tbuckley/cabot-search huggingface dataset:
Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?
Authors: Hui-li Wong, Kathryn M Field, Jeanne Tie, Suzanne Kosmider, Jeremy David Shapiro, Joseph McKendrick, Phillip Parente, Lara Rachel Lipton, Desmond Yip, Sagun Parakh, Louise M. Nott, Peter Gibbs
Journal: Journal of Clinical Oncology (2013)

e14583 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centers. Results: Of the 864 patients entered, 161 (18.6%) had an ECOG PS ≥ 2. In total, 95 (11.0%) were PS 2, 54 (6.3%) PS 3 and 12 (1.4%) PS 4. Chemotherapy was administered to 65 (68.4%) PS 2 and 17 (31.5%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (51.6% versus 86.8%, p&lt;0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (67.5% vs 81.1%, p=0.0057) or bevacizumab (31.3% vs 55.8%, p&lt;0.0001). Overall survival (OS) was reduced with declining PS, with medians of 28.7, 8.9, 3.5 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p&lt;0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.0 vs 3.5 months for untreated patients, p&lt;0.0001). At one and two years, 24 (28.9%) and 7 (8.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.
Assessing the need for a Geriatric Oncology Assessment Clinic: A successful partnership among specialties
Authors: T.-T. Huynh, S. Sanchez-Reilly, A. Karnad
Journal: Journal of Clinical Oncology (2005)

8268 Background: Geriatric population is rapidly growing. 60% new cancers are diagnosed in patients >65, and account for >70% cancer deaths. Elderly patients are underrepresented in cancer clinical trials (13%). There are few experts in geriatric oncology (7 centers in the US). Also, geriatric minority population is growing, such as Hispanics (HP), the largest US minority. HP are likely to have lower insurability rates. Screening methods for cancer and access to geriatric oncology care are a concern in elderly HP. Objective: To identify the population with common cancer diagnoses at a major cancer center to establish the need for a culturally competent Geriatric Oncology clinic. The Cancer Treatment and Research Center (CTRC) is affiliated with the University of Texas Health Science Center and is one of two National Cancer Institute designated centers in Texas. CTRC is located in San Antonio, where 56% of its population are HP. Methods: Chart review of data pertinent to subject’s demographics and cancer diagnoses registered at first encounter from 1996–2004. Results: Of the 89,960 subjects, 47% subjects are >60. 49% female, 61% Whites, 29% HP, 3% African Americans. The predominant malignancy diagnoses are: 1)Prostate: 84% subjects with prostate cancer are >60(43% are 60–69, 48% are 70–79, 9% are age >80); 2)Lung: 68% subjects with lung cancer are >60(49% are 60–69, 41% are 70–79, 10% are age >80); 3)Colorectal: 53% subjects with colorectal cancer are >60(51% are 60–69, 38% are 70–79, 11% are age >80) and 4)Breast: 37% subjects with breast cancer are >60(54% are 60–69, 35% are 70–79, 11% are age >80). Conclusions: Elderly patients are the most afflicted group suffering from most common cancers. A comprehensive multidisciplinary approach is required to address elderly needs. A Geriatric Oncology clinic is an ideal setting to screen and optimize geriatric patients for appropriate cancer treatment, to achieve functional improvement and enhance participation in clinical trials. HP accounted for 29% patient population. A new geriatric assessment clinic has been started at our institution. It will aim to be culturally competent for HP elderly. Further research will be needed to evaluate clinical outcomes and future benefits. No significant financial relationships to disclose.
Mutational analysis of <i>K-RAS</i> and <i>EGFR</i> implicates <i>K-RAS</i> as a resistance marker in the Southwest Oncology Group (SWOG) trial S0126 of bronchioalveolar carcinoma (BAC) patients (pts) treated with gefitinib
Authors: P. H. Gumerlock, W. S. Holland, H. Chen, W. A. Franklin, F. R. Hirsch, P. C. Mack, A. M. Davies, J. McCoy, H. J. West, D. R. Gandara
Journal: Journal of Clinical Oncology (2005)

