tbuckley/cabot-search huggingface dataset:
Phase II multicenter study of erlotinib with radiation therapy (RT) for elderly patients (pts) with esophageal carcinoma (EC): Final report.
Authors: R. V. Iyer, G. Yang, T. E. Schefter, W. Tan, H. R. Nava, C. Levea, A. Litwin, M. Robins, N. I. Khushalani
Journal: Journal of Clinical Oncology (2011)

135 Background: Elderly pts with comorbidities have limited Rx options for localized EC. High EGFR expression correlates with poor response to RT. We examined the safety and efficacy of erlotinib, an oral EGFR tyrosine kinase inhibitor with RT in these pts. Methods: Pts older than 65 yrs ineligible for platinum based Rx with carcinoma of the thoracic esophagus or gastroesophageal junction received erlotinib 150mg PO QD for one year starting D1 of RT [50.4 Gy D1-28 (M-F) at 1.8 Gy per fraction]. Assessments- mucosal response by EGD 4-8 wks post RT; RECIST response by CT q3mo. Endpoints: Primary- overall survival (OS), secondary- quality of life (QOL) using the FACT-E QOL tool, progression free survival (PFS) and toxicity; correlative- pre-treatment tumor EGFR and pEGFR expression by immunohistochemistry (IHC). Results: The study was closed after 17 of planned 35 pts were included due to poor accrual. Baseline characteristics: median age 78 yrs (66-91); gender M/F: 11/6; ECOG PS 0/1/2=2/12/3; stage I-1, II=5, III=7 and IVa= 4; histology: adenocarcinoma 16, squamous cell 1; dysphagia at baseline 13/17 (76%). Median OS was 7.3 months (95% CI: 4.5-22.3) with 12 pts dead (5 alive, 3 still on treatment). Reason for coming off study (n=14): disease progression (n=6), toxicity (n=5), withdrew consent, completed one year of treatment, death from unrelated cause (n=1 each). There were 2 mucosal CRs and one residual carcinoma in situ, 3 partial endoscopic responses of the 9 pts who had post RT endoscopy. Estimated PFS is 5.3 months (95% CI: 2.4-11). Sites of progression- distant 3, locoregional 6, unknown 5 and too early 3. Estimated one year survival is 26 %, 3 pts lived &gt;12 months. Smoking status- current/past/never 3/12/2. Treatment related toxicities (any grade n=or&gt;5) were, rash (16), fatigue (16), diarrhea (11), lymphopenia (10), anorexia (7) and dehydration (6) and 21 grade 3/4 toxicities occurred. IHC results- EGFR, neg: 1/16; pos: 15/16 and pEGFR, neg: 2/16; pos:14/16. Conclusions: For elderly pts with localized EC and no chemotherapy options, erlotinib monotherapy with RT is a tolerable therapy with modest activity. Further studies are needed to define the role of EGFR inhibition with RT in EC. No significant financial relationships to disclose.
Breast cancer disparities in Duval County, Florida.
Authors: Laila Samiian, Dale F. Kraemer, Ryan Butterfield, Sarah Rausch Osian
Journal: Journal of Clinical Oncology (2013)

117 Background: The age-adjusted death rate from breast cancer in Duval County is higher than the national average, with 26 deaths per 100,000 for all women. Breast cancer mortality is 38% higher for black women (37 per 100,000) in Duval County, than for white women (24 per 100,000). We sought to evaluate county specific breast cancer disparity data, in an effort to begin designing effective targeted interventions to reduce the disparities. Methods: Data on female breast cancer cases from 2004-2010 was extracted using the Florida Cancer Data System (FCDS). This data was analyzed using traditional descriptive statistics. Additional classification included health zones within Duval County, race, insurance, and age. Government (Tricare) and private or commercial insurance were combined in one group. The primary outcome was Stage at diagnosis, and time from diagnosis to treatment. Results: Using the FCDS, 6,502 new breast cancers were identified in Duval County from 2004–2010. Of these women, 73% were white, 24% black, 5% Hispanic, 2% Asian, and 2% unknown/other. Health Zone 1 which represents the urban core, has the largest population of Black women with breast cancer (76%), followed by health zone 5 and 4 (35% and 19%). Health Zone 1 has the highest volume of uninsured (10% vs 4% average for zones 2-6), and Medicaid breast cancer patients (8% vs 4% average for zones 2-6), and the lowest number of breast cancer patients with Government/Private insurance (33% vs 56%). Black women had higher percentage of advanced stage IV disease than any other race (8 % vs 4 %, p&lt; .001). Women in Health Zone 1 are more likely to present with stage IV breast cancer than any other health zone in Duval County (10% vs 5%, p&lt;0.01). Medicaid patients followed by the uninsured had the highest rate of stage IV at diagnosis (20% and 12% vs 4%, p&lt;.001). Time from diagnosis to treatment was found to be longest in Black women (29 days vs 26 days, p&lt; .001), Health Zone 1 (30 days vs county average 27 days, p&lt;. 001), and those who were uninsured or had Medicaid (34 days vs 25 days for private insurance, p&lt;0.001). Conclusions: Living in the urban core, black race, lack of insurance, and Medicaid funding was significantly associated with advanced stage at diagnosis and longer time from diagnosis to treatment in Duval County, Florida.
A phase I study of ifosfamide, oxaliplatin, and etoposide (IOE) in pediatric patients with refractory solid tumors.
Authors: L. M. McGregor, S. L. Spunt, D. Ward, J. Wu, C. Billups, S. P. Ivy, V. M. Santana, M. Fouladi, W. L. Furman
Journal: Journal of Clinical Oncology (2011)

