tbuckley/cabot-search huggingface dataset:
Incorporating trans-arterial radioembolization (TARE) in the treatment of metastatic pancreatic adenocarcioma: A single center experience.
Authors: Alexander Y. Kim, Keith Robert Unger, Michael J. Pishvaian
Journal: Journal of Clinical Oncology (2016)

346 Background: There is a lack of data on the potential efficacy of the incorporation of trans-arterial radioembolization (TARE) for metastatic pancreatic adenocarcinoma. We retrospectively evaluated the efficacy of TARE in the management of patients with liver dominant metastatic pancreatic adenocarcinoma Methods: Sixteen patients were treated with concurrent systemic therapy and TARE for liver-dominant pancreatic adenocarcinoma from February, 2014 to August, 2015. Electronic chart review was performed for this group of patients to assess response Results: Eleven male and 5 female patients were treated for liver dominant metastatic pancreatic adenocarcinoma with Yttrium-90 resin microspheres. The average age was 64 (50 - 77). All patients were treated with at least one line of systemic therapy. Five had prior or concurrent SBRT treatment for the primary lesion. Eleven patients had extra-hepatic disease with evidence of nodal, pulmonary and/or omental disease on pretreatment imaging. All patients had adequate hepatic reserve and functional status at treatment. Eight of the 16 patients were alive at the time of analysis. The median overall survival from diagnosis of liver metastases to time of analysis is 22 months (11 – 50, 95% CI). The median time of survival from TARE is 12.5 months (4 – not reached, 95% CI). The estimated survival rate at 6 months, 1 year, 2 year and 3 years from diagnosis is 100%, 84%, 39% and 26%. Follow up imaging was available on 13 patients. Local PR, SD and PD based on RECIST criteria were seen in 4 (31%), 7 (54%) and 2 (15%) patients. The average local and systemic PFS was 4.9 and 3.4 months, respectively Conclusions: We found promising results for the incorporation of TARE in the treatment of patients with metastatic pancreatic adenocarcinoma. In our cohort, the median overall survival from the time of metastatic diagnosis was 22 months, a significant improvement from the expected median survival. Although our data is promising, there are inherent weaknesses of our study due to the small number of patients and its retrospective nature. Further studies are needed to validate our findings. For this purpose, a prospective trial is currently being in development.
Final phase II results of NCI 6981: A phase I/II study of sorafenib (S) plus gemcitabine (GEM) and capecitabine (CAP) for advanced renal cell carcinoma (RCC).
Authors: S. T. Tagawa, A. Saran, N. H. Akhtar, S. Goel, G. Mileo, S. Kung, H. Beltran, M. I. Milowsky, M. Mazumdar, J. J. Wright, D. M. Nanus
Journal: Journal of Clinical Oncology (2011)

e15165 Background: The phase I portion defined toxicity and recommended phase II dose (RP2D): S 200 mg BID D1-21, GEM 750 mg/m2 D1 & D8, and CAP 415 mg/m2 BID D1-D14 in 21-day cycles and demonstrated initial signs of efficacy, with RECIST response rate (RR) 29%, median progression free survival (PFS) 7.5 months (mo), and median overall survival (OS) not reached with follow up of 28.8 mo (Tagawa et al, Am J Clin Oncol 2010) Methods: In this NCI-CTEP sponsored study, a Simon 2-stage, single-arm study of patients (pts) with advanced RCC of any histology with measurable disease who received up to 1 prior immunotherapy and up to 2 prior targeted therapies (excluding sorafenib) was performed at the RP2D. The primary endpoint of the study was RR by RECIST 1.0. At least 2 confirmed responses in the 1st 12 pts were necessary to proceed to the 2nd stage of an additional 23 pts. Results: 11 pts (median age 58) were enrolled: 91% ECOG PS 0-1; 3-clear cell, 5-papillary, 1-chromophobe, and 2-unclassified; 27% with sarcomatoid differentiation; 36% with extrapulmonary visceral metastases; MSK good risk-3, intermediate-6, poor risk-2. Nine pts were treatment naïve, 1 progressed on cytokines, 1 on sunitinib, and 1 on pazopanib. Similar to the phase I study, no significant attributable Gr >2 non-heme or Gr >3 heme toxicity was seen. 3 pts developed Gr 2 hand/foot syndrome and 1 had Gr 2 hypertension. By RECIST, 1 pt had >30% reduction after 9 cycles that was not confirmed after 12 cycles, 7 had SD, and 3 PD and enrollment was stopped based on futility. 55% had some improvement in measurable disease. Median PFS was 4.1 mo [95% CI 3.2, 5.0] and median OS was 17.8 mo [7.6, 28.0]. In an analysis including phase I pts treated at the MTD (n=17), RR is 12.5%, PFS 5.0 mo, OS 18.3 mo. Overall, in the phase I/II study (all doses), RR is 16%, PFS 6.1 mo, OS 18.3 mo. Conclusions: The combination of S plus GEM and CAP is tolerated at attenuated doses in a U.S. population. While acknowledging that RR may not be the most accurate judge of efficacy in the current era, it appears that initial encouraging anti-tumor activity seen in the phase I portion (by RECIST) and that demonstrated by the Spanish group was not confirmed in the phase II component of our study.
Younger survivors' insurance concerns.
Authors: Ruth Rechis, Stephanie Nutt, Carla Bann, Linda Squiers
Journal: Journal of Clinical Oncology (2013)

