tbuckley/cabot-search huggingface dataset:
High-dose bolus interleukin-2: Correlating response rate with number of doses received.
Authors: Jolly Patel, Mayer N. Fishman, Dawn Goetz
Journal: Journal of Clinical Oncology (2013)

452 Background: Administration of high-dose interleukin-2 (IL-2) in metastatic renal cell carcinoma (MRCC) has higher response and survival rates when compared to low dose or subcutaneous administration. In patients who achieve a response, it may be at the expense of more toxicity risk, from more doses. The association of the major response rate with the number of high dose boluses or cumulative dose received is of interest. The primary objective of this study is to evaluate a direct correlation with response and cumulative dose or the total number of doses received. Methods: A retrospective chart review was conducted of all patients at H. Lee Moffitt Cancer Center diagnosed with metastatic renal cell carcinoma who received high dose bolus IL-2 from September 30 th , 1999 to September 30 th , 2010. The cumulative dose and the number of doses of IL-2 received was recorded and associated with categorical complete response [CR], partial response [PR], stable disease [SD] or progressive disease [PD] response, by treating physician assessment. Sites of metastasis were also documented. The incidence of adverse effects such as renal failure, transaminitis, cardiac arrhythmias, thrombocytopenia as well as rates of infection and ICU transfers were tabulated. Results: 31 out of 55 patients analyzed were assessed at least with stable disease in response to IL-2. Six achieved a CR, 11 achieved a PR, 14 had stable disease and 24 patients had PD as best responses. Among those with CR or PR to IL-2, they received approximately 30 doses of IL-2 (p=0.027 vs. those not in that category). Converesely, those who received a higher cumulative dose were also more likely to respond (p=0.0077). With respect to adverse events, 58% of patients experienced acute renal insufficiency, 63% transaminitis, 40% arrhythmias, and 45% thrombocytopenia. 55% required dopamine use at any point and 11% required use of additional pressors; 15% required an ICU transfer at some point, and approximately 4% developed a documented infection. Conclusions: Cumulative dose or number of high dose bolus doses received is associated with a statistically significant difference in response rate, within the limitations of this retrospective analysis.
Internet Use by Patients with Lymphoma and Caregivers.
Authors: Antonia A. Garcia-Nieto, Soledad S. Duran, Maria Carmen M.C. Fernandez-Valle, Eduardo E. Rios, Juan Nicolas J.N. Rodriguez, Maria Vicencia M.V. Martin-Reina, Jose J. Duran, Alicia A. Bailen, Pilar P. Lopez, Manuel M. Almagro, Francisco Javier F.J. Capote
Journal: Blood (2006)
Patients as partners in defining outcomes.
Authors: Barbara L. Summers, Heidi Wied Albright, LaToi Shanel Tatum, Elizabeth Bassett, Thomas W. Feeley
Journal: Journal of Clinical Oncology (2013)

148 Background: The aim of this project was to develop an understanding of how patients conceptualize the term “outcomes” as it relates to their cancer experience and to determine patient preference for receiving and using outcomes-related information. When asked to rank cancer outcomes, most health care professionals suggest survival is the most significant outcome metric. We sought to determine if patients felt the same way. Methods: Focus group methodology was used in cancer patients with one of five major disease sites: breast, colon, lung, prostate, and head and neck. Participants were diverse with respect to age, ethnicity, income level, education level, and gender. Participants received semi-structured questions intended to elicit the patient’s personal conceptualization and use of outcomes information during their cancer continuum. Results: Patients identified a range of phenomena as their preferred definition of outcome and were sometimes confused by the term. Participants reported finding it difficult to interpret survival data without a basis for comparison or medical knowledge. Results of the focus groups will be presented and will address the wide variety of outcome definitions defined by patient participants. Conclusions: We found a large disconnect between what providers consider important and what patients consider important. We are continuing to evaluate patient perceptions of outcomes information by conducting further focus groups, and these qualitative findings will be used to develop a rigorous survey tool that can be administered to a greater number and wider variety of patients. Ultimately, the finding from these focus groups will allow for the creation of useful tools that educate patients and empower them to be full partners in their care.
Targeting I2PP2A by FTY720: A novel, mechanism-based treatment strategy for patients with advanced and previously treated non-small cell lung cancer (NSCLC).
Authors: G. R. Simon, S. Saddoughi, A. Mukhopadhyay, Y. Peterson, C. E. Senkal, J. Oaks, D. Perrotti, Y. Hannun, B. Ogretmen
Journal: Journal of Clinical Oncology (2011)