9545 Background: Carboplatin and cisplatin are highly active chemotherapeutic agents but have significant toxicities. Oxaliplatin is active in cisplatin-resistant cell lines with a different clinical toxicity profile (less renal, bone marrow, and ototoxicity). The combination of ifosfamide, carboplatin and etoposide is active in pediatric tumors but myelosuppression is dose-limiting. Substituting oxaliplatin in this regimen may allow further dose intensification or be useful in cisplatin-resistant tumors. This study evaluated the safety and estimated the maximum tolerated dose (MTD) of IOE in children with refractory solid tumors. Methods: Oxaliplatin was given intravenously (IV) on day 1 with IV ifosfamide and etoposide on days 1-3 of a 21-day course. Cohorts of 3-6 patients were enrolled at 2 dose levels (see table). A third level with filgrastim or pegfilgrastim (GCSF) support was also evaluated. Results: Twelve evaluable patients (median age 6 yrs, 8 M) received a total of 38 courses (median 2, range 1-7). Two inevaluable patients withdrew during course 1 with no dose-limiting toxicity (DLT). The table summarizes enrollment and DLT. Grade 4 thrombocytopenia occurred in 21 courses with a median of 1 platelet transfusion per course (range 0-10). Febrile neutropenia (one grade 4) complicated 6 courses. There was no hearing loss, >grade 1 elevated creatinine, or >grade 2 neurotoxicity. Of 8 patients with neuroblastoma previously treated with cisplatin, carboplatin, cyclophosphamide, and etoposide, 1 had a partial response after 4 courses, but electively withdrew before response confirmation, and 5 had stable disease (median 4 courses, range 2-7). Conclusions: IOE is tolerable with evidence of antitumor activity, even in some patients with prior cisplatin exposure. Neutropenia is the DLT. The MTD and recommended phase II dose without GCSF is oxaliplatin 130 mg/m2 onday 1, with ifosfamide 1200 mg/m2/day and etoposide 75 mg/m2/day on days 1-3. Dose level Oxaliplatin mg/m2 (day 1) Ifosfamide mg/m2/day (days 1,2,3) Etoposide mg/m2/day (days 1,2,3) No. of patients (No. evaluable) DLT (No. of patients) 1 130 1,500 75 4 (3) Neutropenia (2) 0 130 1,200 75 6 Neutropenia (1) 0 + GCSF 130 1,200 75 4 (3) None
Influence of dual use on outcomes of care for a nationwide cohort of elderly veterans with colorectal cancer: improved outcomes or increased health disparities?
Authors: K. S. Virgo, M. P. Valentine, L. Dauz, L. H. Marietta, B. S. Adams, S. Devarajan, W. E. Longo, F. E. Johnson
Journal: Journal of Clinical Oncology (2008)

