tbuckley/cabot-search huggingface dataset:
Comparison of a new prognostic system and five current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma.
Authors: Zhan-Hong Chen, Xing Li, Min Dong, Xiao-Kun Ma, Xiang-Yuan Wu
Journal: Journal of Clinical Oncology (2014)

193 Background: Prognosis of patients with advanced HCC is very poor, median overall survival varies from 3 to 6 months. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical tirals. We have established a new prognostic system called SYSU system (variables and risk classification criteria are listed below, reported in MASCC 2013) and now we want to compare this new prognostic system and 5 current staging systems in predicting the survival rate of patients with advanced HCC. Methods: From September 2008 to June 2010, a total of 253 patients with advanced HCC who were not amendable to locoregional therapy were analyzed. The median follow-up is 38.5 months and the median survival is 7 months. Data were collected to classify patients according to our new system(SYSU system), Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma (BCLC), Advanced Liver Cancer Prognostic System (ALCPS), Chinese University Prognostic Index staging system for HCC (CUPI), OKUDA score system and French scoring system(GETCH) at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 0.822,0.821,0.777,0.756,0.688 and 0.621. AUC of SYSU system and ALCPS is similar and they are significantly better than the other four staging system (p&lt;0.05). When predicting overall survival, likelihood ratio test show χ2 of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 97.7,85, 50.5, 46.4,22.6 and 8.4 and AIC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 1939,1952,1986,1990,2014 and 2028. Our SYSU system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: Our SYSU system is the best score system in prediction of OS and 3-month OS among the 6 systems analyzed for Chinese advanced HCC patients. [Table: see text]
Cost-effectiveness of regorafenib for pretreated metastatic colorectal cancer patients in the United States.
Authors: Brian S. Seal, Ipek Özer-Stillman, John Whalen, Apoorva Ambavane, Avin Yaldo, Vivek Pawar
Journal: Journal of Clinical Oncology (2013)

578 Background: There is an unmet need for treatments that provide a survival benefit for patients with heavily pretreated metastatic colorectal cancer (mCRC). In a randomized, double-blind, placebo-controlled trial, patients treated with regorafenib plus best supportive care (BSC) had significant improvement in overall survival (OS) versus patients in the placebo arm receiving BSC alone. The aim of this study was to estimate the cost-effectiveness of regorafenib for the treatment of patients with mCRC after failure or intolerance to irinotecan-, oxaliplatin-, and fluorouracil-based regimens, from the perspective of a U.S. health care payer. Methods: A cohort-partition model was developed to simulate treatment costs and survival for patients treated with regorafenib or BSC alone. Survival was projected by fitting Weibull distributions to trial data. Mean duration of treatment (3.0 months regorafenib, 2.1 months BSC), utilities (0.71 on treatment, 0.59 post-treatment) and serious adverse event rates were also based on trial data. Monthly drug monitoring and physician fee costs were based on Medicare fee schedules. Routine mCRC care and adverse event unit costs were obtained from an analysis of administrative claims in two large managed care databases. Costs were estimated in 2012 USD. Results: Patients treated with regorafenib had prolonged survival versus BSC alone (0.75 versus 0.60 years) and also had higher lifetime costs ($97,700 versus $59,494). The improvement in quality-adjusted life years (0.47 versus 0.37) was small due to the heavily pretreated nature of the patient population. The increase in costs was attributable to increases in costs for drug acquisition, adverse events , and routine care from increased survival. Conclusions: Regorafenib increases life expectancy for patients with pretreated metastatic colorectal cancer. The cost of this benefit could be considered high; however, it could be justifiable given high unmet need for these patients. The increase in cost is primarily due to drug acquisition costs, similar to other recent treatments for metastatic cancers.
A prospective survey of depressive disorder among patients with advanced lung cancer in South China.
Authors: Li Zhang, Jin Sheng, Xia Liu, Yunpeng Yang, Yuxiang Ma, Yan Huang, Hongyun Zhao
Journal: Journal of Clinical Oncology (2015)

