tbuckley/cabot-search huggingface dataset:
Efficacy and feasibility of neoadjuvant chemotherapy and chemoradiotherapy for elderly patients with stage IB/II/III (excluding T4) esophageal cancer: Retrospective study.
Authors: Takahiro Miyamoto, Takayuki Kii, Masahiro Gotoh, Ken Asaishi, Tetsuji Terazawa, Fukutaro Shimamoto, Shin Kuwakado, Hitoshi Nishitani, Masaru Kawai, Kazuhide Higuchi
Journal: Journal of Clinical Oncology (2016)

135 Background: Neoadjuvant chemotherapy (NAC) of 5-fluorouracil plus cisplatin infusion (FP) is standard therapy for stage IB/II/III (excluding T4) esophageal cancer from results of JCOG9907 and definitive chemoradiotherapy (dCRT) of FP is one of the curative options for resectable esophageal cancer with organ preservation results of JCOG9906 in Japan. However, the efficacy and feasibility of NAC FP and CRT for elderly patients (pts) are unclear. Methods: We examined stage IB/II/III (excluding T4) esophageal cancer pts aged 70 or over, who received NAC FP or dCRT at our institution between April 2008 and August 2015, retrospectively. Results: 16 pts received NAC FP at least 1 course, while 5 pts received dCRT because of intolerability for surgery, reject of surgery, and patient's wish. Median age was 73/75 (NAC FP/dCRT) and pts in NAC FP had more advanced stage cancer compared with pts in dCRT (p = 0.02). With respect to the toxicity, bone marrow depression developed in dCRT with more high frequency compared with NAC FP, but no pts had febrile neutropenia. Adverse effects of fatigue, nausea and appetite loss developed in both group frequently. 3 pts were not performed surgery because of decreased respiratory function, decreased PS and progression disease and 4 pts did not achieved 4 cycle of FP infusion because of leukopenia, decreased renal function, and gastrointestinal toxicity. 12 pts in NAC FP undergone R0 resection surgery and 4 pts had a complete remission. The 5-year progression free survival rate was 50% (95% CI: 12-86%) in dCRT and 50% (95% CI: 20-80%) in NAC FP (p = 0.69). The 5-year overall survival rate was 50% (95% CI: 12-86%) in dCRT and 67% (95% CI: 36-88%) in NAC FP (p = 0.83). Conclusions: NAC FP and dCRT for stage IB/II/III (excluding T4) esophageal cancer might be effective even in pts ≥ 70 years of age. The therapy of dCRT might be one of options for elderly inoperative patients.
Phase II trial of irinotecan and cisplatin combination as first-line chemotherapy in patients with advanced esophageal squamous-cell carcinoma: An interim report.
Authors: X. Zhang, L. Shen, J. Li, Y. Li, J. Zhou, Z. Lu, M. Lu
Journal: Journal of Clinical Oncology (2011)

137 Background: Although the irinotecan and cisplatin combination has been used in esophageal cancer treatment, we tested the combination specifically in unresectable or metastatic esophageal squamous cell carcinoma with different doses to decrease the toxicity and keep the efficacy. Methods: Patients were eligible if they had histologic proof of unresectable or metastatic squamous cell carcinoma of the esophagus, between 18-75 years of age with a Karnofsky performance status ≥ 80. No prior chemotherapy was allowed. Patients were treated with irinotecan 130 mg/m 2 and cisplatin 60 mg/m 2 repeated 3 weeks. Response was evaluated every two cycles of treatment by using RECIST criteria. The sample size was calculated using Simon's 2-stage design. The primary end point of the study was objective response rate. The second end points are PFS and toxicity. Accrual was planned to a total of 46 patients with the targeted response rate of 50%. The first stage requires at least 7 or more out of 16 patients to have a confirmed partial or complete response before proceeding to the second stage. Results: Twenty one patients have been enrolled so far, of which 16 patients were assessable for response. The overall response rate was 43.8%(7/16), including one complete response (6.3%) and six partial response (37.5%). Among 13 patients who presented with dysphagia at baseline, 10 (62.5%) had the symptom either completely resolved or significantly improved. The most common toxicities were neutropenia, diarrhea and alopecia. Seven patients (33.3%) developed grade 3 neutropenia and one had (4.8%) with febrile neutropenia. One patient (4.8%) had grade 3 diarrhea. There were no treatment-related deaths. Conclusions: The combination of irinotecan plus cisplatin with lower doses showed equivalent efficacy and less toxicity in patients with unresectable or metastatic squamous-cell carcinoma of the esophagus. The study is ongoing. No significant financial relationships to disclose.
Quality improvement using lean methods to increase access and utilization of support services in younger breast cancer survivors.
Authors: Deborah Mayer, Adrian Gerstel, Kinley Taylor, Marianne Jackson, Thomas C. Shea, Donald Rosenstein, Lawrence Bruce Marks
Journal: Journal of Clinical Oncology (2012)

