tbuckley/cabot-search huggingface dataset:
Isolation and expansion of circulating tumor cells (CTC) from melanoma patients using a novel cell culture technique.
Authors: John R. McGregor, Wolfram E. Samlowski, Shweta Tharkar, Sreekanth Donepudi, Soldano Ferrone
Journal: Journal of Clinical Oncology (2012)

10614 Background: Identification of rare (&gt;2-5) circulating tumor cells (CTC) in 7.5 ml blood by immunofluorescence assay (IFA) correlates with a poor prognosis in colon, breast, prostate and lung cancer. Changes in CTC count during treatment also predict the eventual patient progression and survival in these cancers. Existing assays do not detect melanoma CTC, however. In addition, isolation of viable CTC remains problematic. To overcome these limitations we attempted to develop novel melanoma CTC assays, using IFA and cell culture approaches. Methods: Blood samples were obtained from patients and controls following informed consent. The buffy coat (white cells + tumor) was isolated by Ficoll/Hypaque centrifugation, and split into 6 replicate cultures in proprietary TrueCells medium. After 21 days in culture, tumor colonies were counted, and stained for melanoma and leukocyte markers. Buffy coat cells from parallel blood samples were stained with a panel of CSPG4-specific mAb (a pan-melanoma marker) on ultraclean glass slides for analysis by immunofluorescence microscopy. Results: Blood samples were obtained from 16 melanoma patients, ages 28-87. Eight patients were men and 8 were women. CSPG4 + events (&gt;2) were detected in 8/16 patients by IFA (range 0-52). In contrast, tumor cell colonies of &gt;50 cells grew in 12 out of 16 patients with Stage 3 or 4 melanoma (range 0-1054), shown in Table. Cells isolated from CTC colonies produced melanin, stained for CSPG4 and other melanoma markers, but not for leukocyte markers. Control cultures grew no tumor colonies. Conclusions: Our pilot study shows that melanoma CTC can be identified by both IFA and cultured from blood in many patients with stage 3 or 4 melanoma. These CTC exhibited cytologic characteristics diagnostic of melanoma. The culture assay may represent a useful means of enumerating, isolating, and expanding viable melanoma CTC for further molecular study. [Table: see text]
Prognostic and predictive value of primary vs secondary platinum resistance for bevacizumab treatment in platinum-resistant ovarian cancer in the AURELIA trial.
Authors: Fabian Trillsch, Sven Mahner, Felix Hilpert, Lucy Claire Davies, Elena García-Martínez, Gunnar Kristensen, Antonella Savarese, Peter Vuylsteke, Maartje Los, Flora Zagouri, Laurence Gladieff, Jalid Sehouli, Chee Lee, Val Gebski, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2015)

5552 Background: Progression-free survival (PFS) and patient-reported outcomes (PRO) were significantly improved with the addition of bevacizumab (BEV) to standard chemotherapy (CT) for platinum-resistant ovarian cancer (OC) in the randomized phase III AURELIA trial. We examined the relevance of primary (PPR) vs secondary platinum resistance (SPR) on treatment efficacy. Methods: Platinum resistance was categorized as PPR if progression was < 6 months after completing first platinum therapy or SPR if not. We performed exploratory Cox and logistic regression analyses to correlate platinum resistance with PFS, overall survival (OS), and PRO from the time of randomization to CT ± BEV. Results: Of the 361 randomized patients (pts), 262 (73%) had PPR and 99 (27%) had SPR. Baseline characteristics were generally similar in the two subgroups, except that FIGO stage IV disease and ascites were more common in PPR pts. In the BEV+CT arm (n = 179), SPR was associated with more favorable PFS (median 10.2 vs 5.6 months [mo] in the PPR subgroup; P < 0.001) and OS (median 22.2 vs 13.7 mo, respectively; P < 0.001) but not PRO (22.0% vs 21.9% with ≥ 15% improvement in abdominal/gastrointestinal symptoms at week 8/9; P = 0.99). In two separate multivariate analyses, SPR remained an independent prognostic factor for better PFS (adjusted hazard ratio [HR] 0.41, 95% CI 0.25–0.67, P < 0.001) and OS (HR 0.49, 95% CI 0.30–0.80, P = 0.005) in the BEV+CT arm. In the CT-alone arm, the prognostic effect did not reach statistical significance for PFS or OS. The magnitude of benefit from adding BEV to CT appeared greater in the SPR than the PPR subgroup for PFS (SPR: HR 0.30, 95% CI 0.18–0.48, P < 0.001; PPR: HR 0.55, 95% CI 0.42–0.71, P < 0.001; interaction P = 0.07) with a similar direction of effect for OS (SPR: HR 0.62, 95% CI 0.37–1.02, P = 0.06; PPR: HR 0.94, 95% CI 0.71–1.24, P = 0.65; interaction P = 0.18). Conclusions: Median PFS and OS were more favorable in SPR than PPR pts treated with BEV+CT but BEV effect on PRO was similar. The PFS and OS benefit of BEV+CT over CT alone was more pronounced in the SPR than the PPR subgroup. PPR vs SPR should be a stratification factor in future trials of anti-angiogenic therapy for OC. Clinical trial information: NCT00976911.