6587 Background: Many individuals are concurrently eligible for multiple sources of government-reimbursed health services (e.g. Department of Veterans Affairs (VA) and Medicare). Unclear is the impact on access, continuity of care, and health disparities. We examined the impact of dual eligibility on outcomes for veterans with colorectal cancer initially treated surgically at VA hospitals. Methods: Retrospective analysis of 13 years of nationwide Medicare and VA utilization data were conducted. Included were patients diagnosed with colorectal cancer, surgically treated for cure, and Medicare-eligible at diagnosis. Survival was analyzed using Kaplan-Meier and Cox regression. Results: Of 6,612 patients treated with curative intent, 4,924 (74%) were staged and 4,550 (92%) were eligible. Of these, 77% and 23% had colon and rectal cancer, respectively. The TNM stage distribution was 2.7% 0, 25.9% I, 33.2% II, 24.7% III, and 13.4% IV. Narrowly defining colorectal services, 13.9 percent of inpatients and 19.7 percent of outpatients were dual users. Combining use types, 5.8 percent of all patients were dual users of both service types and 27.9 percent were dual users of either service type. Dual users of either inpatient or outpatient services were more likely to be younger (p < .01), female (p < .05), married/separated (p < .01), of white race (p < .001), living in Northeast/Mid-Atlantic U.S. Census regions (p < .001), and not from metropolitan statistical areas (p < .001). Dual users were more likely to have rectal cancer (26.6% versus 21.2%; p < .001). Early diagnosis (TNM stages 0-II; p < .001) and shorter length of stay (p < .05) favored dual users. Dual users had a reduced hazard of death (-0.874), controlling for stage, histopathologic grade, region, marital status, age, gender, and tumor site. Conclusions: Disparities in access to care have been widely demonstrated, even in the VA where financial barriers are minimized. Here, identified disparities between patients with a single health benefits source and patients with dually eligibility included significantly shorter lengths of stay and an increased likelihood of survival. Whether needless duplication of services occurs among dually eligible patients is under analysis. No significant financial relationships to disclose.
Yttrium-90 microspheres (SIR) verses transarterial chemoembolization (TACE) in the treatment of inoperable metastatic neuroendocrine tumors (NETS).
Authors: Yuhsin V. Wu, Garin Tomaszewski, Adrienne E. Groman, Renuka V. Iyer, Boris W. Kuvshinoff
Journal: Journal of Clinical Oncology (2012)

300 Background: There are limited modalities in the treatment of inoperable liver NET metastases. This study compares the efficacy and safety of liver-directed yttrium-90 microspheres, SIR-spheres, to TACE. Methods: Medical records and axial imaging studies were retrospectively reviewed for all patients with NET liver metastases who underwent SIR or doxorubicin based TACE at our institution from Jan 2001 to Dec 2010. The demographics, immediate effects, and time to radiologic progression were assessed and compared between the two treatment modalities. Results: A total of 99 liver directed treatments were performed on 46 pts (n=19 Y-90, n=27 TACE). Median post-treatment follow-up was 20 months (range 4-103). Pt characteristics including age, performance status, type of primary NET, and systemic therapy were similar in both groups. Pts in the SIR group waited longer from the time of metastatic diagnosis to liver-directed therapy (SIR 35 mo vs. TACE 15 mo (p=0.0015)). SIR patients had less liver burden (65% with &lt;25% liver burden) than TACE patients (23% with &lt;25% liver burden). Immediate treatment response (1-3 mo) was measured radiologically using WHO criteria multiplied by EASL criteria. SIR pts achieved 26% complete response (CR), 51% partial response (PR), 15% stable disease (SD), and 8% progressive disease (PR). TACE pts achieved 13% CR, 59% PR, 8% SD, and 21% PD. SIR (44 mo) had a longer radiologic effect than TACE (12 mo) (p=0.015). SIR patients underwent less treatments (95% with &lt; 2 treatments) than TACE patients (70% with &lt; 2 treatments) (p=0.045). Both treatments were well tolerated with minimal side effects. With only 11/46 (25%) deaths, there was no statistically significant difference in overall survival between the two groups at a median follow up of 104 months (range 12-267). Conclusions: Liver metastasis from NETs can be successfully treated with yttrium-90 radioembolization. Earlier intervention using SIR allows fewer treatments with more durable responses. Prospective studies controlling for rate of disease progression and disease burden are needed to validate these findings.
A randomized study of two dose levels of intravenous (IV) clofarabine (CLO) in the treatment of patients (pts) with higher-risk myelodysplastic syndrome (MDS).
Authors: E. Jabbour, H. Kantarjian, G. Garcia-Manero, F. Ravandi Kashani, G. Borthakur, Z. Estrov, V. Gandhi, A. Byrd, M. Kwari, S. Faderl
Journal: Journal of Clinical Oncology (2010)

