tbuckley/cabot-search huggingface dataset:
Functional and survival effect of bevacizumab and irinotecan administered at recurrence in a cohort of patients with GBM.
Authors: E. Tabouret, M. Barrie, C. Boucard, M. Matta, D. Autran, A. Loundou, O. L. Chinot
Journal: Journal of Clinical Oncology (2011)

2087 Background: Bevacizumab (BEV) with or without irinotecan (IRI) have demonstrated activity in patients with recurrent GBM. However, survival benefit is debated. In order to explore clinical benefit and impact of BEV administration on survival, we analysed clinical outcome of patients treated with BEV +IRI in our institution, according to initial RPA classes, and recognized prognostic factors at recurrence. Methods: This single center retrospective cohort analysis included all patients with recurrent GBM treated with at least 1 cycle of BEV+IRI at our institution from April 2007 to May 2010, based on pharmacy charter. Overall survival was analysed from initial diagnosed of GBM (OS1) and from initiation of BEV+IRI (OS2). Progression free survival (PFS2) was analysed from initiation of BEV+IRI. Patients were assigned to RPA classes at the time of initial diagnosis as defined by Mirimanoff and col. (JCO, 2006) Results: 100 pts were identified, (M/F: 65/35), with a median age of 57.9 y (18-76). At the time of initial diagnosis, distribution of RPA classes were: III: n=13; IV: n=42; V n=38; not determined n=7. At the time of BEV+IRI initiation, KPS was <70 in 44 pts, ≥70 in 56 pts. Patients were treated at first, second, or third recurrence in 53%, 41%, and 6% respectively. 79% were on steroids. Median OS1 was 18.9 mo (IC95%: 17.5-20.3) for the entire population and 23.2, 18.9, and 18.2 mo for RPA classes III, IV, and V (NS). From the time of BEV+IRI initiation, median PFS2 was 3.9 mo (IC95%: 3.4-4.3)) and PFS at 6 months was 22.4%; OS2 was 6.5 mo (CI95%: 5.6-7.4). KPS was improved in 30 pts, including 14/44 pts with an initial KPS <70. For the 70 pts who presented at anytime a KPS ≥70, median time of functional autonomy (with a KPS≥70) was 3.75 (CI95%: 2.9-4.6). Sex and KPS but not age, steroid intake, number of previous line, time from initial diagnosis affected OS2. Conclusions: BEV+IRI is associated to a valuable functional improvement or maintenance for patients with recurrent GBM. Survival observed in this unselected population with poor prognostic characteristics suggests a survival benefit, with a decrease impact of recognized prognostic factors. Ongoing controlled trials will address more properly these issues.
A phase I/II study of gemcitabine (GEM) and carboplatin (CBDCA) biweekly combination chemotherapy for inoperable stage IIIB, IV non-small-cell lung cancer (NSCLC) (final report)
Authors: Y. Hasegawa, S. Takanashi, H. Nakagawa, K. Okudera, A. Hayashi, T. Morimoto, K. Taima, K. Okumura
Journal: Journal of Clinical Oncology (2005)

7333 Background: The purpose of this study was to determine maximum tolerated dose (MTD) of a combination of GEM plus CBDCA administration on a biweekly schedule for inoperable NSCLC, and to assess the efficacy and safety at that recommended dose (RD). Methods: Patients with inoperable stage IIIB and IV NSCLC included in this study were treated with CBDCA followed by GEM. CBDCA was given intravenously over 30 minutes, and GEM was given intravenously over 30 minutes. Treatment was repeated every 2 weeks. Results: Three patients were enrolled at the dose level 1 (CBDCA AUC=2 and GEM 800 mg/m2), 3 patients at level 2 (CBDCA AUC=2 and GEM 1000 mg/m2), 3 patients at level 3 (CBDCA AUC=2.5 and GEM 1000 mg/m2) and 6 patients at level 4 (CBDCA AUC=3 and GEM 1000 mg/m2), respectively. Consequently, the MTD was not reached and the RD was determined to be level 4 (Hasegawa et al., Proc. ASCO, 2004, abstr. #7237). 17 patients at RD were assessed for efficacy, and 5 patients achieved partial response. The response rate was 29.4%. Grade 3 neutropenia occurred in 3 of 17 patients and grade 4 neutropenia did not. Grade 3 anemia occurred in 2 patients. Grade 3/4 thrombocytopenia did not occur. No other grade 3/4 toxicity was observed. Median survival time (MST) was 8.6 months and one-year survival rate was 32.3%. Conclusions: GEM and CBDCA biweekly combination chemotherapy for inoperable stage IIIB, IV NSCLC was effective and very well tolerated. Thrombocytopenia was mild. We are preparing a phase III clinical trial to compare standard chemotherapy regimen of GEM and CBDCA. No significant financial relationships to disclose.
Factors predicting outcome after postoperative radiotherapy in non-small cell lung cancer with pN2 status
Authors: D. S. Yu, L. Moretti, H. Chen, B. Lu
Journal: Journal of Clinical Oncology (2008)

