INP1 expression was able to reverse MSI2-induced suppression of TNBC cell invasion, whereas ectopic expression of TP53INP1 and inhibition of the ERK1/2 activity blocked MSI2 knockdown-induced TNBC cell invasion. Conclusions: The current study demonstrated that downregulated MSI2 expression was associated with TNBC progression and a poor prognosis and that MSI2 expression inhibited TNBC proliferation and invasion by induction of TP53INP1 stability and inhibition of ERK1/2 activity.
Neoadjuvant chemoradiotherapy combined with surgery in the treatment of potentially operable thoracic squamous cell carcinoma of the esophagus(ChiCTR-OIC-17011648): A phase II single center clinical study.
Authors: Fang Liu, Maohui Yan, Boning Cai, Baolin Qu, Wei Yu, Yanrong Luo, Qianqian Wang, Yao Wang, Lanqing Liang, Mingyue Zeng
Journal: Journal of Clinical Oncology (2019)

e15543 Background: To investigate the efficacy and safety of neoadjuvant radiotherapy and chemotherapy combined with surgery in the treatment of potentially operable thoracic esophageal squamous cell carcinoma. Methods: Nineteen patients with advanced thoracic esophageal squamous cell carcinoma hospitalized in our hospital from July 2016 to June 2018 were prospectively studied. All patients received neoadjuvant concurrent radiotherapy and chemotherapy: intensity modulated conformal radiotherapy (40 ∽ 44Gy/20 ∽22f, 2 Gy/f), chemotherapy (paclitaxel 150 ∽ 175 mg/m 2 d1, 22+lobaplatin 25-30 mg/m 2 d2, 23, 2 cycles). After radiotherapy and chemotherapy, the efficacy and safety of the operation were observed. Results: Two case (10.5%) was completely remitted after neoadjuvant radiotherapy and chemotherapy, 17 cases (89.5%) were partially remitted, and the objective effective rate was 100%. All patients underwent radical surgery successfully, the R0 resection rate was 100% and the pCR rate was 52.6%. The main adverse reactions of neoadjuvant radiotherapy and chemotherapy were granulocytopenia and grade III-IV granulocytopenia. The rate of survival was 16.7%, and anastomotic leakage occurred in 1 patients after operation. Conclusions: Neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma can effectively reduce the volume of the tumor, significantly reduce the pathological grade, improve the resection rate, and have less adverse reactions, which is worthy of clinical application. Clinical trial information: ChiCTR-OIC-17011648.
Effect and utility of targeted and immune therapy as single agent treatment for brain metastases in patients with non-small cell lung cancer.
Authors: Hassan Shalabna, Alejandro Lokiec, Nissim Haim, Mira Wollner
Journal: Journal of Clinical Oncology (2019)

e13581 Background: Brain metastases are estimated to occur in approximately 30% of patients with metastatic non-small cell lung cancer (NSCLC). Patients with brain metastases experience significant morbidity, often with neurological dysfunction and cognitive impairment. While brain radiation therapy was the foundation of management, it is associated with delays in systemic drug therapy and neurocognitive impairment. The use of immunotherapy or targeted therapy (TKIs) in well-selected patients may be effective in all tumor sites, including the central nervous system with a low toxicity profile.Therefore, this study aims to examine the clinical and radiological effect and efficacy of biological treatment or immunotherapy on brain metastases in patients with NSCLC and to present a new therapeutic approach. Methods: This retrospective/prospective study includes all patients referred to Oncology department- Rambam Medical Center from Oct. 2008 till Jul. 2016, and prospective for one year started from 01 Aug. 2016. The patients were diagnosed with NSCLC with brain metastases, and treated with immunotherapy or targeted therapy as single agent without radiotherapy. Treatment response was defined as symptomatic improvement and/or radiologic regression. Results: Overall, 16 patients were included. 12 patients (75%) with EGFR mutation or ALK TRANSLOCATION. 11 patients were treated with targeted therapy, and 5 were treated with immunotherapy. 7 patients (43%) had neurological symptoms and 5 of these had clinical response lasted 3 to 11 months. Of the 11 patients receiving biological therapy, 9 (82%) had a good response with tolerable treatment. Of the 5 patients treated with immunotherapy, 2 patients had a radiologic response. 6 patients with no smoking history had EGFR mutation or ALK TRANSLOCATION and received biological therapy, all of them had radiologic response, accounting for 55% of the total of patients who responded. However, only 5 out of 10 patients who are active smokers or had smoking history, had a response. This implies that all patients who did not respond to the treatment are either current or past smokers. (P = 0.09). There was no difference in response to targeted therapy or immunotherapy in patients who received brain radiation therapy in the past compared to patients who were not radiated previously. Conclusions: There is an intracranial effect of targeted therapy or immunotherapy in NSCLC patients. These treatments can delay or prevent radiation therapy to the brain and all its related neurological damage.
A randomized phase 3 trial of paclitaxel (P) plus carboplatin (C) versus paclitaxel plus ifosfamide (I) in chemotherapy-naive patients with stage I-IV, persistent or recurrent carcinosarcoma of the uterus or ovary: An NRG Oncology trial.
Authors: Matthew A. Powell, Virginia L. Filiaci, Martee Leigh Hensley, Helen Q Huang, Kathleen N. Moore, Krishnansu Sujata Tewari, Larry J. Copeland, Angeles Alvarez Secord, David G Mutch, Alessandro Santin, William Richards, David Philip Warshal, Nicola M. Spirtos, Paul Disilverstro, Olga Ioffe, David S. Miller
Journal: Journal of Clinical Oncology (2019)

