tbuckley/cabot-search huggingface dataset:
Classic and extracavitary primary effusion lymphoma in 51 <scp>HIV</scp>‐infected patients from a single institution
Authors: Stéphanie Guillet, Laurence Gérard, Véronique Meignin, Felix Agbalika, Wendy Cuccini, Blandine Denis, Christine Katlama, Lionel Galicier, Eric Oksenhendler
Journal: American Journal of Hematology (2015)

Human immunodeficiency virus (HIV)-associated primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma with poor prognosis. Lymphoma cells are always infected with human herpesvirus-8 (HHV-8) and in most cases coinfected with Epstein-Barr virus. In classic presentation, PEL is characterized by body cavity effusions with or without mass lesions. A variant with only extracavitary localization has also been described. We report on a large single-center series of patients with PEL in the era of combined antiretroviral therapy (cART). The main objective was to compare the characteristics and the outcome of patients with classic (n = 34) and extracavitary (n = 17) variant PEL. At PEL diagnosis, no major difference was observed between the two groups in terms of demographic and HIV characteristics. Extracavitary localizations were exclusively nodal in six patients and involved various organs in 11 patients. Another HHV-8-associated disease was observed in 31 patients, Kaposi sarcoma in 25, and multicentric Castleman disease in 18 patients, without difference between the two groups. Thirty-two patients were treated with CHOP associated with high-dose methotrexate, 13 were treated with CHOP-derived regimen alone, and six patients received low-dose/no chemotherapy. Complete remission was achieved in 21 (62%) and seven (41%) patients of the classic and extracavitary groups, respectively. The median overall survival (OS) was 10.2 months. Despite a higher disease-free survival in the extracavitary group, there was no difference in OS between the two variants. Based on this series, characteristics of classic and extracavitary variants were very close. Although prognosis of PEL remains very severe in cART era, the median survival compares favorably with earlier series.
Preoperative chemo/radiotherapy with oxaliplatin and 5FU-AF in rectal cancer
Authors: M. Tomirotti, D. Asnaghi, R. Rovej, M. Botturi, B. Galassi, K. Borgonovo, A. Fasolo, F. Onida, P. Sburlati, A. Scanni
Journal: Journal of Clinical Oncology (2004)

3744 Background: Randomized trials demonstrated that pre-operative radiotherapy reduces the risk of local relapse and increases of more than 10% the overall survival at 5 years. European trials are ongoing in order to demonstrate the potential superiority of preoperative chemo-radiotherapy. Methods: We started a multicentric trial in order to evaluate efficacy and safety of preoperative chemo/ radiotherapy in rectal cancer. The enlistment is ongoing. Endpoints: to obtain histologic complete response; to reduce incidence of local relapse; to preserve anal sphincter; to increase overall survival and disease-free survival. Patients main characteristics: histologically documented rectal cancer (stage pT3); PS</=1; age</=75 years; no metastases; no infiltration of near tissues. Treatment schedule: radiotherapy for 5 weeks for total dose of 45 Gy; chemotherapy week 1 and 5 (Oxaliplatin 130 mg/mq i.v. in 2 hours infusion day 1; 5-FU 350 mg/mq i.v. continue infusion and FA 100 mg/mq i.v. bolus days 1,2,3,4,5). Surgery is foreseen between 3 and 6 weeks by the end of treatment. Results: At present we enlisted 22 patients, 12 males, 10 females, median age 55 years (range 39–70). 16/22 patients have been already submitted to surgery. Responses: 1/16 NC, 15/16 OR (4 pathological CR+11 PR); anal sphincter was preserved in 7/16. Toxicity was mild; neutropenia was avoided by G-CSF. Conclusions: If our results and those of other European trials will be favorable, this approach could represent the treatment of choice for locally advanced rectal cancer. No significant financial relationships to disclose.
Wound complications in neoadjuvant versus adjuvant treatment of operable rectal cancer (ORC).
Authors: I. Li, L. Stitt, F. Whiston, S. S. Alkhayyat, M. D. Vincent
Journal: Journal of Clinical Oncology (2010)