7008 Background: S0126 was a phase II trial of the EGFR inhibitor gefitinib in BAC subtypes, a unique form of NSCLC adenocarcinoma. We reported that high levels of tumor p-MAPK correlated with poor overall survival in these pts, while EGFR levels were not predictive. We hypothesized that activation of the MAPK pathway, due to mutated K-RAS, would correlate with poor outcome to EGFR inhibitor therapy. Methods: DNA was extracted from pre-treatment tumor tissue of 66 pts. Exons 18, 19 & 21 in EGFR (64 pts) and codons 12 & 13 in K-RAS (63 pts) were examined by PCR/RFLP analyses with mutations identified by direct sequencing. Results: K-RAS mutations were found in 19 pts (30%), 17 who were current or former smokers. All were 12th codon point mutations. Of 17 pts with K-RAS mutations and measurable disease by RECIST or computer assisted image analysis (CAIA), 1 responded (6%). EGFR mutations were found in 12 pts (19%), with point mutations found at codons 719 (1) and 858 (9), and deletion mutations in exon 19 (2). All EGFR mutations were in former smokers, except a double-base change at codon 858 and one deletion. Both pts with EGFR deletions and 2/8 pts with codon 858 mutations responded [4/12 total; 4/8 with only EGFR mutations (50%)]. Four pts with K-RAS mutations also had EGFR codon 858 point mutations (6%), all were former smokers, and none responded. Transversion K-RAS mutations associated with smoking (G→T or G→C) were found in 9/17 smokers (53%), while both never-smokers had G→A transition mutations. All base change mutations in EGFR were transversions, with 81% found in pts with a history of smoking. Conclusions: These data show that 1) K-RAS transversion mutations are associated with smoking in this BAC cohort (exact p-value=0.006); 2) EGFR mutations in the absence of K-RAS mutations are associated with response to gefitinib (exact p-value=0.026); 3) K-RAS and EGFR mutations are relatively frequent in BAC, each found in smokers; and 4) Concomitant mutations in both genes are infrequent. These data suggest that further study of mutant K-RAS as a resistance marker for response to gefitinib is warranted. (Hope Fndtn, CA32102, CA38926, CA46441) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
A national survey: The patient’s perspective of gaps in the cancer treatment experience.
Authors: Christopher G. Lis, Kamal Patel, Mark Rodeghier, Mark Rogers, Digant Gupta
Journal: Journal of Clinical Oncology (2013)

90 Background: There are expected to be an excess of 1.6 million new cancer cases in the US in 2013. Recent emphasis has shifted to patient-centered care. However, data is lacking on what oncology patients value in their care. We therefore conducted a national survey to evaluate patient experience with service quality. Methods: An online survey was conducted in a national random sample of 1000 cancer patients in Aug-Sept 2012. Importance of 15 service quality items was measured on a 5-point Likert scale ranging from “not at all important” to “extremely important”. Patient experience with those 15 service quality items was captured as a yes/no response. Patient satisfaction was measured on a 5-point Likert scale ranging from “completely dissatisfied” to “completely satisfied”. Results: The top 3 areas of gaps between importance and experience were ‘having a specific individual to coordinate care’ (32%, p &lt; 0.01), ‘after-treatment care and support’ (15%, p&lt;.01) and ‘the presence of an integrated care team’ (15%, p&lt;0.01). Among respondents who rated these areas as very/extremely important, only 43%, 65% and 75% experienced it, respectively. Conclusions: These national findings illustrate a significant void between patients’ desires and care delivered. This survey demonstrates the emphasis patients put on the need for more coordinated cancer care, after-treatment care and an integrated approach. [Table: see text]
KRN330, a fully human antibody against A33, in combination with irinotecan for patients with metastatic colorectal cancer (mCRC).
Authors: J. C. Bendell, J. Marshall, J. Berlin, H. S. Hochster
Journal: Journal of Clinical Oncology (2011)

