tbuckley/cabot-search huggingface dataset:
Role of cryopreserving surplus stem cells during allogeneic unrelated stem cell transplant.
Authors: Rishi Agarwal, Jung Ying, Lois Jeanne Ayash, Zaid Al-Kadhimi, Abhinav Deol, Lawrence G. Lum, Voravit Ratanatharathorn, Joseph P. Uberti, Muneer Hyder Abidi
Journal: Journal of Clinical Oncology (2015)

e18008 Background: The utility of cryopreserving a portion of a HSC harvest is not well established. There is controversy as what the optimal infusion dose of HSC for allotransplant should be. In some cases the transplant physicians may infuse the entire dose of received unrelated HSC or cryopreserve the surplus cells for backup. Through this analysis we tried to identify factors which influence a physician’s decision to use a certain dose. We also compared outcomes of cases in which cryopreservation was done and cases in which it was not done. Methods: We did a retrospective chart review approved by Wayne State IRB to analyze the frequency and outcome of patients who had a portion of their unrelated HSC cryopreserved. The decision to cryopreserve was based on physician’s choice. We included all patients > 18 years, who received an unrelated PBSC transplant between January 2000 and July 2010. Results: 360 unrelated PBSC transplants were performed. A portion of the HSC were cryopreserved in 42(11%) cases. No correlation was found between HSC dose and age, performance status, transplant year, duration of admission, acute GVHD, and chronic GVHD. Mild correlation with engraftment was noted. No significant difference in WBC engraftment, incidence and severity of GVHD and D+100 mortality found in the two groups. In the cryopreserved group, median number of cells acquired was 16.47(8.12-44.63) X 106 cells/kg and infused was 8.14(4.68-14.68) X 106cells/kg. Median duration for cryopreservation was 363(range 211-539) weeks. To date, no patient has received the cryopreserved product, but follow-up is short. Conclusions: No specific factor was found which explains the rationale behind using a particular dose or to cryopreserve backup cells. The outcomes were not affected by the infused HSC cell dose. Cryopreservation of HSC may not have clinical benefit. The optimal dose of CD 34 +ve stem cells is not clear. We don't know the scope of current practice: i.e. if other programs are infusing entire product or are concerned to infuse beyond a certain dose limit. Higher dose may benefit engraftment and impact survival. Further studies are required to establish the optimal dose of HSC for unrelated transplant so over collection and risk to the donor can be avoided.
Lymphadenectomy quality measure for colon cancer: Is it working?
Authors: Jennifer Leigh Paruch, Jeanette Chung, Kellie Leanne Mathis, David Porter Winchester, E. Greer Gay, Daniel P. McKellar, David W Larson, Heidi Nelson
Journal: Journal of Clinical Oncology (2014)

6537 Background: Endorsement of the 12 lymph node colon cancer measure has led to improvements in national performance. However, it is unknown whether hospital performance on this measure is associated with improved outcomes. The objectives of this study were to determine whether improvement on this measure impacts stage migration or survival. Methods: Patients in the National Cancer Data Base undergoing resection for stage I-III colon cancer (1995-2011) were identified. Three hospital improvement groups were created using change in median node count over time (< 5; 5-10; >10). Changes in the ratio of stage III patients over time were compared between groups. A hierarchical Cox model was used to assess the relationship between hospital improvement and 5 year overall survival for stage II patients. Results: A total of 455,155 patients from 1,047 hospitals were identified. Median hospital lymph node counts increased from 10 (IQR 8-10) to 17 (IQR 15-19) over the study period. Increase in stage III patients over time was related to hospital improvement group (1.2% for improvement <5; 3.2% for improvement 5 – 10; 4.4% for improvement > 10; p<.0001). Hospital improvement group was significantly associated with 5-year overall survival in stage II patients (improvement 5-10: HR 0.97 [0.84-0.99]; improvement >10: HR 0.95 [0.91-0.98]). Conclusions: Stage migration and improved stage II survival were related to degree of hospital improvement in median node count. Implementation of this quality measure at Commission on Cancer accredited facilities may have greatest impact on outcomes at centers with most improvement.
Prognostic index model (PIM) for overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) without prior chemotherapy treated with abiraterone acetate (AA).
Authors: Charles J. Ryan, Thian Kheoh, Jinhui Li, Arturo Molina, Peter De Porre, Joan Carles, Eleni Efstathiou, Philip W. Kantoff, Peter F.A. Mulders, Fred Saad, Thomas W. Griffin, Kim N. Chi
Journal: Journal of Clinical Oncology (2015)

