tbuckley/cabot-search huggingface dataset:
R-ICE versus R-ESHAP for salvage therapy in aggressive B-cell non-Hodgkin lymphoma.
Authors: Craig Freyer, Timothy George, Samantha Price, Bijal Dinesh Shah, Celeste M. Bello, Lubomir Sokol, Eduardo M. Sotomayor, Jennifer L. Cultrera
Journal: Journal of Clinical Oncology (2012)

e18509 Background: Standard therapy for aggressive Non-Hodgkin’s lymphoma (NHL) consists of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), however the 5 year relapse rate is 20%. Patients with relapsed/refractory (RR) NHL are offered autologous stem cell transplantation (SCT) after salvage chemotherapy demonstrates chemosensitivity and reduces tumor burden. No standard salvage regimen for RR-NHL exists. Frequently used regimens include R-ICE (rituximab, ifosfamide, carboplatin, etoposide) and R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin). Which regimen provides the greatest efficacy with least toxicity remains unclear. Methods: Patients diagnosed with RR aggressive NHL who received R-ICE or R-ESHAP between 1/1/2000 and 9/30/2011 were identified. Patients may have received either regimen after failure of initial therapy. The primary objective was to determine the overall response rate (ORR) for each regimen. Secondary objectives included determination of overall survival (OS), and proportion of patients able to receive SCT. OS for each regimen was compared using Kaplan-Meier survival curves. Continuous data was compared using the student’s T-test. Results: The median age was 59 years, 27% were female and 90% were described as Caucasian. 78% were diagnosed with diffuse large B cell lymphoma (DLBCL), 13% with transformed follicular lymphoma, 9% with related aggressive NHL subtypes. 55% had a revised International Prognosis Score of 2. Conclusions: No standard of care exists for management of RR-NHL. No regimen has shown superior efficacy or long term outcomes over another. Our trial suggests similar ORR and OS between two commonly used regimens. Although toxicity profiles differ between these regimens, discontinuation rates due to toxicity were similar. The choice of salvage regimen may be determined by ease of administration, toxicity profile and patient/physician preference rather than improved efficacy between R-ICE and R-ESHAP. [Table: see text]
Renal outcomes in patients with AL amyloidosis: Prognostic factors, renal response and the impact of therapy
Authors: Efstathios Kastritis, Maria Gavriatopoulou, Maria Roussou, Magdalini Migkou, Despina Fotiou, Dimitrios C Ziogas, Nikos Kanellias, Evangelos Eleutherakis‐Papaiakovou, Ioannis Panagiotidis, Stavroula Giannouli, Erasmia Psimenou, Smaragdi Marinaki, Theofanis Apostolou, Hariklia Gakiopoulou, Anna Tasidou, Ioannis Papassotiriou, Evangelos Terpos, Meletios A. Dimopoulos
Journal: American Journal of Hematology (2017)

A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m2 ) and proteinuria (≥5 g/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m2 ) was associated with a 2-year progression to dialysis rate of 0% compared to 9% for a ratio of 31-99 and 35% for a ratio ≥100 (P < .001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2-year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (P = .001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib-based therapy was more effective than lenalidomide-based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival.
A phase I dose-escalation and PK study of continuous oral rucaparib in patients with advanced solid tumors.
Authors: Rebecca Sophie Kristeleit, Geoffrey Shapiro, Patricia LoRusso, Jeffrey R. Infante, Michael Flynn, Manish R. Patel, Sara M. Tolaney, John Frederick Hilton, Alan Hilary Calvert, Heidi Giordano, Jeffrey D. Isaacson, Jennifer Borrow, Andrew R. Allen, Sarah S. Jaw-Tsai, Howard A. Burris
Journal: Journal of Clinical Oncology (2013)