5500 Background: Gynecologic carcinosarcomas (CS) are rare yet aggressive epithelial malignancies for which optimal therapy is debated. PI was shown to be superior to I. PC demonstrated compelling phase 2 activity with improved safety and convenience. Methods: Main inclusion: ≥18 y; chemotherapy naïve stage I-IVB or recurrent uterine (U) or ovarian (O) CS. Treatment randomised 1:1 to PC (P 175mg/m2 with C: AUC 6 or 5 if prior RT on D1) or PI (P: 135 mg/m2; I 1.6 g/m2 D1-3; G-CSF support with dose escalation &amp; de-escalation based on nadir counts) q21days for 6-10 cycles. Quality of life (QOL) (FACT-En TOI) and neurotoxicity (FACT/GOG-Ntx subscale) administered at 4 timepoints. A stratified log-rank test compared primary endpoint of overall survival (OS) from entry between treatment groups for non-inferiority (NI) of PC to PI. With 264 events, power was 80% for a null hazard ratio of 1.2 against a 13% greater death rate on PI when type I error is limited to 5% for a one-tail test. NCT00954174. Results: 637 pts accrued with a median follow-up of 61 months. The primary (U, n = 536) and secondary (O, n = 101) cohorts are analyzed separately and included 449 and 90 pts eligible pts, respectively. For the U cohort:PC and PI were randomly assigned to 228 and 221 eligible pts. Stage distribution: I (40%), II (6%), III (31%), IV (15%) and recurrent (8%). The study met its primary objective withPC not inferior to PI (intention-to-treat analysis;Median OS 37 vs. 29 mo, HR = 0.87; 90% CI = 0.70 to 1.075; p &lt; 0.01 for NI, p &gt; 0.1 for superiority (S)).PFS (median on PC 16mo vs PI 12mo; HR = 0.73; p = &lt; 0.01 for NI, p &lt; 0.01 for S). Toxicity (grade 1/2/3/4/5: PC 1/8/40/48/2%; PI 1/32/39/25/1%). Most of increase toxicity for PC was hematologic with G-CSF rarely used (N = 6). Confusion and genitourinary hemorrhage were significantly worse with PI. Both groups had decline in QOL and neurotoxicity scores. Similar trends were noted for the O cohort (OS: PC 30mo vs PI 25mo; and PFS: 15 mo vs 10 respectively). Conclusions: PC was not inferior to PI for OS with longer PFS and similar QOL and neurotoxicity. These results establish a new standard regimen for women with CS. Clinical trial information: NCT00954174.
Health-related quality of life (HRQoL) results from ALTA-1L: Phase 3 study of brigatinib vs crizotinib as first-line (1L) ALK therapy in advanced ALK+ non-small cell lung cancer (NSCLC).
Authors: Rosario Garcia Campelo, Huamao Mark Lin, Maurice Perol, Mohammad Jahanzeb, Sanjay Popat, Yanyan Zhu, Pingkuan Zhang, D. Ross Camidge
Journal: Journal of Clinical Oncology (2019)

