tbuckley/cabot-search huggingface dataset:
Development of a comprehensive geriatric assessment (CGA) measure for older patients (Pts) with cancer: A feasibility study
Authors: A. Hurria, S. Gupta, M. Zauderer, E. Zuckerman, M. Rodin, J. Holland, H. Muss, H. J. Cohen, A. B. Kornblith
Journal: Journal of Clinical Oncology (2004)

8162 Background: As the cancer (CA) population ages, a brief, comprehensive measure is needed to help characterize the “functional age” of a patient (pt), in order to optimize treatment decisions and stratify outcomes based on factors other than chronological age. The purpose of this study was to develop a brief CGA for older pts with CA and to determine the feasibility of administering this assessment. Methods: The geriatrics and oncology literature were reviewed to choose validated measures commonly used in geriatric assessment across the following domains: functional status, comorbidity, cognition, psychological status, social functioning and support, and nutritional status. Criteria applied to measure selection included: reliability, validity, and brevity. The CGA was largely self-administered or administered by a trained research assistant if pts required assistance. Results: 43 pts (mean age 74.4; range 65–87) receiving chemo for breast CA, lung CA, colorectal CA, or lymphoma were enrolled. 68% had stage IV disease. Mean time to completion of CGA was 26.8 minutes (range 8.3 to 45 minutes). 78% were able to complete without assistance. 90% were satisfied with questionnaire length. 95% had comorbid medical conditions (mean 2.9; range 0–11). 38% were dependent in 1 or more instrumental activities of daily living, despite mean physician (MD) reported KPS of 81.8 (range 50–100). There was discordance (≥ 10 points) between MD and pt rated KPS 58% of the time, with pts more likely to report better KPS than MDs. Pts reported wide variability in physical functioning as described by the Medical Outcomes Study Physical Functioning Scale [mean score of 63 (Range 5–100; SD 30)]. One pt demonstrated gross cognitive impairment. 38% experienced >5% weight loss in the last 6 months. Neither age (p = 0.56) nor education (p = 0.99) were associated with ability to complete the questionnaires. Conclusions: This brief CGA can be largely self-administered and completed by the majority of pts without assistance. Prospective trials are needed to determine the ability of CGA to predict the extent of pts' toxicity to chemo, and disease specific or overall survival. No significant financial relationships to disclose.
Discrepancies between two staging systems (European-ENETS versus. American-AJCC) of neuroendocrine neoplasms of the pancreas: A study of 77 cases.
Authors: Javier A. Cienfuegos, Joseba Salguero, Jorge Nuñez, Fernando Rotellar, Pablo Marti-Cruchaga, Gabriel Zozaya, Fernando Pardo
Journal: Journal of Clinical Oncology (2015)

318 Background: Pancreatic neuroendocrine tumors (pNETs) comprise a spectrum of neoplasm with variable biological behaviour and heterogeneous prognosis. The European Neuroendocrine Tumor Society (ENETS) and the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) TNM staging systems have been recently published. The aim of this study was to evaluate the consistency of both staging systems on outcomes for patients with pNETs. Methods: A retrospective clinico-pathological study of 77 consecutive patients with pNETs who were surgically treated from 1993 to 2014 was carried out. Results: The male to female ratio was 1.0 (38 men, 39 women); 56 tumors were non-functionating and 21 functionating. Most of the tumors were G1 (57) and 20 were classified as G2-G3. The AJCC/UICC stage was IA in 29 patients, IB in 14, IIA in 10, IIB in 7 and IV in 17. Meanwhile, according with the ENETS staging system was: stage I in 30, IIa in 14, IIb in 3, IIIa in 6, IIIb in 7 and IV in 17. We found 18 (23.3%) cases of ENETS - AJCC/UICC discrepancies regarding the primary tumor. They included 6 cases (33%) disagreement between IIA (T3 N0 M0) and IIIa (T4 N0 M0); and 7 cases (38.8%) between IIB (T1-T3 N1 M0) and IIIb (anyT N1 M0). Conclusions: The AJCC and ENETS TNM classification staging for pNETs provide meaninful prognostic value of long-term survival por patients with pNETs. The T staging discrepancies between AJCC/UICC and ENETS are relative frequent and should be strictly recognized.
Robustness of response: A new measure of response assessment: Its impact on metricies of response in colorectal cancer
Authors: L. Wang, L. H. Schwartz, M. Mazumdar, A. Smith, N. E. Kemeny
Journal: Journal of Clinical Oncology (2005)