2585 Background: Rucaparib, a potent, oral small molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1 and -2, is being developed for treatment of homologous recombination repair deficient (HRD) ovarian cancer. This study evaluated oral rucaparib as monotherapy. Primary objectives were to define maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and PK of continuous oral rucaparib. Methods: A standard 3+3 dose escalation design was used. Intra-patient dose escalation was allowed. Patients (pts) aged ≥18 with advanced solid tumor that progressed on standard treatments were recruited. Rucaparib was taken orally qd or bid until disease progression. Plasma PK assessments included full profile, trough levels, and food effect. Results: 29 pts (median age 52 yrs [range 21-71]; 26 female; 15 ECOG PS=0; 17 breast cancer (BC), 7 ovarian/peritoneal cancer (OC), 5 other tumor) were enrolled in 6 dose cohorts to date (40, 80, 160, 300 and 500 mg qd, 240 mg bid). Evaluation of 360 mg bid rucaparib is nearly complete. No DLTs have occurred and no pts have discontinued treatment due to toxicity. Treatment-related adverse events (primarily CTCAE grade 1-2) reported in ≥2 of 29 pts include fatigue (n=5), anorexia (n=3), nausea (n=3), vomiting (n=3), and diarrhea (n=2). To date, two pts (1 OC, 1 BC; both BRCA1 mut ) treated with 300 mg qd rucaparib achieved PR at wk 6; both are ongoing in wk 17. An additional 10 pts (5 OC, 4 BC, 1 CRC; 7 BRCA mut , 2 BRCA unk , 1 BRCA wt ) achieved best response of stable disease (SD) &gt;12 wks thus far; 4 pts (3 OC, 1 BC) are ongoing at 17 (n=2) and 30 (n=2) wks. Overall disease control rate (CR+PR+SD&gt;12 wks) in OC pts across all dose levels was 86% (6/7). Dose proportional PK was observed up to 500 mg qd with mean t 1/2 of 15 h (range 4.3 - 29 h). Following qd dosing, steady state was achieved by Day 8. As expected, bid dosing increased trough levels above 2 µM target with low interpatient variability. Conclusions: Continuous oral rucaparib is very well tolerated, with encouraging clinical activity, including objective responses and durable SD, observed during dose-escalation. Once confirmed, the RP2D will be evaluated in platinum-sensitive OC pts with a gBRCA mutation. Clinical trial information: NCT01482715.
NATIONWIDE TRENDS OF SURGICAL AND ENDOVASCULAR REVASCULARIZATION PROCEDURES FOR HOSPITAL ADMISSION, COST UTILIZATION, ALL-CAUSE MORTALITY, AND MAJOR AMPUTATION AMONG ADULTS WITH CRITICAL LIMB ISCHEMIA FROM 2003-2012
Authors: Shikhar Agarwal, Karan Sud, Mehdi Shishehbor
Journal: Journal of the American College of Cardiology (2016)
Is ypT0/isn0 acceptable for Japanese population? JBCRG’s perception.
Authors: Katsumasa Kuroi, Shinji Ohno, Seigo Nakamura, Hiroji Iwata, Norikazu Masuda, Nobuaki Sato, Masakazu Toi
Journal: Journal of Clinical Oncology (2013)

e12011 Background: Pathologic complete response (pCR) is a proposed surrogate endpoint for predicting disease-free survival (DFS) or overall survival (OS). However, several definition of pCR has to be used in NAC studies, and In Japan, JBCRG conducted several study of neoadjuvant chemotherapy using QpCR(including focal residual invasive tumors as pCR) between 2002 and 2006. Methods: The regimen studied were FEC followed by Docetaxel (75 mg/m 2 )(FEC-DOC) (n = 186), FEC-DOC (100 mg/m 2 ) (n = 37),DOC followed by FEC (n = 130), JBCRG-01, 02, 03, respectively. Three studies were pooled and analysed for pCR rates, DFS, OS in terms of several pCR definition and subtypes. We included patients when subtype and long-termfollow-up available for DFS and OS. We compared 5 pCR definitions: absence of invasive cancer and in situ cancer in the breast irrespective of nodal involvement (ypT0, SpCR), absence of invasive cancer and in situ cancer in the breast axillary nodes (ypT0ypN0, SpCRbn), absence of invasive cancer in the breast irrespective of nodal involvement (ypT0/is, CpCR), absence of invasive cancer in the breast axillary nodes with DCIS allowed (ypT0/isypN0, CpCRbn), and QpCR. Subtypes were classified into luminal (ER+ and/or PgR+, HER2-), luminal –HER2 (ER+ and/or PgR+, HER2+), triple-positive (TP) (ER-,PgR-, HER2-), HER2 (ER-, PgR-, HER2+) by using immunohistochemically stained specimen obtained by core needle biopsy. Results: Number of patients in each subtypes were as follows; luminal 206 (58%), luminal -HER2 34(10%), HER2 40 (11%), TN 73 (21%). pCR rate was significantly high in HER2 and TN irrespective of pCR definition (p &lt;0.05). At median follow up 75M, pCR group showed significantly better prognosis. Cox multivariate analysis showed pCR (irrespective of pCR definition) and subtype were the significant predictors of prognosis among study, age, tumor size. Conclusions: Subtype is a useful predictive biomarker of pCR, and ypT0/isn0 is acceptable for Japanese population.
Is gemcitabine (G) reuse possible in early recurrences after its adjuvant application in pancreatic adenocarcinoma (PA) treatment?
Authors: Sina Rosenblender, Jens Stieler, Sven Bischoff, Uwe Pelzer, Marianne Sinn, Jana Kaethe Striefler, Bernd Dörken, Hanno Riess
Journal: Journal of Clinical Oncology (2015)

