tbuckley/cabot-search huggingface dataset:
Prophylaxis of central nervous system (CNS) relapse in high-risk lymphoma patients with liposomal cytarabine.
Authors: M. Sobocinski, W. Jurczak, J. Dzietczenia, T. Ogorka, S. Fornagiel, A. Giza, B. Piatkowska-Jakubas, B. Kumiega, B. Blajer-Olszewska, I. I. C. Cedrych, G. Mazur, A. B. Skotnicki
Journal: Journal of Clinical Oncology (2011)

e18520 Background: CNS relapse is a life threatening complication of 5-10% high risk aggressive NHL. Safety and efficacy of Liposomal Cytarabine as CNS relapse prophylaxis was assessed in a retrospective study. Methods: 60 high risk NHL patients (43 DLBCL, 8 Lymphoblastic lymphoma, 4 PTCL, 3 Burkitt lymphoma and 2 MCL) received Liposomal Cytarabine prophylaxis during first line therapy (n=58, 96%) or systemic relapse (n=2, 4%). High risk was defined as presence at least 2 of the following: elevated LDH (n=53, 88%), involvement of 2 or more extranodal sites (n=20, 33%), IPI 3-5 (n=36, 61%) and specific lymphoma localizations (testis, vertebral column, orbits, sinuses, large mediastinal tumors over 10 cm in diameter; n=36, 60%). None of the patients had neurological symptoms at diagnosis, nor any abnormalities in imaging studies or cerebrospinal fluid analysis (average cellularity 2.5/mm3, range 0-9). Results: Liposomal cytarabine (3.4 doses, range 2-6) was administered at a time of scheduled chemotherapy cycles , eliminating necessity for additional hospital admissions every 2 (n=47) or 3 (n=13) weeks. Moderate side effects were reported in 17 (26%) patients: WHO grade 1-2 headache, nausea, dizziness or fever. Three patients developed grade 3 headache or transient neurological dysfunction. After medium observation time of 14(1– 32) months 54/60 (90%) patients were alive, without CNS relapse. Only 2 (3.3%) cases with late CNS relapse were reported (a systemic/CNS relapse of lymphoblastic lymphoma and isolated CNS relapse in DLBCL patient) after 8 and 19 months respectively. Conclusions: 1)Liposomal Cytarabine is well tolerated, with mild or no adverse events. Its prolonged action allows it to be incorporated into a standard systemic anti-lymphoma therapy, without the necessity of additional hospital admissions. 2) In a described cohort of high risk lymphoma patients, Liposomal Cytarabine reduced the risk of CNS relapse to 3% (2/60 cases).
Approval of new drugs in Brazil.
Authors: Patricia Martins Passos, Patricia Martins Passos, Marcos Coelho Simoes Travassos Soares
Journal: Journal of Clinical Oncology (2015)

e17513 Background: Each country has its own laws on the approval of new drugs. Some countries are at the forefront of research for the development of new drugs and as they developed products bring a real gain for a particular group of patients, approvals are systematic. In developing countries, these approvals typically take considerably longer. This is because for many reasons, but we can highlight at least two major reasons; 1 - financial reasons, as control of government costs and inflation control and 2 - operational reasons, often reflected as the ineffectiveness of the state to follow with the approval processes. Brazil fits these two aspects, controlling costs and ineffectiveness of the regulatory agency, ANVISA. The reflection of this is the long time to approve new products in Brazil, where new drugs used for the treatment of cancer follow the same bureaucracy and have the same relevance of other drugs that have several treatment options. Methods: The aim of this study was to evaluate the time required for approval of new molecules in Brazil after approval by the FDA and discuss the impact of time on the quality of life of cancer patients. The analysis were performed with 27 drugs approved in Brazil in the last 10 years and all new drugs approved by the FDA that are not in the Brazilian market due to lack of registration. Results: In the last decade, ANVISA took about two years to approve a new drug for the treatment of cancer in Brazil after the same drug has been approved by the FDA in the United States. Meanwhile, more than 10 molecules that have entered the American market are still waiting for license to market in Brazil, as Afatinib, Aflibercept, Bendamustine and Lenalidomide. Conclusions: The Brazilian government has indicated a change in this scenario, however, little has been discussed. It is evident that the incorporation of new drugs significantly impacts the cost of health care, but this discussion is necessary and urgent.
The well-being of adult children while caring for a parent in home hospice: Evaluation of an automated remote monitoring and coaching system.
Authors: Kathi Mooney, Patricia Berry, Jacquee Blaz, Gary Donaldson
Journal: Journal of Clinical Oncology (2015)