277 Background: Each year approximately 70,000 adolescents and young adults (AYAs) are diagnosed with cancer—many of whom will experience insurance issues. While the Affordable Care Act (ACA) is intended to address many insurance issues, cancer survivors are dealing with these issues now. Methods: From June to December 2012, LIVESTRONG conducted an online survey modeled after the Medical Expenditure Panel Survey (MEPS) Cancer Survivorship Supplement to understand the practical concerns of survivors, including insurance issues. Analyses here includes 1,209 AYA respondents compared to 3,557 respondents diagnosed over the age 40. Results: Overwhelmingly, participants in this survey had insurance at some point since diagnosis (94%), yet AYAs were significantly less likely to have had insurance (p&lt;.001). AYAs were significantly more likely to have experienced issues with insurance (Table), but both groups were unlikely to have received help for negative effects due to insurance (AYA = 30%; non-AYAs=25%). In terms of help seeking, AYAs were significantly more likely to have received help from family members (p&lt;.001). Both groups indicated a number of reasons for not seeking help for insurance issues - most frequently citing "I have addressed this on my own” (18%) and “I tried to receive help but was unsuccessful” (17%). Conclusions: Results from this study indicate there are many issues related to insurance coverage for survivors, which in most cases were significantly more impactful for AYA survivors. Additionally, there are many challenges survivors face in terms of getting their insurance needs met. Finally, it’s important to consider the full implications of what it means for AYAs to be reliant on family members – for both the survivor and their family. The AYA period often denotes a time that individuals are trying to separate from family, yet cancer may make this separation considerably more challenging. While ACA is intended to address some of these issues, cancer survivors are dealing with insurance issues now, and we should consider how to address these issues more quickly. [Table: see text]
Phase I study of intravesical recombinant fowlpox-GM-CSF (rF-GMCSF) and/or recombinant Fowlpox-TRICOM (rF-TRICOM) in patients with advanced bladder cancer
Authors: E. C. Lattime, R. E. Weiss, M. N. Stein, M. Wojtowicz, M. B. Todd, R. A. Morton, J. Hwang, E. Bancila, T. Ben-Menachem, R. S. Dipaola
Journal: Journal of Clinical Oncology (2005)

4755 Background: We have shown that TCC biopsies express high levels of IL10 mRNA and in preclinical models that this IL10 suppresses antigen presenting cell (APC) activity and antitumor immunity. To enhance APC activity and antitumor immunity, we are accruing a Phase I study of intravesical recombinant fowlpox encoding GMCSF, or LFA-3, ICAM-1, B7.1 (TRICOM) genes in pts with advanced bladder cancer. Methods: In this three arm study (A. rF-GMCSF, B. rF-TRICOM, C. Combination), pts with bladder cancer scheduled for cystectomy receive 4 weekly doses of intravesical virus (3 pts per dose level, initial dose 5.7 - 7 X 107 PFU). Study endpoints are toxicity, MTD, bioavailability (degree of gene transfer in cystectomy specimen); immunity to vector and reporter genes; and local cellular and cytokine responses in the bladder wall. Results: Six pts with high grade invasive bladder cancer have been treated in this ongoing study. Overall, treatment was well tolerated. 3/3 Arm B pts experienced transient elevations in liver transaminases with 1/3 reaching DLT. 2/3 each Arm A, B pts had similar stage and grade disease in cystectomy specimen as in pretreatment biopsy. 1/3 Arm A pts had no tumor identified in the bladder or nodes following treatment. 1/3 Arm B pts had no residual tumor in the bladder but 2/8 positive nodes. H&E staining of the cystectomy specimen showed variable immune cell infiltration of bladder wall and enlarged lymph nodes in both arms. Conclusions: Pts receiving intravesical rF-GMCSF and rF-TRICOM at the initial dose level tolerated therapy. Pathology showed variable immune infiltration of bladder wall, tumor, and enlarged draining lymph nodes. Bioavailability, immunohistochemistry and immune studies are ongoing. No significant financial relationships to disclose.
Whole-brain radiotherapy: Prognostic factors and preliminary results of a radiation boost delivered through a conventional linear accelerator.
Authors: A. Assouline, A. Levy, C. Chargari, I. Lamproglou, J. Mazeron, C. Krzisch
Journal: Journal of Clinical Oncology (2010)

