tbuckley/cabot-search huggingface dataset:
Mini-gene profiling for the prediction of bone metastases in breast cancer patients.
Authors: L. Mercatali, T. Ibrahim, C. Liverani, D. Guerra, D. Amadori
Journal: Journal of Clinical Oncology (2011)

e21030 Background: The process of bone metastasization includes numerous steps such as proliferation, invasion and adhesion, involving molecules, growth factors, chemochines and their receptors that confer the bone-like phenotype. Thus, only cancer cells with specific features will be able to reach and colonize bone tissue. The early prediction of relapse in this site could be clinically useful to select patients for a tailored therapy based on bone specific drugs such as bisphosphonates or RANK-L inhibitors. Methods: The study retrospectively evaluated the levels of TFF1, DKK1, IBSP, HPSE, SPP1, Agr2, SPARC, CTGF, COMP, FST, and RANK transcripts by quantitative real-time PCR in the fresh frozen breast cancer samples of 40 patients to predict cancer relapse and the sites of relapse. Fifteen patients had no evidence of disease (NEDP), 15 had bone metastases (BMP), and 10 had visceral metastases (VMP). The predictive accuracy of each marker was calculated using Receiver Operating Characteristic (ROC) curves. Results: The median values of each marker were calculated for each subgroup: TFF1 median values were about 7 times higher in BMP than in control groups (p=0.05); COMP and HPSE median values were about twice as high in BMP compared to both NEDP and VMP. The area under the curve (AUC) was 0.73 for TFF1, and 0.62 for HPSE and COMP. Considering markers as dichotomous variables, TFF1 expression reached 67% in BMP compared to 21% and 20 % in NEDP and VMP, respectively. TFF1 was also analyzed in combination with other markers and, considering positivity of at least one marker among TFF1, DKK1, and IBSP, an expression level of 80% was reached for the BMP group, whilst the same low expression level was maintained in both control groups (p=0.041). Conclusions: Our preliminary results show that the analysis of 3 gene expression markers, TFF1, DKK1 and IBSP, in primary breast tumors could be useful to predict the patients who will relapse to bone tissue. However, a larger case series should be performed to understand the role of these markers in the selection of patients eligible for adjuvant preventive bone specific therapy.
A randomized trial of exercise versus control for musculoskeletal symptoms from adjuvant anastrozole (A) for postmenopausal early breast cancer (PEBC).
Authors: C. A. Lohrisch, D. McKenzie, P. Truong, D. Jesperson, K. A. Gelmon, S. Premji, H. F. Kennecke
Journal: Journal of Clinical Oncology (2011)

636 Background: Musculoskeletal symptoms, for which there is no standard therapy, are common in women on aromatase inhibitors (AIs) for PEBC. A phase III randomized study explored whether exercise improves arthralgias / myalgias (A/M). Methods: Eligible women with EPBC had A/M related to A and were randomized to an exercise (E) or a control (C) group. E patients exercised 3x weekly for 48 weeks; for the first 12 weeks in a supervised setting; for second 12 weeks, supervised once weekly and twice independently, and for the last 24 weeks independently, using aerobic and resistance programs tailored to their fitness. The primary endpoint was change in SF36 bodily pain domain scores at week 12 (W12). Secondary endpoints included change in bone density (BMD), change in body mass (BMI), strength, and in hot flash (HF) index. Results: The study closed due to poor accrual after 3 years with 22 (11C 11E) of the planned 72 subjects enrolled at two sites among 98 screened. Among 20 evaluable subjects, baseline median age was 62; BMI was 26 kg/m2 in the E and C arms; median number of A/M sites was 5, with a median worst score of 2 (CTC-version 2 criteria). In the E and C arms, respectively, mean baseline SF36 physical domain scores were 7 and 8 (best possible score 12, worst 2). At W12 the score improved in 6 (55%) E and 7 (64%) C subjects. Median weight dropped 4kg in the E and rose 4kg in the C groups by W48. W12 bench press and leg strength did not significantly change in either groups. At W48, there was minimal change in BMD in both groups compared to baseline, with only 1 C subject evolving from osteopenia to osteoporosis. Median baseline HF scores were low in both groups and did not differ significantly at any time point. Conclusions: A 48 week supervised exercise intervention did not have a measurable improvement in A related A/M symptoms as measued by 12W SF36 bodily pain scores. Weight dropped in the E group by a median of 4kg (8kg difference compared to C group). Recruitment is an important consideration in exercise trials and may be challenging among patients more distant from their initial diagnosis of cancer.
Outcome and prognostic significance of phenotypes in breast cancer patients.
Authors: J. M. Jurado, J. A. Ortega, I. Blancas, M. Delgado, I. Zarcos, J. Martínez-Galan, M. Pérez, M. J. Sánchez, R. Del Moral, J. L. García- Puche
Journal: Journal of Clinical Oncology (2010)