PANORAMA 2: A phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma.
Authors: Melissa Alsina, Robert L. Schlossman, Donna M. Weber, Steven E. Coutre, Sagar Lonial, Cristina Gasparetto, Ghulam Warsi, Michael S. Ondovik, Sutapa Mukhopadhyay, Carole S. Paley, Paul Gerard Guy Richardson
Journal: Journal of Clinical Oncology (2012)

8012 Background: Patients (pts) with multiple myeloma (MM) refractory to bortezomib (BTZ) and an immunomodulatory drug have limited treatment options and a poor prognosis. In a phase I study of pts with relapsed or relapsed/refractory MM treated with panobinostat (PAN) + BTZ, clinical responses were observed overall and in pts with BTZ-refractory disease. We report results in PANORAMA 2, a trial in relapsed and BTZ-refractory pts. Methods: PANORAMA 2 is a single-arm, phase II study of PAN + BTZ + dexamethasone (Dex) in pts with relapsed and BTZ-refractory MM. Treatment phase 1 (TP1) consists of eight 3-week cycles of oral PAN + intravenous BTZ + oral Dex. Pts demonstrating clinical benefit enter treatment phase 2 (TP2) which consists of four 6-week cycles of PAN + BTZ + Dex. The primary endpoint is overall response (≥ partial response [PR]) in TP1. Results: Fifty-five pts with BTZ-refractory MM were enrolled with 10 pts ongoing and 28 in follow-up. The median age was 61 years (range 41-88 years). Pts were heavily pretreated: the median number of prior regimens was 4 (range 2-11), and most pts (64%) received prior autologous stem cell transplant. Twenty-seven (49%) and 36 (65%) pts had BTZ and Dex in their most recent prior line of therapy, respectively. Eighteen pts achieved ≥ PR for an overall response rate of 33% (1 near complete response and 17 PR), and 13 pts achieved MR for a clinical benefit rate of 56%. Three pts achieved a VGPR. Eighteen pts completed TP1 and entered TP2, and 2 have completed ≥ 12 cycles. Common adverse events (AEs) of any grade included thrombocytopenia (66%), fatigue (64%), diarrhea (62%), nausea (58%), dyspnea (40%), anemia (38%), decreased appetite (36%), and dizziness (36%). Common grade 3/4 AEs included thrombocytopenia (58%), fatigue (17%), anemia (15%), pneumonia (15%), neutropenia (13%), and diarrhea (13%). Only 1 pt (2%) experienced grade 3/4 peripheral neuropathy. Conclusions: PAN synergizes with BTZ in recapturing responses in heavily pretreated, BTZ-refractory MM pts. The combination of PAN and BTZ is a promising treatment for pts with BTZ-refractory MM that is generally well tolerated, with several pts receiving therapy long term.