534 Background: KRN330 is a recombinant, fully-human monoclonal antibody directed against A33, a surface differentiation antigen on normal colonic epithelium, which is uniformly expressed in 95% of colorectal cancers. A KRN330 monotherapy phase I study showed over 1 year of stable disease in 2 pts with refractory mCRC. We report results of the phase I part of a phase I/II trial of KRN330 in combination with irinotecan in pts with mCRC. Methods: Pts with mCRC who progressed on one or more prior therapies received weekly (QW) or biweekly (Q2W) intravenous doses of KRN330 at 0.5 or 1.0 mg/kg with Q2W irinotecan at 180 mg/m 2 in a standard 3+3 dose escalation design. Results: Nineteen pts were treated. Four pts received 1.0 mg/kg of KRN330 Q2W and irinotecan treatment. Three pts developed DLTs, which included G4 febrile neutropenia and G3 colitis, prolonged G3 diarrhea, and, G4 neutropenia with prolonged G3 diarrhea. KRN330 was then deescalated to 0.5 mg/kg Q2W and 0.5 mg/kg QW. There were no DLTs in 7 of 8 pts in the Q2W cohort. The 1 DLT in this cohort was G3 colitis. None of the 7 pts in the QW cohort experienced DLT. The most common G3/4 toxicities included diarrhea (26.3%) and febrile neutropenia (15.9%), leucopenia (10.5%), neutropenia (10.5%), abdominal pain (10.5%), and colitis (10.5%). Of the 16 pts evaluable for efficacy, 2 pts had PR, 8 SD and 6 PD as best response. The 2 pts with PR had previously received an irinotecan-containing regimen, one with PD on an irinotecan-containing regimen. The responses are being confirmed by independent adjudicator. Conclusions: QW and Q2W intravenous doses of KRN330 at 0.5 mg/kg KRN330 with irinotecan were tolerable and demonstrated antitumor effect in pts who had received previous irinotecan-containing regimens. The phase II part of the phase I/II study of QW KRN330 plus irinotecan in pts with second line mCRC is ongoing. No significant financial relationships to disclose.
CD28 Costimulation of Effector T Cells During An Anti-Tumor Attack Sustains Its Repression by Regulatory T Cells Which Can Be Overcome by Preventing Lck Activation.
Authors: David M Kofler, Markus Chmielewski, Tobias Riet, Andreas Hombach, Michael Hallek, Clemens M Wendtner, Hinrich Abken
Journal: Blood (2009)
G-CSF utilization during abiraterone acetate (AA) and cabazitaxel (C) therapy: A retrospective U.S. claims analysis.
Authors: Maneesha Mehra, Robert Stellhorn, Yvette Ng, Mary Beth Todd
Journal: Journal of Clinical Oncology (2013)

205 Background: AA and C are two recently approved therapies shown to extend survival in men with metastatic castrate-resistant prostate cancer (mCRPC) progressing after docetaxel treatment. The toxicity profiles of AA and C differ, and therefore it was hypothesized that the utilization of concomitant medications and supportive care measures, in particular G-CSF for the treatment of neutropenia, would differ as well. Methods: The Pharmetrics database (2008 to Jan 2012), a nationally representative, nonpayer-owned, integrated, commercial U.S. claims database, was used for this analysis. Eligible patients included those identified with a diagnosis of prostate cancer (ICD 9 code 185.X or 233.4) and a claim for either AA or C (identified by the appropriate NDC or J codes). Use of G-CSF was analyzed during treatment (defined as the period between the first claim to the last claim, full months inclusive) and also analyzed for the year prior to the first claim of either AA or C (index date). Results: 278 patients were identified with a claim for both cohorts. Median ages of patients in the two cohorts were similar (69 years in the AA cohort, 67.5 years in the C cohort). Docetaxel use in the year prior to the index date was 57% and 64% in the AA and C cohorts, respectively. The median duration of follow-up post-index date was 2.6 months in the AA cohort and 6.0 months in the C cohort. While the median number of prescriptions (3) was the same for the AA and C cohorts, the mean was slightly higher for C (4.4 vs 3.3). In the AA cohort, the use of G-CSF was as follows: 35% in the year before the index date and 3% during treatment. In the C cohort, the use of G-CSF was as follows: 42% in the year before the index date, and 67% during treatment. Conclusions: Based on this claims analysis, patients who received C were more likely to receive concomitant G-CSF vs patients who were receiving AA. This finding is consistent with the known risks/precautions relating to neutropenia as described in the TROPIC study for C. Prior to treatment, both cohorts had G-CSF use, which may be attributed to neutropenia during or following docetaxel therapy.
Endpoints used by the FDA for new drug approvals for treatment (TT) of advanced (ADV) cancer: Example of hormone refractory prostate cancer (HRPC)
Authors: B. S. Mann, R. Dagher, G. Williams, J. Johnson, R. Pazdur
Journal: Journal of Clinical Oncology (2005)