6504 Background: CLO is a second-generation deoxyadenosine nucleoside analog with activity in pts with AML. Early reports also suggested activity in MDS. Methods: We designed an adaptively randomized phase II study of IV CLO at 15 vs 30 mg/m2/Dx5 every 4–6 wks. Maximum duration of therapy was 12 cycles. Pts were eligible with MDS and 5% blasts or IPSS int-2 and high-risk, CMML, and RAEB-t by FAB. Growth factor support was permitted. Results: 58 pts (1 RA,15 RAEB-1,26 RAEB-2,9 CMML,7 RAEB-t) were treated. 43 pts (74%) had high- or int-2 risk disease. Median age was 68 yrs. More than 40% of pts were >70 yrs. 15 pts (26%) had history of prior malignancy and 35 (60%) failed prior hypomethylator (10 azacitidine, 17 decitabine, 8 both). Cytogenetics were intermediate in 12 (30%) and poor in 22 (38%). 37 pts received CLO 15 mg/m2 and 21 30 mg/m2. Responses of the 58 evaluable pts are summarized in the Table. Among 35 pts who failed prior hypomethylator, responses were CR in 5 (14%) and HI in 1 (3%). The median number of cycles to response was 1 (1–3). Of 17 pts who received further consolidation cycles, the median number was 1 (1–8). 11 pts (19%) died on study, most commonly related to infections. Common AEs were nausea, vomiting, skin rash, hyperbilirubinemia, and transaminase elevations. Toxicities grade 3 were rare. Acute renal failure occurred in 6 pts (2 [15 mg/m2], 4 [30 mg/m2]) in the context of myelosuppresssion-associated infectious complications. Myelosuppression and hospitalizations for neutropenic fever were common, but prolonged myelosuppression (> 42 days) was rare in responding pts. Infections occurred in 26 (45%) pts and were more frequent in pts receiving CLO at 30 mg/m2. Conclusions: IV CLO achieves a RR of 36% in pts with higher-risk MDS. IV CLO 15 mg/m2 appears as active and less toxic than CLO 30 mg/m2. Future studies should expand exploration of lower doses and combinations with hypomethylating agents. Response Overall N=58 CLO 15 mg/m2 N=37 CLO 30 mg/m2 N=21 Overall (%) 21 (36) 15 (41) 6 (29) CR 15 (26) 10 (27) 5 (24) HI 6 (10) 5 (14) 1 (5) Resistant (%) 26 (45) 17 (46) 9 (43) Death (%) 4-week 7 (12) 4 (11) 3 (15) 8-week 11 (19) 5 (14) 6 (29) 1-year OS (%) 37 37 38 1-year PFS (%) 39 50 25 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis, Wyeth
The impact of modified Glasgow prognostic score on survival in patients with gastric cancer.
Authors: Hironobu Goto, Masanori Tokunaga, Rie Makuuchi, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Yusuke Kinugasa, Yasuhiro Tsubosa, Hideyuki Kanemoto, Katsuhiko Uesaka, Masanori Terashima
Journal: Journal of Clinical Oncology (2013)

104 Background: Modified Glasgow Prognostic Score (mGPS), based on serum C-reactive protein (CRP) and albumin-levels, was reported to be a good prognosticator for survival in patients with lung cancer. However, the role of mGPS in gastric cancer is still controversial. The aim of this study is to clarify the significance of mGPS as a prognosticator in patients with gastric cancer. Methods: This study included 1,062 patients who underwent gastrectomy for gastric cancer at Shizuoka Cancer Center between September 2002 and December 2006. Patients who received neoadjuvant chemotherapy, and those who had other cancers were excluded from the analysis. mGPS is defined by serum CRP level and serum albumin level. Patients with serum CRP level of 1.0mg/dl or lower were classified to mGPS 0 irrespective to the serum albumin level. Patients with elevated serum CRP level (&gt;1.0mg/dl) were classified to mGPS1 or mGPS2 according to the serum albumin level (mGPS1, albumin≥3.5g/dl; mGPS2, albumin&lt;3.5g/dl). We compared relationships between mGPS and clinicopathological characteristics of patients, the incidence of intra-abdominal infectious complications (Clavien-Dindo grade II or more severe), and overall survival. Results: There were 712 male and 350 female patients. The median age was 65 years old. The number of patients classified to the mGPS0, mGPS1, and mGPS2 group were 970 (91.3%), 59 (5.6%), and 33 (3.1%), respectively. The incidences of intra-abdominal infectious complications were 27.1% in mGPS1, and 24.3% in mGPS2, and were significantly higher than that in mGPS0 (9.5%, P&lt; 0.001). Overall five-year survival rates were 74.6% in mGPS0, 61.4% in mGPS1, and 34.6% in mGPS2. The overall survival was significantly worse in patients with mGPS2 than those with mGPS0 or mGPS1 (P&lt;0.001). Conclusions: mGPS was correlated with the incidence of intra-abdominal infectious complications. In addition, mGPS was found to be a prognosticator for survival in patients with gastric cancer. Preoperative nutritional support may lead to reduced incidence of surgical complications and improved survival outcome after gastrectomy in patients with gastric cancer.
Three-year results of stereotactic three dimensional (3-D) conformal multiple dynamic arc radiotherapy for stage I non-small cell lung cancer (NSCLC) using a linear accelerator unified with self-moving CT scanner (Linac-CT unit) and patient’s self-breath and beam control technique
Authors: H. Onishi, T. Komiyama, K. Kuriyama, S. Tanaka, K. Marino, T. Araki
Journal: Journal of Clinical Oncology (2005)