e11002 Background: To evaluate the clinical significance of subtyping breast cancer (BC) by immunohistochemistry. We analyzed and correlated breast cancer subtypes with overall survival (OS) and disease-free survival (DFS) in nodal positive and negative patients treated with adyuvant therapy. Methods: We retrospectively reviewed the medical records of 550 breast cancer patients submitted to Virgen de las Nieves Hospital from 1998 to 2004. Patients were classified by tumor characteristics as (14,5%) triple negative (estrogen receptor ER-negative, progesterone receptor PR-negative, HER2/neu HER2-negative), (8,5%) HER2 (HER2-positive, ER-negative, PR-negative), (68%) luminal A (ER-positive and/or PR-positive and not HER2-positive) and (4%) luminal B (ER-positive and/or PR-positive and HER2-positive). For mutivariante analysis, stratified cox models were built to determine de hazard ratios of breast cancer subtypes adjusting for age (median 54 ± 11 yrs), nodal involvement (N0 62%, N1-3 24%, N>4 13%), tumor size (T1 59% T2 39% T3 1,6%) and grade ( G1 32% G2 39% G3 15%). Results: Median follow-up was 47 months. Actuarial (OS and DFS) at 4 years were luminal A (99,3% and 95,8%), luminal B (95,6% and 80,4%), Her2 (89,8% and 80,9%) and triple negative (74,6% and 58,7%), p=0,0001; for N0 (98,8% and 93,9%) N1-3 (90,8% and 83,6%) and N>4 (87,1% and 71,8%), p= 0,0001. Significant independent prognostic factor for OS were BC subtypes, hazard ratio [HR] (luminal B 4.7, Her2 3.6 and triple negative 12.08), p=0.0001; and the nodal status [HR] (N1-3 6.6 and N>4 8.3), p= 0,004. Significant independent prognostic factor for DFS were BC subtypes [HR] (luminal B 4.8, Her2 3.9 and triple negative 7.7) p=0.0001; the number of positive nodes > 4 [HR] 2.01, p=0.049 and T2 [HR] 2.28 p=0.004. Conclusions: We confirm the worse outcome of triple negative patients and nodal positive status. Our study suggest that breast cancer phenotypes provides independent pronostic value and may be useful for clinical management in the assessment of patients for adjuvant systemic therapy. No significant financial relationships to disclose.
Effectiveness of abiraterone as salvage therapy in patients with docetaxel- and castration-resistant prostate cancer (mDCPC) that progressed during second-line chemotherapy with carboplatin plus weekly docetaxel (DC).
Authors: Michael A. Morgan, Martin Fenner, Viktor Grünwald, Axel S. Merseburger, Arnold Ganser, Christoph W. Reuter
Journal: Journal of Clinical Oncology (2013)

e16064 Background: Our recent data have shown that carboplatin AUC5 on d1 plus docetaxel at a dose of 35 mg/m2 iv on d1, 8, 15 every 4 weeks (q4w) is an effective salvage therapy in mDRPC. Patients (pts) who have progressive disease during DC treatment survive only ~7 months and many are symptomatic. We have demonstrated that high free testosterone (FT) serum levels during DC treatment have a negative prognostic value for PSA response and overall survival in these pts. In this study the impact of abiraterone treatment and other subsequent salvage regimens after DC failure was analyzed. Methods: DC failure was defined as disease progression during DC treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC pts were treated with at least 2 cycles DC until disease progression. At the time of the current analysis 69 pts have progressed and 43 pts received one or more subsequent therapies (1-3). Results: Overall survival (OS) of all 69 pts who have progressed during DC treatment was 8.0 months (CI 95% 3.7, 12.3). 43 pts received subsequent salvage therapies including mitoxantrone-prednisone-etoposide (MPE) (n=10), cabazitaxel (n=13), docetaxel-oxaliplatin (n=8), abiraterone (n=15), enzalutamide (n=5) and doxorubicin-ketokonazol (n=5). OS of these 43 pts was 14.6 months (CI 95% 11.0, 18.2).In pts receiving abiraterone as salvage treatment, OS after DC was 21.8 months versus 11.9 months (CI 95% 9.0, 14.8) in pts receiving other regimens (HR 0.17, CI 95% 0.07, 0.42; p&lt;0.001). Responses of prostate-specific antigen (PSAR; ≥30% and ≥50%) were only frequently observed in pts receiving abiraterone (8/15, 53.3% and 4/15, 26.7%, respectively). Conclusions: Our data demonstrate for the first time that testosterone is an important prognostic factor for PSA response and OS in mDRPC patients receiving DC chemotherapy and that targeting testosterone after DC failure prolongs post-DC survival.
Subpectoral implants in oncoplastic-reconstructive breast surgery: Habit or necessity?
Authors: Stefan Paepke, Sissi Dittmer, Arian Rezai, Evelyn Klein, Marion Kiechle
Journal: Journal of Clinical Oncology (2012)