222 Background: Health and well-being often deteriorates for family caregivers providing home hospice care. This includes adult children managing multiple demands while supporting their parent to remain at home. Automated remote monitoring of patient symptoms has shown promise in home cancer care and could be extended for monitoring and supporting the wellbeing of adult child caregivers (ACC) providing care to their parent at home. Methods: In a RCT, 97 ACCs were monitored using a telephone based automated reporting and coaching system, and randomly assigned to the ACC care intervention (Rx) (N = 51) or usual care (UC) (N = 46). All ACCs were asked to call the system daily reporting presence and severity (0-10 scale) of their own fatigue, poor sleep, depressed mood, anxiety and interference with normal activities. The Rx ACCs received automated tailored coaching based on reported patterns of moderate to severe symptom levels and alert reports were also sent to their hospice nurse. Results: ACCs were females (78%) with a mean age of 51. There were no differences between groups on any demographic or baseline measures. Utilizing negative binomial modeling, Rx ACCs had significantly fewer days/week of moderate-severe symptoms overall (.6 vs 2.4, p &lt; .001) and for each individual symptom (all p &lt; .001). Among those attempting to maintain work, Rx ACCs were able to work 80% of work days and UC ACCs worked 68% of work days. Six weeks after their parent’s death, there was a statistical trend (p = .07) for Rx ACCs to be less depressed than UC ACCs (11.94 vs 18.04). This is a clinically significant finding as UC ACCs’ CESD scores were at the clinically actionable level ( &gt; 16) for referral for evaluation of depression. Rx ACCs’ CESD scores had dropped an average of 1.37 points below their baseline whereas UC ACCs’ scores had increased an average of 3.86 points from baseline at 6 weeks post death. Conclusions: Automated remote monitoring and coaching for adult child family caregivers offers impressive benefit in reducing the physical burden and psychosocial distress of caregiving during and after parental hospice care. Clinical trial information: NCT02112461.
Survival outcomes of nonoperative therapy (NOT) alone versus NOT followed by surgery (NOTS) in patients with esophageal cancer (EC): SEER analysis 2000-2007.
Authors: N. F. Saba, H. M. Kim, B. F. El-Rayes, S. A. Kono, S. S. Ramalingam, T. K. Owonikoko, J. C. Landry, D. L. Miller, D. M. Shin, F. R. Khuri, M. Goodman
Journal: Journal of Clinical Oncology (2011)

e14569 Background: It remains unclear if surgery following (NOT) is needed in patients with localized EC. This population-based analysis compared survival of patients receiving NOT alone to patients that received NOT followed by surgery (NOTS). Methods: Incident cases of EC were identified from the Surveillance Epidemiology and End Results (SEER) database and included patients under 70 years age, diagnosed with stage III or IVa (AJCC 6th ed) EC between 2000 to 2007. Patients with multiple primary cancers were excluded. Patients were grouped by treatment as NOT versus NOTS. Although chemotherapy information is not available, it is reasonable to assume that those who underwent radiation received essentially NOT. The two groups were compared with respect to their clinical and demographic characteristics. Relative survival (RS) was defined as the observed survival among cancer patients divided by the expected survival in the general population with the same age, sex and race characteristics. All RS estimates were accompanied by 95% confidence intervals (CIs). Results: A total of 1,449 patients were included, 1,082 (74.7%) had NOT and 367 (25.3%) had NOTS. The NOT group included significantly greater number of pts over 60 years of age (48% versus 35%, p=0.009), African-Americans (AA) (11% versus 5%, p<0.001) and squamous cell (SC) (34% versus 16%, p<0.001). The NOT group had lower (p<0.05) 36-month RS (27.3%, 95% CI 23.5%-31.3%) compared to NOTS (38.7%, 95% CI: 30.8%-46.4%). This difference in RS between the two treatment groups was more pronounced among older patients, males, AAs, and those with SC histology and was more similar across stage and grade categories. Conclusions: The observed difference in RS between the two groups appears present in all population strata and suggests a benefit to adding surgery. Limitations include lack of chemotherapy data, and the inability to take into account co-morbidities. Our findings stress the need for additional randomized trials or meta-analyses to better define the role of surgery in patients with locally advanced EC treated non-operatively.
[<sup>18</sup>F]fluoro-L-thymidine (FLT) uptake in baseline positron emission tomography (PET) as a prognostic marker in patients with advanced non-small cell lung cancer (NSCLC) treated first-line with erlotinib.
Authors: M. Scheffler, T. Zander, L. Nogova, C. Kobe, D. Kahraman, M. Dietlein, I. Papachristou, S. Querings, E. Stoelben, W. Engel-Riedel, B. Neumaier, J. Wolf
Journal: Journal of Clinical Oncology (2011)