7574 Background: Protein phosphatase 2A (PP2A) is a tumor suppressor enzyme, whose activity is inhibited by I2PP2A (inhibitor 2 PP2A) in NSCLC cell lines. Our structural, molecular, genetic, and pharmacologic studies reveal that PP2A activity is regulated by direct and selective binding of C18-ceramide to I2PP2A, which then relieves PP2A, allowing it to exert its tumor suppressor function. The freed C18-ceramide is then released in the serum. Methods: NSCLC cell line and xenograft studies were done by standard procedures. Cell lines and A549 xenografts were treated with FTY720, a sphingosine derivative that targets I2PP2A, to demonstrate reduction in tumor proliferation and induction of apoptosis. We also measured C18-ceramide in to the serum of the treated mice by liquid chromatography/mass spectrometry (LC/MS). Additionally primary human NSCLC and adjacent normal lung were examined for I2PP2A expression by immunohistochemistry (IHC). Results: We found that I2PP2A is highly expressed, while C18-ceramide levels are down-regulated in the majority of primary human NSCLC specimens compared to their adjacent normal lung tissues. FTY720 was found to directly bind to I2PP2A through a ceramide-binding domain resulting in inhibition of growth in the tested human lung cancer cell lines and A549-xenograft-derived tumors. The reduction in tumor size in xenograft studies were accompanied by an increase in serum C18-ceramide levels. Conclusions: Our studies suggest I2PP2A is a key intracellular therapeutic target for NSCLC. I2PP2A levels can be routinely estimated by IHC and therefore the presence or absence of this target can be estimated in diagnostic biopsy specimens. FTY720 targets I2PP2A and has been shown to decrease proliferation and enhance apoptosis in NSCLC cell lines and xenograft studies. Tumor response to FTY720 can be measured by LC/MS in serum. Based on these novel data a phase II clinical trial with FTY720 for the treatment of patients with previously treated advanced NSCLC that overexpress I2PP2A is to be initiated soon. Details of preclinical, xenograft studies and the design of the clinical trial will be presented at the meeting.
Patient-centered wait time measurement in Ontario.
Authors: Leonard Kaizer, Monika Karolina Krzyzanowska, Sherrie Hertz, John Srigley, Julian Dobranowski, Jonathan Irish, Padraig Richard Warde, Julia Gao
Journal: Journal of Clinical Oncology (2012)

233 Background: Since 2005, a concerted effort to measure and manage access to chemotherapy services in Ontario has resulted in a significant reduction in several specific wait time intervals (referral for medical oncology consultation and medical oncology consultation to first treatment). To identify other opportunities to improve access, a comprehensive analysis of the all-inclusive wait times from cancer diagnosis to the start of adjuvant chemotherapy for patients with early stage colon, breast, and lung cancer (patient centered wait time) has been undertaken. Methods: The study cohort comprised all Ontario patients who received adjuvant chemotherapy in 2009 for early stage colon, breast, and lung cancers. The Ontario Cancer Registry, linked to several administrative healthcare databases in Ontario, was used to identify the cohort and variables of interest. Wait time from diagnosis of cancer to the initiation of adjuvant chemotherapy was measured and separated into segments based on the dates of diagnosis (D), surgery (S), referral to medical oncology (R), medical oncology consultation (C), and first adjuvant chemotherapy treatment (T), and each was analyzed for variation at a regional and institutional level. The times from surgery to pathology sign-out (TTPR) and for peripherally inserted central catheter (PICC) acquisition were also studied in a subset of cases. Results: In 2009, 86% of patients with stage III colon cancer, 80% of patients with stage I to III breast cancer and 63% of patients with stage II lung cancer who received adjuvant chemotherapy started their treatment within 120 days of diagnosis. There was significantly better performance and less regional variation for colon cancer patients (82-93%) than for breast cancer patients (63-90%). For the whole cohort of breast cancer patients, the median total time from diagnosis to adjuvant chemotherapy was 81 days with the following segmental breakdown D-S (30 days), S-R (19 days), R-C (16 days), and C-T (16 days). The mean TTPR for colon cancer patients was 11.6 days and PICC insertion was &lt; 7 days in 92% of patients. Conclusions: A number of opportunities for process improvement were identified, including shortening the pathology reporting interval and the timing for initiating referral to a medical oncologist.
Elevated expression level of laminin 5 γ2 chain may be a negative predictive factor for the response to gefitinib in lung cancer
Authors: S. An, Y. Wu, J. Zhu, Z. Chen, G. Zhang, Z. Wang, Z. Xie, S. Chen, Y. Huang, A. Guo, J. Lin
Journal: Journal of Clinical Oncology (2008)