3569 Background: To illustrate a new method of quantifying and comparing response assessment techniques known as robustness of response (ROR) and to evaluate unidimensional measurement (RECIST criteria) versus bidimensional measurement (WHO criteria) with respect to their impact on assessment including response classification, time to tumor progression (TTP) and time to best overall response (BOR) in patients with colorectal cancer. Methods: 68 patients with metastatic colorectal cancer on clinical trials of HAI Floxuridine and Dexamethasone with systemic oxaliplatin with 5FU/LV and/or Irinotecan were retrospectively reviewed. The studies of a total of 2735 measurements included 68 baselines and 200 follow-up CT examinations of the chest, abdomen and pelvis. Response assessment and progression-free survival were calculated with RECIST and WHO. ROR was determined and compared among and between discordant and concordant cases. Results: There was a 92.6% agreement rate and a 7.4% disagreement rate in BOR between RECIST and WHO. The median TTP assessed by RECIST was 5.83 months compared to 5.40 months assessed by WHO (P=0.006). Time to BOR was not significantly different comparing RECIST and WHO (P=0.82). Mean percentage decrease in tumor size among the 27 unidimensional responders and 28 bidimensional responders was 65.0% and 79.7%, respectively. Mean increase in size among the 36 unidimensional progressors and 48 bidimensional progressors was 61.8% and 139.1%, respectively. The average robustness value was -35.3% by RECIST and 53.9% by WHO among the 17 discordant pairs and -25.9% by RECIST and 78.9% by WHO among the 51 concordant pairs. A comparison of ROR in time to BOR found an average robustness value of 35.7% by RECIST versus 24.8% by WHO among the 10 discordant cases, and 5.3% by RECIST versus 60.6% by WHO among the 58 concordant cases. Conclusions: In colorectal cancer, time to tumor progression was different between WHO and RECIST. This may impact clinical trials whose results are interpreted with RECIST and WHO. A new method of measuring “ROR” may indicate disease sites or therapies that are affected by measurement technique, and help to define the degree of response or progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Byrne Foundation and NIH Cancer Chemotherapy Program Project (CA05826-35), Experimental Therapeutic Center
TS and MTHFR gene polymorphisms in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head or neck (SCCHN) treated with pemetrexed (P) and bevacizumab (B)
Authors: M. Romkes, T. M. Feinstein, S. Zhong, S. Buch, M. K. Gibson, K. Skovira, A. Argiris
Journal: Journal of Clinical Oncology (2009)

e17011 Background: P inhibits multiple enzymes in folate metabolism. We examined polymorphisms in thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) in patients with SCCHN treated in a phase II clinical trial with P and B (ASCO 2008; A6069). Methods: All pts were treated with P 500 mg/m 2 and B 15 mg/kg, given IV every 21 days until progression. Primary endpoint was time to progression (TTP). DNA was isolated from whole blood samples using commercially available kits. Polymorphisms examined were MTHFR (C677T, A1298C and G1793A) and TS (TS2R3R, TSG2RG and TSmut6). The MTHFR SNPs were detected using TaqMan based SNP genotyping kits from Applied Biosystems, run on the ABI Prism 7700 Sequence Detection systems v 1.7 (Foster City, CA). The TS promoter repeat and promoter SNP polymorphisms and the 3’ untranslated region 6 bp deletion polymorphism were determined using published methods to detect PCR product size and RFLP-PCR assays respectively. Results: 22 pts were genotyped from 34 enrolled. There was no significant difference in characteristics between pts with and without genotype data. For the MTHFR polymorphism C677T, there was a trend towards decreased disease control rate (DCR) (CR/PR/SD) (p = 0.058, Jonckheere-Terpstra trend test) and worse TTP (p = 0.04) transitioning from variant CC to CT to TT; comparing TT genotype versus CT and CC combined, pts with TT had inferior DCR (p = 0.03) and TTP (p = 0.0003); homozygotes with TT had a median TTP of 2.6 months (mo) 95% CI (1.4, NA) versus 5.6 mo (4.2, 11.4) for pts with CT or CC variants. For the MTHFR A1298C SNP, there was no significant difference in DCR between variants, median TTP for homozygotes pts with AA was 4.1 mo (2.6, NA) vs. 6.7 mo (5.1, NA) in pts with AC or CC variants (p = 0.084); median overall survival for AA was 10.2 mo (7.6, NA) and for AC or CC 17.6 mo (17, NA) (p = 0.045). The MTHFR G1793A and TS polymorphisms did not impact DCR, TTP or overall survival. There was no association between any polymorphism and the incidence of grade &gt;2 toxicities. Conclusions: Polymorphisms in MTHFR are potentially associated with antitumor efficacy of P-based therapy in recurrent or metastatic SCCHN. These results warrant validation in larger studies with P in SCCHN. No significant financial relationships to disclose.
Tegafur combined with oxaliplatin and 5-FU versus FOLFOX4 for advanced colorectal cancer: a randomized controlled study
Authors: L. Lingxiang, S. Yongqian, L. Ping, H. Puwen, Y. Yongmei
Journal: Journal of Clinical Oncology (2006)