e14099 Background: Preoperative chemoradiation is currently the standard of care for ORC. The rate of post-op wound healing delays (WD) is currently unknown. The aim was to identify WD rates and impact on chemo completion, recurrences and death compared to adjuvant treatment. Methods: This retrospective study compared the rates of WD. Data on wound infection rates, time (t) to postop chemo, recurrences and deaths were also reviewed. Chi-square test was used for data analysis. Results: 96 neoadjuvant (neo), 95 adjuvant (adj) were reviewed. Median age was 63 (range 35 to 88). WD was observed in 32.3% neo vs. 15.8% adj pts (p = 0.0077). Infection rates were 21.9% and 12.6% (p = 0.0911). Median t to post-op chemo with WD was 85.8 ± 36.4 d (neo), 71.7 ± 25.4 d (adj); non-WD 53.3 ± 22.3 d (neo), 67.8 ± 32 d (adj). More than half of neo-WD experienced chemo delay > 14 w vs. neo non-WD > 7 w. 25.8% in neo-WD received no post-op chemo at all; whereas all adj-WD did. Total recurrences were similar in neo (13/96) and adj (14/95) grps. Rates of recurrence in neo-WD was 16.1% vs. 12.7% in neo non-WD (p = 0.6506) whereas 0 recurrences in the adj-WD. 77% of recurrences in neo- WD occurred if chemo was given beyond 6 w from surgery. Death rate differences were nonsignificant. Anemia was predictive for neo-WD (p = 0.0031); obesity (p = 0.081) and weight loss (p = 0.122) demonstrated a predictive trend towards neo-WD. Conclusions: Neoadjuvant treatment is associated with a higher risk of wound healing delays and infectious complications with a numerically higher recurrence rate. Certain clinical factors will likely prove predictive for neoWD. Increased FOLFOX usage in neoadjuvant grp may have offset the recurrence difference that may have otherwise happened. Additional pts are being analysed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
SPIO-enhanced MR imaging at 3T for accurate diagnosis of sentinel node metastases to avoid sentinel node biopsy in patients with breast cancer.
Authors: Kazuyoshi Motomura, Takahiro Nakayama, Yasuhiro Tamaki, Yuri Ito, Katsuyuki Nakanishi
Journal: Journal of Clinical Oncology (2014)

68 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging at 1.5T for the detection of metastases in sentinel nodes identified by computed tomography lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol 2011, ASCO 2012). The aim of this study was to evaluate whether SPIO-enhanced MR imaging at 3T improved the diagnostic accuracy for the detection of metastases in sentinel nodes. Moreover, these results were compared with those of the diagnosis using CT-LG according to the size criteria. Methods: Seventy patients with breast cancer and clinically negative nodes were included. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging at 3T. Sentinel node size was measured on CT-LG and a node larger than 5 mm in short axis diameter was considered metastatic. Sentinel nodes localized by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 55 years (range, 29-78). Sentinel nodes were identified by CT-LG successfully in 69 (98.6%) of 70 patients. The mean number of sentinel nodes identified by CT-LG was 1.4 (range, 1-3). All 19 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Forty-eight of 50 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on the imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 100%, 96.0%, and 97.1%, respectively, on a patient-by-patient basis. Those of CT-LG were 78.9%, 56.0%, 62.3%, respectively. The specificity and accuracy of MR imaging were superior to those of CT-LG (McNemar test; p &lt; .0001 and = .0015, respectively). Conclusions: SPIO-enhanced MR imaging at 3T can accurately diagnose the sentinel node metastases, and therefore sentinel node biopsy may not be required for most patients with breast cancer.
Association of estimated glomerular filtration rate (eGFR) with odds of a renal lesion
Authors: G. Hruby, J. Van Batavia, M. Wosnitzer, M. Benson, M. Desai, J. McKiernan, J. Newhouse
Journal: Journal of Clinical Oncology (2009)

