tbuckley/cabot-search huggingface dataset:
Outcomes and prognosticators in patients with pathologic T4 renal cell carcinoma.
Authors: Leonardo Borregales, Dae Y. Kim, Wei Qiao, Pheroze Tamboli, Eric Jonasch, Nizar M. Tannir, Surena F. Matin, Christopher G. Wood, Jose A. Karam
Journal: Journal of Clinical Oncology (2015)

514 Background: The 2010 American Joint Committee on Cancer (AJCC) TNM staging system defines pathological T4 renal cell carcinoma (RCC) as extension of tumor beyond Gerota’s fascia and/or invading contiguously into the adrenal gland. This subset of patients with the highest stage and locally advanced disease demonstrate poor outcomes with an estimated 5 year-survival rate of 20-30%. For this high-risk population, patient selection is imperative for proper patient counseling and to identify patients who would benefit from surgical intervention. Our objective was to study patient outcomes and determine prognostic variables predicting survival in pT4 RCC. Methods: From July 1992 to January 2012, we identified 64 patients at our institution who underwent radical nephrectomy and were found to have pT4 disease. The clinical and pathological variables were studied using univariate analysis to identify prognostic variables predicting survival using the Cox proportional hazards model. Survival plots were estimated using Kaplan-Meier method and survival analysis was performed using log-rank test. Results: Median patient age was 56 years (35-82), and 46 (68.7%) were male. Fifty-two (83%) patients had ECOG Performance Status 0 or 1. At diagnosis, 20 (32%) patients were M0 and 42 (68%) were M1. Median tumor size was 13 cm (5.5-25). Forty-nine (76%) patients had clear cell RCC and 26 (40%) had sarcomatoid features. Forty-seven (73.4%) patients had Fuhrman grade 3 or 4. Twenty-eight (44%) patients were pN0, 16 (25%) were pN1, and 20 (31%) were pNx. On multivariate analysis, the significant predictors of survival (p &lt; 0.05) were M stage at time of nephrectomy, pN stage, performing LN dissection, Fuhrman grade, and presence of sarcomatoid features. Conclusions: Survival in patients with pT4 remains poor. Predictors of survival in pT4 RCC patients include M stage, N stage, LN dissection, Fuhrman grade, and sarcomatoid features. Preoperative identification of patients with pT4 needs refinement, and could help improve patient management and selection for inclusion in neoadjuvant trials.
The evaluation of the hydrotalcite effectiveness on prophylaxis and treatment of mucositis due to high dose methotrexate treatment in osteosarcoma patients: A prospective crossover trial
Authors: G. Utkan, I. Tek, H. Doruk, B. Yalcin, A. Buyukcelik, H. Akbulut, A. Demirkazik, F. Icli, A. Pamir
Journal: Journal of Clinical Oncology (2005)

8263 Background: Mucositis is an important morbidity that may affects quality of life, impairs the chemotherapy dose intensity and may causes fatal infective complications. Methotrexate (MTX) is an antimetabolit drug with dose limiting myleosuppresion and mucositis toxicities. Hydrotalcite (HT) is an antiasid agent with gastrointestinal mucosa protective effect mediated by increased epithelial and fibroblast growth factor levels. We evaluated the protective effect of HT on mucositis in cancer patients receiving high dose MTX. Methods: Osteosarcoma patients receiving HDMTX (12 gr/m2) were recruited in a cross-over design. The patient receiving HT in one cycle were not given the drug in the following cycle. HT was given 8 times a day as mouthwash before swallowing it for 7 days begining with the MTX infusion. At the end of trial we compared the mucositis seen in HT cycles with the cycle without HT. Stomatitis and releated symptoms (diarhhea, abdominal pain, odynophagia) were evaluted. Results: Ninety six courses of HDMTX treatment evaluated in 14 patients. In 45 courses of patients received HT (HT+group) and 51 did not (HT - group). Mucositis rates, duration and related symptoms are shown in the Table1. Conclusions:Although the use of HT has been expected to have a mucosal protective effect in cancer patients receiving HDMTX, the current small clinical trial did not demonstrate any benefit. No significant financial relationships to disclose.
Single institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).
Authors: Krishna Soujanya Gunturu, Jaykumar Ranchodbhai Thumar, Howard S. Hochster, Stacey Stein, Xiaopan Yao, Xiangyu Cong, Jill Lacy
Journal: Journal of Clinical Oncology (2012)