5047 Background: Models that predict prognosis may aid in treatment planning for mCRPC. We previously presented a PIM for radiographic progression-free survival from the phase 3 COU-AA-302 trial in mCRPC pts without prior chemotherapy (ECC 2013, #P370). In the final analysis of COU-AA-302, AA + prednisone (P) significantly prolonged median OS vs P (34.7 mo vs 30.3 mo; HR: 0.81; 95% CI 0.70 - 0.93; p = 0.0033). Using the final analysis dataset from COU-AA-302, we developed a PIM for OS in mCRPC pts in the AA + P arm. Methods: The complete set of baseline data was available from 493/546 pts (90%), and formed the basis for the modeling. Accepted values for lower (LLN) and upper (ULN) limits of normal were used to dichotomize laboratory factors; other factors were dichotomized for ease of interpretation. Factors were assessed for association with OS through a univariate Cox model and used in a multivariate Cox model with a stepwise procedure. Internal validation of the predictive performance of the final model was assessed by a bootstrap resampling procedure. Model discriminatory power was estimated by the C-index. Results: Four factors associated with poor prognosis were included in the final model: Brief Pain Inventory 2 - 3 (HR: 1.71, p < 0.0001), lactate dehydrogenase > ULN (234 IU/L) (HR: 2.03, p < 0.0001), alkaline phosphatase > ULN (131 IU/L) (HR: 1.60, p = 0.0004), and ≥ 10 bone metastases (HR: 1.92, p < 0.0001). Pts were categorized into good (n = 296), intermediate (n = 117), and poor (n = 131) risk groups based on number of risk factors. Median OS was calculated for each group (Table). The C-index was 0.67 ± 0.016. Conclusions: We identified 4 readily available clinical and laboratory factors to generate a PIM for OS in mCRPC, and categorized pts into 3 distinct risk groups. If validated in an independent dataset, this PIM may be useful for estimating OS in mCRPC and designing risk-adapted treatment strategies. Clinical trial information: NCT00887198. Number of risk factors Median OS, months (95% CI) HR (95% CI)a 0 or 1 (good) n = 296 53.6 (47.6 - not estimable) — 2 (intermediate) n = 117 38.4 (33.7 - 45.8) 2.04 (1.57 - 2.66) 3-5 (poor) n = 131 26.6 (24.5 - 28.5) 3.77 (2.94 - 4.84)
Prognostic impact of primary tumor location in patients with metastatic colorectal cancer (mCRC) at the salvage lines.
Authors: Tomoyuki Nagaoka, Takeru Wakatsuki, Eiji Shinozaki, Izuma Nakayama, Mitsukuni Suenaga, Naoki Fukuda, Hiroki Osumi, Tomohiro Matsushima, Takashi Ichimura, Mariko Ogura, Masato Ozaka, Daisuke Takahari, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

741 Background: Recently it has been suggested that primary tumor location may have a clinical impact on the front line chemotherapies; namely, right-sided tumor benefit less from cytotoxic and targeted agents compared with left-sided tumor. Regorafenib and TAS 102 have recently emerged and the prognostic impacts of tumor location on these agents are unknown. Methods: Clinical information of patients who were administrated Regorafenib and/or TAS 102 was retrospectively collected. Patients’ demographics by tumor location were compared using Fisher’s exact test. Time to treatment failure (TTF), and overall survival (OS) by tumor location were calculated using Kaplan-Meyer Methods and compared using Log-rank test. In addition, subgroup analyses were performed to see the interactions between tumor location and covariates in each agent. All tests were performed at the two-sided .05 significance level. Results: The median TTF (mTTF) and OS (mOS) were 2.0 and 8.0 months in the regorafenib group (n = 98) and were 2.4 and 7.9 months in the TAS102 group (n = 95), respectively. In the regorafenib group, 71 patients had a left-sided tumor and 27 patients had a right-sided tumor. In the TAS102 group, 64 patients had a left-sided and 31 patients had a right-sided tumor. There was no significant difference between right and left sides in both groups with the exception that a greater number of older patients was seen in right-sided in the TAS102 group. No significant difference of TTF and OS by primary site were observed in regorafenib (HR 0.92, 95% CI 0.68-1.70, P = 0.71 for TTF, HR 1.09, 95% CI 0.68-1.81, P = 0.74 for OS) and in TAS 102 (HR 0.84, 95%CI 0.53-1.36, P = 0.48 for TTF, HR 1.26, 95% CI 0.72-2.33 P = 0.43 for OS). Significant interactions were shown between presence of liver metastasis and tumor location both in TTF and OS in regorafenib (p &lt; 0.05). On the other hand, in TAS102, significant interactions were shown between period from 1 st line chemotherapy and tumor location in TTF and between time to metastasis and tumor location in OS (p &lt; 0.05). Conclusions: In contrast to front line chemotherapy, no clinical impact of tumor location was demonstrated at the salvage lines in mCRC.
Pathologic complete response (pCR) with weekly nanoparticle albumin bound (nab-P) plus carboplatin (C) followed by doxorubicin plus cyclophosphamide (AC) with concurrent bevacizumab (B) for triple-negative breast cancer (TNBC).
Authors: Jessica Nicole Snider, Jasgit C. Sachdev, Jeffrey Warren Allen, Lee Steven Schwartzberg, Robyn R. Young, Ahmed Yasir Javed, Furhan Yunus, Carmel S. Verrier, Mohammad Jahanzeb
Journal: Journal of Clinical Oncology (2013)

