tbuckley/cabot-search huggingface dataset:
Preliminary experience with imatinib mesylate therapy of Ph+ chronic myelocytic leukaemia in Ile-Ife Nigeria
Authors: M. A. Durosinmi, J. O. Faluyi, C. C. Okany, S. A. Akanmu, I. A. Adediran, N. O. Akinola, L. Salawu, O. G. Ibegbulam, O. C. Okocha
Journal: Journal of Clinical Oncology (2005)

3216 Background: Imatinib mesylate (glivec) is a specific inhibitor of bcr-abl tyrosine kinases that is capable of inducing durable cytogenetic remission and therefore cure of Ph+CML. We report experience of treating some Nigerians with Ph+CML with imatinib. Methods: Consenting Nigerians with Ph+ CML, irrespective of previous therapy were enrolled into the free therapy under the Novartis GIPAP initiative. Participants included individuals with active CML and patients in haematologic remission. Every patient underwent pretreatment bone marrow karyotyping, clinical and laboratory examinations. 400 mg imatinib capsules were given to patients in chronic phase and/or remission and 600mg for accelerated or blastic phase. Blood counts were checked 2-weekly. Presence of Grade III neutropenia and/or thrombocytopenia was an absolute indication for withholding therapy. Marrow karyotyping was repeated six monthly. Results: There were 20 patients (10males, 10 females), aged 16–61 years (median - 36); 15 in chronic phase, 1 in accelerated phase and 4 in haematologic remission at enrolment. The duration of imatinib therapy ranged from 0.4–156.3 (median = 16.0) weeks. Fifteen (93.8%) of 16 patients in active disease achieved haematologic remission within one month of therapy. The patient in accelerated phase died of blastic transformation 5 weeks into therapy. Imatinib was withheld in 5 (25%) patients with grade three neutropenia (+ thrombocytopenia in 1). Other complications noted were myalgias (x 4), weight gain (x 8), massive ascites (x 1) and severe unilateral tinnitus, requiring drug withdrawal (x 1). Repeat karyotyping in 4 patients during remission revealed no Ph+ cells in 3 patients, but persistent Ph+ in 1 person. Conclusions: Compared to conventional chemotherapy and even alpha interferon, as previously used in Nigeria, imatinib is capable of inducing early cytogenetic remission in Ph+CML patients and toxicity is tolerable. No significant financial relationships to disclose.
MD Anderson Cancer Center Ongoing Professional Practice Evaluation (OPPE): We can see clearly now.
Authors: Joyce Roquemore, Leslie Kian
Journal: Journal of Clinical Oncology (2012)

277 Background: Reviewing clinical practice by provider has been an ongoing process for quite some time. The metrics reviewed and how the review was conducted were not clearly defined and, as a result, has varied widely between organizations. Recredentialing or some self-imposed process were the main drivers until The Joint Commission required a more regular review of the clinicians’ practice in a hospital and clinics setting. MD Anderson embraced the requirement as an opportunity to improve its clinical review process and create a more robust infrastructure. Methods: Organizational and technological support was critical for success. The OPPE effort is led by the V.P. for Medical Affairs. A new faculty role, Quality Officer (QO), was established in each clinical department. The Office of Performance Improvement (OPI) was enlisted for data support and provided educational resources to the QOs. The Information Services staff maintains the technology to support the project long term. The Medical Staff Office has administrative responsibility for the program. Results: Two bi-annual OPPE reviews for credentialed providers (physicians and mid-levels) have been completed under the new process. Electronic display and processing has eliminated volumes of paper needed to track OPPE for 1,000+ faculty. External audit requirements are easily supported. Early adopters of the new OPPE tools have been complimentary of the support provided by display of values in control chart versus table formats. The application of statistical process control rules help QOs understand variation in performance among faculty and aid in identifying statistically valid quality issues. Conclusions: MD Anderson leveraged the OPPE requirements to make organizational changes and create processes that enhance review of clinical practice with electronic tools that improve decision making and analytical capabilities. The implementation of clinical quality metrics has made it clearer to see how each practice is doing based on criteria they defined, as well as create a path towards developing oncology performance metrics that can be considered nationally.