216 Background: Depression frequently compromises quality of life and prognosis for patients with cancer. However, this psychiatric disorder is often overlooked. This ongoing multi-center investigation was designed to prospectively evaluate the prevalence of depressive disorder in patients with advanced lung cancer in South China. Methods: Patients diagnosed with advanced lung cancer will be screened by two items from the nine-item Personal Health Questionnaire (PHQ-9). For individuals who endorse either item (or both) as occurring for more than half of the time or nearly every day within the last 2 weeks (ie, score of ≥ 2), the remaining 7 items are suggested to be completed. Patients will receice standard palliative chemotherapy according to the preference of oncologists. Demographic variables and clinical information were statistically analyzed. Results: By now, this study have enrolled 97 patients for initial screen, 58 (59.8%) were chemotharapy-naïve. Based on the PHQ-9 questionnaire, the percent of patient suffered from various degree depressive symptomes was 76.3% (74 patients). 51.5% patients (50 cases) were proved with mild depressive symptomes but not met the criteria for depression. Meanwhile, the incidence of moderate or severe depression were separately 17.5% and 7.3%. There were few consistent correlates of depression. Hitherto, 49 patients completed the second investigation after 1or 2 cycles of palliative chemotherapy. In terms of the PHQ-9 score, no statistically significant difference was detected around cytotoxic treatment (mean value: 6.67 and 6.43, p = 0.65). Although the mild depressive symptomes were decreased from 53.1% to 42.9% after palliative chemotherapy, the percent of moderate or severe depression remained the same (17/49, 34.7%). Conclusions: The preliminary result showed that the incidence of depressive disorder among patients with advanced lung cancer may be underestimated. No evidence was found yet to demonstrate the impact of demographic variables on depression. There is unmet need for psychological intervention for advanced lung cancer patients with depressive disorder, especially for those with moderate or severe degree at diagnosis.
Immunogenicity of GI-4000 vaccine in adjuvant consolidation therapy following definitive treatment in patients with stage I-III adenocarcinoma of the lung with G12C, G12D, or G12V <i>KRAS </i>mutations.
Authors: S. P. D'Angelo, B. J. Park, L. M. Krug, C. Crevar, C. E. Medina, D. K. Sumner, J. Richman, C. Coeshott, D. Apelian, A. Cohn, M. G. Kris, C. G. Azzoli
Journal: Journal of Clinical Oncology (2011)

7070 Background: All patients at MSKCC with lung adenocarcinoma undergo reflex testing for EGFR and KRAS mutations at the time of surgical resection. KRAS mutations occurred in 19% of resected lung adenocarcinomas at MSKCC from 2006- 4/2009. GI-4000 is a recombinant, yeast-based vaccine (S. cerevisiae) engineered to express one of 4 mutated RAS oncoproteins. Methods: GI-4000 was administered as adjuvant therapy to patients with stage I-III lung adenocarcinomas and G12C, G12D, or G12V KRAS mutations after the completion of curative therapies. All patients were disease free at their first post-treatment assessment. GI-4000 was given for 3 weekly doses, 6 monthly doses, then every 3 months for up to 3 years. The primary endpoint was vaccine-induced T cell responses documented by interferon-γ ELISpot assay in peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with RAS peptide pools from the specific mutation present in their tumor. Results: 24 subjects were enrolled. Women=17, Stage IA=10, IB=4, II=2, III=8, median age 67 (range 50-80), G12C=15, G12V=3, G12D=6, median # of doses per subject =9 (range 1-16). To date, there have been no serious adverse events related to GI-4000. 17/24 patients had adequate immune sampling to be analyzed by ELISpot assay, G12V patients (n=3) are still undergoing testing. 8/17 (47%) of the patients developed an immune response to mutant RAS; 5/9 (55%) developed a treatment emergent response and 3/8 (37%) developed an improvement in a pre-existing baseline response based on pre-specified immunologic criteria. Conclusions: MSKCC’s program of reflex testing of lung adenocarcinoma resection specimens permits the identification of patients for KRAS specific therapy. GI-4000 is immunogenic in targeting mutated KRAS as an adjuvant “consolidation” therapy in patients with stage I-III lung adenocarcinomas harboring KRAS mutations. These data warrant further study of GI-4000 in KRAS mutant lung adenocarcinomas and other cancers with these specific mutations.
The prognostic significance of perineural invasion in patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy.
Authors: Ankur Kaushik Patel, Xueliang Jeff Pan, Terence M Williams, Evan John Wuthrick
Journal: Journal of Clinical Oncology (2016)