143 Background: A variety of ‘structured support services’ (SS) are available to patients (e.g., genetics, fertility, counseling, physical functioning, nutrition). Many of these SS have value for breast cancer survivors (BCS) as they are often likely to face issues regarding genetic factors, fertility, parenting, relationships, work, and financial hard-ships. As part of an ongoing CDC-funded initiative, we report our preliminary findings regarding perceived needs and actual rates of use of these SS, and identified barriers to their use for BCS. Methods: We assessed the needs for and utilization of SS by 1) conducting a survey of younger breast cancer survivors; and 2) performed chart reviews for documentation of assessment and referral for each SS. To identify barriers to the receipt of SS we 1) conducted key informant interviews, and 2) performed extensive observations in the clinic to value-stream map the flow of the patient throughout the care process. Results: Survey results: Women (n= 59/283) responded with a mean age of 39 (range 19-46) at the time of diagnosis. The most common limitations to using SS included lack of information about SS (60%), distance from services (54%), and inconvenient times (51%). Chart results: We reviewed 57 charts from 2011 for assessment and referral for any SS. The lack of consistent documentation made it challenging to extract meaningful data. Observation and interview results: Common barriers to the receipt of SS include lack of patient and staff education about available services, lack of consistent referral mechanisms, heavy burden on the provider to make referral, and poor feedback loop between SS and provider. Conclusions: Patients and providers both perceive many challenges to the delivery of support services. We are applying lean processes to improve the delivery of consistent information about SS to patients and providers, to standardize methods to refer patients for them, and to provide feedback to providers, in order to improve the delivery of SS to BCS, therefore improving their quality of care.
Barriers and facilitators of navigator-led advance care planning conversations in older patients with cancer.
Authors: Elizabeth Ann Kvale, Chao-Hui Huang, Soumya J Niranjan, J Nicholas Dionne-Odom, Kelly Kenzik, Kerri S. Bevis, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2016)

17 Background: National guidelines and most individuals endorse advance care planning (ACP) as essential; however, few individuals engage in such planning. Little is known about the role of lay navigators in supporting ACP. We sought to understand facilitators and barriers of successful implementation of ACP conducted by lay cancer navigators. Methods: Semi-structured interviews were conducted with 26 lay navigators at 11 sites across the Southeast who were engaged in ACP implementation using Respecting Choices©. Interview topics included quality of ACP training, ACP conversation knowledge and comfort, barriers and facilitators, and perceived role in navigating patients with advanced cancer. Audio-recorded interviews were transcribed verbatim; thematic content analysis was conducted using NVivo 10 Software. Transcripts were reviewed for major themes and subthemes generated via line-by-line coding. Inter-rater agreement (2 primary coders) was assessed using Cohen’s Kappa ( = 0.81), indicating high agreement. Results: Navigators completed 672 ACP conversations across sites. Facilitators and barriers emerged across 3 domains: patient, navigator, and system domains. System facilitators included physician engagement and oncology-team consultation support while barriers included lack of time and space, lack of stakeholder support, and cultural suspicion. At the navigator level, established rapport was a necessary facilitator while personal discomfort and timing issues were barriers. At the patient level, prior experience with a family member was a facilitator while barriers included limited health literacy, fears, lack of readiness, and a “battle” mentality. Conclusions: Lay navigators can be trained to facilitate advance care planning conversations with cancer patients. Lay navigators identified several areas where additional training and infrastructure support might facilitate ACP in patients with advanced cancer. Future work should focus on designing and evaluating systems of healthcare delivery to support this activity.
Defects in DNA repair genes and sensitivity to cisplatin based neoadjuvant chemotherapy (NAC) for bladder cancer.
Authors: Elizabeth R. Plimack, Roland Dunbrack, Timothy Brennan, Mark D. Andrake, Yan Zhou, Ilya Serebriiskii, Essel Dulaimi, Jean H. Hoffman-Censits, Marijo Bilusic, Yu-Ning Wong, Alexander Kutikov, Rosalia Viterbo, Richard E. Greenberg, David Y. T. Chen, Costas D. Lallas, Edouard John Trabulsi, Roman Yelensky, Vincent A. Miller, Erica Golemis, Eric A Ross
Journal: Journal of Clinical Oncology (2015)