A Blunted Response to the Anti-Inflammatory Cytokine IL-10 Contributes to Excessive TNF Production in Myeloproliferative Neoplasm
Authors: Hew Yeng Lai, Sarah J Morse, Thanh Kim Nguyen, Samuel B Luty, Michael Garbati, Grover C. Bagby, Brian J. Druker, Angela G Fleischman
Journal: Blood (2015)
Revealing the metabonomic variation of esophageal cancer using 1H-NMR spectroscopy and its association with the clinic pathological characteristics.
Authors: I. Sheyhidin, A. Hasim
Journal: Journal of Clinical Oncology (2011)

e14522 Background: The aim of this study is to detect body fluid metabolites between esophageal cancer (EC) patients’s vs. healthy controls to analyze the variation between patients with esophageal cancer and to explore the potential application of EC biomarkers using 1H MR-based metabonomics. Methods: Preoperative plasma and urine of 108 patients with EC and 50 healthy donors were subjected to the analysis by 1H-NMR spectroscopy, and after data reduction, OPLS-DA (orthogonal partial least-squares discriminate analysis) was applied for pattern recognition, and results were further evaluated by comparison with parameters of histopathology. Results: Based on the data derived from the analysis by OPLS-DA, we identified a general metabonomic profile of EC with a series of metabolites existing in a significantly lower or higher abundance in plasma of patients with EC compared to healthy donors. Leucine, alanine, isoleucine, valine, glycoprotein, lactate, acetone, acetate, choline, isobutyrate, unsaturated lipid, VLDL,LDL, 1-methylhistidinedecreased in EC patient’s plasma with statistical significance (P<0.05), dimethylamine, α-glucose, β-glucose, citric acid increase in the EC patient’s plasma (P <0.05). Mannitol, glutamine, r-propalanine, phenylalanine, acetic acid, allantoin, pyroracemic acid, tyrosine, β- glucose and chinoline in urine of EC patients increased significantly (P<0.05), N- acetylcysteine, valine, dihydrothymine, benzoylglycine, methylguanidine, 1-methyl-nicotinamide and citric acid decreased significantly comparing to health control’s urine (P <0.05); there were significant variation between well differentiated and moderate-poorly differentiated squamous cell carcinoma, and associated with the positive rate of lymph node metastasis and the depth of invasion greater than 15 mm as well as differentiation states of cancer. Conclusions: This study suggested that present NMR based spectrometry approach combined with statistical analysis contributed to deduce the small molecular weight metabolites as cancer biomarkers in the future.
Efficacy analyses of a randomized phase III clinical trial of combined therapy with CPT-11/CDDP versus CPT-11 alone in patients with advanced or recurrent gastric cancer refractory to prior S-1 chemotherapy.