146 Background: Perineural invasion (PNI) is the process of neoplastic invasion of nerves. PNI has been reported as a prognostic indicator in malignancies of the pancreas, stomach, colon, rectum, prostate, head and neck, and biliary tract. However, studies examining the prognostic significance of PNI in esophageal cancer have shown inconsistent results. Analyses in patients with esophageal adenocarcinoma (EAC) have alternatively shown PNI to be a significant and a nonsignificant predictor of OS and DFS in both univariate and multivariate analysis. The majority of these studies analyzed patients who had not received any preoperative therapy. We sought to identify the prognostic significance of PNI in patients with EAC treated with neoadjuvant chemoradiotherapy (nCRT). Methods: We performed a retrospective analysis of 108 patients treated with nCRT and surgery for EAC at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute from 1996-2015. The final analysis identified 73 patients with data on PNI. We evaluated the association of PNI with disease-free survival (DFS), loco-regional progression-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) using log-rank and Cox proportional hazard modeling. Results: Of 73 patients, 17 patients (23%) had PNI and 56 patients (77%) did not have PNI at the time of surgery. The median follow-up was 15.3 months (range 5.8 to 179.3 months). The median DFS was 12.4 months for PNI+ and 36.4 months for PNI- (p = 0.042). The median LRFS was 48.2 months for PNI+ and median not reached for PNI- (p = 0.003). We did not detect a significant association between the presence of PNI and worse OS or DMFS. In a multivariate model including age, sex, gastric involvement, biopsy grade, presence of pathologic complete response, and pathologic N stage, PNI remained a significant independent predictor of LRFS (HR 0.37, 95% CI 0.14 to 1, p = 0.05). Conclusions: In patients with esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy, PNI discovered at the time of surgery is significantly associated with worse DFS and LRFS.
Induction chemotherapy with cisplatin, 5-fluorouracil, and cetuximab followed by radiotherapy and cetuximad in head and neck cancers: Preliminary results of a modern integrated approach.
Authors: R. M. D'Angelillo, L. Trodella, F. Cellini, M. Fiore, C. Greco, B. Floreno, L. E. Trodella, A. Iurato, E. Ippolito, S. Ramella
Journal: Journal of Clinical Oncology (2011)

e16030 Background: To determine feasibility and efficacy of induction chemotherapy (ICT) with cisplatin, 5-fluorouracil and cetuximab, followed by concurrent cetuximab and radiotherapy (RTCT), in patients with stage III-IV, non metastatic, head and neck cancer. Methods: ICT consisted of two cycles of cisplatin 100 mg/m2 and 5-FU 1,000 mg/m2i.v.c. d1-4 q28, and weekly cetuximab 250 mg/m2 (after loading dose of 400 mg/m2) followed by RTCT. Staging and restaging procedures include CT, MRI and 18F-FDG PET scan. All patients received IMRT. The total dose delivered was 70/60/50 Gy in 2Gy/fx to macroscopic and metabolic active disease/nodal high-risk areas of microscopic disease/nodal low risk areas. Toxicity was recorded and scored according to the NCI-CTC 3.0 scale. A one-stage design tested the null hypothesis that the true objective response rate is <= 60% versus the alternative hypothesis that it exceeds 60%. Assuming a type I error rate of 5% and a power of 80%, this trial required 37 response-evaluable patients. Actually 19 have completed the whole treatment and results are show below. Results: From October 2008 to July 2010, 19 patients have been evaluated. The median age was 58 years (range 37-70 years). All patients had a good performance status (ECOG Score 0-1). Stage was III/IVa-b in 3/16. Tumor location was oral cavity/pharynx/larynx in 5/10/4. During induction chemotherapy grade 3-4 hemathological toxicity was: NEU/PLT/HB in 5/2/1 patients. Only one neutropenic fever have been recorded. Hypomagnesemia was mild (Grade 1) in 10 patients. Overall response rate to ICT was 17/19 (89.4%). During RTCT grade 2-3 skin toxicity and mucositis was in 11 and 12 patients respectively. One patient drop off treatment due to declining in performance status. Thus 18 patients are evaluable for clinical response. Complete response rate was recorded in 14/19 patients (73.7%). After a median of follow-up of 13 mounths, only 2 patients experienced progression (one local the other pulmonary). Conclusions: This regimen seems safer than those that include docetaxel induction schemes.
Lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed multiple myeloma (MM): Final results of a multicenter phase I/II study.
Authors: K. C. Anderson, E. Weller, S. Lonial, A. J. Jakubowiak, S. Jagannath, N. S. Raje, D. Avigan, R. D. Knight, D. Esseltine, P. G. Richardson
Journal: Journal of Clinical Oncology (2010)