e14534 Background: FOLFIRINOX significantly increases survival in metastatic PC compared to gemcitabine (Conroy. New Engl J Med 2011;364). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in advanced PC pts. Methods: We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 07/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and RR were compared to Conroy’s data using one sample proportion test. Overall survival (OS) and progress free survival (PFS) were estimated by Kaplan-Meier method. Results: 35 pts with ECOG PS 0/1 were treated. Pt characteristics: LAPC 16; MPC 19; median age 61 yrs (range 48-77); male 13; prior chemotherapy 5. Median (med) number of cycles was 10 (range 1-26). FOLFIRINOX was dose attenuated with the first cycle in 29 pts: IRI reduced in 27 and omitted in 1, OX reduced in 10, bFU reduced in 9 and omitted in 7, LV decreased in 11, FU infusion reduced in 3. Med doses of OX, IRI, bFU, and infusion FU were 90%, 68%, 68%, and 100%, respectively, compared to 78%, 81%, 82%, and 82%, respectively, in Conroy’s FOFIRINOX arm (control). We are following pts for PFS and OS. RRs were 50% and 47% in pts with LAPC and MPC. RR in MPC didnot differ significantly from the control (p=0.19). We observed significantly less grade 3/4 fatigue (p=0.008) and neutropenia (p&lt;0.0001) compared to the control group. Conclusions: Our findings suggest that dose attenuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent RR compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.
Are families the barrier? Evaluating attitudes toward early integration of palliative care in pediatric hematopoietic stem cell transplant.
Authors: Deena R. Levine, Justin N. Baker
Journal: Journal of Clinical Oncology (2016)

112 Background: The benefits of early integration of palliative care (PC) in oncology have been well established yet, there remain significant barriers to PC integration, especially in the setting of pediatric hematopoietic stem cell transplant (HSCT). HSCT patients are prone to a great degree of treatment related toxicity and are at high risk for morbidity and mortality and, while ideally suited to benefit, inherent factors in this cure oriented field preclude the integration of PC services. Most notably, family receptivity to PC is often perceived as a barrier in HSCT yet there is no data on family attitudes toward PC in this setting. This study aimed to evaluate perceived symptom burden and patient and parent attitudes toward early PC integration in pediatric HSCT. Methods: After IRB approval, development and pre-testing, novel survey tools were administered to HSCT patients and parents. Eligibility criteria included parent of an HSCT recipient &lt; age 10 or patient/parent dyad for patients aged 10-17, time from HSCT &gt; 1 month and &lt; 1 year, English-speaking, and consent/assent. Data was assessed for trends in response content frequencies, percentages and parent/child concordance. Results: Interim analysis of the first 34 participants revealed high levels of perceived symptom related suffering in the first month of HSCT with suffering from: nausea 96%, loss of appetite 88%, diarrhea 88%, pain 83%, depression 79%, anxiety 75%, and constipation 42%. 90% of patients and 71% parents expressed that a great deal or a lot of attention should be paid to quality of life from the start of HSCT. The majority of patient and parent respondents (60/46%) indicated they would likely want to meet with PC early in HSCT and very few reported definite opposition (0% children, 4% parents). Conclusions: Pediatric HSCT patients experience a high degree of symptom related suffering, perceive quality of life as a high priority, and are largely in favor of early PC involvement. Our findings suggest that family receptivity should not be a barrier to early PC in pediatric HSCT and that aggressive cure directed therapy can and should be accompanied by aggressive quality of life directed care through early PC integration.
A Novel Erythroid Regulator MLF1IP Promotes Proliferation in Mice By Regulating Cell Cycle
Authors: Tianjiao Zhang, Xiaotang Ma, Bing Li, Gang Huang, Robert Peter Gale, Yue Zhang, Zefeng Xu, Tiejun Qin, Josef T. Prchal, Zhijian Xiao
Journal: Blood (2015)
The adverse effects of androgen-deprivation therapy: Comparison between gonadotropin-releasing hormone agonists and orchiectomy in the SEER-Medicare population.
Authors: Maxine Sun, Ole-Petter Riksfjord Hamnvik, Guillermo de Velasco, Wei Jiang, Stacy Loeb, Paul L. Nguyen, Quoc-Dien Trinh, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