7562 Background: We reviewed our experience to clarify the role of postoperative radiation therapy (PORT) in resected stage III non-small cell lung cancer (NSCLC) with pN2 status, since well-designed phase III studies are lacking. The correlation of different clinicopathologic factors and the impact of radiotherapy on recurrence free survival (RFS) and overall survival (OS) were analyzed in this retrospective study. Methods: 83 NSCLC patients, who underwent a lobectomy or pneumonectomy at Vanderbilt University Medical Center between July, 1994 and December, 2004 were included in the study. Criteria required pN2 status and no neoadjuvant therapy. Median follow-up time was 14 months. The relationship between nine prognostic variables, including gender, age of diagnosis, histology, tumor size, number of nodal stations involved, surgical margin status, extra-capsular extension (ECE), use of postoperative chemotherapy, and use of PORT with 3 year RFS and OS was evaluated. Univariate survival analyses were conducted using Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. Results: The use of PORT was significantly associated with an improvement in RFS (p = 0.002) and OS (p = 0.013). Although negative surgical margins were predictive of a better OS (p = 0.016), they had no impact on RFS. Negative ECE, however, was associated with an improvement in RFS (p = 0.004). In subset analysis for patients with negative ECE, PORT was associated with an increase in RFS (p = 0.042) and OS (p = 0.003). For patients with positive ECE, PORT had no impact on survival. Conclusions: PORT is associated with an increase in RFS and OS for patients with resected pN2 NSCLC with negative ECE but not for positive ECE. Absence of ECE may serve as a useful prognostic variable in the decision to use PORT for resected pN2 NSCLC. No significant financial relationships to disclose.
Expression of ERCC1, TUBB3, BRCA1, and TS as predictive markers of neoadjuvant chemotherapy for squamous cell carcinoma of the esophagus.
Authors: Toshiyasu Ojima, Mikihito Nakamori, Masaki Nakamura, Masahiro Katsuda, Keiji Hayata, Shuichi Matsumura, Tomoya Kato, Hiroki Yamaue
Journal: Journal of Clinical Oncology (2016)

47 Background: No predictive biomarker of the response to neoadjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil (NAC-DCF) is available for patients with squamous cell carcinoma of the esophagus (SCCE) in a clinical setting. The aim of this study was to identify the biomarkers associated with chemotherapeutic efficacy and long-term survival for patients with advanced SCCE who had received NAC-DCF followed by surgery. Methods: This study included 45 patients with advanced SCCE who received NAC-DCF between January 2008 and December 2012. The NAC-DCF was conducted as a phase II study (UMIN000007408). The expressions of excision repair cross-complementing-1 (ERCC1), class III beta-tubulin, breast cancer susceptibility gene I (BRCA1), and thymidylate synthase were investigated simultaneously in the pre-treatment endoscopic tumor biopsy samples. Results: The multivariate logistic regression analysis indicated that pathological responses were significantly associated with tumors with low ERCC1 expression (P = 0.016) and with tumors with high BRCA1 expression (P = 0.014). The incidence of pathological responses to DCF in patients with low ERCC1 and high BRCA1 expressions was 100%. The multivariate Cox proportional hazard model analysis for relapse-free survival (RFS) revealed tumors with high BRCA1 expression (P = 0.031, hazards ratio, 4.39) as independent prognostic factors. Conclusions: Low ERCC1 expression and high BRCA1 expression in patients with SCCE were predictive biomarkers for chemotherapeutic efficacy. High BRCA1 expression was considered as prognostic factors for long-term RFS. These results may be a helpful tool for tailoring chemotherapy of patients with SCCE. Prospective validation of this biomarker panel is warranted. Clinical trial information: UMIN000007408.
Risk factors for loss of lean body mass after gastrectomy for gastric cancer.
Authors: Toru Aoyama, Tsutomu Sato, Kenki Segami, Yukio Maezawa, Kazuki Kano, Taiichi Kawabe, Hirohito Fujikawa, Tsutomu Hayashi, Takanobu Yamada, Norio Yukawa, Takashi Oshima, Yasushi Rino, Munetaka Masuda, Takashi Ogata, Haruhiko Cho, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2016)