1068 Background: TNBC are mostly “basal-like” tumors, that have been shown to overexpress Secreted Protein Acidic and Rich in Cysteine (SPARC). Endothelial transcytosis of nab-P via albumin- gp60 -cav1 and binding of albumin to SPARC results in high intratumoral levels of nab-P. Exploiting this and the dysfunctional DNA repair in basal tumors, we hypothesized that nab-P + C would produce high rates of pCR in TNBC, further enhanced by antiangiogenesis properties of B. Methods: Eligible women had operable TNBC ≥ 2 cm. pCR in the breast and pCR in the breast + nodes were primary &amp; secondary end points respectively. We needed 57 evaluable patients to demonstrate 40% pCR vs. 25% (P0) in a single stage phase II design (α: 0.05, β: 0.2).Schema: C AUC 6 d1 + nab-P 100mg/m 2 d 1, 8 &amp; 15 Q 28 d x 4 cycles followed by AC d1, Q14d x 4 cycles preoperatively with B 10mg/kg Q 14d for the first 6 cycles of preoperative chemotherapy, resuming postoperatively to complete 1 year of treatment.Baseline tumor biopsies &amp; serial serum/blood samples were collected. Results: Due to slow accrual, study was closed after 42 patients. They were women between 35 and 68 years of age (median 52); 51% were African American and 46% were node positive. Safety population: N=41. Four patients came off study prior to surgery while 7 are still on pre-op treatment. Grade ¾ hematologic AEs: neutropenia (Gr3: 56%; Gr4:24%) febrile neutropenia (4%), thrombocytopenia (32%), anemia (22%). 7 patients had SAEs, with 1 grade 5 event. To date, thirty of 31 patients who had surgery (efficacy population) are considered evaluable per protocol. In-breast pCR rates are 55% (17/31) and 56% (17/30) and the rates of pCR breast + nodes are 52% (16/31) and 53% (16/30), for the efficacy and evaluable populations respectively. Conclusions: Majority of the patients in our study achieved a pCR, which is among the highest rates reported compared to anthracyclines+ taxanes without B in TNBC. Correlative analyses are planned. An ongoing randomized intergroup study is evaluating the individual contributions of carboplatin &amp; bevacizumab to pCR in TNBC. Clinical trial information: NCT00777673.
Plasma osteopontin and the prognosis of pleural mesothelioma.
Authors: Harvey I. Pass, Jessica S. Donington, Shirish M. Gadgeel, Abraham Chachoua, Antoinette J. Wozniak, Geoffrey Liu, Ming Sound Tsao, Marc de Perrot, Chandra Goparaju
Journal: Journal of Clinical Oncology (2013)