13566 Background: To determine the activity and side-effect of tegarfur injection combined with L-OHP and 5-FU, comparing with FOLFOX4 as the therapy for advanced colorectal cancer. Methods: 60 patients, proved pathologically, were divided into 2 groups at random. Group A received the intravenous administration of tegafur(800mg/m 2 IV 3hrs qd d1–5),leucovorin(100mg/m 2 IV 2hrs qd d1–5) and L-OHP(130mg/m 2 IV 2hrs d1) every 21 days. FOLFOX4 was applied in the group B. The endpoint included response rate (RR), progression free survival (PFS), overall survival(OS) and quality of life(QOL). Results: The response rate was 39.3% in the group A, while median time to progression was 9.5 months with median survival time of 11.6 months. In the group B, the response rate was 48.1% and median time to progression was 9.4 months with median survival time of 12.1 months. No significant differences were found between treatment arms in curative effect, survival time and side effect(P&gt;0.05). With respect to QOL, the group A achieved higher PS than B during treatment (P&lt;0.001). Conclusions: The intravenous administration of tegafur, leucovorin and L-OHP is a well-tolerated, effective, and feasible schedule for advanced colorectal cancer that yields comparable efficacy and side effect compared with FOLFOX4. Meanwhile, the former achieves the better QOL. No significant financial relationships to disclose.
131I-Metaiodobenzylguanidine (131I-MIBG) double infusion with autologous stem cell transplant for neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) study
Authors: K. K. Matthay, A. Quach, J. Huberty, B. Franc, S. Groshen, S. Shusterman, J. Veatch, P. Brophy, G. Yanik, J. Maris
Journal: Journal of Clinical Oncology (2006)

9011 Background: 131 I-MIBG provides targeted radiotherapy with &gt;30% response in refractory neuroblastoma, but the activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum tolerated dose of 131 I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem cell transplant (ASCT) 2 weeks after the second dose. Methods: The 131 I-MIBG was escalated in a 3+3 Phase I trial design, with levels calculated by total red marrow radiation index (RMI) from the double infusion. The first infusion of 131 I-MIBG was 12, 15, 18 and 21 mCi/kg for levels 1, 2, 3 and 4 respectively. Using detailed dosimetry, the second infusion was adjusted to achieve the target RMI, except at Level 4, where the second infusion was capped at 21 mCi/kg. Results: Twenty-one patients were enrolled at Level 1–4, with 18 evaluable for toxicity. Median age at enrollment was 7 years, all were heavily pretreated, including 12 with prior high dose therapy and ASCT, and 12 patients had bone marrow tumor. Cumulative 131 I-MIBG given to achieve the target RMI ranged from 18 mci/kg to 49 mCi/kg. RMI delivered per mCi of MIBG decreased in 15/19 patients by mean of 0.21 cGy/mCi with the second infusion. Hematologic toxicity was acceptable, with median time to ANC&gt;500 after ASCT of 13 (4–27) days. Platelet transfusion was required in 15/18 patients, with median time to platelet independence of 18 (6–47) days after ASCT. There were no non-hematologic toxicities above grade 2 attributed to therapy, though 9 patients had grade 1–2 elevations of transaminase, and 1 had grade 2 hypothyroidism. Responses in 17 evaluable patients included 1 PR, 4 MR, 6 SD, and 6 PD. Eleven patients are alive at median of 361 days (46–483); 5 died of PD and 1 of unrelated toxicity. Conclusion: The lack of toxicity with this approach allowed dramatic dose intensification of 131 I-MIBG, with minimal toxicity and the possibility of improved response. [Table: see text] No significant financial relationships to disclose.
Role of expression of FIP200 protein in progression of hepatocellular carcinoma
Authors: H. Ueda
Journal: Journal of Clinical Oncology (2009)