79 Background: Lean body mass loss after surgery, which decreases compliance of adjuvant chemotherapy, is frequently observed in gastric cancer patients who underwent gastrectomy for gastric cancer. However, the risk factors of lean body mass loss remain unclear. Methods: The present study retrospectively examined the patients who underwent curative gastrectomy for gastric cancer between June 2010 and March 2014 at Kanagawa Cancer Center. All patients received perioperative care of the enhanced recovery after surgery protocol. % Lean body mass loss was calculated by percentile of lean body mass at one month after surgery to preoperative lean body mass. Severe lean body mass loss was defined as % lean body mass loss over 5%. Risk factors for severe lean body mass loss were determined by both univariate and multivariate logistic regression analyses. Results: Four-hundred eighty five patients were examined. Median age was 67 years. Operative procedure was total gastrectomy in 190 patients and distal gastrectomy in 295 patients. Surgical complications of grade 2 or more defined by Clavien-Dindo classification was observed in 78 patients including pancreatic fistula in 19, anastomotic leakage in 11 and abdominal abscess in 7. Mortality was observed in one patient. Both univariate and multivariate logistic analyses demonstrated that surgical complications (odds rate 3.576, p = 0.001), total gastrectomy (odds rate 2.522, p = 0.0001), and gender (odds rate 1.928, p = 0.001) were significant independent risk factors for severe lean body mass loss. Conclusions: Male, surgical complications, and total gastrectomy were significant risk factors for 5% of lean body mass loss at first month after gastrectomy. To maintain lean body mass after gastrectomy, the physician need careful attention for the patients who had these risk factors.
Phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in patients with unresectable metastatic colorectal cancer (mCRC).
Authors: Takeshi Kato, Tomohiro Nishina, Kentaro Yamazaki, Takayuki Yoshino, Yoshinori Miyata, Taito Esaki, Toshikazu Moriwaki, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2012)

611 Background: The results from a randomized phase II trial in the first-line treatment of mCRC indicated that SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) had promising activity with well-tolerated toxicities compared to mFOLFOX6 (Ojima et al, ESMO 2011). The median progression-free survival (PFS) for SOL and mFOLFOX6 was 9.6 and 6.9 months, respectively (HR=0.83). We evaluated the efficacy and safety of adding BV to SOL regimen in this study. Methods: The inclusion criteria were; 1) histologically proven adenocarcinoma of colon or rectum, 2) age ≥ 20 years, 3) no prior treatment for metastatic disease, 4) at least one target lesion by RECIST ver1.0 criteria, 5) ECOG Performance Status 0-1. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week and L-OHP (85 mg/m 2 ), and BV (5 mg/kg) on day 1, every 2 weeks. The primary endpoint was the response rate (RR). Results: From October 2009 to April 2010, 31 pts were enrolled, and 29 pts were regarded as the population of full analysis set. Present data included the results of efficacy and safety up to 24 cycles. RR assessed by the independent review committee was 86.2 % (CR: 0 pts, PR: 25 pts), and disease control rate (DCR) was 100%. The median PFS assessed by investigators was 12.5 months, while further follow up is ongoing. One year survival rate was 100%. The incidence of grade 3/4 adverse drug reactions were; neutropenia 16.7%, diarrhea 10.0%, hypertension 16.7%, and sensory neuropathy 53.3%. The median cumulative oxaliplatin dose was 915.0 mg/m 2 (range 330-1735 mg/m 2 ). The high prevalence of grade 3 neuropathy seemed due to the prolonged treatment duration. Reasons for discontinuation were progressive disease in 13 pts, and metastatectomy by tumor regression in 6 pts. The resection rate was 17.2 %. Conclusions: SOL+BV showed promising activity with high RR, DCR, PFS and resection rate with well tolerated toxicities in pts with unresectable mCRC. This trial was supported by Taiho Pharmaceutical CO.,LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881).
Outcomes for Myeloma in the Era of Lenalidomide Maintenance Are Not Different Among Ethnic Groups Following Autologous Transplant
Authors: Chandra Pooja, Ajay K. Nooka, Monica S. Chatwal, Sungjin Kim, Zhengjia Chen, Jeanne Kowalski, Jonathan L. Kaufman, Sagar Lonial, Leon Bernal-Mizrachi
Journal: Blood (2014)
Adoptive Donor T-Cell Infusions Are Necessary and Efficient To Induce Lasting Molecular Remissions after Highly Purified CD34+ Sibling Donor Transplants for First Chronic Phase Chronic Myeloid Leukemia - Final Report and Long-Term Follow-Up of a Phase II Study.
Authors: Ahmet Elmaagacli, Rudolf Peceny, Michael Koldehoff, Hellmut Ottinger, Rudolf Trenschel, Nina K. Steckel, Dietrich W. Beelen
Journal: Blood (2006)
The North American Shwachman-Diamond Syndrome Registry: Genetically Undefined Shwachman-Diamond Syndrome
Authors: Kasiani C. Myers, Audrey Anna Bolyard, Jamie Leung, Joan Moore, Sara Loveless, Leann Mount, Richard E. Harris, Stella M. Davies, Sioban Keel, David C. Dale, Akiko Shimamura
Journal: Blood (2015)
Results from Ongoing Phase 1/2 Trial of SL-401 in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Authors: Myo Htut, Cristina Gasparetto, Jeffrey Zonder, Thomas G. Martin, Emma C. Scott, Janice Chen, Shay Shemesh, Christopher L. Brooks, Dharminder Chauhan, Kenneth C. Anderson, Paul G. Richardson, Claudia E. Paba-Prada
Journal: Blood (2016)
Differential response of patients with metastatic renal cell carcinoma to sunitinib according to the Fuhrman grading of their targeted tumors.
Authors: E. Visvardis, J. Waxman, P. Savage
Journal: Journal of Clinical Oncology (2011)