7591 Background: Since the introduction of targeted therapy into the treatment of advanced NSCLC molecular imaging tools gain in importance for assessment of pharmacodynamics, prognosis and prediction of therapeutic outcome. We evaluated the prognostic value of 3'-deoxy-3'-[18F]fluoro-L-thymidine (FLT) uptake measured by positron emission tomography (PET) as a noninvasive proliferation marker in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. Methods: We retrospectively analyzed FLT uptake in 41 chemonaive patients with advanced NSCLC (stage IV) treated with erlotinib first-line prior to systemic therapy. The peak SUV of the lesion with the highest SUV (SUVpeak) as well as sex, age, ECOG performance state at presentation, EGFR mutational status and adenocarcinoma/BAC histology were analyzed in univariate analysis using Kaplan-Meier statistics and log rank test for its association with survival. Multivariate analysis was performed using Cox regression. Results: Median follow-up was 21.9 months. In univariate analysis, patients with an SUVpeak ≤3.1 had a significantly better overall survival (15.67 months [95% CI 6.4 to 25 months]) compared to patients with an SUVpeak >3.1 (3.2 months [95% CI 0 to 8.2 months]) (p=0.008, log rank). In addition, age was significantly associated with overall survival (p=0.046 log rank test). In this cohort none of the clinical parameters gender, histology, ECOG performance status or EGFR mutational status were significantly associated with overall survival. In multivariate analysis including age and SUVpeak, SUVpeak was a significantly strong prognostic factor for overall survival (p=0.020). Conclusions: FLT uptake of the most active tumor manifestation site is a strong prognostic marker for overall survival among patients with advanced NSCLC treated with erlotinib first-line.
Overtreatment of prostate cancer in Florida.
Authors: Scott Michael Gilbert, Carl Henriksen
Journal: Journal of Clinical Oncology (2013)

140 Background: Although most evidence suggests that older men with localized prostate cancer do not benefit from treatment, many men with relatively limited (&lt;10 years) life expectancy continue to seek and receive treatment. Given mounting concerns regarding overtreatment, we sought to better understand geographic differences in the potential overtreatment of prostate cancer. Methods: We used the Florida Cancer Data System (FCDS) to identify treated and untreated cases of prostate cancer between 2004-2007. The FCDS is a large statewide cancer registry that collects clinical, demographic and treatment information for incident cancers. We defined potential overtreatment according to risk of disease (Gleason &lt;=7, stage T2 and less) and age ( &gt;75 years). We used Geographic Information Systems (GIS) to map differences in overtreatment across Health Service Areas (HSAs) in Florida. We then examined the relationship between the number of urologists and radiation oncologists reported in the Area Resource File and potential overtreatment using linear regression models. All analyses were performed using standard statistical software (SAS and ArcGIS). Results: Among men older than 75 years (n=10,411), 9.2% received surgery, 38.7% received external radiation therapy, 15% received brachytherapy and 10.5% received primary androgen deprivation therapy; only 26.6% of patients were managed expectantly. Overtreatment varied significantly across Florida. Among some HSA clusters in Central and Panhandle Florida, overtreatment was estimated in less than 21.6 % of cases. Much higher rates of overtreatment (36-52% of cases) was observed among other HSAs, particularly in South Florida. Although the number of urologists (per 100,000 male population) was not associated with an increased propensity for overtreatment in regression models, the concentration of radiation oncologists was associated with an increase of 0.64 cases of overtreatment (per 100,000 men) for each additional radiation oncologist (p&lt;0.0001). Conclusions: Treatment among older men with low- and intermediate-risk localized prostate cancer is more common than expectant management. The propensity for overtreatment varies considerably according to geographic and healthcare market factors.
The role of early response after 40-46 Gy concurrent radiochemotherapy (RTCT) on outcomes in locally advanced non-small cell lung carcinoma (NSCLC).
Authors: Y. Vano, C. Ortholan, P. Bondiau, J. Mouroux, C. Hebert, P. Hofman, P. Marcy, N. Venissac, M. Poudenx
Journal: Journal of Clinical Oncology (2011)

e17503
Improving oncology quality through the implementation of evidence-based clinical pathways in a payer’s oncology network.
Authors: Daniel McCrone, Dudley Gill, Cecilia Tran, Michael Sturgill
Journal: Journal of Clinical Oncology (2013)