304 Background: Androgen-deprivation therapy (ADT) through surgical castration is equally effective as medical castration in controlling prostate cancer (PCa). However, the adverse effect profiles of both ADT groups have never been compared. Our objective was to provide a comparative effectiveness analysis of the adverse effects of gonadotropin-releasing hormone agonists (GnRHa) vs. bilateral orchiectomy in a homogeneous population. Methods: A total of 3295 men with metastatic PCa aged ≥ 66 years old, treated with GnRHa or bilateral orchiectomy between 1995 and 2009 were identified. Multivariable competing-risks regression models were performed, with the adjustment of all-cause mortality and treatment propensity score. Secondary analyses examined the effect of increasing duration of GnRHa treatment, and expenditures. Our main examined measures were: [1] any fractures, [2] peripheral arterial disease, [3] venous thromboembolism, [4] cardiac-related complications, [5] diabetes mellitus, [6] cognitive disorders, and [7] total expenditures. Results: In adjusted analyses, orchiectomy was associated with significantly lower risks of any fracture (HR: 0.80, 95% CI: 0.65–0.97), peripheral arterial disease (HR: 0.70, 95% CI: 0.53–0.92), and cardiac-related complications (HR: 0.82, 95% CI: 0.69–0.97) compared to those treated with GnRHa. No statistically significant difference was noted between orchiectomy and GnRHa for diabetes and cognitive disorders. When compared to individuals treated for ≥ 35 months with GnRHa, the increased risk for GnRHa compared to orchiectomy was noted for fractures, peripheral arterial disease, venous thromboembolism, cardiac-related complications, and diabetes mellitus (HR: 1.69, 2.19, 1.60, 1.62, and 1.36, respectively, all P≤ 0.04). No difference with respect to total expenditures was observed between GnRHa and orchiectomy (odds ratio [OR]: 1.21, 95% CI: 0.92–1.58). Conclusions: GnRHa was associated with higher risks in 3/7 examined adverse effects: any fractures, peripheral arterial disease rates, and cardiac-related complications.
Genetically Reengineered K562 Cells Significantly Expand Cord Blood (CB) Natural Killer (NK) Cells Ex-Vivo Expanded with Increased NK Cell Activation and Cytolytic Activity Both In-Vitro and In-Vivo: Potential Use In Adoptive Cellular Immunotherapy (ACI)
Authors: Michele Levin, Janet Ayello, Frances Zhao, Andrew Stier, Lauren Tiffen, William Quish, Carmella vandeVen, Laxmi V. Baxi, Jessica Hochberg, Mitchell S. Cairo
Journal: Blood (2010)
Comparative effectiveness and survival benefit of various treatment modalities in HCC: A SEER-Medicare analysis.
Authors: Nader Hanna, Ian Michael Breunig, C. Daniel Mullins, Brian S. Seal, Viktor Chirikov, Fadia T. Shaya
Journal: Journal of Clinical Oncology (2013)

319 Background: In the United States, the incidence of HCC has increased from 1.6 per 100,000 in 1975 to 4.9 per 100,000 in 2005. Care for HCC patients remains specialized and complex with transplant and surgery offering the only potential for long survival. However no comparative effectiveness of various treatment modalities across various stages of HCC exists. Methods: Medicare enrollees, older than 65 with an initial diagnosis of primary HCC between 2000-2007 were followed up through the end of 2009. For patients with stages I, II, III, and unstaged, data were obtained from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Multivariate Cox proportional hazards models were used to assess overall and HCC related mortality in relation to receipt of various/no treatments, adjusting for concomitant therapies, demographics, general health status (Charlson comorbidity index), and liver conditions, moderate-severe liver disease. Results: Distributions across stages: males 64-71%, Caucasians 72-77%, African Americans 8-10%, Hispanics 12-14%; a majority (72-75%) was age 65-84; Hepatitis C was the most prevalent (17-41%). Conclusions: Compared to untreated patients, improved all-cause and HCC-related mortality was observed in all stages in the following order: transplant, surgical resection, liver directed therapy, and chemotherapy. Greater impact on HHC-related mortality was seen across all treatment groups. [Table: see text]
Phase II trial of irinotecan, S-1, and bevacizumab (IRIS/Bev) combination chemotherapy as second line for advanced colorectal cancer (NCCSG04).
Authors: Yasumasa Takii, Kouichi Hurukawa, Satoshi Maruyama, Toshiyuki Yamazaki, Jun Nishimura, Mikako Kawahara, Takemi Tomiyama, Kohei Akazawa, Katsuyoshi Hatakeyama
Journal: Journal of Clinical Oncology (2013)