e16025 Background: Patients with ESRD on long term hemodialysis are known to be at an increased risk for renal cell carcinoma. We postulate that some component of chronic renal failure not corrected by dialysis might be the tumor-inducing factor. We sought to determine if chronic renal insufficiency is a risk factor for developing renal cell carcinoma. Methods: A case- control study was used to determine a relationship between renal carcinoma and glomerular filtration rate (MDRD) (eGFR) and using patients with prostate cancer as controls. 1,298 patients from the Columbia University Urologic Oncology Database were identified with either prostate or kidney cancer who had sufficient information to predict eGFR. eGFR calculations were performed for both groups. eGFR was divided into two groups based upon the cut-off value of ≥90. eGFR was also categorized according to the MDRD definitions of chronic kidney disease (CKD), CKD1–4 (values≥90, 60≤values&lt;90, 30≤values&lt;60, and values&lt;30, respectively). Logistic regression techniques were used to quantify the association between pre-operative glomerular filtration rate and the presence of renal or prostate cancer. Results: The mean age of the prostate (n=713) and kidney (n=585) group was 59.9 and 61 years, respectively (p=0.041). The mean weight was 83.9 and 87 kg, respectively (p=0.005). The mean serum creatinine was 1.01 and 1.29 mg/dL, respectively (p&lt;0.001). The mean eGFR was 85 and 73.8, respectively (p&lt;0.001). Two models were fit to analyze the association of eGFR. The first model found eGFR &lt;90 was significantly associated with the presence of a renal carcinoma when controlling for age and race (OR=1.93, CI=1.49–2.49). The second model investigated the eGFR-CKD categories while controlling for age and race and was able to predict the presence of renal cancer (p &lt; 0.001). Patients with an eGFR value of 60≤X&lt;90 had an OR of 1.47 (CI= 1.13–1.92) for renal cancer when compared to patients with normal eGFR levels. Patients with an eGFR value of 30≤X&lt;60 and &lt;30 had an OR of 6.26 (CI=4.10–9.55) and 21.11 (CI=4.87–91.42), respectively. Conclusions: Diminished renal function showed a significant association with the presence of renal cancer. Chronic renal insufficiency may be a risk factor for the development of renal carcinoma. No significant financial relationships to disclose.
Preliminary evaluation of response to combination of RAD001 and cetuximab using [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET)
Authors: A. N. Avadhani, M. L. Veronese, R. Perini, C. R. Divgi, K. Harlacker, E. Sherman, W. Griggs, K. T. Flaherty, P. J. O’Dwyer
Journal: Journal of Clinical Oncology (2008)

14525 Background: RAD001 inhibits mTOR (mammalian target of rapamycin), a downstream effector of the PI3K/AKT pathway. Preclinical studies suggest that RAD001 may restore sensitivity to EGFR inhibitors. 18FDG-PET has been used in pre-clinical studies as a pharmacodynamic marker of mTOR inhibition. In this phase I dose escalation study, 18FDG-PET was incorporated as a PD marker for RAD001, alone and with cetuximab. Methods: Pts with EGFR-expressing solid tumors were randomized to a 3-week run-in of single agent RAD001 (30–70 mg PO) or cetuximab (400 mg/m2 IV loading, 250 mg/m2 IV maintenance) weekly, followed by the combination weekly. 18FDG-PET was performed at three timepoints (baseline, run-in, and combination), to assess for early changes in tumor metabolic activity, and for subsequent correlation to treatment response (CT or MRI evaluation after every two cycles of combination). Up to five target lesions/patient were identified based on qualitative assessment of 18FDG uptake, and the percentage difference in the sum of maximum standard uptake values (SUVmax) was calculated for each scan. Response by 18FDG-PET was determined by the EORTC PET Study Group Response Criteria. Results: 13 pts were treated at three dose levels, with 3 per dose order. Observed toxicities were all grade 1–2. 9 patients are evaluable for response, including four with SD ranging from 4–12 mos (parotid, ovarian, and anal squamous cell CA). Mean % change in SUVmax from baseline for those treated with RAD001 during run-in (n=7) was −20 (−49 to +1.6), in comparison to pts treated with cetuximab (n=6), at +.33 (−30 to +32). Mean % change in SUVmax from baseline for the group with SD (n=4) were as follows: −12.85 (−49 to +4) during run-in, versus −39.75 (−59 to −13) during combination tx. Mean % change in SUVmax from baseline for the group with PD (n=5) was much lower during combination therapy. Conclusions: Combined RAD001 and cetuximab are tolerated at full doses with minimal toxicity. Metabolic response by 18FDG-PET during early combination therapy may be associated with tumor response by RECIST. No significant financial relationships to disclose.
Abstract 2408: A novel multiplex droplet digital PCR approach to KRAS mutation detection in circulating tumor DNA
Authors: Alexandra Pender, Isaac Garcia-Murillas, Sareena Rana, David Gonzalez de Castro, Nicholas Turner, Sanjay Popat, Julian Downward
Journal: Cancer Research (2015)