6069 Background: Belief exists that new drug approvals by the FDA for TT of ADV cancer require overall survival (OS) prolongation. Some view OS prolongation as an unrealistic EP in ADV solid tumors (Di Leo, Buyse JCO 5/03). Endpoints (EPs) used by the FDA for new cancer drug approvals are published (Johnson JCO 4/03). For approval a TT must show safety (S) and efficacy (E). E is a clinically meaningful benefit to patients, eg a longer or better life. Prospectively defined & reliably measurable EPs in adequate & well-controlled trials may provide substantial evidence of E required for drug approval. Methods: Review of EPs in recent clinical trials leading to new drug approvals for different indications in TT of ADV HRPC. Results: Pivotal trial for Mitoxantrone (M)+Prednisone (P) approval used EP of Palliative Response- a 2 point improvement on a 6 point pain intensity scale with stable analgesic score lasting >/= 6 weeks. 29% patients in M+P arm vs 12% in control arm (P 0.011) had Palliative Response of 229 vs 53 days respectively (P 0.0001); no statistically significant (SS) OS prolongation was observed. Pivotal trial for Zoledronic acid (Z) approval used a composite EP of skeletal related events (SRE)- pathological bone fractures or spinal cord compression or surgery/radiation to bones for pain relief/fracture prophylaxis or use of radioisotopes/new antineoplastic therapy for increased pain. Proportion of patients with at least one SRE- 44% vs 33% (P 0.021) favored Z over placebo; no SS OS prolongation was observed. Pivotal trial for Docetaxel (D)+P approval used EP of OS. Longer median OS of 18.9 vs 16.5 months (P 0.0094) favored q 3 weekly D+P over M+P. Conclusions: Adequate and well controlled clinical trials can provide the required evidence of a clinically meaningful benefit to the patients using OS or other prospectively defined & reliably measurable EPs. Recent trials leading to new drug approvals for ADV HRPC TT used OS or EPs based on symptoms/disease manifestations/interventional events. OS is not the only EP used by the FDA for new drug approval. View that OS prolongation is an unrealistic EP in clinical trials of new drugs for TT of ADV solid tumors is not supported by the available evidence. No significant financial relationships to disclose.
A randomized phase II study of neoadjuvant chemoradiotherapy with 5-FU/leucovorin or irinotecan/S1 in patients with locally advanced rectal cancer.
Authors: Minkyu Jung, Sang Joon Shin, Seungtaek Lim, Ji Soo Park, Woong Sub Koom, Ki Chang Keum, Nam Kyu Kim, Seung Hyuk Back, Byung Soh Min, Hyuk Hur, Ho Geun Kim, Jun Seok Lim, Tae IL Kim, Jae Kyung Roh, Young Suk Park, Joong Bae Ahn
Journal: Journal of Clinical Oncology (2013)

511 Background: The purpose of this study was to evaluate rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) with 5-FU/leucovorin (FL) versus Irinotecan/S-1 (IS) and surgery followed by fluoropyrimidine based adjuvant chemotherapy. Methods: Patients with resectable, locally advanced (cT3-4 and/or cN positive) adenocarcinoma of rectum were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25-28 daily fractions) and concomitant chemotherapy with bolus injections of 5-FU 400 mg/m 2 /day and LV 20 mg/m 2 /day for 3 consecutive days every 4 weeks for 2 cycles (FL group), or with irinotecan 40 mg/m 2 on days 1, 8, 15, 22, 29 and S-1 35mg/m 2 twice on the day of irradiation (Monday-Friday) (IS group). Curative surgery was performed for about 4-8 weeks after the completion of chemoradiotherapy. Postoperative chemotherapy regimen is FL. The primary endpoint was pCR rate. Results: 142 eligible patients were randomly assigned. Of 142, 130 patients (91.5%) underwent total mesorectal excision. The pCR was achieved 11 (17.2 %) of 64 patients in the FL group and was 16 (24.2%) of 66 patients in the IS group (p=0.1). When pCR was combined with few residual cells, the rate was significantly higher in IS group compared to FL group (57.6 % vs. 39.1 %, p-value=0.035). Preoperative rate of grade 3-4 toxicity was 1.4% with FL and 7.0 % with IS group (p=0.095). Conclusions: The results have suggested that neoadjuvant CRT using IS is feasible and effective for patients with locally advanced rectal cancer. Longer follow-up is needed to assess survival. Clinical trial information: NCT01269216.
Transitioning chemotherapy administration from the inpatient setting: Creating bed capacity and improving the patient experience.
Authors: Regina Cunningham, Michael Vozniak, Kathleen Wiley, Colleen Kucharczuk, Brandi Swisher, Danielle Land, Robert Tobin, Marianna Holmes, Mauri Sullivan, Tonita Bell
Journal: Journal of Clinical Oncology (2012)