e22147 Background: FIP200 protein is a newly identified protein, and recent report has shown that FIP200 interacts with p53 and inhibit progression and proliferation. Although expression of FIP200 has been confirmed in normal liver,the expression and function in human HCC is completely unknown. In this study, we examined expression of FIP200 in HCC cell lines and investigated the involvement of FIP200 in proliferation and apoptosis. We also examined expression of FIP200 using HCC tissues and the correlation between FIP200 expression and clinical outcome. Methods: The study was conducted using HCC cell lines (HepG2, HuH7, and Hep3B). P53 status in HepG2, HuH7 and Hep3B are wild type, mutant type and deficient types respectively. Expression of endogenous FIP200 was assessed by western blotting. To investigate antitumor function, we carried out BrdU incorporation assay with transfected FIP200. TUNEL was carried out for identification of apoptosis. We also reviewed 14 patients who had undergone initial liver resection for HCC. Immunohistochemistry analysis for FIP200 was performed and we investigated the FIP200 expression levels according to differentiation degree of HCC tissues. Results: Endogenous FIP200 was detected in all cell lines, and those expression levels were different among cell lines. Overexpression of FIP200 significantly decreased BrdU incorporation in HepG2 and HuH7 but not Hep3B. In the study of TUNEL, apoptosis was observed for p53 wild HepG2 transfected with FIP200. In Hep3B, there was no significant difference observed. As for clinical samples, FIP200 were detected in all HCC and non-HCC tissues. FIP200 expression levels in HCC tissues were decreased compared to non-HCC tissues. Furthermore, as differentiation degree poored, those expression levels were decreased in the same tissue as well as in the different tissue. Conclusions: Endogenous FIP200 was expressed in all cell line. Those expression levels were different according to p53 status. Our study demonstrated that FIP200 inhibit proliferation in HCC expressed p53, and induce apoptosis in p53 wild HCC but not p53 deficient HCC. Furthermore, the FIP200 expression levels were significantly associated with differentiation degree. These data suggest that FIP200 plays an important role in promoting tumor progression in HCC. No significant financial relationships to disclose.
Early toxicity of sunitinib as a potential predictive biomarker in advanced hepatocellular carcinoma (HCC) patients.
Authors: G. D. Duda, M. Ancukiewicz, J. W. Clark, R. A. Miksad, C. Fuchs, D. P. Ryan, R. K. Jain, A. X. Zhu
Journal: Journal of Clinical Oncology (2010)

4081 Background: We previously reported efficacy and toxicity data from a phase II study of sunitinib (37.5 mg daily for 4 weeks followed by 2 weeks break) in patients with advanced HCC (Zhu et al, J Clin Oncol 2009). Sunitinib significantly decreased the number of circulating hematopoietic progenitor/stem cells, and that modulation of circulating inflammatory factors (e.g., IL-6) correlated with survival outcomes. Since hematologic toxicities are frequent after sunitinib therapy, we studied the early kinetics of these adverse events and explored their association with circulating biomarkers and clinical outcome. Methods: Toxicity of sunitinib was evaluated every two-weeks during the first cycle of therapy. Biomarker level changes from baseline were tested using the exact paired Wilcoxon test. P-values were adjusted for multiple comparisons over time, using the false discovery rate control method with weights proportional to the square root of the number of data points. Correlation between toxicities and overall survival or progression-free survival was evaluated in a Cox model using log-transformed levels of biomarkers or biomarker change after stratifying by Cancer of the Liver Italian Program (CLIP) score and for baseline biomarkers. Results: We found that sunitinib significantly and rapidly decreased all myeloid and lymphoid circulating cell populations (by 20%-50%), but increased erythropoiesis (p < 0.05 for all). The extent of the early decrease in neutrophils, platelets and monocytes, as well as the development of non-hematologic toxicities (i.e., skin toxicities), was significantly associated with improved survival outcomes (p < 0.05). Finally, circulating cell kinetics significantly associated with specific changes in plasma biomarkers (e.g., changes in platelets with changes in VEGF-C and soluble VEGFR3; changes in neutrophils with changes in IL-8, TNF-α and soluble VEGFR2). Conclusions: The adverse effects of sunitinib, particularly on the hematopoietic system, are rapid and may be directly related to its activity in advanced HCC. This exploratory study suggests that early hematopoietic toxicities from sunitinib may predict survival outcomes in advanced HCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Dyax, Genentech, Genomic Health, ImClone Systems, Merck, Millennium, Pfizer, Regeneron, Roche, SynDevRx SynDevRx Genentech, Pfizer AstraZeneca, Dyax, Pfizer
Zoledronic acid (Z) as palliative treatment in cancer patients with bone metastases: Interim results of a prospective, open-label trial
Authors: A. Kretzschmar, T. Wiegel, S. E. Al-Batran, H. F. Hinrichs, M. Kindler, T. Steck, H. J. Illiger, U. Haus, A. Kirner, G. Ehninger
Journal: Journal of Clinical Oncology (2004)