Abstract Microdroplet digital PCR can be used to detect low frequency mutations in oncogene-driven lung cancer. Detection of circulating tumour DNA in plasma can be limited by paucity of material, particularly during response to anti-cancer therapy. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach for efficient mutation detection in circulating DNA. We designed and optimised 3 droplet digital PCR multiplex assays investigating 9 different KRAS mutations using PrimePCR™ ddPCR™ Mutation Assays and the Bio-Rad QX100 system. DNA was extracted from FFPE tissue and plasma from patients with advanced lung adenocarcinoma and was analysed to assess for the presence of these KRAS activating mutations. Multiple sub-clonal KRAS mutant populations were detectable in both tissue and circulating tumour DNA at low frequency (up to 0.1%). Similar KRAS allele frequency was observed using multiplex or duplex assays (r2 = 0.99). Sub-clonal population representation varied over the disease course. Multiplex microdroplet digital PCR assays can be adapted to be used to efficiently identify tissue and circulating KRAS mutations in advanced lung adenocarcinoma. Variation in sub-clonal populations between tissue and plasma, and at different time points over the disease course, illustrates the potential use of circulating DNA analysis as a more readily accessible, non-invasive and accurate representation of the molecular profile of NSCLC throughout treatment. Citation Format: Alexandra Pender, Isaac Garcia-Murillas, Sareena Rana, David Gonzalez de Castro, Nicholas Turner, Sanjay Popat, Julian Downward. A novel multiplex droplet digital PCR approach to KRAS mutation detection in circulating tumor DNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2408. doi:10.1158/1538-7445.AM2015-2408
EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201) in chemotherapy-resistant ovarian cancer cell lines.
Authors: C. E. Richter, E. Cocco, S. Bellone, F. Casagrande, M. Bellone, D. Silasi, M. Azodi, P. E. Schwartz, T. Rutherford, A. Santin
Journal: Journal of Clinical Oncology (2010)

e15524 Background: To evaluate the expression of epithelial cell adhesion molecule (EpCAM) and to determine the cytotoxic potential of MT201 (adecatumumab), a fully human recombinant IgG1 anti-EpCAM antibody, against multiple primary chemotherapy- resistant ovarian cancer cell lines in vitro. Methods: EpCAM expression was evaluated by real time-PCR and flow cytometry in a total of seven primary ovarian cancer cell lines established from patients who showed disease progression on multiple chemotherapeutic regimens. Sensitivity to MT201 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) was tested in these primary ovarian cancer cell lines expressing different levels of EpCAM in standard 5-hour 51Cr assays. To investigate the effect of interleukin-2 (IL-2) on MT201-mediated ADCC, 5-hour 51Cr assays were also conducted after stimulation with low doses of IL-2. Results: Five papillary-serous and two clear cell ovarian carcinoma cell lines were evaluated. High EpCAM surface expression by flow cytometry and high mRNA expression by real time-PCR was detected in 71% of primary ovarian cancer cell lines (five out of seven cell lines). While these cell lines were highly resistant to CDC and natural killer dependent cytotoxicity in vitro (range of killing 0% to 7%), EpCAM-positive cell lines showed very high sensitivity to MT201-mediated ADCC (range of killing 27% to 66%). Incubation with IL-2 in addition to MT201 significantly increased the cytotoxic activity against EpCAM-positive ovarian cancer cell lines (p < 0.0001). Conclusions: EpCAM is highly expressed in primary chemotherapy- resistant ovarian carcinoma cell lines, and these chemotherapy-resistant tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients harboring chemotherapy-resistant ovarian carcinoma. No significant financial relationships to disclose.
The fate of bone marrow micrometastases in patients with primary breast cancer.
Authors: J L Mansi, U Berger, T McDonnell, A Pople, Z Rayter, J C Gazet, R C Coombes
Journal: Journal of Clinical Oncology (1989)