GDPT Versus CHOP in Newly Diagnosed Peripheral T-Cell Lymphoma: A Prospective Randomized Controlled, Open-Label Study (No.NCT01664975)
Authors: Ling Li, Wenjing Duan, Ken H. Young, Zhaoming Li, Lei Zhang, Xiaorui Fu, Xin Li, Zhenchang Sun, Xudong Zhang, Jiaqin Yan, Feifei Nan, Yu Chang, Li Lin, Mingzhi Zhang
Journal: Blood (2016)
Infectious disease associations in advanced stage, indolent lymphoma (follicular, FL, and nonfollicular, nFL): A prospective trial of antibiotic therapy.
Authors: Carol S. Portlock, Paul A. Hamlin, John F. Gerecitano, Ariela Noy, Maria Lia Palomba, Janelle Walkley, Stacie Corcoran, Genovefa A Papanicolaou, Arnold Markowitz
Journal: Journal of Clinical Oncology (2013)

8571 Background: The antigen-drive association of gastric MALT with H. pylori (HP) is well recognized. Successful antibiotic (Ab) can result in lymphoma remission. We have studied a 3 mo course of clarithromycin (substituting lansoprazole/amoxicillin/clarithromycin, Prevpak , in the first 2 wks if HP +) in non-bulky, advanced stage indolent lymphoma as the first step to such a lymphoma treatment/prevention strategy. Methods: Patients with new diagnosis indolent lymphoma (FL and nFL), stages II (abdominal), III and IV fulfilling GELF criteria for observation were eligible. Stool HP done in all patients. Hepatitis B and C positive excluded. All patients had CT and PET prior to and 1 mo post Ab. Results: 32 evaluable patients were enrolled: 14 females, 18 males; median age, 53.5 years (36- 81); 22 FL, 10 nFL; stage II (2), III (16), and IV (14). HP + patients: 4 (3 FL, 1 nFL). We have observed lymphoma responses 1 mo post Ab in 7 of 32 (Table). With continued followup post Ab, best response to date in 9 of 32: PET CR ( 2 FL; 2 nFL); CT CR/PR ( 1/3 FL, 1/0 nFL). Median followup for all patients, 23.7 mos; and for those not needing lymphoma treatment, 54.9 mos. To date, no patient with PET CR has required lymphoma treatment (22.5+ to 62.8+ mos). Among 22 with FL, 8 have progressed, 3 had histologic transformation, possibly suggesting a different biology. Conclusions: H pylori eradication/3 mos clarithromycin has achieved lymphoma responses in advanced stage indolent lymphoma. PET negative CRs have been durable for 22.5 – 62.8 + mos following Ab alone. This prospective study may be a first step toward developing a lymphoma prevention strategy and deserves further clinical/biological study. Clinical trial information: NCT00461084. [Table: see text]
Systematic review and meta-analysis of the safety and efficacy of minimally invasive compared to open thymectomy for thymic malignancies.
Authors: Adam J. Friedant, Elizabeth Handorf, Stacey Su, Walter Joseph Scott
Journal: Journal of Clinical Oncology (2015)

6082 Background: Complete resection is the standard of care for the treatment of thymoma. The use of minimally invasive surgery remains controversial. Methods: We searched online databases and identified studies from 1995 to 2014 comparing minimally invasive (MIS) (video assisted or robotic-assisted) to open thymectomy for thymic tumors. Study endpoints included operative blood loss, operative time, pulmonary complications, atrial fibrillation, length of stay (LOS), R0 resection, and tumor recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated odds ratios (OR) for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios (IRR) for the number of recurrences, accounting for total person-time observed in each study. Results: 36 studies (with 935 patients) were analyzed. Masaoka stage I-II comprised 88.5% (n = 522) of MIS patients and 80.4% (n = 413) of open. Mean tumor size was 4.49 cm (MIS) and 4.99 (open). 32/522 (6.13%) MIS cases were converted to open. MIS patients had significantly less blood loss (226 vs. 169 mL, std diff = -0.78, 95% CI -0.97 – 0.57, p < 0.01) but no significant difference in operating time (164.92 vs. 147.18 min, std diff = 0.13, 95% CI -0.28 – 0.54, p = 0.53), cardiac complications (7 MIS vs. 21 open, OR = 0.73, 95% CI 0.28 – 1.92, p = 0.52), respiratory complications (13 MIS vs. 38 open, OR = 0.79, 95% CI 0.29 – 2.16, p = 0.64), or overall complications (32 MIS vs. 63 open, OR = 0.90, 95% CI 0.41 – 1.93, p = 0.78). LOS was shorter for MIS patients (8d MIS vs. 9d open, std diff = -0.88, 95% CI -1.52 – -0.24, p < 0.01). Analyzing Masaoka I - II patients only, there was no difference in R0 resection rate (97.36% vs. 97.25%, OR = 0.98, 95% CI 0.23 – 4.14, p = 0.88) or overall recurrence rate (2.86% vs. 2.91%, IRR = 2.10, 95% CI 0.39 – 11.25, p = 0.39). There was one postoperative death (open group). Conclusions: The results of this unadjusted meta-analysis of published reports comparing MIS to open thymectomy suggest that MIS thymectomy is safe and can achieve similar oncologic outcomes to open thymectomy in selected patients with thymic malignancy.