11109 Background: Cytoreductive surgery for malignant pleural mesothelioma (MPM) should be reserved for patients with favorable tumor biology. Osteopontin (OPN) and the ratio of absolute neutrophil to absolute lymphocyte counts (NLR) have been reported as possible prognostic biomarkers. These were studied with other clinical/ laboratory variables in a mixed surgical/non-surgical MPM population to define independent predictors of survival (OS) and progression (TTP). Methods: Forty-four MPM patients (12 F, 32M; 26 cytoreduction, 18 no cytoreduction; 31 epithelial, 13 non-epithelial; 15 Stage I/II, 29 Stage III/IV) were examined with regard to pretreatment plasma OPN (ELISA, R&amp;D, Minneapolis, MN), NLR age, gender, therapy, histology, stage, platelet count and WBC count. Cut points for age, OPN, NLR, platelets, and WBC were determined by X-tile Software (Yale, New Haven, CT) and univariate/multivariate Cox analyses performed. Results: Median OS were 11 m, 21m, and 8m for all 44 MPMs, cytoreduced and non-cytoreduced MPMs, respectively. Of platelet count, WBC, NLR, and OPN, only OPN was statistically significant between Stage I/II and Stage III/IV (80.3 ng/ml vs 148 ng/ml, p&lt;0.018). The only independent covariate predictive of OS was plasma OPN. For TTP in cytoreduced patients, only age, stage, platelet count, and OPN were significant in univariate analysis, and multivariate modeling retained stage (p=0.04, HR=2.75, 95% CI=1.0517 to 7.1879) and OPN (p=0.0008, HR=17.471, 95% CI=3.3054 to 92.3461). Conclusions: Plasma OPN is promising for the stratification of tumors into good or bad risk categories and to help select potential candidates for cytoreduction and further postoperative therapy. [Table: see text]
Risk perception and knowledge of breast and colon cancers in a diverse population.
Authors: Katherine Lang, Maria Gyure, Vivian Rodriguez, Rosalie Corona, Donna McClish, Deborah Bowen, Alex Krist, Joseph Borzelleca, Joann Bodurtha, John Quillin
Journal: Journal of Clinical Oncology (2012)

1563 Background: The accuracy of cancer risk perception has implications for preventive behaviors. Studies show that despite receiving personalized breast and colon cancer risk information, people continue to overestimate their numeric risks. It is still not fully understood why this occurs. Breast cancer, especially, is highly visible in the media so an individual may hear more about breast cancer, increasing general knowledge but potentially inflating risk perceptions. This study explores relationships between general knowledge and numeric risk perceptions for breast cancer (BC) and colon cancer (CC) among women. We hypothesize that general knowledge of BC will be high relative to CC, but risk perception for BC will be less accurate. Methods: Data was obtained from the first 369 (final N=490) patients recruited for the Kin Fact study from a Women’s Health Clinic. Kin Fact is a randomized controlled trial examining effects of an intervention to increase cancer risk communication in families. Women complete baseline surveys including knowledge and numeric risk perception measures for BC and CC. We use CA Gene software to calculate actual lifetime risk for BC and CC. Correlations, t-tests and linear regressions were used for the analysis. Results: Women averaged 33 years old, and 58% were African American. Average lifetime risk was 3% for CC and 11% for BC. Women overestimated their numeric risk for both BC and CC, but the mean overestimation for BC (24%) was significantly larger than for CC (19%) (p&lt;0.001). Average scores for BC knowledge were also significantly higher than for CC (p&lt;0.001). Compared to knowledge about CC, women who had greater knowledge of BC also were more inaccurate in terms of their perceived numeric risk (r= -0.131, p=0.016). This finding remained significant controlling for age, race and genetic literacy. Conclusions: Results endorse an apparently paradoxical effect that compared with CC, women with increased knowledge of BC have less accurate risk perception for BC. Inaccuracies in perceived risk can affect psychosocial well-being and adherence to screening and prevention recommendations. Findings reveal a need for increasing knowledge about cancer without adversely impacting the accuracy of risk perceptions.
On Lumping, Splitting, and the Nosology of Clinical Trial Populations and End Points - Reply
Authors: Karla Ballman, Murielle Mauer, Ulrich Wedding, Supriya G Mohile, Hyman Muss, Martine Extermann, Andrea Luciani, Harvey Jay Cohen, Arti Hurria, Stuart M Lichtman, Giuseppe Curigliano, Hans Wildiers
Journal: Journal of Clinical Oncology (2014)
FOLFIRI-cetuximab: A multicenter phase II proof-of-concept study of a tailored triple combination therapy for safe dose intensification.
Authors: Michele Boisdron-Celle, Olivier Capitain, Jean-Philippe Metges, Antoine Adenis, Jean-Luc Raoul, Thierry Lecomte, You Heng Lam, Roger Faroux, Claude Masliah, Anne-Lise Septans, Virginie Berger, Alain Morel, Erick Gamelin
Journal: Journal of Clinical Oncology (2014)