320 Background: Cisplatin based NAC prior to cystectomy is standard of care for MIBC, with 40-50% expected to respond with ≤pT1N0M0. Biomarkers predictive of response are lacking. Methods: MIBC pts who received 3 cycles of cisplatin based NAC on 1 of 2 prospective multicenter clinical trials were included. Pts treated with accelerated methotrexate, vinblastine, doxorubicin + cisplatin (AMVAC) provided the discovery set [n=34, 15/34 (44%) ≤pT1N0M0]. Pts treated with dose dense gemcitabine + cisplatin (DDGC) provided the validation set [n=24, 11/24 (46%) ≤pT1N0M0]. DNA from pre-treatment tumor tissue underwent sequencing for all coding exons of 287 cancer related genes and was analyzed for presence of base substitutions, indels, copy number alterations, and selected re-arrangements. The mean number of variants and variant status for each gene were correlated with response using two-sample t-test and Fisher’s exact tests. Variant data were used to create a classification tree to discriminate responders vs. non-responders in the AMVAC discovery cohort. The resulting decision rule was then tested in the independent DDGC validation set. Overall survival analysis was performed using Kaplan-Meier. Results: Pts with pT0 had significantly more alterations than those with residual tumor in both the AMVAC discovery (p=.024) and DDGC validation (p=0.018) set. In the AMVAC discovery set, alteration in ≥1 of the three DNA repair genes ATM, RB1 or FANCC predicted for ≤pT1N0M0 (p&lt;0.001, 87% sensitivity, 100% specificity) and improved overall survival (OS) (p=0.007). This test remained predictive for ≤pT1N0M0 in the DDGC validation set (p=0.033), with a trend towards improved OS (p=0.07) at short median follow up of 14.3 mo. Conclusions: Alterations in ≥1 of ATM, RB1 and FANCC predict response to cisplatin based chemotherapy defined as ≤pT1N0M0 in both our AMVAC discovery and DDGC validation sets. We hypothesize that defects in these genes, which are important for maintenance of chromatin structure and DNA repair, confer sensitivity to DNA damaging chemotherapy and explain the accumulation of alterations seen among pts with pT0. External validation in collaboration with the cooperative groups is planned.
Fiducial markers vs. PET/CT for esophageal cancer GTV delineation for radiotherapy treatment planning using a standard SUV threshold and background uptake method.
Authors: Jasmine A Oliver, Puja Venkat, Jaime Montilla-Soler, Jason Klapman, Gautumy Chikiti Dhadham, Cynthia L. Harris, Karen Emanuel, Joan Werner, Will Jin, Jessica M. Frakes, Thomas J. Dilling, Geoffrey Zhang, Eduardo G Moros, Sarah E. Hoffe, Kujtim Latifi
Journal: Journal of Clinical Oncology (2016)

