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Papers by Roland Bassett

$Research paper thumbnail of Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors$

Annals of Oncology, 2015

ABSTRACT High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curativ... more ABSTRACT High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ²1.8 mg/dL and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-yr relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. We enrolled 43 male pts, median age 30 (20-49), with absolute refractory (N=20), refractory (N=17) or cisplatin-sensitive (N=6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N=24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N=8), PRm(-) (N=7) or complete response (N=4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N=12) showed necrosis (N=4), mature teratoma (N=2), necrosis/teratoma (N=2) and viable tumor (N=4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Sequential bevacizumab/GemDMCÐbevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.This trial was registered with ClinicalTrials.gov, No. NCT00936936. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

$Research paper thumbnail of Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: Long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome$

Cancer

The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chron... more The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chronic lymphocytic leukemia (CLL) is not well established. The authors report on long-term experience with NST in relapsed/refractory CLL and define prognostic factors associated with outcome. The authors reviewed the outcome of 86 patients with relapsed/relapsed CLL enrolled in sequential NST protocols. The median patient age was 58 years. Patients were heavily pretreated before transplantation, and 43 required immunomanipulation after NST for persistent or recurrent disease. Immunomanipulation included withdrawal of immunosuppression, rituximab, and step-wise donor lymphocyte infusions. Of 43 patients receiving immunomanipulation, 20 (47%) experienced a complete remission. Patients with human leukocyte antigen (HLA) genotype A1(+) /A2(-) /B44(-) were more likely to experience a complete remission (P = .0009), with rates of 9%, 36%, 50%, and 91%, respectively, for 0, 1, 2, and 3 of these HL...

Journal of Psychosomatic Research, 2015

The Journal of investigative dermatology, Jan 7, 2015

Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence... more Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels, or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation) and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery dataset and replicated in two validation datasets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single SNP explained 13.1% of variability in log[IL-12p40]. The most significan...

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 16, 2015

To investigate the association between blood levels of C-reactive protein (CRP) in patients with ... more To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival. Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable ad...

Blood, Jan 2, 2014

Myelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity ... more Myelosuppression, graft-versus-host disease (GVHD), and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. In this phase 1/2 study, we tested the safety and efficacy of escalating doses of bendamustine (70, 90, 110, and 130 mg/m2 per day for 3 days), coupled with our historical fixed doses of fludarabine and rituximab (BFR), as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma (n = 41) and chronic lymphocytic leukemia (CLL) (n = 15). Ten patients entered the phase 1 study; none experienced a dose-limiting toxicity. Forty-six additional patients were then treated in the phase 2 study at the maximum dose of 130 mg/m2 per day for 3 days. The proportions of transplants from matched siblings or unrelated donors were 54% and 46%. Remarkably, 55% of patients did not experience severe neutropenia. Forty-nine patients (88%) did not require platelet transfusion. The incidence of acute grade II-IV GVHD was 11%. T...

European journal of nuclear medicine and molecular imaging, 2014

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available ab... more Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available about on value of (18)F-FDG PET/CT in ACC. We evaluated the impact of PET/CT on the management of ACC. We performed a retrospective review in patients with ACC who had undergone PET/CT. The impact of PET/CT on the management plan was evaluated by comparing the findings on PET/CT to the findings on contrast-enhanced CT. The sensitivity, specificity, and accuracy of each form of imaging were calculated. The correlations between PET/CT parameters, including maximum standardized uptake value (SUVmax), total lesion glycolysis, and decline in SUVmax after chemotherapy, and clinical outcome were evaluated. Included in the analysis were 106 patients with 180 PET/CT scans. Of the 106 patients, 7 underwent PET/CT only for initial staging, 84 underwent PET/CT only for restaging, and 15 underwent PET/CT for both initial staging and restaging. PET/CT changed the management plan in 1 of 22 patients (5%)...