e15219 Background: Although recurrences occur after most curatively intended PA resections with ensuing adjuvant G chemotherapies, it remains unclear, whether and from which point in time after adjuvant therapy completion G could be reutilized in palliative first-line therapy and might foster a good outcome compared to other chemotherapies. Methods: We retrospectively analysed prospectively collected data of 89 eligible patients treated chemotherapeutically for recurrent PC at “Charité Campus Virchow-Klinikum” between 1991 and 2014. Periods of survival among which primary endpoints were PFS and OS from palliative first-line therapy initiation were calculated by use of the Kaplan-Meier method and compared with the aid of log-rank-test with two-sided p-values of < 0.05 regarded as statistically significant. Results: Under repeated use of single-agent G, a median PFS of 8.51 (95% CI: 4.45-12.57) and OS of 14.42 (95% CI: 8.78-20.07) months, under reapplication of G with additional 5-FU, leucovorin and Cisplatin, a median PFS of 10.09 (95% CI: 3.23-16.95) and OS of 14.98 (95% CI: 13.42-16.54) months were attained. Those survival times were longer than under therapies with G+Erlotinib, FOLFIRINOX and OFF, where also DFS was mostly markedly shorter, indicating that often, patients with longer DFS were selected for G reuse. Nevertheless, 23.1% of the secondary treatments with G alone and 50% of its combination therapies were effected in early recurrences within the first six months of adjuvant therapy completion, here after a median interval of 3.5-4 months. No statistically significant differences were detected between the PFS of 6.24 (95% CI: 5.74-6.74) months after early re-expositions to G with that of 10.45 (95% CI: 6.96-13.94) months following subsequent recurrences ( ≥ 6 months) (p = 0.273); this showed likewise in comparing OS, with 14.42 (95% CI: 4.44-24.41) vs. 15.84 (95% CI: 13.49-18.18) months (p = 0.439). Conclusions: In selected patients, a de novo use of G after its adjuvant application seems to be possible even in early recurrences, after a therapy pause of 3.5-4 months. In these patients, reexposition achieves better results than early switching to second-line therapies.
Genomic diversity between primary tumor tissue and tumor circulating cell-free DNA (cfDNA) in patients (pts) with metastatic prostate cancer.
Authors: Emma Carroll, David Michael Gill, Austin Poole, Andrew W. Hahn, Erin B. Bailey, Jessica Streeter, Julia A. Batten, Sumati Gupta, Neeraj Agarwal, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2017)

189 Background: Tumor tissue and tumor cfDNA next-generation sequencing (NGS) tests are obtained in pts with metastatic prostate cancer and have demonstrated a diverse genomic landscape. High-level evidence does not exist for utilizing these tests to guide treatment selection in these pts. Targeted therapies are available for metastatic prostate cancer treatment and clinical trials are investigating drugs targeting specific molecular pathways. The objective of this study was to assess type and number of genomic aberrations between tumor tissue and cfDNA. Methods: Pts with metastatic prostate cancer who had both tissue and cfDNA results were selected and genomic profiles were compared between these two technologies. The mean number of tissue mutations was compared to cfDNA mutations for all pts using the t-test. The mutations for both tests were then categorized into five pathways: DNA repair, cell cycle regulation, PI3K, epigenetics, and androgen receptor (AR). For each pathway, the total number of patients with a mutation was compared between tissue and cfDNA using the Mann-Whitney test. Results: Nineteen pts were identified with both tissue and cfDNA results. The mean number of mutations identified was significantly less with cfDNA (95% CI, 2.7-5.3) compared to tissue (95% CI, 7.0-9.7; P &lt; 0.0001). There were significantly more patients with PI3K pathway mutations identified in the tissue compared to cfDNA (73.7% vs 21.1% P = 0.0018), as well as epigenetic mutations (47.4% vs 0.0% P = 0.0012). There was no difference in the number of patients identified to have DNA repair, cell cycle regulation, and AR variances between the two tests. Conclusions: The lower number of aberrations detected by the cfDNA test may have occurred due to lower sensitivity of cfDNA compared to tissue based NGS. Discordance in the type of genomic variances between the two tests suggests intra-individual genetic diversity, and these results may have implications in treatment selection of pts with metastatic prostate cancer. Data are hypothesis generating and need further investigation in a larger cohort.
The kinetics of the excision repair cross-complementing group-1 (ERCC1) gene in patients with colorectal cancer.
Authors: Amartej Merla, Atrayee Basu Mallick, Titto A Augustine, Imran Chaudhary, Srikanth Gajavelli, Radhashree Maitra, Cecilia Daroqui, Santiago Aparo, Raviraja Seetharam, Lakshmi Rajdev, Andreas Kaubisch, Stephan Madajewicz, Abdissa Negassa, John Mariadason, Mohammad Haroon Ghalib, Sanjay Goel
Journal: Journal of Clinical Oncology (2012)