161 Background: We perform nipple-sparing subcutaneous mastectomies since 2002. Herein we report on 352 cases, in 156 of which acellular dermis (ADM) or meshs (tetanized polypropylene-mesh) as tissue interponates were used. The standard procedure of subpectoral implant positioning with or without caudo-lateral tissue interponates (acellular dermis or mesh) can lead to postoperative problems due to detachment of muscle. Against this background we did not form a submuscular pocket in individual cases, but instead placed the implant in a cranially and caudally covering ADM or mesh pocket. Methods: Between 06/11 and 03/12 17 patients were operated according to the above protocol, and the short-term follow up analyzed. Patients that had to get radiation therapy were not admitted to the study. Furthermore, we only included patients that were planned to get a second, contralateral operation so that corrections of the first operation were possible. Patients were between 34 and 58 years old. One patient had to receive radiotherapy due to a nodal involvement not diagnosed before. Results: Four patients had received prior surgery. Indications for subcutaneous mastectomies comprised invasive carcinomas with large DCIS, R1 resections or secondary prophylaxis. Mastectomy weights ranged between 225 and 1100 g; implant volumes ranged between 225 and 800 cm 3 . The cosmetic outcome was excellent, the margins of the implants were not visible. In three cases there was a partial necrosis of the nipple and in two cases a partial skin necrosis with the necessity of a wound revision. Conclusions: Using a ADM- or mesh-pocket instead of subpectoral positioning of the implant makes the operation in individual cases easier. Post-operative mobility is immediate and unrestricted. Since the implant size has to be chosen according to the tissue weight removed, a bilaterally identical cosmetic result can be archieved. Complications inculde a mild seroma formation without the necessity to puncture. However, the small number of cases and the short term follow up do not allow to make any statements about consecutive capsular fibrosis.
Phase I dose-finding study of epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer (AGC).
Authors: S. Sym, J. Hong, J. Park, E. Cho, W. Lee, M. Chung, Y. Park, J. Lee, D. Shin
Journal: Journal of Clinical Oncology (2011)

123 Background: To determine the recommended dose (RD) and dose-limiting toxicity (DLT) of EOS combination in patients with previously untreated AGC. Methods: Previously untreated patients with histologically proven metastatic or recurrent AGC and ECOG performance status 0-2 were enrolled. Fixed dose of epirubicin (50 mg/m 2 ) and oxaliplatin (130 mg/m 2 ) was administered i.v. on day 1. The dose of S-1 was escalated as following schedule: Level I: 30 mg/m 2 , Level II: 40 mg/m 2 , Level III: 45 mg/m 2 , Level IV: 50 mg/m 2 . S-1 was administered orally twice a day on days 1-14. Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment. Results: Nineteen patients were enrolled: 13 patients in dose-escalation phase and 6 patients in the extension at the RD. Median age was 53 years (range, 40-71 years). At dose level II, 1 DLT (grade 4 neutropenia lasting more than 5 days) was found among 6 patients while at dose level III, 2 DLTs (grade 3 diarrhea and nausea) were observed among 4 patients. Therefore, the dose level II was determined as RD. Cumulative (all cycles) grade 3/4 toxicity included neuropenia (58%), leucopenia (32%), thrombocytopenia (11%), diarrhea (11%), and nausea (5%). Of 13 patients with measurable lesions, 8 achieved partial response and 3 showed stable diseases, and the objective response rate was 62% (95% CI, 36-88%). The median progression-free survival was 6.5 months (95% CI, 4.7-8.2 months). Conclusions: The RD of the EOS regimen in patients with previously untreated AGC was epirubicin 50 mg/m 2 and oxaliplatin 130 mg/m 2 on day 1 and S-1 40 mg/m 2 twice a day on days 1-14 of every 21-day cycle. This regimen seems to have promising preliminary activity. No significant financial relationships to disclose.
Treatment of patients with metastatic renal cell carcinoma (RCC) and end-stage renal disease (ESRD) with targeted therapy (TT): A case series.
Authors: Amber Flaherty, Marc Ryan Matrana, Bradley J. Atkinson, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2012)