e15056 Background: It has been more than 28 years since Fuhrman et al. introduced what became later a world-wide acknowledged nuclear grading system of renal cancer cells, which was based on nuclear size, morphology and nucleolar features and predicted both survival and metastatic potential. Since the introduction of sunitinib as first-line treatment in mRCC the overall survival has improved significantly. We explored the impact of Fuhrman grading on the survival benefit of sunitinib treatment. Methods: A cohort of sixty-five patients with mRCC treated with sunitinib in our institution was retrospectively analysed, spanning a period of 40 months, from May 2007 to September 2010. Data including demographics, staging, nephrectomy or biopsy details and histopathological analyses were reviewed. The nuclear Fuhrman grading was retrieved. The length of treatment with sunitinib until further progression of disease was evaluated up to the censor date. Dose adjustments or withdrawals of treatment due to toxicities were also recorded. Survival probabilities were estimated using the Kaplan-Meier Method and comparisons were calculated using the Log-Rank test. Results: The distribution of Fuhrman nuclear grading in our mRCC cohort was 4.5%, 48% and 30.5% for grades 2, 3 and 4 respectively. Fuhrman criteria for nuclear scoring were not applicable in 17%. The proportion of grade 2 patients was too small for comparison. Fuhrman grade 3 mRCC patients were found to have a mean progression free survival (PFS) on sunitinib treatment of 17.5months (SE: 3.45, 95%CI: 10.73-24.26) whereas grade 4 patients had a mean PFS of 4.2months (SE: 0.93, 95%CI: 2.43-6.06). The differential response between grade 3 and 4 groups was significant (x2 7.04, p 0.008). The interrelation of the PFS lengths from diagnosis to metastasis and from sunitinib initiation to further progression as a function of Fuhrman grading was also analysed. Conclusions: Sunitinib increases 4 times the mean PFS at the metastatic setting, in RCC tumors of Fuhrman grade 3 compared to grade 4. A significant prognostic role of the Fuhrman nuclear grade to effective tyrosine kinase inhibition is evident.
Improving the treatment of patients with low-risk neutropenic fever: A quality improvement project at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Lindsey Martin Goodman, Jessica Lau, Erika M. Gallagher, Machelle Moeller, Carolyn Best, James Stevenson
Journal: Journal of Clinical Oncology (2016)