e12531 Background: Assess prognostic factors for overall survival and the potential benefit of a radiation boost delivered through a conventional linear accelerator by conformal method after whole brain radiation therapy (WBRT) for brain metastasis. Methods: From 2002 to 2006, a retrospective analysis was made from 250 unselected and consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Five potential prognostic factors have been studied: primary tumor type, gender, number of metastases, surgical resection of the metastasis and improvement of neurologic symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in the group of patients who presented with less than three metastases, performance status < 2, and no surgical resection of their metastasis. Results: Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10% respectively. Performance status, surgical resection, neurological improvement after treatment and total dose of radiotherapy were significant factors for overall survival. Median overall survival was 105 days in patients with no radiation boost, versus 244 days in patients with radiation boost (p < 0.001). Conclusions: Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment. No significant financial relationships to disclose.
Single-center experience with paclitaxel (T), carboplatin (C), and capecitabine (X) in the treatment of advanced esophagogastric cancer.
Authors: Carl Alex Ruoff, Bennett Hong, Barry H. Kaplan, Simcha Pollack
Journal: Journal of Clinical Oncology (2013)

116 Background: Epirubicin, cisplatin, and 5-FU (ECF) improves overall survival for advanced esopgagogastric adenocarcinoma compared with other protocols but is associated with considerable toxicity. A triple chemotherapy with TCX has shown improved survival with less toxicity at our institution. The aims of this study were to retrospectively analyze overall survival and toxicity of TCX in our patient population and to compare them with published results from ECF and paclitaxel, cisplatin, and 5-FU (TCF), a similar regimen to ours. Methods: We analyzed pts with locally advanced and/or metastatic esophagogastric adenocarcinoma treated in our institution from 2005 to 2012 with TCX (paclitaxel 80mg/m^2 day 1 &amp; 8, carboplatin 5 AUC day 1, capecitabine 750mg/m^2 BID for 14 days). Pts had received no prior chemotherapy. Primary endpoint was overall survival and secondary endpoint was toxicity. We compared our data to historical results from trials of ECF and TCF. Results: 35 pts who received TCX were identified. The median age was 64 years (range 37-91). 20 pts had metastatic disease and 15 had locally advanced disease. Median survival was 21 months (95% CI: 13, 25 months). 1 year survival was 72% (95% CI: 54%, 90%). These data compare favorably to published ECF data (table) with a significant survival benefit of TCX over ECF (p&lt;0.05%). When compared to TCF in pts with metastatic disease 2 year survival was 18%, compared to 32% (95% CI: 10%, 54%) with TCX. Though there is a survival benefit, it was not statistically significant. Grade 3-4 toxicity with ECF has been documented in several studies as above 40%. In our patients treated with TCX, only 4 pts (11%) suffered grade 3-4 toxicity (nausea, vomiting, hearing loss, and neutropenia). Conclusions: In our patient population, triple therapy of paclitaxel, carboplatin, and capecitabine (TCX) is associated with significant improvement in overall survival in advanced esophagogastric cancer with a low rate of toxicity compared to published ECF results. [Table: see text]
Circulating tumor cells detection and evaluation of their apoptotic status in patients with localized breast cancer before and after surgery.
Authors: M. Bertolin, J. Pigozzo, H. Koussis, C. Ghiotto, S. Valente, S. Michieletto, C. Magro, E. Rossi, R. Zamarchi, F. Bozza, A. Jirillo, V. Chiarion-Sileni, A. Amadori
Journal: Journal of Clinical Oncology (2011)