161 Background: Physicians and health plans are collaboratively exploring clinical pathway strategies to improve patient outcomes, reduce treatment variation, and reduce oncology cost. One landmark study found that 33.2% of insured patients did not receive guideline cancer therapy. Additional studies have demonstrated that the use of pathways can lower the cost of care and that oncologist participation is a critical element for success. New Century Health (NCH), in partnership with a leading health plan and one of its Midwestern oncology networks, had two quality goals with the implementation of a chemotherapy prior authorization system: review all chemotherapy regimens for all patients and measure treatment plan adherence to evidence-based clinical pathways. Methods: As one component of a mandatory chemotherapy prior-authorization program, an online prior authorization system was used by oncology practices to submit chemotherapy treatment plans to NCH for approval. The system captured detailed patient clinical information and measured compendium and preferred pathway adherence rates. These data were shared with participating oncology practices on a quarterly basis. For analysis, an average Baseline compendium adherence rate was determined reflecting participating practices for six cancer diagnoses (Breast, Colon, Lung, Lymphoma, Multiple Myeloma, and Prostate). The Baseline rate was compared to the Review period rate. Results: A comparison of the Review and Baseline period metrics indicated a statistically significant increase in the level of compendium-based chemotherapy treatment plans submitted by participating providers. Conclusions: Implementation of an oncology prior authorization system that measures compendia-based adherence rates is associated with increased levels of evidence-based chemotherapy treatment plans by participating providers. [Table: see text]
A phase II trial of neoadjuvant ABI-007, carboplatin, and gemcitabine (ACG) in patients with locally advanced carcinoma of the bladder.
Authors: D. C. Smith, P. Grivas, S. Daignault, K. Hafez, D. P. Wood, C. T. Lee, J. E. Montie, A. Z. Weizer, J. Montgomery, M. Hussain
Journal: Journal of Clinical Oncology (2011)

244 Background: Neoadjuvant cisplatin-based chemotherapy benefits patients with bladder cancer, particularly in the 30% with pathologic complete response (pCR) at cystectomy. Many patients with bladder cancer are not candidates for cisplatin. Taxane-based regimens have activity in urothelial cancer. ABI-007 is an albumin-bound paclitaxel with increased activity and decreased toxicity compared to standard paclitaxel preparations. Methods: Eligible pts have T 2-4, N 0 ,M 0 or T any, N 1- 3, M 0 bladder cancer with ECOG PS 0-1, and adequate marrow (granulocyte count &gt; 1,500/mm 3 , platelet &gt; 100,000/mm 3 , and hemoglobin &gt; 9.0 g/dl), hepatic (transaminases &lt; 2.5 X upper limit of normal, alkaline phosphatase &lt; 2.5 X upper limit of normal, and bilirubin &lt; 1.5 mg/dl) and renal function (serum creatinine &lt; 2.0 mg/dl and/or creatinine clearance &gt; 40 ml/min). Pts are treated with intravenous ABI-007 260 mg/m 2 and carboplatin (target area under the curve=5) on day 1 with gemcitabine 800 mg/m 2 on days 1 and 8, followed by radical cystectomy after three cycles of therapy. The primary study endpoint is the proportion of patients with pCR at cystectomy. Results: 27 patients have been enrolled. By clinical staging, 20 had T2 disease, 5 had T3, 2 had T4, and 2 had nodal enlargement. All are evaluable for toxicity with 22 evaluable for response (exclusions-3 for change in dose schedule, 1 each for refusal of cystectomy and withdrawal from study). 25/27 patients received all three cycles (78 total cycles) with doses reduced in 26 cycles for toxicity. All patients had transient grade 3-4 neutropenia and 17 received filgrastim, but only two had febrile neutropenia. Six pts had pCR with an additional 5 having residual carcinoma in situ (CIS) and 1 with T1 disease at cystectomy. 54% of evaluable patients had no muscle invasive disease at cystectomy. Conclusions: Neoajuvant ACG is active in bladder cancer with pCR rate nearing 30% and nearly as many patients with CIS but no residual invasive disease. Marrow toxicity is significant but manageable. [Table: see text]
Phase 1 trial of monthly doses of the human anti-CTLA4 monoclonal antibody CP-675,206 in patients with advanced melanoma
Authors: A. Ribas, V. A. Bozon, G. Lopez-Berestein, D. Pavlov, J. M. Reuben, C. A. Parker, E. Seja, J. A. Glaspy, J. Gomez-Navarro, L. H. Camacho
Journal: Journal of Clinical Oncology (2005)