14664 Background: Our previous study showed that laminin 5 (LN5) mRNA level in the carcinoma tissues is associated with the histological status, cigarette smoking, and gender of the patients with lung cancer. We noticed that this subgroup is identical with the lower level of LN5 expression level. This implies that LN5 mRNA lower level may be a molecule marker for predicting gefitinib sensitivity. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response, and the overall survival were evaluated. In vitro study were carried out by adding exogenous LN5 and gefitinib to A549 lung cancer cell line, and Western- blotting was performed to investigate the phosphorylation level of EGFR, Akt, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut-point group, and 17.6% for the above cut-point (P=0.009). Survival analysis showed that there was a significant difference between below and above cut-point group of the LN5 mRNA level (P=0.0253). There is no significant difference between EGFR mRNA expression level and response to gefitinib and survival (P>0.05). The exogenous LN5 neutralized the inhibition of phospho Akt by gefitinib in vitro. Conclusions: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients. No significant financial relationships to disclose.
Loss of lean body mass within one week as a major determinant for total weight loss at one month after gastrectomy for gastric cancer.
Authors: Toru Aoyama, Takaki Yoshikawa, Taiichi Kawabe, Hirohito Fujikawa, Tsutomu Hayashi, Takanobu Yamada, Tsutomu Sato, Takashi Oshima, Yasushi Rino, Takashi Ogata, Haruhiko Cho, Munetaka Masuda
Journal: Journal of Clinical Oncology (2015)

219 Background: Postoperative changes in body weight and composition during first 1 month after gastrectomy remained unclear. Methods: The patients who underwent gastrectomy for gastric cancer between May 2010 and October 2013 were examined. Body weight and composition were evaluated by bioelectrical impedance analyzer within 1 week before surgery (first measurement), at 1 week after surgery (second measurement), and at 1 month after surgery (third measurement). The changes of the early period were defined as the differences until the second measurement, while those of the late period as the differences from the second to the third measurement. Results: Two-hundred forty four patients were selected for this study. Total body weight loss (BWL) within 1 month was -3.4 kg and the rate of body weight at 1 month to the preoperative body weight was 94.1%. BWL was significantly greater in the early period rather than that of the late period (-2.1 kg vs -1.2 kg, p&lt;0.001). In the early period, loss of lean body mass was significantly greater than loss of fat mass (-1.5 kg vs -0.6 kg, p&lt;0.001). The same trend was observed regardless of type of gastrectomy and surgical approach. Conclusions: Loss of lean body mass within 1 week was a major determinant for total body weight loss at 1 month. To maintain lean body mass within 1 week and total body weight at 1 month, future trial should be focused on not the surgical approach but nutritional intervention within 1 week.
Metastatic pancreatic adenocarcinoma in complete remission after three and a half years of combination therapy with cetuximab
Authors: K. Mochlinski, D. Cunningham, B. Sharma, M. Uzzell
Journal: Journal of Clinical Oncology (2005)