496 Background: The FIRIS study (Muro K et al. Lancet Oncol 2010;11:853-860) previously demonstrated the non-inferiority of Irinotecan plus S-1 (IRIS) to FOLFIRI for metastatic colorectal cancer (mCRC), with progression-free survival as the primary endpoint. IRIS plus bevacizumab (IRIS/Bev) was reported an active and generally well-tolerated first-line treatment for mCRC (Yuki et al. ASCO 2012 #3593). We planned a Phase II trial to evaluate the efficacy and safety of IRIS/Bev as second-line therapy for patients with mCRC. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m 2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m 2 and Bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety. Results: From 08/12 until 11/06, 35 patients were enrolled. One patient did not start therapy. Thirty-four patients were investigated. Median age was 63 years (range, 38 to 82). Twenty-five patients were male. The mean of relative dose intensity of TS-1/Irinotecan/Bev were respectively 92.1%/87.0%/86.2%. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 9.3 months, median TTF was 8.2 month and median survival time 23.1 month. On safety analysis, the incidence of grade 3 or 4 adverse reactions were as follows: neutropenia, 14.7%; fatigue, 14.7%; white blood cell decreased, 11.8%; anorexia, 8.8%; anemia, 8.8%; diarrhea, 2.9%; proteinuria, 5.9%; thromboembolic event, 2.9%. Conclusions: IRIS/Bev is an active and well-tollarated second-line treatment for patients with mCRC. Clinical trial information: UMIN000001631.
A Calcineurin Inhibitor Does Not Affect the Post-Transplantation Cyclophosphamide -Induced Regulatory T Cell Expansion after Bone Marrow Transplantation in a Murine Chronic Gvhd Model
Authors: Kyosuke Saeki, Yoshinobu Maeda, Keisuke Seike, Katsuma Tani, Taiga Kuroi, Shohei Yoshida, Hisakazu Nishimori, Mitsune Tanimoto
Journal: Blood (2016)
Phase I trial of CG53135–05 to prevent mucositis in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT)
Authors: M. W. Schuster, T. B. Shore, J. Greenberg, B. Jalilizeinali, S. Possley, Y.-D. Halvorsen, V. Annino, W. Hahne
Journal: Journal of Clinical Oncology (2005)

6656 Background: Mucositis is a painful side effect of many transplant conditioning regimens. A new class of drugs in the fibroblast growth factor family is being investigated for ameliorating or preventing oral mucositis (OM). CG53135–05, recombinant human fibroblast growth factor-20 (rhFGF-20) purified from E. coli, promotes epithelial and mesenchymal cell proliferation in vitro and is being investigated to reduce the incidence or duration of severe OM following HDCT and PBSCT. Methods: A phase I trial was conducted to evaluate safety, tolerability and pharmacokinetics (PK) of CG53135–05. Patients (pts.) with hematologic malignancies undergoing HDCT and autologous PBSCT were enrolled. CG53135–05 was administered as single dose IV infusion over 15 min 24h after stem cell infusion. Evaluation of safety and PK was assessed for up to 30 days post dosing. Pts were scored daily for presence of OM using both the WHO and OMAS grading scales. Results: 30 patients (ages 25–75) treated with escalating doses of study drug, including (no. of pts): 0.03 mg/kg (10), 0.1 mg/kg (10), 0.2 mg/kg (8), and 0.33 mg/kg (2). Pts had multiple myeloma (n=16), non-Hodgkin’s lymphoma (n=12), acute myelogenous leukemia (n=1), or desmoplasmic round cell tumor (n=1). In general, CG53135–05 was well tolerated with no significant side effects up to a dose of 0.33 mg/kg. At that dose, 2 pts experienced infusional reactions with no further pts treated at that dose level. Pharmacokinetics were measured at all dose levels. Preliminary results confirmed dose dependent plasma exposure. Among the 30 pts who completed the study, 10 pts experienced no OM (including 5 Mel 200 pts), 13 pts experienced only WHO Grade 1 (n=7) or Grade 2 (n=6) OM, while 7 pts experienced severe Grade 3 or 4 OM. 2 pts experiencing Grade 4 OM required TPN. Conclusion: CG53135–05 is well tolerated in autologous stem cell transplant patients at doses up to 0.33 mg/kg. 23/30 pts did not develop severe (WHO Grades 3–4) mucositis following HDCT. A larger Phase II clinical trial has been initiated to evaluate the efficacy of CG53135–05 in preventing HDCT induced OM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CuraGen CuraGen CuraGen
Molecular analysis of adrenocortical carcinoma (ACC) tumors.
Authors: M. C. Pastor, T. Frew, M. G. Yeh, S. G. Wong
Journal: Journal of Clinical Oncology (2011)