453 Background: Studies have shown that RCC is more prevalent in patients with ESRD, and RCC outcomes in patients with ESRD differ from those of the general RCC population. There is limited data regarding the use of TT in patients with metastatic RCC (mRCC) who are maintained on dialysis for ESRD. Methods: We retrospectively reviewed records of patients with mRCC who were seen at UT MD Anderson Cancer Center and received TT (sunitinib, sorafenib, pazopanib, temsirolimus, everolimus, erlotinib, or bevacizumab) over the last eight years (2003-2011) and who also had ESRD and underwent hemodialysis (HD) or peritoneal dialysis (PD). Overall survival (OS) was determined from initiation of TT to death. Results: Eleven patients (6 males; 8 with clear cell, 3 with papillary) were identified who met the above inclusion criteria. Median age was 57.4 years. Comorbidities included hypertension in 10, diabetes in 4, and hyperlipidemia in 6. Median number of TT was 4 (range, 1-6). Median time on treatment (TOT) was 769 days (range, 73-1792), Seven patients have died. Seven patients were on both HD and TT for over 1 year. Median OS was 1075 days (95% CI, 722-1428). TT related adverse events (AEs) included hypertension (HTN), hand-foot skin reaction (HFS), fatigue, diarrhea, rash and pneumonitis [Table]. There were no treatment related deaths. Conclusions: In this small retrospective series of patients with mRCC and ESRD who were treated with TT, adverse events were acceptable, and relatively prolonged disease courses were noted. [Table: see text]
Extracellular vesicles-mediated noncoding RNAs transfer in cancer
Authors: Pei Ma, Yutian Pan, Wei Li, Chongqi Sun, Jie Liu, Tongpeng Xu, Yongqian Shu
Journal: Journal of Hematology & Oncology (2017)

Extracellular vesicles (EVs) are small membranous vesicles secreted from numerous cell types and have been found involved in cell-to-cell communication by transferring noncoding RNAs (ncRNAs) including microRNAs, long noncoding RNAs, and circular RNAs. Emerging evidence shows that EV-associated ncRNAs play important roles in a wide range of diseases, particularly in cancer where they function through regulating protein expression of the pivotal genes that make contributions to tumorigenesis. Given their stability and abundance in serum, EV-associated ncRNAs can act as new diagnostic biomarkers and new therapeutic targets for cancer. Herein, we review the properties of EV-associated ncRNAs, their functions, and potential significance in cancer.
Phase II study of preoperation mFOLFIRINOX and chemoradiation for high-risk resectable and borderline resectable pancreatic adenocarcinoma.
Authors: Gauri R. Varadhachary, Jason B. Fleming, Christopher H. Crane, David R. Fogelman, Rachna T. Shroff, Jeffrey Edwin Lee, Jeffrey H. Lee, Eric P. Tamm, Priya Bhosale, Prajnan Das, Sunil Krishnan, Milind M. Javle, Brian Weston, Huamin Wang, Robert A. Wolff, Matthew H. G. Katz
Journal: Journal of Clinical Oncology (2015)