e14019 Background: Oxaliplatin is an integral drug in the management of patients with colorectal cancer (CRC); however, half the patients fail to benefit from it. We know that in vitro, the excision repair cross-complementing group-1 (ERCC1) gene is inducible and contributes to cellular resistance to oxaliplatin. Using peripheral blood mononuclear cells (PBMC) as a surrogate tissue, we sought to confirm in vivo, the inducibility of ERCC gene expression and its relationship to clinical outcomes. Methods: Patients with CRC who received oxaliplatin consented to blood (PBMC) sampling at 0, 2, 48 hours, and 14 days during any cycle of chemotherapy. Clinical benefit from oxaliplatin was determined using the parameters of response rate and progression free and overall survival (PFS and OS). ERCC1 gene expression was quantified by qPCR (quantitative real time polymerase chain reaction) and WB (western blotting). Results: A total of 52 patients have been enrolled of which 29 patients have sampling at all 4 time points. ERCC1 gene expression was induced in 48.5% and 66.7% by mRNA and WB, respectively. Down regulation was observed in 30.3% and 8.3% by mRNA and WB, respectively. No change was noted in rest of the patients. The median PFS in patients with ERCC1 induction by qPCR was 7.25 months and was numerically shorter than the 13 months noted in patients with stable or reduced ERCC. This may suggest that in patients with ERCC induction, there is compromised PFS, but our data is limited by the small sample size. The difference in induction noted between qPCR and WB remains unclear. We did not find any significant difference in PFS when taking baseline expression of ERCC into consideration. Conclusions: This study confirms the inducibility of ERCC gene expression in vivo, in a sub-population of patients with CRC when they are treated with oxaliplatin. This gene induction is a potential marker of resistance to chemotherapy. We failed to find an association between clinical benefit and baseline ERCC expression. The factors that influence the inducibility of this gene remain unknown requiring further studies.
Opportunities for improving outcomes in pancreatic cancer patients: Characterizing the unresected “resectable” population.
Authors: Jonathan Kish, Bruce A. Feinberg, Tracy Maida, Craig Biggs, Urvi Mujumdar, Dhruv Chopra, Jalyna R. Laney, Eugene Kennedy
Journal: Journal of Clinical Oncology (2017)

274 Background: Resection is the only curative intent therapeutic option for pancreatic adenocarcinoma (PA). Recent studies suggest adjuvant chemo can significantly improve overall survival (OS). Patients who may be eligible for, but do not receive, a resection (“resectable”) may represent an opportunity to improve pancreatic cancer outcomes. This research sought to characterize this population using real-world data. Methods: Individuals with pancreatic cancer (ICD-9=157.x, excluding 157.4) diagnosed between 03/2012-06/2015 were selected from the Inovalon More 2 claims database. Resection was defined as the presence of any of the following codes on any claim following diagnosis: CPT=48140, 48146, 48150, 48152-5. A diagnosis of metastatic disease was said to occur if any of the following ICD-9 CM codes were present on a claim: 196.0-196.3, 196.5-196.6, 197.0-197.8, and 198.0-198.8. Patients were deemed “resectable” if there was no claim for surgical resection and if their claim for metastatic disease was post-initiation of chemotherapy. Results: Of 7,159 patients identified with PA, 85.8% (n=6,145) were unresected, 40.8% (n=2,924) had received chemotherapy which included 54.4% (n=552) of resected patients and 38.6% (n=2,372) of non-resected patients. Of unresected patients receiving chemotherapy, 27.4% had no record of a metastatic diagnosis, 51.9% had a metastatic diagnosis prior to the start of chemotherapy (mean time metastatic diagnosis = 0.4 months) and 20.7% had a metastatic diagnosis after the initiation of chemotherapy (mean time metastatic diagnosis = 4.8 months). Overall, 18.5% (n=1139) of non-resected patients were classified as unresected “resectable”. Conclusions: The vast majority (85.8%) of pancreatic cancer patients did not undergo a surgical resection. We estimate as many as 18.5% of non-resected patients may be unresected “resectable” given 4.8 months between diagnosis, chemotherapy start and documentation of metastases. As surgical resection is the only curative intent therapeutic option, and prolongs survival even in those not cured, identifying patients who may be eligible for resection is critical to improving pancreatic cancer outcomes.
68Ga-DOTATOC PET/CT Imaging in Solitary Fibrous Tumor of the Pleura
Authors: Filippo Lococo, Cristian Rapicetta, Massimiliano Casali, Salvatore Bellafiore, Giulio Rossi, Giorgio Treglia, Elisa Gasparini, Massimiliano Paci
Journal: Clinical Nuclear Medicine (2017)