152 Background: Administration of selected multiday chemotherapy regimens typically requires an inpatient stay at an academic quaternary care facility. A growing oncology population exceeding the capacity of oncology allocated beds led to occasional cancellation of patients scheduled for curative-intent treatment, necessitating a reevaluation of our processes. A multidisciplinary group formed to pilot a process by which certain regimens would be transitioned to the outpatient arena and others would be split, requiring only a portion of the regimen to be given inpatient. Methods: The utilization of a variety of quality improvement tools and processes determined the feasibility and safety of transitioning previously inpatient-based regimens to the outpatient setting and identified those regimens that were most appropriate to pilot. An evaluative ranking process identified high-dose cytarabine for treatment of acute myeloid leukemia and infusional cyclophosphamide for multiple myeloma as most appropriate to be home-based regimens. Phase II of the pilot involved developing a process for the administration of select rituximab-based regimens between the inpatient and outpatient setting, with tightly fitted communication to ensure seamless transitions in care. Patients receive rituximab in the ambulatory clinic and are then admitted to a reserved hospital bed for the remainder of the regimen. Results: Since pilot inception and abstract submission, 20 patients have either received their entire regimen as an outpatient or by using our split location process. Preliminary analyses reveal an increased bed capacity for acute patients and outside hospital referrals by preventing scheduled admissions and reducing overall length of stay for rituximab-based regimens. Survey responses from patients and families are overwhelmingly positive. Conclusions: Care delivery models must be continually evaluated to adapt to change in this dynamic health care era. Our pilot suggests beneficial outcomes for patients and health care systems alike. As an institution, we have seen the effects that integrated team communication and tighter care coordination have on patient care and outcomes.
Will neoadjuvant chemotherapy affect the lymphatic routes to the sentinel lymph node? Investigation using indocyanine green fluorescence method.
Authors: Shigeru Tsuyuki, Yukiko Kawata, Ayane Yamaguchi, Kosuke Kawaguchi, Miru Okamura, Nobuko Kawaguchi, Yukihiro Kono
Journal: Journal of Clinical Oncology (2012)

164 Background: Neoadjuvant chemotherapy (NAC) is a standard therapy for breast cancer. However, the changes in the lymphatic route to the sentinel lymph node (SLN) before and after NAC are unclear. Indocyanine green (ICG) fluorescence method of SLN biopsy (ICG-SLNB) is useful because of its high identification rate of the SLN and ability to visualize lymphatic routes. Using ICG-SLNB, we compared the lymphatic routes to the SLN (sentinel lymphatic routes) before and after NAC and investigated whether chemotherapy affects the sentinel lymphatic routes. Methods: From October 2010 to April 2012 20 patients received NAC. In 13 cases of clinical node-negative cancer, we performed SLNB before NAC. We recorded the sentinel lymphatic routes before NAC and confirmed the routes at surgery after NAC by using the same method. In 7 cases of clinical node-positive cancer, we recorded the localization of SLN and lymphatic routes by using the ICG fluorescence method before NAC. After NAC, we performed SLNB with axillary dissection and recorded the sentinel lymphatic routes by photography and drawing. Results: Regardless of the presence or absence of lymph node metastasis, the SLN and sentinel lymphatic routes could be detected before and after NAC in all cases. All sentinel lymphatic routes reached the same location of the SLN before and after NAC. In 3 cases, the number of sentinel lymphatic routes had increased after NAC, but the location of the SLN was the same before and after NAC. Other cases showed no changes in the sentinel lymphatic routes. In clinical node-positive cases of pathological complete response, there was no metastasis to the SLN, but there were 2 metastases in the lymph nodes after back-up dissection. Conclusions: ICG fluorescence method provided visual confirmation that the sentinel lymphatic routes were not affected by NAC. This result suggests that SLNB after NAC can be used to safely and positively identify the SLN in clinical node-negative patients. Further investigation would be required to safely perform SLNB after NAC in clinical node-positive patients.
Tumor Necrosis Factor-α Enhances DMSO-Induced Differentiation of HL-60 Cells through Activation of ERK/MAPK Pathway.
Authors: Jinny Park, Young-Rae Lee, Eun-Mi Noh, Myung-Kwan Han, Jung Ryul Ahn, Young Sang Kim, Se Hoon Park, En Kyung Cho, Dong Bok Shin, Jae Hoon Lee, Jong-Suk Kim
Journal: Blood (2007)