Complete radiographic responses in pediatric patients with <i>BRAF</i><sup>V600</sup>-positive tumors including high-grade gliomas: Preliminary results of an ongoing phase 1/2a safety and pharmacokinetics (PK) study of dabrafenib.
Authors: Mark W. Kieran, Kenneth J. Cohen, Francois Doz, Ira J. Dunkel, Darren R Hargrave, Trent Ryan Hummel, Irene Jimenez, Sarah Leary, Andrew DJ Pearson, Christine A. Pratilas, James Whitlock, Michael Durante, Diana M. Gibson, Patricia Haney, Mark W. Russo, Benjamin B. Suttle, Birgit Geoerger
Journal: Journal of Clinical Oncology (2014)

10056 Background: Dabrafenib is a selective inhibitor of V600 mutant BRAF kinase activity with a mechanism of action consistent with adenosine triphosphate-competitive inhibition. Dabrafenib has demonstrated anti-tumor efficacy in adult patients (pts) with BRAFV600 mutant tumors, including melanoma, papillary thyroid cancer (PTC), and non-small cell lung cancer. Methods: This 2-part study was designed to identify phase 2 recommended dose, safety, PK, and clinical activity in pediatric pts who have had ≥1 previous therapy. Part 1 is a PK-driven dose escalation. Part 2 is an expansion study to evaluate the safety and activity of dabrafenib in pediatric pts with 1 of 4 pre-specified tumor types. Pts are treated with dabrafenib orally twice daily, using capsules or a powder for oral suspension. Serial PK samples are obtained on days 1 and 15. Imaging is performed every 2 cycles, and responses require confirmation on a follow-up scan at least 4 weeks later. Results: From May 2013 to Jan 2014, 8 pts (median age, 11 y; range 3-17 y) with recurrent/refractory BRAFV600 mutant solid tumors including 6 high grade glioma (HGG), 1 each of Langerhans cell histiocytosis (LCH), and PTC were enrolled at dose levels 3mg/kg (n=3) and 3.75mg/kg (n=5). Radiographic responses for the HGG pts included 3 complete responses (2 confirmed and maintained at the 6 month assessment [both anaplastic astrocytoma], 1 unconfirmed [pleomorphic xanthoastrocytoma]), and 2 progressive disease. The LCH pt continues to exhibit stable disease at week 16. Data are not yet available for a PTC pt and 1 HGG pt. There were no DLTs or drug-related grade 3/4 toxicities in these 8 pts. No dose reductions have been required, and PK data analysis and dose escalation continues. Two pts (1 in each cohort) achieved plasma dabrafenib concentrations associated with clinical efficacy in adults. Conclusions: Dabrafenib shows encouraging initial clinical activity in this small number of evaluable pediatric pts with BRAFV600 mutant solid tumors, including primary brain tumors. The preliminary safety profile in pediatric pts is consistent with that in adults. Clinical trial information: NCT01677741.
Effect of dose to penile bulb (PB) on patient and clinician-reported erectile function (EF) in standard (SF) and hypofractionated (HF) prostate IGRT.