Authors: Hitoshi Inagaki, Kazuhiro Nishikawa, Kazumasa Fujitani, Naotoshi Sugimoto, Tadashi Shigematsu, Tohru Ishiguro, Akira Tsuburaya, Masato Nakamura, Atsushi Nashimoto, Takao Yamane, Makoto Yamada, Motohiro Imano, Shohei Iijima, Yoshio Oka, Masato Kataoka, Shuichi Hironaka, Hideaki Andoh, Satoshi Morita, Junichi Sakamoto, Toshimasa Tsujinaka
Journal: Journal of Clinical Oncology (2013)

69 Background: There has been no established regimen as the second-line treatment for advanced gastric cancer (AGC), though CPT-11 showed survival benefit over BSC. Combination of CPT-11 with CDDP is one of the promising regimens as the second-line chemotherapy after S-1 mono-therapy. Methods: This is a prospective, multicenter randomized phase III study comparing CPT-11+CDDP (Arm A) vs. CPT-11 alone (Arm B) in patients with advanced or recurrent gastric cancer resistant to S-1 mono-therapy or prior adjuvant chemotherapy using S-1. Eligibility criteria include histologically confirmed gastric adenocarcinoma, age over 20 years old, PS: 0-2, adequate organ functions and written informed consent. Arm A: patients received CPT 11 60mg/m 2 and CDDP 30mg/m 2 on day 1, q2w. Arm B: patients received CPT-11 150mg/m 2 on day 1, q2w. Stratification was made according to PS, advanced or recurrence cases, institution and presence or absence of measurable target lesions. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), time to treatment failure (TTF), response rate (RR), and safety. Results: 168 patients were registered between 2007 and 2011. Arm A (n=84) and Arm B (n=84) were well balanced for baseline factors. Median age was 67 vs 68 years old, number of advanced/recurrence after resection was 36/48 vs 35/49, and median number of treatment course was 5 vs. 6 (range:0-31, 0-39). Common grade 3/4 toxicities in Arm A vs. Arm B were neutropenia; 35.4% vs. 27.2% (p=0.259), anemia; 15.9% vs. 3.7% (p=0.009), diarrhea; 0% vs. 2.5% (p=0.152), nausea; 3.7% vs. 4.9% (p=0.687), vomiting; 1.2% vs. 3.7% (p=0.305), anorexia 6.1% vs. 8.6% (p=0.534). The rate of patients who were required dose modification for these toxicities was 22.9% vs 21.4%. The pooled OS, PFS and RR for both Arms were as follows; 13.8 months (95% CI, 10.7 to 17.5), 4.5 months (95% CI, 3.7 to 5.1), and 13.7%. Conclusions: There was no significantly difference in the incidence and severity of adverse events in both Arms except for anemia. Updated efficacy data of secondary endpoints will be presented. Clinical trial information: UMIN000002571.
Rechallenge with docetaxel after a first response in metastatic breast cancer: A significant activity with manageable toxicity.
Authors: M. Debled, N. Madranges, C. Donamaria, V. Brouste, M. Durand, L. Mauriac, M. Toulmonde
Journal: Journal of Clinical Oncology (2011)

e11557 Background: Docetaxel (Dc) is a major drug in metastatic breast cancer (MBC). At progression, rechallenge with docetaxel can be discussed based on the previous efficacy and tolerance. No data on this pragmatic strategy are avalaible in MBC. Methods: We identify 73 patients (pts) with the following criteria: (i) objective response or stable disease with a previous line of treatment with Dc in MBC, (ii) rechallenge with Dc (on a three weekly schedule) for progressive disease after a minimal Dc-free interval of 3 months. The main objectives were to evaluate the overall response, the time to progression (TTP) and toxicity at reintroduction of TXT. Results: Median age was 57 years (34 - 84). Patients had already received 1, 2, 3, ≥ 4 lines of chemotherapy (including the first use of Dc) in 20%, 47%, 18% and 15% of cases, including capecitabine, anthracycline, and vinorelbine in 56%, 40% and 21% of cases, respectively. Visceral disease was described in 80% of cases. The median number of cycles was 6 (1-18). Overall, 57 pts (78%) obtained a symptomatic benefit from the treatment. Among the 32 pts (44%) with disease assessed according to RECIST criteria, 14 (44%) had a partial response and 11 (34%) had a stable disease > 3 months. Among the 41 pts without an available evaluation according to RECIST, 22 (54%) experienced a biological partial response. The median TTP was 5.9 months (95%CI [4.9-6.9]). The median overall survival (OS) was 10.8 months (95%CI [9.1-12.5]). Toxicity was manageable. Forty seven pts (64%) reported grade 1/2 toxicity, mostly mucositis (37%), asthenia (34%) and nails toxicity (30%). Twenty six pts (36%) experienced grade 3/4 toxicity, mostly neutropenia (16%) and fluid retention (11%). Predictive factors of benefit at re-introduction of TXT are in progress. Conclusions: This retrospective analysis supports the pragmatic strategy to retreat patients with MBC with Dc provided that this drug had shown previous activity and was stopped for other causes than progression.