e21174 Background: Personalized medicine has become increasingly important in the management of oncology patients. Traditional approaches require a large numbers of unselected patients to enroll on clinical studies with empirically derived therapies. Newer approaches include analysis of tumor specimens to determine potential predictive and prognostic clinical biomarkers. Recently, a study by Von Hoff and colleagues utilized a molecular analysis of freshly biopsied tumors to determine gene array profile along with immunohistochemical staining in effort to generate potential targets for therapeutic intervention. This approach led to 28% of the study patients achieving a 33% increase in progression free survival. Adrenocortical carcinomas (ACC) occur in only one out of one million people and many patients have metastatic disease at the time of diagnosis (1). The rarity of this disease makes it difficult to study and with few treatment options the prognosis is poor (5). The standard management of this disease is largely surgical, with a role for adjuvant mitotane post-operatively, and palliative chemotherapy in the case of metastatic disease (9). Methods: Six consecutive unselected patients at UCLA Medical Center were chosen for this study. The patients had surgery at UCLA and had a portion of their tumors fresh frozen and sent CARIS MPI where molecular analysis was performed. A gene microarray profile that focused on 81 genes, potentially important in oncogenesis and oncomaintenance, was run as well as immunohistochemistry staining of 50 proteins important in cell growth and division. Genetic data were categorized, qualitatively reviewed, and attempts at correlations were made. Results: The microarray data provided some consistencies across the patients. All the patients were found to overexpress DNA associated molecules such as; TOP2A, RRM2, TK1, and TYMS also found to be underexpressed were molecules involved in signaling pathways such as; PDGFRA and ECGF1. Conclusions: While many cancers have known genetic defects contributing to their molecular phenotype ACC has yet to have any clearly defined molecular defect. This brief molecular study and clinical description of six ACC patients illustrates the heterogeneity of this disease.
Personal history of atypical ductal hyperplasia and risk of multifocal breast cancer among newly diagnosed women: Implications for workup and management.
Authors: Curtis Lee Petersen, Tracy Onega
Journal: Journal of Clinical Oncology (2014)

300 Background: Multifocal breast cancer (MFBC) is associated with a higher risk of mortality than unifocal and often changes evaluation and management compared to unifocal breast cancer. Although there are known risk factors for invasive breast cancer, including atypical ductal hyperplasia (ADH), none have been explicitly associated with risk of MFBC. Our objective was to determine if there is an association between ADH and MFBC to help guide clinical decisions in workup and management in women with newly-diagnosed breast cancer. Methods: Using data (1999-2008) from the New Hampshire Mammography Network (NHMN) – a longitudinal breast imaging registry, including pathology data – we identified a cohort of 3,039 women (median age: 59) with a diagnosis of invasive or in situ breast cancer, and ascertained all prior biopsy results if applicable. We performed multivariable logistic regression to test the association of ADH with MFBC v. unifocal, adjusting for other benign breast disease, family history, breast density, age, race, and DCIS/invasive. Results: Of the 3,039 women with breast cancer during the study period, 498 had a diagnosis of ADH (16.4%) and 277 had MFBC (9.1%). Women with a history of ADH had over a two-fold greater likelihood of having MFBC compared to women without an ADH diagnosis (OR: 2.20, 95% CI: 1.61-2.99). No notable difference in this association was noted for DCIS v. invasive, and no other risk factors were found to have a significant difference, except for number of biopsies. Conclusions: We found that ADH diagnosis is positively associated with MFBC among women with a diagnosed invasive or in situ breast cancer. Our results suggest that among women with a newly diagnosed breast cancer, history of an ADH diagnosis increases the pre-test probability of MFBC, which may influence evaluation of extent of disease, such as adding breast MRI, and ultimately in treatment and management.