362 Background: Patients with high risk resectable and borderline resectable pancreatic adenocarcinoma (BRPC) are at a high risk for R1/R2 resection, early relapse with upfront surgery and poor OS. Preop therapy has a sound rationale and current retrospective data suggest resection rates of 40-60% with a possible impact on OS. Methods: We planned a prospective study of 33 pts. Eligibility includes diagnosis of pancreatic ductal carcinoma (PC) and &gt;=1 criteria of BRPC (radiographic) A: (i) PC involves SMV with vein deformity or segmental occlusion; (ii) PC involves &lt;=180 0 SMA, CA or its branches (iii) abutment or encased short segment of CHA and/or BRPC (high-risk) B: (iv) CA19-9 &gt;=500 mg/dl (v) malignant peripancreatic nodes outside planned surgical field (vi) indeterminate liver or peritoneal lesions. Enrolled pts receive mFOLFIRINOX (oxaliplatin 75 mg/m 2 d1+ irinotecan 150 mg/m 2 d1+ 5-FU 2000mg/m 2 46h CI) for 6 cycles. Those without progression &amp; good PS undergo EBRT 50.4Gy with weekly Gemcitabine 350 mg/m2. Surgery is planned 4-6 weeks after CRT in pts without progression. Results: 24/33 pts accrued. 18(75%) with A criteria alone; 1(4%) with B criteria alone and 5 (21%) with both. Median age is 66 yrs; ECOG PS0 42%, PS1 58%. Median CA19-9 is 219 (1-1185) mg/dl. 20/24 have completed all preop therapy and 10 underwent surgery (50%).10 patients did not proceed to surgery due to disease progression (5), poor PS (3) or withdrawal of consent (2). Grade ¾ hematologic and non-hematologic toxicity noted in 8/21 (38%). Of the 10 resected pts, all underwent vein reconstruction and R0 rate is 80%. Major pathologic response rate (&gt;50 % tumor kill) was 30%. One (bleeding) major complication occurred within 90 d of surgery. 5/10 resected pts relapsed &lt;1yr after surgery with a median TTP from surgery of 5mo (3-7mo). SMAD4 and CTC analysis pending. Conclusions: Although the sample size is limited, using strict criteria, resection rates with preop FOLFIRINOX and Gem-RT mirror retrospective data (50%). Half of the resected pts have recurred early suggesting aggressive preop therapy does not rescue aggressive biology. Further analysis may allow identification of pts who are poor candidates for an aggressive preop approach. Clinical trial information: NCT01560949.
Long-term survival in Hodgkin’s disease: A tumor registry study
Authors: S. Waheed, Y. Hull, F. Buadi, R. Womeodu, K. Wright, D. Przepiorka
Journal: Journal of Clinical Oncology (2005)

6720 Background: Hodgkin’s Disease (HD) is a curable malignancy. SEER data suggest a stable if not declining incidence and mortality of HD, but whether this is true for all subgroups is not clear. Methods: To determine what factors affect survival of HD patients in our area, and whether survival has improved significantly, we performed a retrospective analysis of 229 patients diagnosed 1980–2000 with HD, identified from a hospital tumor registry. Cox regression analysis was performed to identify demographic variables prognostic for survival. Results: The study cohort was comprised of 164 Caucasions, 63 African Americans (AA), and 2 other. There were 110 females and 119 males. Median age of cohort was 31 years (range 12–84). Histology was nodular sclerosing in 142 patients, mixed cellularity in 56, lymphocyte depleted in 11, classical in 11, and not specified in 9. Staging was performed according to the tumor registry method. HD was localized for 54 patients, regional for 57, distant for 65 and unknown for 53. Median overall survival was 15 yrs. Patients were divided into four groups based on quintile of date of diagnosis. For all patients, there was no significance difference in survival over time (p=0.11). In a multivariate analysis, factors significantly prognostic for mortality included age >50 years (HR 2.51, 95% CI 1.98–3.18, p<0.001), AA race (HR 1.80, 95% CI 1.19–2.75, p=0.006), and female gender (HR 0.66, 95% CI 0.44–0.98, p=0.4). Conclusions: We do not confirm the reports that survival is improving for patients with HD. Further studies will be needed to determine whether this is due to changes in the proportion of patients with adverse prognostic factors seen at our center. No significant financial relationships to disclose.
Choosing Wisely: Opportunities for improving value of cancer care in the Deep South.
Authors: Maria Pisu, Gabrielle Betty Rocque, Kelly Kenzik, Bradford E. Jackson, Yufeng Li, Aras Acemgil, Richard A. Taylor, Terri Salter, Edward E. Partridge
Journal: Journal of Clinical Oncology (2016)

13 Background: Under the Choosing Wisely (CW) Campaign, the American Society of Clinical Oncology (ASCO) and the American Society of Therapeutic Radiology and Oncology (ASTRO) recommend against non-evidence-based costly medications, tests, and procedures. CW recommendation adherence in the Deep South is largely unknown, and opportunities to reduce overuse and costs may exist. Methods: Analysis of administrative claims and tumor registry data from 12 cancer centers of the University of Alabama Health System Cancer Community Network, for Medicare beneficiaries ≥65 years old with cancer. Main outcome: percent of beneficiaries adhering to 9 CW recommendations. Results: 2012-2015 (Q1) adherence varied across CW recommendations and cancer centers, and increased over time for CW 2 and 7, decreased for 3, 5, and 6, and did not change for others. Conclusions: Opportunities to improve quality and value of cancer care exist in the Deep South. Research should understand how to minimize use of non-evidence based medications, tests, and procedures. [Table: see text]