Differences in the toxicity and efficacy in phase I studies between cytotoxic and molecular-targeted therapies
Authors: Y. Goto, I. Sekine, K. Yamada, H. Nokihara, N. Yamamoto, H. Kunitoh, Y. Ohe, T. Tamura
Journal: Journal of Clinical Oncology (2008)

13527 Background: In recent phase I trials, many molecular-targeted agents have been studied, but the differences in the toxicity and efficacy between cytotoxic and targeted agents have not yet been evaluated. Methods: We reviewed phase I trials published between 1999 and 2004 collected by a Medline search. Molecular-targeted agents, defined as agents designed and developed to inhibit specific molecules involved in the growth, invasion or metastasis of cancer cells, were compared with cytotoxic agents in terms of the toxicity and efficacy. Results: A total of 200 studies were collected, of which 8 were excluded because these did not evaluate the agents for their antitumor effect. The numbers of patients per number of studies evaluating molecular-targeted and cytotoxic treatments were 1369/44 and 4634/148, respectively. As for the molecular-targeted agents evaluated in the 44 studies, the agents employed were small molecules in 33, antisense agents in 5, and others in 6 studies. The molecular target was the extracellular matrix in 10, the EGFR/HER2 signal pathway in 9, angiogenesis in 6, and others in 20 studies. Four studies were restricted to patients with biological markers for targeted molecule, and 18 evaluated biological markers. The dose-limited toxicities reported in the studies of the molecular-targeted and cytotoxic agents, respectively, were as follows: 8 (18%) vs. 69 (47%) for leukopenia, 6 (14%) vs. 54 (36%) for thrombocytopenia, 14 (32%) vs. 64 (43%) for nausea or vomiting, 16 (36%) vs. 48 (32%) for liver disorders, and 6 (14%) vs. 19 (13%) for renal disorders. The numbers of deaths related to the use of the molecular-targeted and cytotoxic agents were 1 (0.1%) and 21 (0.5%), respectively. Of the total, complete or partial responses were observed in 28 (2%) and 101 (2%) patients, and stable disease was observed in 251 (18%) and 670 (15%) patients, respectively, in the groups treated with molecular-targeted and cytotoxic agents. Conclusions: The prevalences of hematological toxicities, nausea and death were lower in the molecular-targeted therapy studies, but those of other toxicities were similar. Although the proportion of patients with stable disease was slightly higher in molecular-targeted agent, the response rates did not differ between the 2 groups. No significant financial relationships to disclose.
Gemcitabine-cisplatin-anastrozole concomitant chemo-hormonal treatment in locally advanced breast cancer in postmenopausal women
Authors: Z. Nadeem, A. Shaharyar, M. Hafeez, S. Tahir
Journal: Journal of Clinical Oncology (2008)

11532 Background: The gemcitabine and cisplatin doublet has been frequently used in advanced breast cancer. However, the use of gemcitabine and cisplatin concomitant with anastrozole has not been studied well in Asian women. The objective of this study was to evaluate the efficacy and toxicity of concomitant gemcitabine-cisplatin-anastrozole chemo-hormonal treatment in postmenopausal women with locally advanced breast cancer. Methods: Histopathologically documented female breast cancers with locally advanced UICC stage III disease and a KPS > 70 were eligible. Patients were required to be postmenopausal, hormone receptor positive and Her 2 Neu negative. Adequate marrow, renal and hepatic function was required. Anastrozole 1 mg was given daily. Gemcitabine 1,250 mg/m2 was given on day 1 & 8 with cisplatin 70 mg/m2 on day 1 of three weekly cycles. CTCAE version 3.0 of NCI and RECIST was used. All patients underwent MRM after four cycles. Miller and Payene criteria was used for evaluation of pathologic response. Results: From January 2006 to December 2007, 25 patients were enrolled. Median age was 47 years (Range 28–70). Pathologic complete response was seen in 4 (16 %) patients and partial response in 19 (76 %) with an overall response rate of 92 %. One patient ( 4%) had stable disease and one patient ( 4%) developed progressive disease during treatment. Grade 2 neutropenia, thrombocytopenia, vomiting and serum creatinine elevation was seen in 32 %, 12%, 28% and 16 %, respectively. Grade 3 neutropenia and vomiting was seen in 20 % and 4 %, respectively. Persistent grade 2 arthralgia was seen in 28 % and myalgia in 20 %. Conclusions: This treatment schedule is an effective first line treatment of LABC patients and provides an excellent overall pathologic response rate and manageable toxicity. No significant financial relationships to disclose.