Using an immunocytochemical technique, micrometastases have been found in the bone marrow of approximately 26% of patients with primary breast cancer at the time of initial surgery. To determine the fate of these cells, both in patients receiving and not receiving adjuvant therapy, multiple bone marrow aspirates were repeated in 82 patients at a median time of 18 months after surgery but prior to overt relapse. In both treated and untreated patients micrometastases were only found in one of 45 (2%) and one of 37 (3%) patients, respectively. However, when multiple marrow aspirates were taken from patients with local recurrence the incidence of micrometastases was 19% (three of 16), and this increased to 30% (three of ten) in patients with disease at distant sites other than bone, and 100% (ten of ten) in patients with radiologically proven bony disease. Three of 11 (27%) patients in whom the primary tumor remained in situ while receiving adjuvant therapy before definitive surgery had micrometastases at the time of diagnosis and at follow-up 3 months later. These results suggest that many of the micrometastases from breast cancer patients are the result of "shedding" of cells from the primary carcinoma and that a proportion are not viable. The technique is currently insufficiently sensitive to accurately monitor adjuvant therapy in breast cancer patients.
‘Low-Dose Metronomic Temozolomide’ in Recurrent Tmz-Refractory Glioblastoma Patients: a Retrospective Analysis of National Data in Korea
Authors: Y. Choi, M.S. Yun, S.H. Lim, S. Bae, Y. Na, Y.H. Kim, K.S. Kang, S. Lee
Journal: Annals of Oncology (2014)
A multicenter randomized phase II study of docetaxel (D) plus vinorelbine (VRB) and docetaxel plus estramustine (EMP) in combination for the treatment of hormone refractory prostate cancer (HRPC): HOG GU-0009
Authors: N. M. Hahn, W. Fisher, R. Langdon, R. Zon, B. Mark, C. J. Sweeney
Journal: Journal of Clinical Oncology (2005)

4568 Background: Docetaxel plus prednisone provides a modest survival benefit for men with HRPC. We evaluated the feasibility and toxicity of two docetaxel based combined microtubule inhibition doublets in men with HRPC. Methods: Patients with HRPC were randomized to one of two arms: Arm A - D 60 mg/m2 IV d2 + EMP 280 mg PO tid d1–5 q21d cycle with dose-escalation of D to 70 mg/m2 IV d2 after cycle 1; Arm B - D 25 mg/m2 IV d1,8 + VRB 20 mg/m2 IV d1,8 q21d cycle. The primary outcome measure was the rate of Grade 3 and 4 toxicity associated with each arm. Results: Patient characteristics: 64 patients were randomized. Baseline characteristics were similar in both arms. Toxicity: Nine of 32 patients (28.1%) (95% CI 6.4%, 39.8%) experienced grade 3 or 4 toxicity in Arm A compared to 5 of 32 patients (15.6%) (95% CI 5.0%, 32.0%) in Arm B. Response and Survival: Among patients with measurable disease in Arm A, 6 of 9 patients (66.7%) had a partial or complete response compared to 4 of 12 patients (33.3%) in Arm B. A PSA reduction of 50% or more of baseline was observed in 42.9% of the patients in arm A and 20.0% of those in Arm B (p=0.16, Fisher’s exact test). Median progression free survival was 5.7 months (95% CI 5.1, 7.1 months) in Arm A and 6.2 months (95% CI 5.0, 8.0 months) in Arm B. Overall median survival was 19.7 months (95% CI 12.0 months, NR) in Arm A and 16.2 months (95% CI 13.1, 25.2 months) in Arm B. Conclusions: The combination of D+VRB is less toxic than D+EMP for the treatment of HRPC. However, the biochemical response and survival data suggest that D+VRB would not be more effective than docetaxel plus prednisone. No significant financial relationships to disclose.
Pediatric‐inspired therapy compared to allografting for <scp>P</scp>hiladelphia chromosome‐negative adult ALL in first complete remission
Authors: Matthew D. Seftel, Donna Neuberg, Mei‐Jie Zhang, Hai‐Lin Wang, Karen Kuhn Ballen, Julie Bergeron, Stephen Couban, César O. Freytes, Mehdi Hamadani, Mohamed A. Kharfan‐Dabaja, Hillard M. Lazarus, Taiga Nishihori, Kristjan Paulson, Wael Saber, Stephen E. Sallan, Robert Soiffer, Martin S. Tallman, Ann E. Woolfrey, Daniel J. DeAngelo, Daniel J. Weisdorf
Journal: American Journal of Hematology (2015)

For adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia-free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At 4 years of follow-up, incidence of relapse after HCT was 24% (95% CI 19-28) versus 23% (95% CI 15-32) for the non-HCT (chemo) cohort (P=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort [HCT 37% (95% CI 31-42) versus chemo 6% (95% CI 3-12), P<0.0001]. DFS in the HCT cohort was 40% (95% CI 35-45) versus 71% (95% CI 60-79) for chemo, P<0.0001. Similarly, OS favored chemo [HCT 45% (95% CI 40-50)] versus chemo 73% [(95% CI 63-81), P<0.0001]. In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT [hazard ratio 3.12 (1.99-4.90), P<0.0001]. For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. Am. J. Hematol. 91:322-329, 2016. © 2015 Wiley Periodicals, Inc.