9084 Background: Results from ALTA-1L (NCT 02737501 ), an international, multicenter trial, showed that brigatinib vs crizotinib as 1L ALK therapy significantly prolongs progression-free survival (PFS; HR: 0.49, 95% CI, 0.33, 0.74) in advanced ALK+ NSCLC. HRQoL was evaluated as a secondary objective. Methods: ALK+ NSCLC patients were randomized 1:1 to brigatinib 90 mg daily for 7 days, then 180 mg daily or crizotinib 250 mg twice daily as 1L ALK therapy; treatment cycles were 28 days. HRQoL was assessed with the EORTC QLQ-C30 and LC13. Change from baseline, duration of improvement and time to worsening were analyzed in the ITT-PRO population (n = 131 for both groups). Results: HRQoL compliance was &gt; 90% for brigatinib and crizotinib. Global health status (GHS)/QoL improved starting at cycle 2, with clinically meaningful improvement (≥10-point increase) noted with brigatinib at cycles 5−8, 10−13, 17 and 19 and crizotinib at cycle 6. Brigatinib substantially improved overall HRQoL vs crizotinib, as demonstrated by the estimated mean difference on change from baseline (4.1, P&lt; 0.05) and duration of improvement for GHS/QoL (HR = 0.16, P&lt; 0.001). Improved GHS/QoL with brigatinib vs crizotinib was also supported by improvement in several functional domains (Table) and for these symptoms ( P&lt; 0.05): fatigue, nausea/vomiting and appetite loss. No domains significantly favored crizotinib. Brigatinib showed a trend to prolong time to worsening of dyspnea vs crizotinib (HR 0.65, 95% CI 0.38, 1.12). Table: HRQoL results brigatinib vs crizotinib Clinical trial information: NCT02737501. Conclusions: Consistent with the prolongation of PFS seen in 1L treatment of advanced ALK+ NSCLC, brigatinib improved HRQoL and prolonged the duration of improvement in GHS/QoL, and the majority of functional and symptom domains vs crizotinib.[Table: see text]
Factors associated with extended survival for patients with platinum-resistant ovarian cancer treated with modified vaccinia oncolytic virotherapy.
Authors: Madhavi Manyam, Amanda J. Stephens, Jessica A. Kennard, Christine K. Fitzsimmons, James Erasmus Kendrick, Nathalie Dauphin McKenzie, Jane LeBlanc, Jamie L. Smith, Sarfraz Ahmad, Robert W. Holloway
Journal: Journal of Clinical Oncology (2019)

e17070 Background: VIRO-15 phase IB trial included 11 patients (pts) with platinum-resistant ovarian cancer (PROC), extensive tumor burden and a median of 5 prior lines of therapy who were given intra-peritoneal Olvi-Vec (GL-ONC1), a modified vaccinia oncolytic virus (OV). Four pts had apparent clinical benefit with &gt; 5 mos progression-free survival (PFS) following OV. This analysis aimed to determine factors that predict clinical benefit from OV. Methods: Comparative analyses included: anti-vaccinia neutralizing antibody (NA) as a measure of immune-competence, virus-encoded glucuronidase activity (GA) indicating viral replication, tumor shrinkage by RECIST 1.1, tumor burden (serum LDH), PD-L1 status, Prognostic Nutritional Index (PNI), absolute lymphocyte count, C-reactive protein, albumin, ECOG performance score (PS), no. of prior lines of therapy and platinum therapies, BRCA status, CA125 tumor marker, &amp; circulating tumor cells (CTCs). Results: Mean age was 66.3±9.3 years and BMI 24.8±4.7 kg/m 2 . Median prior chemotherapy lines = 5 (range 2-10), median prior platinum lines = 3 (range 2-6), and 9 pts had prior Avastin. Following OV, 4 pts (Group A) had mean PFS 10.9±5.1 (range 5.4-16.4) mos compared to 7 pts (Group B), with mean PFS 2.4±1.1 (range 1.3-4.1) mos ( p&lt; 0.05). Mean OS for Group A was 21.7±8.2 (range 7.8-28.3) mos vs 3.6±1.5 (range 1.6-6.2) mos for Group B ( p&lt; 0.05). 3 Group A pts are alive with PS 0, and one with stable disease died at 8 mos from pulmonary embolism. Factors that predicted clinical benefit were: i) PNI [mean 49.0±5.7 vs 42.1±4.3 ( p&lt; 0.05)], ii) Week-5 CA125 values &lt; Week-2 [4/4 vs 0/7 (p &lt; 0.01)], iii) absence of CTC [3/4 vs 1/7 pts ( p&lt; 0.05)]. Baseline PD-L1 expression and BRCA status were not predictive markers. Conclusions: Factors associated with clinical benefit using GL-ONC1 monotherapy in PROC include PNI &gt; 44.5, absence of CTCs, and Week-5 CA125 less than Week-2 levels. Absent these factors, cytotoxic therapy should be considered by Week-6 following GL-ONC1. Three patients are currently alive at 22.8-28.2 mos, following additional therapies. A multi-institutional phase II trial is currently enrolling. Clinical trial information: NCT02759588.
Analgetic Drugs
Authors: Leroy D. Vandam
Journal: New England Journal of Medicine (1972)

ONE important characteristic of the potent analgetics or opioids is addiction liability, which requires that their prescription be regulated. The restrictions thus imposed have led to hesitation in prescribing potent analgetics and to a concern out of proportion to the possibility of causing harm.The older terms habituation and addiction are confusing. Recently, they have been replaced by "drug dependence," a state arising from the repeated use of drugs on a periodic or continuous basis. Dependence can develop from the use or abuse of many drugs and is designated as morphine-type, barbiturate-type, amphetamine-type and the like. "Dependence" may further be . . .