70 Background: Often in esophageal targets that move with respiration, endoscopically implanted fiducial markers are placed under ultrasound guidance within 1 cm from the superior and inferior tumor border. Our group has previously reported the stability of this method. 3D 18F-FDG PET/CT is obtained for initial staging of esophageal cancer and has altered the tumor volume in many sites. The correlation of these two methods for GTV delineation is currently undefined. Methods: Twenty-one patients with esophageal cancer were selected for this retrospective, IRB-approved analysis. Each patient underwent fiducial placement (by one of six endoscopists) at the inferior and superior borders of the tumor and received PET/CT prior to Radiotherapy (RTx). PET/CT images were imported into an image analysis software system for measurements. The distance between fiducial markers and MTV defined by 2.5 SUV contour (method 1) and MTV using a threshold above mean liver uptake (method 2) was calculated. The fiducials were located on CT. The distance between the centroid and MTV border was measured. The Concordance Correlation Coefficient (CCC) was calculated to determine the correlation between results from the two methods. Results: In method 1 the median distance between MTV (2.5 SUV) and fiducials was 1.0 cm (0.0 cm - 2.8 cm) and 1.0 cm (0.0 cm - 6.9 cm) for inferior and superior borders, respectively. In method 2 median distance between MTV and fiducials was 1.14 cm (0.0 cm - 2.62 cm) and 1.64 cm (0.33 cm – 6.84 cm) for inferior and superior borders, respectively. The CCC indicated poor agreement between methods for both distances (0.57 and 0.87 for inferior fiducial distance and superior fiducial distance, respectively). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the endoscopist that performed the fiducial implantation. Conclusions: Although the methods of defining the MTV had poor strength of agreement, both methods demonstrated a robust correlation between inferior fiducial marker placement and inferior PET/CT uptake. The superior fiducial marker and MTV border illustrated discordance – unrelated to the endoscopist.
Appointment (appt) access for new cancer patients (pts).
Authors: K. Gogineni, K. Armstrong
Journal: Journal of Clinical Oncology (2011)

6128 Background: Cancer pts may face access barriers given a looming shortage of oncologists, rising cancer burden due to an aging populace, and tepid economy. This study’s objective was to determine the ability of test pts to get appts in a representative sample of 160 U.S. hospitals and whether access varied by insurance status. Methods: Using a paired testing study design, trained research assistants (RAs) simulated pts newly diagnosed with inoperable hepatocellular carcinoma who had no insurance, Medicaid, or private insurance. RAs asked hospitals for their affiliated cancer center/outpatient medical oncology clinic and attempted to contact each outpatient site with all three insurance scenarios to request a new pt appt. Ability to schedule an appt was the main outcome measure. Reason for denial was a secondary outcome of interest. Results: Of 432 test pt scenarios analyzed, RAs reached a scheduler in 79.2% of encounters, but got appts only 29% of those times. Of the 99 appts scheduled, 64.7% required one call. Over one-third (35.4%) of the time, multiple calls were required and in nearly a quarter (24%), callers never reached staff despite three attempts. The rate of new appts was 29.1% among uninsured, 22.4% among privately insured, and 17.4% among Medicaid patients (p=0.062). Appt rates were higher among uninsured even after aggregating outcomes among insured (29.1% and 19.9% respectively; p=0.034). Demand for medical records (39.3%), not being able to reach schedulers (24%) and referral requirements (17.7%) were the major reasons pts couldn’t get appts. More insured than uninsured were denied appts based on lack of referral (18.9% versus 15%) and medical records (41.6% versus 34%). Conclusions: Despite a rare and advanced cancer warranting timely care, getting an appt was challenging and not necessarily facilitated by insurance. Undue delay in evaluation may arise if pts are expected to navigate the complex process of obtaining scans, pathology, and physician notes before appts are scheduled. Fewer expectations regarding records and referrals posit a plausible explanation as to why uninsured may have had easier access, if insured pts faced more non-price barriers. Pt navigators could play a critical role if made available to pts at the point of earliest contact.
A randomized phase III study of cisplatin and docetaxel with or without irinotecan in pts with advanced non-small cell lung cancer: Okayama Lung Cancer Study Group OLCSG 0403.
Authors: K. Kiura, M. Tabata, N. Takigawa, S. Kuyama, Y. Segawa, H. Kamei, T. Shibayama, K. Hotta, K. Matsuo, M. Tanimoto
Journal: Journal of Clinical Oncology (2010)