e14539 Background: A multicenter phase II trial explored individual 3-drug simultaneous tailoringfor advanced colorectal cancer patients treated with FOLFIRI-Cetuximab regimen using pharmacogenetics and PK-monitoring approaches. Methods: Patients were stratified by their pharmacogenetic/phenotypic status. CPT11 standard dose (180mg/m2) was adjusted per UGT1A1 mutational status. Conventional initial 5-FU dose (2400mg/m2) was adapted according to DPD activity screening (5-FUODPMTox) then dose optimization was PK-guided (5-FUODPMProtocol). Cetuximab PK was performed but dosage remained unchanged. Results: 104 patients were enrolled (18% first line, 82% second line). Mean CPT11 dose at 3 months were: 256±50 mg/ m2 for 6/6 (58), 184±53 mg/ m2 for 6/7 (38) and 127±14 mg/ m2 for 7/7 (8) patients. Initial 5-FU dose was reduced (>20%) for 5.8% of patients but mean 5-FU dose at 3 months was 2580 ±480 mg/ m2 (722 to 4117mg/m2). No grade 4 diarrheas, grade 4 neutropenias in 5.2% of 6/6 patients, 7.9% of 6/7 patients, none in 7/7 patients. Objective response rate was 32.2% total, 58% in WT KRAS tumors vs 25% in mutant KRAS. Hepatic secondary resection was done for 26.9% of patients, even in 2nd line. Median PFS was 217 and 181 days in 1st and 2nd line respectively, no statistical difference. PFS remained unchanged through UGT1A1 genotypes (199 days for 6/6, 181 for 6/7 and 152 for 7/7). Neither UGT1A1 status nor first/second line therapy was predictive factors of PR or PFS. In parallel, a strong relationship was shown between cetuximab AUC and regimen efficacy (1). Conclusions: the concept of3 drugsimultaneoustailoring in FOLFIRI cetux in the purpose of individual maximum tolerated dose is confirmed. It allows safe and efficient individual dose intensification. Clinical trial information: AFSSAP 050832.
Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC): Hoosier Oncology Group BRE09-146.
Authors: Sujaata Dwadasi, Yan Tong, Tom Walsh, Michael A. Danso, Cynthia X. Ma, Paula Silverman, Mary-Claire King, Susan M. Perkins, Sunil S. Badve, Kathy Miller
Journal: Journal of Clinical Oncology (2014)

1019^ Background: Patients (pts) with triple negative breast cancer (TNBC) who have residual disease after preoperative chemotherapy have a high risk of recurrence. No standard systemic therapy has proven benefit. Data suggest that some pts with TNBC and/or BRCA mutations may be sensitive to DNA-damaging chemotherapy and PARP inhibition. Methods: Eligible pts with TNBC or known BRCA mutations who had residual lymph node involvement or > 2 cm invasive disease after anthracycline or taxane neoadjuvant therapy were assigned 1:1 to postoperative cisplatin (C: 75 mg/m2D1 q3 wks x 4) +/- rucaparib (R: 24-30 mg IV D1,2,3 q3 wks x 4 followed by rucaparib 30 mg IV or 100 mg orally wkly for 24 wks). BROCA analysis (U. Washington) was used to identify deleterious germline mutations. The primary objective is 2-yr DFS. Results: 128 pts were enrolled. Median age was 48; 6 pts were known at study entry to have BRCA1 or BRCA2 mutations. Neoadjuvant therapy included anthracyclines in 57% and taxanes in 91%. Median tumor size at surgery was 1.9 cm (0-11.5) with median LN involvement 1 (0-38); Toxicity required C dose reduction (20% of pts) or delay (~43% of pts) in both arms. R dose reduction was uncommon (6%). Overall 73% of pts completed planned C. With a median follow-up of 9 months, 1-yr DFS was similar (~76%) in both treatment groups. BROCA identified deleterious mutations in 22/101 (22%) pts (8 BRCA 1, 12 BRCA 2, 2 BRIP1). 1-yr DFS in the 22 pts with mutations was ~85% compared to 79% without mutations. Whole transcriptome sequencing of paired pre vs. post preoperative chemotherapysamples will be reported separately (Radovich et al, ASCO 2014). Conclusions: The addition of low dose rucaparib (current phase II monotherapy dose 600 mg orally twice daily) did not impact the toxicity of cisplatin or improve 1-yr DFS. Comparison to predicted DFS based on residual cancer burden (RCB) is planned to investigate potential benefit from cisplatin. Genetic testing was underutilized in this high risk population with only 30% of BRCA1 and BRCA2 mutations identified as part of routine clinical care. Clinical trial information: NCT01074970.