4278 Background: Ductal adenocarcinoma of the exocrine pancreas has a poor prognosis with one-year survival rates of around 10% and 5-year survival of less than 4%. Long-term survivors derive from patients with resectable disease at the outset, who constitute less than 20% of the total diagnosed, while median survival with metastatic disease remains less than 6 months. To improve the outcome in a patient with advanced disease at presentation, the addition of the EGFR-targeting monoclonal antibody Cetuximab to the standard available therapies was used. Methods: A 49 year old male was diagnosed as having a poorly-differentiated adenocarcinoma of the pancreas body and tail with liver metastases. He received Docetaxel and Irinotecan for 30 weeks before and 15 weeks after surgical resection of the primary tumour and hepatic metastatectomy. On liver relapse (evident on MRI and PET scans), Gemcitabine and Oxaliplatin were used for 58 weeks resulting in complete remission (CR) radiologically (on CT, MRI and PET scanning) and pathologically (on repeat laparotomy and biopsies). Cetuximab was administered from the first day of treatment and then throughout, subsequently now being continued for over one year as maintenance monotherapy following documentation of CR. His formal consent was obtained for presentation of his case history. Results: Overall therapy very well tolerated, with excellent long term quality of life. Maximal toxicity recorded involved nausea and vomiting (G3) on the initial chemotherapy; peripheral sensory neuropathy (G2) and hypersensitivity (G3) from Oxaliplatin; neutropoenia (G4) but only after 27 months from starting chemotherapy; skin toxicity (G2) due to Cetuximab, settling over time. CR has been maintained now for 18 months, with the patient currently remaining disease-free on single agent Cetuximab at 3.5 years after diagnosis with metastatic pancreatic adenocarcinoma. Conclusions: These observations in a single patient suggest a benefit for long-term Cetuximab in pancreatic carcinoma. Long term use, including peri-operative administration, appears to be safe and well tolerated. Further evaluation of Cetuximab in this disease is recommended. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, sanofi-aventis Merck, sanofi-aventis
Phase I study of gefitinib and rapamycin in patients with recurrent or progressive glioblastoma (Gbm)
Authors: A. Das, M. Badruddoja, D. Tryciecky, J. Yu, K. Black
Journal: Journal of Clinical Oncology (2005)

1572 Background: GBMs overexpress epidermal growth factor receptor (EGFR) and gefitinib inhibits EGFR tyrosine kinase. The protein mTOR also promotes GBM growth and rapamycin blocks the interaction of mTOR with its target proteins. Therefore, the combination of gefitinib and rapamycin should have a synergistic effect in treating GBM. The primary objectives of this study are to evaluate the safety and toxicity of gefitinib and rapamycin, while secondarily determining time to tumor progression, overall survival and quality of life assessments in progressive or recurrent GBM. Methods: Patients aged 18 years or older with progressive or recurrent GBM and KPS of 40% or greater are included. Gefitinib is dosed at 500 mg/day with those receiving dexamethasone or enzyme inducing anti-epileptic drugs (EIAED) escalated to 1000 mg/day. Rapamycin is dosed at 2 mg/day and adjusted to levels of 4–12 nanograms/mL. Neurologic exam, KPS, laboratory parameters and NCI CTC are initially obtained every 2 weeks and then monthly. MRI scans of the brain and FACT-Br are performed every two months. Those patients with stable disease, partial or complete responses continue study medications until tumor progression or dose-limiting toxicities occur. Results: To date 10 patients have enrolled and 7 are assessable. There are 6 men and 1 woman with a median age of 57 years (range 31 to 72 years) and a median KPS of 60% (range 50–80%). Previous treatments included surgery, with 4 patients having undergone 1 craniotomy and 3 patients had 2 craniotomies. All patients had received radiation and chemotherapy, and 4 participated in a phase I immunotherapy trial. Six patients were taking steroids and 3 were taking EIAED. Toxicities included fatigue, rash, diarrhea and infection. Of the 7 patients, 4 were assessable for response with 0 CR, 1 PR, 2 PD, and 1 SD. The median progression free and median survival times have yet to be attained. Conclusions: The combination of gefitinib and rapamycin is well tolerated in this heavily pre-treated group. No significant financial relationships to disclose.
Clinicopathological features in metastatic colorectal cancer patients with <i>KRAS</i> wild type compared with codon 12 and codon 13 mutant: Results from a multicenter, cross-sectional study by the Japan study group of <i>KRAS</i> mutation in colorectal cancer.
Authors: T. Yoshino, T. Watanabe, K. Yamazaki, H. Uetake, M. Ishiguro, K. Sugihara, Y. Ohashi
Journal: Journal of Clinical Oncology (2011)