Authors: Julia Murray, Jamie Dean, Helen Mossop, Clare Griffin, Emma Hall, David P. Dearnaley, Sarah Gulliford
Journal: Journal of Clinical Oncology (2017)

71 Background: PB dose has been hypothesised as predictor of EF post RT, however, PB dose volume effects are not well established. We determined PB dose response characteristics &amp; dose volume constraints using data from randomised trial of prostate IGRT with patient (PRO) &amp; clinician reported (CRO) outcomes. Methods: 293 men were treated within CHHiP IGRT substudy (CRUK/06/16) &amp; randomised to receive 2Gy (SF) or 3Gy (HF) per fraction, without or with daily online IGRT with standard (SM) or reduced (RM) CTV-PTV margins. EF was assessed with RMH CRO &amp; at one time-point (&gt;3 years after RT) with IIEF-5. Men were excluded if impotent at baseline. Planning CT &amp; dose distributions were imported into analysis software (VODCA) &amp; PB contoured. All dose distributions were converted into EQD2 (α/β ratio 3Gy), a separate analysis was done using physical dose (PD) for HF cohort. PB dose volume parameters were analysed &amp; atlases of complication incidence (ACI) evaluated using PRO &amp; CRO. Dose volume constraints using PD &amp; EQD2 were derived using ROC analysis (Youden index) &amp; assessed against the no information rate. Results: Complete dosimetric with CRO &amp; PRO data were available for 175 &amp; 100 men respectively. Of these, men treated with SM vs RM had a higher rate of impotence at 2 &amp; 4 years (49% vs 40% &amp; 47% vs 39%). This was also seen in men recording severe ED (46% vs 37%). ACI indicated a dose volume response. Statistically significant PB dose constraints were derived using EQD2 (SF &amp; HF) &amp; PD for HF cohort (Table). Results using PRO were more pronounced than with CRO. Conclusions: There is a dose volume effect between PB &amp; EF characterised using PRO &amp; CRO. Results suggest that reduction of mean PB dose to &lt;20Gy may lead to an increase of potency preservation rates after prostate RT for both 2Gy &amp; 3Gy schedules. Clinical trial information: ISRCTN97182923. [Table: see text]
Ejaculation frequency and prostate cancer: A large, prospective study with 16 years of follow-up.
Authors: Jennifer R Rider, Kathryn M Wilson, Philip W. Kantoff, Edward L. Giovannucci, Lorelei A. Mucci
Journal: Journal of Clinical Oncology (2013)

5078 Background: A prospective study in the Health Professionals Follow-up Study (HPFS) cohort published in 2001 found significantly lower risks of prostate cancer (PCa) among men with more frequent ejaculation. Because associations were stronger among men at older ages, which could be indicative of reverse causation (i.e., men ejaculating less because of symptoms associated with PCa) and few advanced cases were included, we conducted an updated study with an additional 8 years of follow up. Methods: We included 31,929 men aged 46-81 years from the HPFS who answered ejaculation frequency questions on the 1992 questionnaire. We assessed average frequency per month at three time points: age 20-29, age 40-49, and in 1991 (the year prior to the questionnaire). These data were also combined to estimate average lifetime frequency. Using follow up through January 31, 2008, we used Cox proportional hazards models to estimate relative risks (RR) and 95% confidence intervals (95% CI) for total PCa risk, as well as risk of advanced, lethal, and high-grade (Gleason 8-10) disease. As sensitivity analyses, we also examined associations within a subgroup of highly screened men and a subgroup of men without erectile dysfunction at baseline. Results: During 16 years of follow up, 3403 men were diagnosed with PCa; 455 were advanced, 360 were high grade, and 304 were lethal. Three percent of men reported a lifetime average frequency of &gt;21 times per month while 34% reported 4-7 times per month. Compared to a frequency of 4-7 times per month, multivariate RRs for total PCa for men with &gt;21 ejaculations per month were 0.81 (95% CI: 0.71-0.91) for ages 20-29; 0.76 (95% CI: 0.66-0.88) for ages 40-49; 0.68 (95% CI: 0.53-0.86) in 1991; and 0.57 (95% CI: 0.43-0.75) for lifetime average frequency. RRs for advanced PCa were of similar magnitudes at ages 20-29 years and 40-49 years but not statistically significant. Results were similar when we included only highly screened men or men without a history of erectile dysfunction. Conclusions: With extended follow up, ejaculation frequency continues to be strongly inversely associated with risk of total PCa. These findings are unlikely to be attributable to underlying disease or screening frequency.