Biology of Blood and Marrow Transplantation, 2014

Central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (HS... more Central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) confers a poor prognosis in adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS relapse after HSCT remains a therapeutic challenge, and criteria for post-HSCT CNS prophylaxis have not been addressed. In a 3-center retrospective analysis, we reviewed the data for 457 adult patients with ALL who received a first allogeneic HSCT in first or second complete remission (CR). All patients received CNS prophylaxis as part of their upfront therapy for ALL, but post-transplantation CNS prophylaxis practice varied by institution and was administered to 48% of the patients. Eighteen patients (4%) developed CNS relapse after HSCT (isolated CNS relapse, n ¼ 8; combined bone marrow and CNS relapse, n ¼ 10). Patients with a previous history of CNS involvement with leukemia had a significantly higher rate for CNS relapse (P ¼ .002), and pretransplantation CNS involvement was the only risk factor for post-transplantation CNS relapse found in this study. We failed to find a significant effect of post-transplantation CNS prophylaxis to prevent relapse after transplantation. Furthermore, no benefit for post-transplantation CNS prophylaxis could be detected when a subgroup analysis of patients with (P ¼ .10) and without previous CNS involvement (P ¼ .52) was performed. Finally, we could not find any significant effect for intensity of the transplantation conditioning regimen on CNS relapse after HSCT. In conclusion, CNS relapse is an uncommon event after HSCT for patients with ALL in CR1 or CR2, but with higher risk among patients with CNS involvement before transplantation. Furthermore, neither the use of post-HSCT CNS prophylaxis nor the intensity of the HSCT conditioning regimen made a significant difference in the rate of post-HSCT CNS relapse.

Gynecologic Oncology, 2009

To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating f... more To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. In this phase II study, patients with recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer were treated with subcutaneous GM-CSF and rIFN-gamma1b before and after intravenous carboplatin until disease progression or unacceptable toxicity. All patients had measurable disease and a chemotherapy-free interval &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 months. Response was determined using RECIST criteria and CA 125 levels. Between 2003 and 2007, 59 patients received a median of 6 cycles of therapy (range, 1 to 13 cycles). Median age at enrollment was 61 years (range, 35 to 79 years). Median time to progression prior to enrollment was 11 months (range, 6 to 58 months). Of 54 patients evaluable for response, 9 (17%) had a complete response, 21 (39%) had a partial response, and 24 (44%) had progressive disease. The overall response rate was 56% (95% CI: 41% to 69%). With a median follow-up of 6.4 months, median time to progression was 6 months. Myeloid derived cells and platelets increased on day 9 of each chemotherapy cycle. The most common adverse effects were bone marrow suppression, carboplatin hypersensitivity, and fatigue. Responders reported improved quality of life. This pre and post-carboplatin cytokine regimen resulted in a reasonable response and a hematologic profile that could invite further evaluation of its components in the treatment of patients with ovarian cancer.

Clinical Cancer Research, 2007

Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidon... more Purpose: To describe the eicosanoid profile and differentially expressed eicosanoid and arachidonic acid pathway genes in tissues from patients with advanced epithelial ovarian cancer (EOC). Experimental Design: We first employed electrospray tandem mass spectrometry to determine tissue-specific concentrations of the eicosanoids prostaglandin E 2 (PGE 2 ), the hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and leukotriene (LTB 4 ), selected for tumor growth potential, and two other bioactive lipids (15-HETE and 13-HODE) with tumor cell proliferation interference potential. The cellular location of eicosanoid activity was identified by immunofluorescence antibody costaining and confocal microscopy. Differential analysis of eicosanoid and arachidonic pathway genes was done using a previously validated cDNA microarray platform. Tissues used included EOC tumor, tumor-free malignant peritoneum (MP), and benign peritoneum (BP) from patients with benign pelvic disease. Results: (a) Eicosanoid products were detected in tumor, MP, and BP specimens. PGE 2 levels were significantly elevated in tumors in an overall comparison with MP or BP (P < 0.001).

Breast Cancer Research and Treatment, 2012

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER... more Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age &amp;amp;amp;amp;amp;amp;amp;gt; 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

Biology of Blood and Marrow Transplantation, 2007

column-passed fractions at day 21. In summary our data show that by increasing the starting purit... more column-passed fractions at day 21. In summary our data show that by increasing the starting purity of CD4ϩFoxp3ϩCD27ϩ cells a greater expansion of the Treg population can be achieved, making it more feasible to obtain clinically useful doses of Treg for immunotherapy protocols to prevent or treat GVHD. Rapamycin at doses of 5-10 ng/mL inhibits the expansion of cells without the phenotype and function of Tregs, but higher doses (50-200 ng/mL) are toxic to Tregs.