7524 Background: CP-675,206 had a manageable safety profile and antitumor activity in a prior Single-Dose phase I trial (Camacho et al. ProcASCO 2004). The safety, tolerability and recommended phase II dose of Monthly CP-675,206 was assessed in this study. Methods: Eligibility: stage IIIc-IV melanoma, measurable disease, ECOG 0–1, no active brain metastasis. 3 dose levels were sequentially tested. Results: 14 pts (9 M, 5 F) mean age 55 (range 42–67) were enrolled (3 at 3.0 mg/kg, 3 at 6.0 mg/kg, 8 at 10.0 mg/kg). 57% had stage IVc. All pts at 3 and 6 mg/kg received 2 doses, at 10 mg/kg received a median of 4.5 (range 2–8) monthly doses for a total of 51 doses administered. No G4 treatment-related toxicities were observed. G3 diarrhea in 1 pt at 3 mg/kg, none at 6 mg/kg, 2 pts at 10 mg/kg. G2 treatment-related adverse events included 4 dermatitis, and 1 each of diarrhea, pruritus, hypothyroidism, urticaria, and myalgias. Preliminary PK analysis suggests little accumulation of CP-675,206 with multiple dosing and no evidence of HAHA. 1 pt at 10 mg/kg has an ongoing response in multiple in-transit metastasis and continues on therapy after 10 doses. PK at this dose suggests maintained therapeutic plasma levels of CP-675,206. Despite the 10 mo CTLA4 blockade, toxicities in this pt have been limited to autoimmune thyroiditis requiring hormonal replacement, de novo vitiligo and chronic pruritus. 4 biopsies of residual lesions revealed no melanoma in most areas with a dermo-epidermal CD3/CD8 lymphocytic infiltrate. An area with viable melanoma cells had a prominent intratumoral infiltrate by CD3/CD8 lymphocytes. Another pt at 10 mg/kg developed new brain metastasis at 2 mo. After XRT, no new metastases were noted for 7 mo with stable lymph node metastasis. Conclusions: CP-675,206 can be safely administered and has antitumor activity in melanoma at monthly doses consistent with prolonged CTLA4 blockade. Tumor regression is associated with intratumoral infiltration by cytotoxic T lymphocytes (CTL). 10 mg/kg every month is the recommended dose for further exploration in an ongoing Phase 2 trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer Pfizer
Effect of the revised AJCC staging (7th edition) on prognostic stratification in patients with surgically resected esophageal squamous cell carcinoma.
Authors: Gloria Terase Minella, James D. Luketich, Jon M. Davison, Dan Winger, Ryan M. Levy, Michael K. Gibson, Arjun Pennathur, Katie Sue Nason
Journal: Journal of Clinical Oncology (2013)

4103 Background: Historically, the AJCC esophageal staging system separated patients into prognostic groups based on tumor, node, and metastasis (TNM) classifications. In 2010, the 7th edition (AJCC 7) significantly modified esophageal squamous cell cancer (ESCC) staging by separating ESCC from adenocarcinoma, incorporating tumor grade and location for node negative cancers, and stratifying by the number of involved regional nodes for node positive cancers. Our study aim was to determine whether AJCC 7 stage groupings provide improved survival prognostication compared to 6th edition (AJCC 6). Methods: We abstracted pathology and survival for 150 consecutive ESCC patients who underwent esophagectomy (1994-2012); 44 patients received induction therapy. AJCC 6 and AJCC 7 stages were assigned and overall survival analyzed from esophagectomy to death or most recent alive contact and censored at 60 months. Discriminatory ability and homogeneity within subgroups was assessed with Kaplan-Meier curves and monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) used to assess model fit. Results: Compared to AJCC 6, AJCC 7 upstaged 32 patients from IIa to IIb and 1 patient from IIb to IIIa and downstaged 3 patients from stage IIa to Ib. AJCC 7 subclassified 42 AJCC 6 stage III patients (17 IIIa, 10 IIIb and 15 IIIC). Median overall survival was 19 months. Kaplan-Meier log-rank statistic indicated stronger differentiation in AJCC 7 (19.8 vs 29.7). Cox regression likelihood (19.5 vs 26.1), AIC (618.1 vs 611.6), and linear trend chi-squared at 24- (17.5 vs 24.3) and 60-months (13.3 vs 17.3), were all superior for AJCC 7 stage groupings (AJCC 6 vs AJCC 7, respectively). Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, tumor location and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected ESCC patients, including patients who received induction therapy.