e21127 Background: Circulating tumor cells (CTCs) are an independent prognostic factor in metastatic breast cancer patients. However few data exist on the potential role of CTCs in patients with operable breast cancer. The presence of CTCs in localized breast cancer could predict an increased risk for relapse. We integrated the quantitative data of the CTCs numbers with a new tool for quantifying apoptotic and non apoptotic CTCs. Methods: The presence of CTCs was evaluated by ten milliliters of peripheral blood taken from 10 consecutive breast cancer patients in stage I-IIIA: before surgery, 12 hours after surgery, and before to start any adjuvant treatment (median 30 days after surgery). The automated sample preparation and analysis platform for computing CTCs (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The CTC M30 negative was classified as non apoptotic. Results: One to two CTCs were found in 2/10 patients immediately before breast surgery; 12 hours after breast surgery one to two CTCs were found in 3/10 patients and 30 days after breast surgery 8/10 patient present one to three CTCs in blood samples. At least one M30 negative CTC (non apoptotic) was found in the two CTCs positive patients before surgery, in 2/3 CTCs positive patients 12 hours after surgery and in 2/8 CTCs positive patients 30 days after surgery. One patient that presented CTCs+ and M30- before surgery was always CTCs positive with at least one M30- CTC in the following two controls. All the patients didn’t present metastatic disease. Conclusions: This preliminary study provides evidence of the presence of CTCs and at least one non apoptotic CTC in operable breast cancer patient before, 12 hours and especially 30 days after surgery. We noted also that not immediately after surgery but 30 days after surgery, a large part of the patients (8/10) were CTCs positive before to start any adjuvant therapy. The study is ongoing.
Associations between the EGFR status as well as KRAS mutations and clinical outcome in colorectal cancer (CRC) patients (pts) treated with erlotinib monotherapy in 2<sup>nd</sup> or 3<sup>rd</sup> line—A study of the Arbeitsgemeinschaft Internistische
Authors: J. Stoehlmacher, E. Goekkurt, D. Arnold, U. Keilholz, N. Niederle, T. Hohler, U. Mogck, F. Lordick, S. Kubicka, H. Schmoll
Journal: Journal of Clinical Oncology (2008)

14574 Background: Genetic aberrations within the EGFR pathway including KRAS mutations and polymorphisms of EGFR have been demonstrated to be associated with response to EGFR inhibitors like cetuximab and panitumumab in CRC. Here, we investigated whether these genetic changes may impact response and survival in CRC patients treated with erlotinib monotherapy. Methods: Within a multicenter phase II trialCRC patients who failed 2 0r 3 previous chemotherapies with 5-FU, irinotecan or oxaliplatin were treated with erlotinib monotherapy (150 mg/day p.o.) until disease progression. Response was evaluated every 8 weeks according to RECIST criteria. Analyses of the EGFR pathway including KRAS-mutations, EGFR polymorphisms (CA repeat intron 1, HER-497, EGFR-216G>T, - 191C>A), EGFR gene amplification and protein expression were performed in 38 pts. Analyses were carried out following microdissection of the tumor. Results: Patients possessing the HER-497 Lys/Lys genotype demonstrated a significantly improved median progression- free survival with 4.7 months compared to 1.8 months in Arg/Lys and in Arg/Arg patients (p=0.03, Chi-square test). Patients homozygous for the EGFR-216 T/T genotype demonstrated inferior median PFS with 0.85 months compared to 1.87 and 1,84 months in patients showing a G/G or G/T genotype, respectively (p<0.001, Chi-square test). KRAS mutations (codon 12, 13) were detected in 9/31 (29%) pts. Disease control at 8 weeks was seen in 41% of pts with KRAS wild-type (9/22) compared to only 22% of pts with KRAS mutation(2/9) (p=0.4). No associations between PFS or tumor control and EGFR FISH or expression analyses were detected. Associations with overall survival will be demonstrated at the meeting. Conclusions: EGFRpolymorphisms (HER-497, EGFR-216) may be associated with progession-free survival of CRC patients treated with erlotinib monotherapy in 2nd or 3rd line. To our knowledge this is the first report demonstrating a relationship between EGFR polymorphism and erlotinib in CRC. The role of EGFR polymorphism and KRAS mutations for erlotinib therapy in CRC warrants further investigation in larger trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffmann-La Roche
Predictors of radiotherapy-related gastrointestinal toxicity from anal cancer DP-IMRT: Secondary analysis of RTOG 0529.
Authors: Jeffrey R. Olsen, Jennifer Moughan, Robert J. Myerson, Andre Abitbol, Charles Kunos, Douglas Johnson, Tracey Schefter, Yuhchyau Chen, Barbara Jean Fisher, Jeff M. Michalski, Samir Narayan, Albert Chang, Christopher H. Crane, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2014)