Biology of Blood and Marrow Transplantation, 2009

Graft-versus-host disease (GVHD) following bone marrow transplantation (BMT) is mediated by allor... more Graft-versus-host disease (GVHD) following bone marrow transplantation (BMT) is mediated by alloreactive donor T lymphocytes. Migration and activation of donor-derived T lymphocytes play critical roles in the development of GVHD. Leukocyte function-associated antigen-1 (LFA-1) regulates T cell adhesion and activation. We previously demonstrated that the I-domain, the ligand-binding site of LFA-1, changes from the low-affinity state to the high-affinity state on LFA-1 activation. Therapeutic antagonists, such as statins, inhibit LFA-1 activation and immune responses by modulating the affinity state of the LFA-1 I-domain. In the present study, we report that lovastatin blocked mouse T cell adhesion, proliferation, and cytokine production in vitro. Furthermore, blocking LFA-1 in the low-affinity state with lovastatin reduced the mortality and morbidity associated with GVHD in a murine BMT model. Specifically, lovastatin prevented T lymphocytes from homing to lymph nodes and Peyer's patches during the GVHD initiation phase and after donor lymphocyte infusion (DLI) after the establishment of GVHD. In addition, treatment with lovastatin impaired donor-derived T cell proliferation in vivo. Taken together, these results indicate the important role of lovastatin in the treatment of GVHD.

Journal of …, 2006

Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential... more Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory ...

American Journal of Roentgenology, 2008

The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissecte... more The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease. High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured. Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected. In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.

Molecular cancer therapeutics, Jan 5, 2015

Although sequencing provides the gold standard for identifying colorectal carcinoma (CRC) with BR... more Although sequencing provides the gold standard for identifying colorectal carcinoma (CRC) with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 CRCs (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results to melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated CRCs, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type CRCs, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥20%...

PURPOSE To determine the capability of MRI in detecting the second breast carcinoma among women w... more PURPOSE To determine the capability of MRI in detecting the second breast carcinoma among women with a personal history of breast carcinoma. METHOD AND MATERIALS This retrospective review of breast MRI examinations performed from 2007 to 2011 yielding 798 women who had a personal breast history. Of the 798 patients, 445 had adequate follow up data and 348 had MRI, mammography and ultrasound within 6 months intervals. The sensitivity, specificity of MRI in detecting the second breast carcinoma was calculated. The recall rate and PPV of MRI was also calculated. RESULTS Of the 798 patients, 49 second breast carcinoma was found and the incidence of the second breast carcinoma was 6.1%. Forty-five breast carcinomas were detected by MRI. The sensitivity and specificity of MRI in detecting the second breast carcinoma was 91.8% and 92.2%, respectively. The recall rate of MRI was 9.5% and PPV was 59.2%. The sensitivity of MRI, mammography and ultrasound in detecting the second breast carcino...

The aim of our study was to retrospectively evaluate whether maximum standardized uptake value (S... more The aim of our study was to retrospectively evaluate whether maximum standardized uptake value (SUV max ), total lesion gylcolysis (TLG), or change therein using 18 F-FDG PET/CT performed before and after initial chemotherapy were indicators of patient outcome. Methods: Thirty-one consecutive patients who underwent 18 F-FDG PET/CT before and after chemotherapy, followed by tumor resection, were retrospectively reviewed. Univariate Cox regression was used to analyze for relationships between covariates of interest (SUV max before and after chemotherapy, change in SUV max , TLG before and after chemotherapy, change in TLG, and tumor necrosis) and progression-free and overall survival. Logistic regression was used to evaluate tumor necrosis. Results: High SUV max before and after chemotherapy (P 5 0.008 and P 5 0.009, respectively) was associated with worse progression-free survival. The cut point for SUV max before chemotherapy was greater than 15 g/mL* (P 5 0.015), and after chemotherapy it was greater than 5 g/mL* (P 5 0.006), as measured at our institution and using lean body mass. Increase in TLG after chemotherapy was associated with worse progressionfree survival (P 5 0.016). High SUV max after chemotherapy was associated with poor overall survival (P 5 0.035). The cut point was above the median of 3.3 g/mL* (P 5 0.043). High TLG before chemotherapy was associated with poor overall survival (P 5 0.021). Good overall and progression-free survival was associated with a tumor necrosis greater than 90% (P 5 0.018 and 0.08, respectively). A tumor necrosis greater than 90% was most strongly associated with a decrease in SUV max (P 5 0.015). Conclusion: 18 F-FDG PET/CT can be used as a prognostic indicator for progression-free survival, overall survival, and tumor necrosis in osteosarcoma.