407 Background: The KRAS mutation mainly located in the codon 12 and 13 indicates unresponsiveness of patients with metastatic colorectal cancer (CRC) to anti-epidermal growth factor receptor (EGFR) antibodies. Many studies have reported that approximately 30%-40% of CRC patients have KRAS mutations. However, the clinicopathological features of KRAS mutant CRC have not been fully clarified, especially in Asian populations. This study aimed to clarify the clinicopathological features of KRAS mutant CRC in comparison with KRAS wild type in large-scale Japanese population. Methods: The key eligibility criteria included histologically confirmed colorectal adenocarcinoma with adequate tumor samples. Formalin-fixed paraffin-embedded tumor blocks or thinly sliced tumor sections from 389 centers were sent to commercial laboratories. Almost all KRAS point mutations in the codon 12 and 13 were investigated by direct sequencing (96%). The logistic regression analysis was used to estimate the odds ratios (ORs) and compute 95% confidential intervals (CIs). Results: Of 5,887 registered tumor samples between Oct. 2009 and Mar. 2010, the KRAS testing were performed for 5,790 samples. As of the cut-off date, Sep. 2010, we have successfully determined the KRAS mutational status of 5,732 samples (99%).The median age was 65 years old, and 61% were male. The primary tumor site was right colon, left colon, and rectum in 30, 38, and 32% patients, respectively. The frequency of KRAS mutation was 37.6% (2,155/5,732), of which the 80% (1,714/2,155) mutations were located in codon 12. On logistic regression analysis, female gender (OR=1.212, 95% CI=1.083-1.356), older age &gt; 50 years (OR=1.312, CI=1.056-1.628) and right colon (versus left: OR=2.177, CI=1.905- 2.489; versus rectum: OR=1.500, CI=1.308-1.720) were independent risk factors of KRAS mutant CRC. Clinicopathological features were similar between codon 12 and 13 mutant CRC. Conclusions: This study disclosed that KRAS mutant CRC was different from KRAS wild type CRC in terms of clinicopathological features. No significant financial relationships to disclose.
In vitro reproduction and explanation of an abiraterone acetate withdrawal phenomenon.
Authors: Paul Thelen, Hubertus Jarry, Lutz Trojan, Sabine Brookman-May, Felix Bremmer
Journal: Journal of Clinical Oncology (2014)

154 Background: Androgen deprivation and direct androgen receptor (AR) antagonism are standard treatments for castration resistant prostate cancer (CRPC). The advent of new drugs such as abiraterone acetate (AA) and enzalutamide rendered highly efficient implementations of both anti-androgen strategies. However, reports of therapy resistance or cross resistance soon accompanied reports of successful clinical trials of these new drugs. Moreover, case reports of an AA-withdrawal phenomenon surfaced, an outcome normally associated with AR antagonism e.g. by bicalutamide with high AR-affinity and the potential to switch from antagonism to AR-activation. Methods: CRPC cell model VCaP and VCaP resistant to permanent treatment of 5 µmol/L AA (Janssen-Cilag, Germany) were analyzed under AA and for AA withdrawal. Expression of AR, AR-V7, androgen regulated genes, CYP17A1 and AKR1C3 was quantitated by real time RT-PCR. Further analyses were performed by western blots, prostate-specific antigen (PSA) ELISA kits and cell proliferation BrdU tests. Results: VCaP cells resistant to 5 µmol/L AA after 7 months revealed excessive AR and CYP17A1 expression and a marked decline of tumor cell proliferation in response to AA withdrawal or to a similar extent to added 1 nmol/L testosterone. Proliferation dropped to less than 50% when both procedures were combined. Elimination of tumor cells was accompanied by a massive release of PSA which was most pronounced in the combined treatment. Conclusions: Overexpression of AR turning into a liability as a therapeutic target for a testosterone surge has been reported by several research groups. AA withdrawal from AA resistant cells complies with these necessities by overexpression of AR and CYP17A1 formerly arrested by AA. In patients a PSA decline upon AA withdrawal may be explained by an excessive loss of PSA secreting tumor cells. Therefore, AA qualifies uniquely for effective intermittent androgen deprivation of CRPC.