Here we describe a 77-year-old man with a solitary fibrous tumor of the pleura showing increasing tracer uptake at 68Ga-DOTATOC PET/CT, demonstrating that solitary fibrous tumor of the pleura may overexpress somatostatin receptors, therefore mimicking neuroendocrine tumors at somatostatin receptor PET/CT.
Prospective clinical study of precision oncology in solid tumors.
Authors: Davendra Sohal, Brian I. Rini, Alok A. Khorana, Robert Dreicer, Jame Abraham, Gary Procop, Yogen Saunthararajah, Nathan A. Pennell, James Stevenson, Robert James Pelley, Bassam N. Estfan, Dale Randall Shepard, Pauline Funchain, David J. Adelstein, Brian James Bolwell
Journal: Journal of Clinical Oncology (2015)

6585 Background: Advances in tumor genomic profiling offer the promise of precision oncology but a systematic prospective evaluation is lacking. We conducted a prospective cohort study of tumor genomic testing to identify prevalence of actionable alterations and their impact on management decisions. Methods: Patients provided written informed consent for this prospective cohort study approved by the Cleveland Clinic Institutional Review Board. Eligibility requirements included pathologic diagnosis of select solid tumor malignancies without a known curative option, age ≥ 18 years, and ECOG PS 0-2. Tumor samples were sequenced for up to 315 candidate genes using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board (GTB) for biologically actionable alterations, defined as those linked to an approved therapy in the solid tumor under study or another solid tumor, a clinical trial, or a contraindication to a targeted therapy. Sample size was 250 patients. Outcomes were feasibility and clinical impact of tumor sequencing. Results: From Aug 2013 to Oct 2014, all 250 patients were enrolled. Median age was 60 years; 128 (51%) were female; 220 (88%) were white. Colorectal (25%), breast (18%), lung (13%), pancreatobiliary (12%), and head and neck (10%) cancers were common diagnoses. Median time from consent to genomic test result was 25 days (range, 3-140), with 27 (11%) samples having insufficient tissue for analysis. Of 223 resulted samples, an alteration was found in 96% (n = 214), with a median of 4 (0-20) alterations per sample. At GTB review, a biologically actionable alteration was declared in 63% (n = 141) of cases. However, only 10% (n = 22) of patients received tumor genomics-driven targeted therapies: 12 went on clinical trials, 3 received on-label drugs, and 7 received off-label drugs. Lack of clinical trial access was the most common reason for non-recommendation/receipt of genomics-driven therapy. Conclusions: This prospective study shows that routine tumor genomic profiling is feasible, with almost two-thirds of resulted samples having a biologically actionable alteration, but paucity of genomics-driven clinical trials of targeted therapies is a barrier to the success of precision oncology.
Cutting salt could reduce need to urinate at night, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Cutting salt intake could reduce people’s need to get up in the night to urinate, says a preliminary study presented at the European Association of Urology congress in London.1

The Japanese study included 321 men and women with a mean age of 64.3 who experienced nocturia during sleep time and had a high dietary salt intake (≥8 g/day in men and ≥7 g/day in women).The participants were given written guidance and support on reducing their salt intake and were followed up for 12 weeks.

The volume and frequency of urination …
Women cancer survivors have higher risk of preterm births, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Young women who have survived cancer have an increased risk of having a preterm birth and a low birthweight baby, a large case control study of cancer survivors has found.1

Five year survival rates are now over 80% in patients who have had adolescent and young adult cancers. Studies show that around two thirds of young women who survive cancer want the possibility of having children, …