101 Background: NF is an oncologic emergency and has historically resulted in inpatient (inpt) management. The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify NF pts at LR for complications who can be safely managed in the outpatient (outpt) setting. Despite established guidelines supporting outpt management of LRNF, provider awareness is low and inpt admission for intravenous antibiotics (abx) continues to be standard of care. Methods: A multidisciplinary team performed a QI project to improve management of LRNF (baseline cohort of LRNF pts treated from Jan - Mar 2014, N = 13). Inpt provider education began in the Q2 2014. Providers calculated MASCC scores for pts with non-leukemia hematologic malignancies and solid tumors at the time of admission. Data was collected in a prospectively maintained registry. Pts identified as LR by MASCC score were admitted under observation and placed on oral abx. If exclusion criteria and social barriers were not identified, discharge (dc) within 24 hrs of admission was planned. To ensure pt safety, close follow up included phone follow up within 48 hrs of dc and a provider visit within 72 hrs. Results: 52 pts were admitted to the TCI inpt oncology unit with NF from Oct 2014 - June 2015. 34 pts (65%) had LRNF (MASCC score, &lt; 21). 9 pts (26%) were dc within 24 hrs. Only 2 LRNF pts had a culture proven infection – both Enterococcus UTIs. 3 pts required readmission for reasons other than scheduled inpt chemotherapy: 1 high risk pt for new symptoms and 2 LRNF pts (22%) dc within 24 hours for recurrent fever; neither had culture proven infection. Pts with LRNF had an average LOS of 3.3 days compared to 6.2 days in the historical cohort. There were no deaths due to NF in either cohort. Conclusions: Calculating a MASCC score at admission identifies pts who are potential candidates for outpt, oral abx therapy. This pilot study demonstrates that provider education followed by implementation of a system to ensure close follow up may result in earlier dc for LRNF pts without increasing risk of complications or readmission. Further follow up will occur Q3 2015 and data will be presented on changes in cost measures.
Role of hypoalbuminemia in the development of venous thromboembolism in cancer chemotherapy patients.
Authors: Z. Li, W. B. Webb, J. Mao, S. Gautam, S. Singh, G. H. Lyman
Journal: Journal of Clinical Oncology (2011)

9032 Background: Chemotherapy is associated with increased risk of venous thromboembolism (VTE) in cancer patients. We retrospectively evaluated the association between pre-chemotherapy albumin levels and the development of an index VTE event in a large cohort of community-based cancer patients. Methods: All adult patients who started chemotherapy at a 29 center community practice from 2007 to 2009 were included. Several variables for each patient were determined, including primary cancer site, age, sex, body mass index (BMI), and personal history of VTE. In addition, pre-chemotherapy lab values were determined including albumin (Alb), hemoglobin (Hgb), white blood cell (WBC) and platelet (Plt) counts. New VTE events in the 183 days after chemotherapy initiation were identified by diagnostic codes (ICD9), hospitalizations and administration of treatment dose anticoagulation. Logistic regression was conducted to examine the association of VTE with categorical Alb at two levels of adjustment: none, CaseMix (site, age, sex, BMI, prior VTE, Hgb, WBC, Plt). Patients without an Alb value were treated as a special category. Patients without Hgb, WBC or Plt were excluded from the CaseMix analysis. Results: 8.7% (495/5703) patients developed VTE during the study period. Top primary cancer sites were breast (32.7%), lung (20.2%), colorectal (13.5%) and lymphoma (12.1%). 10% (577/5703) of patients had no CBC results. Table 1 shows the patient and event distribution and the relative risk (RR) by Alb level. Conclusions: Hypoalbuminemia is a strong predictor of index VTE events among cancer chemotherapy patients in the community setting. In this study, the predictive role of Alb for VTE persisted with adjustment for pre-chemotherapy CBC values, cancer site, age, VTE history and BMI. Alb level (g/dL) Total patients N (%) VTE n (%)* RR Unadjusted P Adjusted§ P <3.0 457 (8.0%) 57 (12.5%) 3.17 <0.01 2.37 <0.05 3.1 - 3.5 951 (16.7%) 115 (12.1%) 3.06 <0.01 2.43 <0.05 3.6 - 4.0 1,784 (31.3%) 146 (8.2%) 1.98 0.06 1.78 ns 4.1 - 4.5 1,210 (21.2%) 66 (5.5%) 1.28 ns¶ 1.26 ns ≥ 4.6 186 (3.3%) 8 (4.3%) 1.00 Reference 1.00 Reference Missing 1,115 (19.6%) 103 (9.2%) *Trend test p<0.0001 for nonmissing categories. § Adjusted by CaseMix; ¶ ns: p>0.1.