8016 Background: Bortezomib (VELCADE, Bz) or lenalidomide (REVLIMID, Len) plus dexamethasone (dex) demonstrate substantial activity in front-line MM; the three-drug combination has shown efficacy in the relapsed setting. This was the first prospective study of the three-drug regimen in front-line MM. Methods: Patients (pts) received eight 3-wk cycles of Bz 1.0–1.3 mg/m2 (d 1, 4, 8, 11), Len 15–25 mg (d 1–14), and dex 40 or 20 mg (d 1, 2, 4, 5, 8, 9, 11, 12) at 5 dose levels (phase I) and the maximum tolerated/planned dose (MTD; phase II). Responding pts could receive maintenance therapy or ASCT. Pts received prophylactic anticoagulants and anti-viral therapy. Primary endpoints were MTD and response rate. Results: 66 pts were treated (35 in phase II). Median age was 58 (range 22–86); 55% were men; 44%/47%/9% had ISS stage I/II/III MM; 68%/23%/9% had IgG/IgA /light chain MM; 57% had any of del 13q, del 17p, t(4;14), and t(11;14). Pts received a median of 10 cycles, including medians of 8, 10, and 8 cycles of Bz, Len, and dex, respectively. Two pts had dex-related DLT (grade 3 hyperglycemia, grade 3 ALT elevation). Phase II dosing was Bz 1.3 mg/m2, Len 25 mg, dex 20 mg. The most common toxicities were sensory neuropathy (80%), fatigue (64%), and constipation (61%), with only 2%, 3%, and 0% grade 3, respectively. Other grade 3/4 toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6%). There was no treatment-related mortality. All pts achieved ≥PR to Len-Bz-dex (Table). Twenty- eight pts (42%) proceeded to ASCT. With median follow-up of 21 months, estimated 18-month PFS and overall survival rates among all pts after Len-Bz-dex with/without ASCT were 75% and 97%, respectively. Quality/rate of response and PFS appeared unaffected by adverse cytogenetic abnormalities. In a 1-yr landmark analysis, PFS was similar between ASCT/non-ASCT pts. Conclusions: Len-Bz-dex demonstrates favorable tolerability and is highly effective in newly diagnosed MM, with no impact seen from adverse cytogenetics on response or PFS, and similar outcomes with or without ASCT. Best responses (%) to Len-Bz-dex All (N=66) Phase II (N=35) CR/nCR 39 57 ≥VGPR 67 74 ≥PR 100 100 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Dana-Farber Cancer Institute, Millennium Amgen, Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Facet Biotech, Johnson & Johnson, Merck, Millennium, Novartis Celgene, Johnson & Johnson, Millennium Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Millennium, Novartis AstraZeneca, Bristol-Myers Squibb, Celgene, Facet Biotech, Glouchester, Millennium, Novartis
Outcome assessment of an oral chemotherapy management clinic: A preliminary report.
Authors: Siu-Fun Wong, Cham Phuong Nguyen, Mark Bounthavong, Kezia Bechtoldt, Elvin Hernandez
Journal: Journal of Clinical Oncology (2012)