7220 Background: The early stage lung cancer patients are increasingly detected due to the popularization of CT examination. The purpose of this study is to evaluate results in 3 years of our novel irradiation technique for stage I non-small-cell lung cancer (NSCLC): 3-D stereotactic irradiation with patient’s self-breath-hold and self-switching radiation-beam on and off. Methods: Fifty-four patients with stage I (26 T1N0, 28 T2N0) NSCLC were enrolled. The patients ranged from 64 to 92 years of age with a median of 77 years. The histology was adenocarcinoma in 29, squamous cell carcinoma in 18, and unclassified in 7 cases. The three-dimensional treatment plans were made using 10 different non-coplanar dynamic arcs. A total dose of 60Gy at the minimum point of planning target volume (PTV) in 10 fractions was delivered with 6MV X-ray. Patients exercised well in holding their breath at a reproducible position. After the isocenter of the PTV was adjusted to the planned position using CT combined with the linac, patients hold the breath and turned the radiation-beam on and off repeatedly at their own agreeable pace by a handheld switch. Results: Follow up period ranged from 12 to 48 (median=24) months. CR and PR rates were 31% and 61%, respectively. Pulmonary complications of NCI-CTC grade greater than 2 were noted in 2 patients. Six patients (1/26 stage IA cases and 4/28 stage IB cases) developed local progression, and the two-year local control rate was 83%. Ten patients (3/26 stage IA cases and 7/28 stage IB cases) developed regional lymph nodes or distant metastases. Two-year overall and cause-specific survival rates of total cases were 61% and 89%, respectively. In medically operable cases, the two-year overall survival rate was 87%. Conclusions: This new irradiation technique permitted us to perform the high dose stereotactic irradiation surely and safely. A satisfactory local control and survival rate in medically operable patients almost equal to general results by surgery can be achieved with minimal symptomatic complications for stage I NSCLC. No significant financial relationships to disclose.
A case of the utilization of genomic information in the management of metastatic colorectal cancer.
Authors: Renata D'Alpino Peixoto, Yvonne Li, Erin Pleasance, Stephen Yip, Yongjun Zhao, Jacquie Schein, Yaoqing Shen, Howard John Lim, Daniel John Renouf, Karen A. Gelmon, David Huntsman, Steven Jones, Marco Marra, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2013)

444 Background: Anectodal success using genomic information to personalize and guide cancer therapy in rare tumours has been reported. This is a case report of the use of genomic information in the management of metastatic colorectal cancer. Methods: A 31 year old female presented with metastatic disease from the colon to the liver and retroperitoneal lymph nodes. She was treated with aspirin and 4 cycles of 5FU/Irinotecan/Bevacizumab before blood and liver biopsies were taken. Sections from the primary tissue embedded in paraffin were compared to metastatic disease in the liver and blood. Two platforms were used: a targeted deep sequencing of 46 genes via a cancer specific amplicon assay and whole genome sequencing and RNA sequencing followed by bioinformatics approaches were employed to identify genes with somatic variants, copy number variations, losses of heterozygosity, structural variation, and expression changes. Results: Genome sequencing followed by bioinformatics analysis detected ~100 somatic mutations, ~100 amplified genes with increased expression, and ~90 down-regulated genes with copy number loss in the metastasis. Other interesting observations included increased allelic frequencies in BRAF V600E, and SMAD4 R361C as well as high gene copy amplifications in VEGFA and MAGI from the primary to the metastasis, and lack of somatic mutation in KRAS. Conclusions: The upregulation of VEGF pathways from the primary compared to the metastasis suggests a significant shift in tumour biology likely as a result of the bevacizumab and COX-2 inhibition from aspirin; this may have implications when anti-VEGF therapy is withdrawn. The BRAF mutation and wild type KRAS status may suggest that combination of a BRAF inhibitor with EGFR inhibition is warranted. This information demonstrated the benefit of therapy on a genomic level and aided in determining possible future targets and modifications to conventional therapy.