8140 Background: Bone metastases in cancer patients may lead to severe bone pain, pathological fractures, and hypercalcemia. The development of osteolytic destruction is due to activation of osteoclasts by release of tumor-derived stimulating factors. The bisphosphonate (BP) Z is known to inhibit osteoclast function and thus to alleviate the adverse effects of tumor-induced increase in osteoclastic bone resorption. We investigated the effects of Z in patients with bone metastases in a broad range of tumor types Methods: BP-naive patients with at least one detectable bone lesion irrespective of the primary tumor were eligible for enrolment in this prospective, multicenter study with a single treatment arm, in which patients receive Z at a dose of 4 mg every 3–4 weeks for a maximum of 12 infusions. Primary study endpoints are the treatment-emergent changes in pain sensation assessed by a 100 mm visual analog scale (VAS) for bone pain, and in the concomitant consumption of analgesics, assessed by a five-point scale ranging from 0–4 in according to the analgesic capacity (both documented by a patient diary). Here, we present the data of an interim analysis after 24 weeks. Results: 606 patients in 67 centers have been included. 408 of them were valid for the efficacy analysis (non-validity mostly due to missing data from patient diaries). The age of this subset (61% females) ranged from 31–90 years. Predominant types of primary cancer were breast (49%) and prostate cancer (18%). 319 patients regularly completed treatment up to Week 24. The mean VAS value for pain decreased by 13.8 ± 30.6 from 36.9 ± 28.2 to 23.1 ± 23.8 (p<0.0001, t-test, (“last observation carried forward” procedure for drop-outs). Accordingly, the mean analgesic score not only remained stable, but even decreased by 0.37 ± 1.30 from 1.65 ± 1.56 to 1.28 ± 1.61 (p<0.0001, t-test). Conclusions: Based on the presented results, we conclude that treatment of bone metastases in a broad range of tumor types with Z acid provides substantial benefit to cancer patients also in terms of pain relief and thus improves their quality of life. (supported by Novartis Pharma GmbH, Nürnberg, Germany) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma GmbH Germany
Spontaneous immune responses to melanoma-associated antigens in melanoma, vitiligo and healthy controls
Authors: S. Adams, M. Lowes, A. Pavlick, S. Schachterle, D. O’Neill, N. Bhardwaj
Journal: Journal of Clinical Oncology (2005)

9682 Background: To evaluate the immunogenicity of peptide-based vaccines for melanoma, it is of critical importance to provide immunological correlates by which to gauge clinically protective immune responses. A valuable model is the autoimmune disorder vitiligo in which there is evidence of the involvement of cellular immunity eliminating melanocytes through recognition of autoantigens. In mice, skin depigmentation develops after immunization with human tyrosinase-related protein (TRP)-2, suggesting a cytotoxic immune response against antigen-bearing cells, a desired result of vaccine therapies in melanoma. In addition, skin-homing melanocyte-specific cytotoxic T cells have been demonstrated in vitiligo patients. In this study we examined the underlying cellular immunity and the extent of these immune responses to several HLA A2-restricted melanoma-associated antigens (MAA) in patients with vitiligo and melanoma. Methods: We accrued 12 healthy volunteers (controls), 11 patients with malignant melanoma and 14 subjects with vitiligo, the study was IRB approved at Rockefeller University. Enzyme-linked immunospot assays (ELISPOT) were performed on peripheral blood mononuclear cells of HLA A2.1 positive patients to enumerate antigen-specific T-cells secreting interferon-gamma after exposure to the MAA. Five HLA A2-restricted melanoma-associated peptides: gp 100209–217, tyrosinase368–376, Melan A26–35, MAGE 3271–279, TRP-2180–188 were chosen as well as Flu-MP (positive control). Less than 50% of individuals were HLA A2.1 positive. Conclusions: In contrast to expected results, melanoma antigen-specific T cell responses were not observed in the peripheral blood of vitiligo subjects. Therefore, studies are planned utilizing more sensitive assays, different antigens and removal of regulatory T-cells. No significant financial relationships to disclose.