Results from a longitudinal breast MRI surveillance study: Psychological impact for high-risk women.
Authors: L. J. Patrick-Miller, A. R. Bradbury, R. Pius, K. Wroblewski, M. S. Verp, S. Jackson, C. Gulden, G. Newstead, H. Abe, O. I. Olopade
Journal: Journal of Clinical Oncology (2011)

1563 Background: Annual breast MRI screening as an adjunct to mammography has been recommended for BRCA1/2 mutation carriers, their first-degree relatives, and women with >/= 20% lifetime risk. The long term psychological impact of intensive (MRI) screening of women at high-risk of breast cancer (HRW) is unknown. Methods: Longitudinal study of 217 high risk women (48% BRCA1/2 positive; 33% personal cancer history; 88% white; mean age 44 YO) undergoing annual mammography, plus semi-annual breast MRI. High risk women reported anxiety (STAI), depression (Beck), and mental health quality of life (SF-36) semi-annually from baseline to 30 months. Cross-sectional between-group differences were assessed by t-tests. With-in and between group longitudinal changes evaluated by random-effects regression analysis. Results: For high risk women, baseline levels of anxiety, depression, and mental health quality of life were significantly lower than population norms (p =0.043; p< 0.01; p< 0.01), and level s of anxiety, depression and general mental health improved significantly from baseline to 30 months (p<0.01; p= 0.04, p< 0.01). Anxiety declined significantly for women with a BRCA2 (p < 0.01) or unknown mutation status (p < 0.01), and most significantly for women with a cancer history (p <0.01). Additionally, depression decreased significantly for women with a cancer history (p = 0.02) or a BRCA1 mutation (p =0.01). Conclusions: Over 30 months, multiple mental health indicators improved significantly for high risk women undergoing intensive multi-modality breast cancer surveillance. Data suggest surveillance programs including breast MRI for cancer survivors, and women with a BRCA1/2 mutation or unknown mutation status might have a positive impact on their psychological well-being. Ongoing analyses over 60 months will inform durability and long term implications of these results.
Effect of technologic advancements in radiotherapy on postoperative pulmonary complications after neoadjuvant chemoradiation in esophageal cancer.