105 Background: Many oral chemotherapy (OC) drugs are used in the United States. The dosage regimens of OC increase the risks of nonadherence and drug interactions leading to potential adverse consequences affecting therapeutic outcomes and patient safety. A new OC management clinic was developed where patients (pts) receive comprehensive OC and concurrent medication (CM) education and symptom management services. Follow-up cares are provided to assure continual patient education, monitoring, and safety assessments. Currently there are no published data in OC clinic practice model and outcomes. We design this evaluation to measure the effectiveness of this practice model in patient care. Methods: Pts referred to the OC management clinic by the medical oncologists were enrolled. Pt demographics, depression scores, CMs, and types and outcome of interventions at initial, 3-day, 7-day, and 3-month follow-ups were collected. Adherence and persistence rates were monitored. Results: Retrospective cohort analyses were performed in 30 pts (9 males and 21 females, mean age 64.5). Majority of pts were college and high school graduates; social drinkers; non-smokers; with advanced stage cancer (stage III = 37%, IV = 27%); and no caregiver. Pts were predominately not depressed with Zung self-rating mean score of 36 (SD, 7.72) at baseline. The most common cancer diagnosis was breast (20%), followed by colon (17%), rectal (13%), and lung (6.7%). Capecitabine was the most common agent prescribed. Pts had an average 12.7 CMs and co-morbid conditions of hypertension (43%), chronic pain (43%), and diabetes (37%). Number and complexity of interventions (categories: adverse events (ADR), adherence, drug-interactions, medication error, symptom management) decreased over measured time periods. Complete resolution or improved response seen in 67% of interventions resulting in cost avoidance (49%). Optimal adherence (no missed dose) and persistence (completion of therapy) of OC were detected in at least 67% of patients. Conclusions: This evaluation demonstrated the effectiveness of OC management clinic in delivering early interventions, resulting in decreased incidence of ADR, non-adherence, drug interactions, and medication errors over time.
Late cause-specific mortality in long-term survivors of childhood and adolescent cancer: An update from the Childhood Cancer Survivor Study (CCSS)
Authors: A. C. Mertens, Y. Yasui, Y. Liu, J. P. Neglia, L. L. Robison
Journal: Journal of Clinical Oncology (2005)

8536 Background: The CCSS is a retrospective cohort study designed to determine late effects in children and adolescents diagnosed with cancer. Methods: Eligibility criteria for entry into this cohort are: subjects diagnosed between 1970–1986 at one of 25 consortium centers, before 21 years of age, and survived at least five years after diagnosis. This analysis investigates the mortality rates and the specific cause of death in cohort members. Standardized mortality ratios (SMR) were calculated using age- and sex-specific rates from U.S. Mortality Statistics, National Center for Health Statistics for all causes of death. Information on the underlying cause of death was obtained from death certificates on cases who resided in the United States and had died before Dec 31, 2002. Deaths were categorized as death due to: recurrent disease, treatment sequelae of cancer treatment, or other causes. Results: In this cohort of 20,505 five-year survivors, 2878 (14.0%) subjects died. The highest percentage of deaths was seen in CNS tumor (19.8%) and Hodgkins disease (19.2%), with a relatively low proportion of deaths among five-year survivors of Wilms tumor (5.8%) and neuroblastoma (6.7%). Subjects accrued a total of 342,657 person years (PY) of follow-up. The annual absolute all-cause mortality rate for five-year survivors was 8.4 per 1000 PY. The overall SMR for this cohort was 8.3 (95% CI=8.0, 8.6). SMR were higher in females (13.2, 95% CI=12.5,14.0) than males (6.6, 95% CI=6.3,7.0). SMR differed by type of cancer received, with the highest seen with combination chemotherapy, radiation and surgery (10.1, 95% CI=9.5,10.8). Recurrence of cancer was the leading cause of death in survivors of childhood cancer, with 58% having died from their original cancer diagnosis. Risk of death was also high for treatment sequelae: second neoplasm (14.8%), cardiac-related (7.0%), respiratory disease (1.8%), and other sequelae (16.7%). Conclusion: While recurrent cancer represents a major cause of late mortality, long-term treatment-related complications account for a sizable proportion of deaths. No significant financial relationships to disclose.