FGFR1 amplification and EGFR mutation in Chinese squamous cell lung cancer.
Authors: Zhigang Wei, Jie Wang, Hua Bai, Tongtong An, Zhijie Wang, Minglei Zhuo, Meina Wu, Lu Yang
Journal: Journal of Clinical Oncology (2012)

7545 Background: Squamous cell lung cancer (SCC) lacks for effective targeted therapies. FGFR1 amplification has emerged as a potential biomarker. This study aimed to explore clinicopathologic characteristics of FGFR1 amplification in Chinese SCC patients and further explore the correlation between FGFR1 amplification and EGFR mutations. Methods: One hundred seventy-seven SCC patients were included in this retrospective study. Gene copy number of FGFR1 and EGFR mutations were detected by fluorescence in situ hybridization (FISH) and denaturing high-performance liquid chromatography (DHPLC), respectively. Results: FGFR1 amplifications were detected in 24.9% (44/177) Chinese SCC patients. FGFR1 amplification in SCC was more common in male (28.0%, 40/143) and smokers (28.7%, 39/136) than female (11.8%, 4/34, p=0.049) and nonsmokers (12.2%, 5/41, p=0.032). FGFR1 amplification and EGFR mutations were mutually exclusive (p=0.006), fourty-one of 139(29.4%) patients with wild-type EGFR had FGFR1 amplification, while 3 of 38 (7.9%) patients with EGFR mutation had FGFR1 amplification. Conclusions: FGFR1 amplification was common in Chinese squamous cell lung cancer, and mutually exclusive with EGFR mutations.
A randomized phase II trial of docetaxel plus carboplatin versus docetaxel in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial.
Authors: Esther W. Bouman-Wammes, Linda de Munck, H Pieter van den Berg, Aart Beeker, Carolien H. Smorenburg, Henk M.W. Verheul, Winald R. Gerritsen, Alfonsus Johannes Maria van den Eertwegh
Journal: Journal of Clinical Oncology (2017)

166 Background: Docetaxel is the standard first-line chemotherapy for patients with castration resistant prostate carcinoma (CRPC). Docetaxel re-challenge has never been tested in a prospective randomized clinical trial. As some studies supported the addition of carboplatin to docetaxel in this setting, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel monotherapy in docetaxel pre-treated CRPC patients. Methods: Patients with CRPC with a progression-free interval (PFI) of at least 3 months after initial treatment with docetaxel were randomized between docetaxel 75mg/m 2 or docetaxel 60mg/m 2 plus carboplatin AUC 4, both plus prednisone in a 3-weekly schedule. Treatment was continued until progressive disease, unacceptable toxicity or completion of 10 cycles. The primary endpoint is progression-free survival (PFS) (PSA and/or RECIST). Secondary objectives are overall survival, toxicity, PSA response and quality of life. Results: As a result of insufficient recruitment, the study was discontinued early after inclusion of 75 patients, instead of the targeted 150 patients. The median PFS was comparable between both groups (docetaxel 12.7 months versus combination therapy 11.7 months p = 0.99), and no difference in OS was found (median OS 18.5 months versus 18.9 months, p = 0.88). Rates of PSA response were comparable (response/stable PSA in 42.1%/39.4% of the patients in the monotherapy arm versus 35.1%/48.6% in the combination arm, NS). The incidence of grade 3-4 infections and gastro-intestinal (GI) side effects was higher in the docetaxel plus carboplatin arm (GI side effects 0% versus 13.9% p = 0.03; infection 2.7% versus 16.7% p = 0.056). The difference in febrile neutropenia (0% versus 11.1%) is not significant. Conclusions: For patients with CRPC and an initial good response to docetaxel, re-treatment with docetaxel monotherapy is a feasible, save and effective treatment. Addition of carboplatin resulted in more toxicity. Docetaxel re-challenge is a viable therapeutic option for selected patients. Clinical trial information: NTR3070.