Authors: Bevan H. Myles, Caimiao Wei, Ritsuko Komaki, Ara A. Vaporciyan, Reza J. Mehran, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani, Zhongxing X. Liao, James D. Cox, Steven H Lin
Journal: Journal of Clinical Oncology (2012)

110 Background: Although 3D conformal radiation therapy (3D-CRT) is currently the de facto standard for the treatment of esophageal cancers, technologies such as Intensity Modulated Radiation Therapy (IMRT) or Proton Beam Therapy (PBT) are increasingly being used, but the evidence for the clinical benefits of these technologies are lacking. We hypothesized that radiation technology influences perioperative complications in esophageal cancer patients treated with neoadjuvant chemoradiation. Methods: We evaluated 423 patients (3D-CRT (n=208, 1998-2008), IMRT (n=165, 2004-2011), and PBT (n=50, 2006-2011)) treated with surgical resection after chemoradiation from 1998-2011 at M. D. Anderson Cancer Center. Postoperative complications (Pulmonary, GI, cardiac, wound healing) were recorded up to 30 days postoperatively. Kruskal-Wallis tests and Chi-square or Fisher’s exact tests assessed associations between continuous and categorical variables and the radiation technology, respectively. Logistic regression model tested the association between treatment technologies and complications adjusting for other significant patient characteristics. Results: While radiation modality was not significantly associated with postoperative GI (leak, ileus, fistula), cardiac (MI, AF, CHF), and wound complications, there was a significant reduction in postoperative pulmonary complications (ARDS, pleural effusion, respiratory insufficiency, pneumonia) for IMRT compared to 3D-CRT (OR 0.46, 95%CI 0.25, 0.83) and PBT compared to 3D-CRT (OR 0.26, 95%CI 0.09, 0.70), but not when IMRT was compared to PBT (OR 1.74, 95%CI 0.66, 4.61) after adjusting for preRT DLCO level. The median length of hospital stay was also significantly different between treatment modalities (12, 10, and 8 days for 3D-CRT, IMRT, and PBT, respectively, p&lt;0.0001). There was no significant association between treatment year with pulmonary complication rates. Conclusions: Radiation technologies such as IMRT and PBT reduced postoperative pulmonary complication rates compared to 3D-CRT in esophageal cancer patients. This result needs to be confirmed in larger prospective studies.
Association of anxiety and depressive symptoms with differing needs among recent breast cancer (BC) survivors.
Authors: Steven C Palmer, Angela DeMichele, Marilyn M. Schapira, Karen Glanz, Abigail Blauch, Donna A. Pucci, Linda A. Jacobs
Journal: Journal of Clinical Oncology (2016)

244 Background: Although unmet needs are associated with general distress in long term BC survivors, it is unclear is different needs are associated with specific outcomes such as anxiety and depression among recent BC survivors. Such work may provide insight into the interventions needed to improve outcomes early in survivorship for patients. Methods: Eligibility included non-metastatic BC treated &lt; 1 year prior. Prior to an initial survivorship visit, participants completed a PRO symptom measure and reported unmet need for assistance for symptoms experienced. Overall unmet need and unmet need domains (physical, psychosocial, sexual, hormonal) were examined. Anxiety and depressive symptoms were assessed using the HADS. Results: Participants (N = 137) were primarily white (72%), middle-aged (M = 55 yr), and treated for Stage I (47%) or II (38%) BC. Anxiety (M = 5.57, SD = 4.08) and depression (M = 3.21, SD = 3.33) were in the normal range, on average. 29% and 13% met “caseness” (i.e., above criteria for significant elevation) for anxiety and depression, respectively. Caseness for anxiety and depression were not significantly related to demographic variables, time from end of treatment, disease characteristics or treatment exposures (all p &gt; 0.05). Meeting criteria for depression was associated with greater overall unmet need (M = 6.11 vs. M = 2.11, p &lt; 0.001) and need in the physical (M = 2.66 vs. M = 0.83; p &lt; 0.001) and psychosocial (M = 2.56 vs. M = 0.49; p &lt; 0.001) domains, but unrelated to unmet sexual or hormonal needs (all p &gt; 0.05). Meeting criteria for anxiety was associated with greater unmet need in the hormonal (M = .47 vs. M = 0.17; p &lt; 0.05) and psychosocial (M = 1.33 vs. M = 0.55; p &lt; 0.002) domains, but unrelated to unmet overall, physical or sexual needs (all p &gt; 0.05). Conclusions: Unmet needs relate differentially to anxiety and depression in recent BC survivors. In particular, depression is associated with more than 3 times the number of unmet physical needs, while anxiety is associated with more than 2.5 times the number of unmet hormonal needs. Assessing psychosocial outcomes in the absence of unmet needs may represent a missed opportunity for intervention to improve outcomes for specific groups of survivors.