460 Background: Radiation Therapy Oncology Group (RTOG) 0529 assessed feasibility of dose-painted intensity-modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient (pt) and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods: RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel (SB), loosely contoured anterior pelvic contents (APC), and uninvolved portions of colon outside the clinical target volume (UC). T-tests were performed to evaluate differences in the mean absolute volumes of each critical structure receiving doses ≥ 5 to 60 Gy (V5-V60) in 5 Gy increments between pts with and without ≥ grade (G) 2, acute and late GI AEs, and ≥G3 acute GI AEs using the NCI Common Terminology Criteria, version 3. Acute is defined as ≤ 90 days from the start of treatment and late is &gt; 90 days. Additional factors (age, location, gender, race, Zubrod, grade, size, stage, prone vs supine position) were also evaluated in multivariate (MV) logistic regression (acute AEs) or Cox proportional hazards models (late AEs) to evaluate correlation with GI AEs. Results: Among 52 evaluable pts, ≥G2 acute, ≥G2 late, and ≥G3 acute GI AEs were observed in 35, 17, and 10 pts, respectively. Trends (p&lt;0.05) towards statistically significant associations were observed between: ≥G2 acute GI AEs and SB dose (V20-V40); ≥G2 late GI AEs and APC dose (V60); ≥G3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size &gt;4cm, and worse Zubrod. SB and APC dose parameters remained correlated with GI AEs on MV analysis. Treatment in the prone vs supine position correlated with lower SB V10-V35 and APC V5-V20, although no significant differences in GI AEs were observed. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlates with RT dose to the SB and APC. Further analysis is underway to determine critical structure cut-point parameters that may aid treatment plan optimization for anal cancer DP-IMRT. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. Clinical trial information: NCT00423293.
Extrapleural pneumonectomy followed by IMRT: Results of a phase I/II study
Authors: C. Stevens, D. Rice, K. Forster, Z. Liao, T. Guerrero, A. Correa, A. Vaporciyan, W. R. Smythe
Journal: Journal of Clinical Oncology (2005)

7178 Background: Malignant pleural mesothelioma (MPM) usually recurs locally despite conventional radiotherapy after extrapleural pneumonectomy (EPP). We hypothesized that the highly conformal nature of intensity modulated radiation therapy (IMRT) might improve outcomes compared with standard therapy. Methods: 32 patients entered a phase I/II study of EPP followed by IMRT. Minimum dose was 45 Gy in 12 patients and 50 Gy in 20 patients. The AJCC stage distribution was 2 Stage I, 1 Stage II, 26 Stage III, and 3 Stage IV. All patients had resectable tumors confined to one hemithorax. No patients received chemotherapy before recurrence. Results: Despite the large irregular CTV (some over 8 liters), an average of 97% of the CTV was covered to the target dose (range 92–100%). Major side effects were nausea/vomiting (80%), fatigue (24% grade 3) and dyspnea (17% developed grade 3). Esophagitis was mild (34% grade1/2). There was no difference in toxicity between the 45 and 50 Gy arms. One patient developed fatal radiation pneumonitis soon after radiotherapy. With a median follow-up of 13 months, only one patient failed in-field and one patient failed adjacently (both at 50Gy). 16 patients failed systemically including the contralateral lung (8 pts) and peritoneal cavity (4 patients) with a median time to recurrence of 7 months. Cause of death was mesothelioma in 14 patients. 7 patients died of other causes including infectious pneumonia (2 pts), pulmonary embolus (2 pts), pneumonitis (1 pt) and unknown causes (2 pts). Median overall survival was 15 months. 3-year survival for the 12 patients without nodal metastases was 30%. Conclusions: In this small series there was no evidence for a dose-response for toxicity or local control. Excellent local control can be obtained with EPP followed by IMRT however systemic failure remains problematic. Patients without nodal metastases also do quite well, even with advanced T stage. It may be appropriate to combine novel agents prior to EPP to improve systemic control. No significant financial relationships to disclose.