7584 Background: Cisplatin (CDDP)-based doublet chemotherapy prolonged survival significantly in untreated pts with advanced non-small cell lung cancer (NSCLC). However, its benefit remains modest and further improvement is needed. We conducted a phase II trial of triplet chemotherapy with CDDP, docetaxel (DOC) and irinotecan (CPT), demonstrating a response rate of 57.1% and MST of 17 months (JTO 2007). We conducted a phase III study to compare this regimen with CDDP/DOC doublet chemotherapy in the first-line setting. Methods: Pts with chemotherapy-naive NSCLC were randomly allocated to the triplet therapy (A arm; CDDP 60 mg/m2, day 1; DOC 60 mg/m2, day 1; and CPT 60 mg/m2, day 2; q 3 wks, determined based on our phase I study result) or doublet chemotherapy (B arm; CDDP 80 mg/m2, and DOC 60 mg/m2, day 1; q 3 wks). The primary endpoint was OS and secondary endpoints included response rates, PFS, and toxicity. Results: Between 2004 and 2009, 120 pts were enrolled (A/B: 60 pts each). Demographics of the pts were as follows: M/F: 91/29, Ad/others: 82/38, ECOG-PS 0/1: 40/80, and smoker/non-smoker: 90/30. A median number of cycles administered was 4. The dose was reduced in 31 pts in arm A (52%), whilst the doses were modified for 12 pts in arm B (20%). Objective response was obtained in 18 pts each in arms A and B, respectively (30% each, p = 0.571). The major toxicity was myelosuppression, with grade 3-4 neutropenia of 93% vs. 58% (p < 0.001). Although grade 3 febrile neutropenia was observed in 53% and 18% of the pts (p < 0.001), none of whom further developed grade 5 toxicity. In addition, grade 3 or greater diarrhea developed more frequently in Arm A (15% vs. 3%, p = 0.016). The survival data are premature, and at the time of data analysis with a median follow-up time of 37.7 months, MST and median PFS time were 12.1 and 4.2 months, respectively. Conclusions: This triplet chemotherapy produced identical antitumor activity with more severe toxicities as compared with the standard CDDP/DOC doublet chemotherapy. OS will be analyzed in 2011. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) <i>KRAS</i> metastatic colorectal cancer (mCRC).
Authors: Allen Lee Cohn, J. Randolph Hecht, Shaker Dakhil, Mansoor N. Saleh, Bilal Piperdi, Vivian Jean M. Cline-Burkhardt, Ying Tian, William Y. Go
Journal: Journal of Clinical Oncology (2013)

3616 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (Table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]
Outcomes in phase II trials of metastatic breast cancer: Where is the bar?
Authors: A. Kamal, T. Zhang, A. Schneider, K. Patel, E. P. Hamilton, P. K. Marcom, J. M. Peppercorn
Journal: Journal of Clinical Oncology (2011)

2590 Background: Phase II trials serve to provide safety and efficacy data for evaluating novel interventions that may be selected for large Phase III trials. To help define benchmarks for efficacy, we evaluated outcomes of all recently published metastatic breast cancer Phase II trials (MBP2). Methods: All English language MBP2 published from June 2005 through June 2010 were identified by Pubmed search. Trial characteristics (type, line, regimen), tumor type, and outcomes were analyzed. Line of therapy was categorized as first-line (first line only), early-line (2nd and 1-2 line), and any/late-line (2+ lines or not specified). Descriptive statistics, Wilcoxon signed rank, and univariate linear regression were performed. Results: 226 Phase II trials were abstracted. 31% were first-line, 30% early-line, and 39% any/late-line. 83% (187) were single-arm design; 12% (27) and 5% (11) were randomized and cohort studies, respectively. Overall response rate (ORR) was reported in 204 (90%) MBP2, stable disease (SD) in 127 (56%), time to progression (TTP) in 185 (82%), progression free survival in 20 (9%), and overall survival (OS) in 143 (63%). SD was defined as 6 months in 29%, but definitions varied, and SD was not defined in 43%. Overall, median ORR was 36% (IQR: 16-52, range 0-98%); TTP was 27 weeks (IQR: 15-36, range 4-122), and OS was 65 weeks (IQR: 52-95). For first-line, median ORR, TTP, and OS were 53%, 35 weeks, and 97 weeks, respectively. In first-line, ORR ranged from 5%-98%, TTP from 9-72 weeks, and OS from 13-884 weeks. For early-line vs. any/late line, median ORR was 30% vs. 22%, median TTP was 24 vs. 19 weeks, and median OS was 60 vs. 56 weeks. ORR, TTP, and OS differed significantly by line of therapy (all p<0.0001). Univariate linear regression demonstrated a significant association between ORR, TTP, and OS (p<0.005). Conclusions: Appraisal of recent trials can provide benchmarks for evaluation of novel therapy. As with standard interventions, outcomes in MBP2 vary by line of therapy. Standardization in reporting outcomes, particularly definition of SD, would improve assessment and support rational decision making for which interventions should move forward to Phase III trials.