Publications by authors named "Patrick Sfumato"

14 Publications

  • Page 1 of 1

Circulating Tumor Cells and Bevacizumab Pharmacokinetics during Neoadjuvant Treatment Combining Chemotherapy and Bevacizumab for Early Breast Cancer: Ancillary Analysis of the AVASTEM Trial.

Cancers (Basel) 2021 Jan 5;13(1). Epub 2021 Jan 5.

CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Aix Marseille University, 13009 Marseille, France.

The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics (PK). The main objective was to assess the prognostic (relapse-free survival and overall survival) and predictive (pathological complete response, pCR) values of CTCs (CellSearch technology) and bevacizumab PK (ELISA). Seventy-five patients were included. Out of them 50 received bevacizumab-chemotherapy and 25 received chemotherapy alone. CTC results were available for 60 patients and PK data for 29 patients in the experimental arm. The absence of CTC at inclusion was correlated to better outcome. Five-years overall survival (OS) was 91% for CTC-negative patients vs. 54% for CTC-positive cases (HR = 6.21; 95%CI (1.75-22.06), = 0.001, log-rank test). Similar results were observed for RFS with 5 y-RFS of 78% vs. 44% (HR = 3.51; 95%CI (1.17-10.52), = 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR ( = 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56; 95%CI (0.19-12.67); = 0.68 for OS and HR = 2.76; 95%CI (0.60-12.61); = 0.17 for RFS, log-rank test). Bevacizumab serum levels could not predict pCR and survival. PK values were not associated with treatment-related toxicities. In conclusion, CTCs detection at baseline is a prognostic marker for breast cancer receiving a neoadjuvant chemotherapy-bevacizumab combination independently of tumor response.
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http://dx.doi.org/10.3390/cancers13010140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796232PMC
January 2021

Socioeconomic deprivation is associated with decreased survival in patients with acute myeloid leukemia.

Cancer Epidemiol 2020 06 13;66:101699. Epub 2020 Mar 13.

Hematology Department, Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Marseille, France. Electronic address:

Background: Socioeconomic deprivation is associated with poor prognosis in patients with solid tumors. However, few studies have assessed the association between socioeconomic parameters and prognosis in Acute Myeloid Leukemia (AML), and these report conflicting results. Our monocentric study assessed the impact of socioeconomic deprivation using the validated EPICES (Evaluation of Deprivation and Inequalities in Health Examination Centers) score in a prospective cohort of intensively treated AML patients.

Methods: EPICES questionnaires were given to patients receiving intensive chemotherapy for newly diagnosed AML at the Paoli Calmettes Institute between July 2012 and December 2014. Study participants were categorized as non-deprived (score <30.17), deprived (score 30.17-48.51), or very-deprived (score ≥ 48.52). The primary endpoint was Overall Survival (OS). The independence of EPICES score effects was analyzed via Cox regression with adjustment for confounding factors.

Results: 209 AML patients received the questionnaire, 149 (71.3 %) patients responded. The median EPICES score was 23.6; 26.8 % and 10.1 % of patients were deprived and very deprived, respectively. OS was 23.16 months (95 %CI [17.15-33.31]). According to multivariate analysis, a very-deprived EPICES score, European Leukemia Net categories, age, smoking, and the absence of allogeneic stem cell transplantation were independent factors associated with decreased OS.

Conclusion: Our results underscore the importance of integrating nonbiological factors in the prognostic stratification of AML patients. The very deprived population exhibited worse OS, confirming that socioeconomic parameters play a role in patient outcomes in AML. Very deprived patients with AML should receive specific attention and adapted clinical management.
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http://dx.doi.org/10.1016/j.canep.2020.101699DOI Listing
June 2020

Analysis of a large single institution cohort of related donors fails to detect a relation between SDF1/CXCR4 or VCAM/VLA4 genetic polymorphisms and the level of hematopoietic progenitor cell mobilization in response to G-CSF.

PLoS One 2020 5;15(3):e0228878. Epub 2020 Mar 5.

Etablissement Français du Sang PACA Corse, Biologie des Groupes Sanguins, Marseille, France.

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058310PMC
June 2020

Impact of sarcopenia status of muscle-invasive bladder cancer patients on kidney function after neoadjuvant chemotherapy and post cystectomy complications.

Minerva Urol Nefrol 2020 Feb 19. Epub 2020 Feb 19.

Department of Surgical Oncology 2, Institut Paoli-Calmettes, Marseille, France -

Background: Sarcopenia is suspected to influence the complication rates in patients undergoing radical cystectomy (RC). The aim of our study was to assess variations in sarcopenia in patients scheduled for neoadjuvant cisplatin-based chemotherapy (NAC) and RC for muscle invasive bladder cancer (MIBC) and to explore the impact of sarcopenia on complications linked to NAC or surgery.

Methods: Between 2012 and 2017, 82 consecutive patients who underwent NAC and RC for cT2-T4 N0 MIBC were retrospectively selected. Using CT scan before and after NAC, Lumbar Skeletal Muscle Index (SMI) was assessed by two observers. We defined severe sarcopenia as SMI <50 cm2/m2 for men and SMI <35 cm2/m2 for women. We evaluated pre- and post-NAC cisplatin-based chemotherapy renal function and post-operative complication rates after cystectomy using the Clavien-Dindo classification. We explored risk factors of complications by logistic regression models.

Results: According to the SMI, 47 patients (57.3%) were classified as sarcopenic and 35 patients (42.7%) non-sarcopenic. Patients' characteristics between sarcopenic and non- sarcopenic patients were not significantly different except for BMI (p<0.001). Among patients non-sarcopenic before NAC, 9 (25.7%) became sarcopenic after NAC. In multivariate analysis, sarcopenia was an independent significant predictor of renal impairment after NAC (p=0.02). Moreover, sarcopenia and ASA score were independent significant predictors of postoperative early complications (p=0.01 and p=0.03 respectively).

Conclusions: We observed significant changes in sarcopenic status during NAC. Sarcopenia, estimated by the lumbar SMI measurement, was an independent predictor associated with the risk of renal impairment during NAC and early postoperative complications after RC.
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http://dx.doi.org/10.23736/S0393-2249.20.03616-4DOI Listing
February 2020

Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer.

J Clin Med 2019 May 6;8(5). Epub 2019 May 6.

Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France.

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, = 0.06), but survival was not improved (OS: = 0.89; DFS: = 0.45; and RFS: = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.
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http://dx.doi.org/10.3390/jcm8050612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572380PMC
May 2019

Addressing heterogeneity in the design of phase II clinical trials in geriatric oncology.

Eur J Cancer 2018 11 14;103:120-126. Epub 2018 Sep 14.

Biostatistics Unit, Institut Claudius Regaud-IUCT-O, Toulouse, France. Electronic address:

Introduction: Cancer in the elderly is a major public issue. However, older patients have long been debarred from clinical trials. There is a high unmet medical need for specific trials addressing oncology strategies adapted to older patients' conditions. While randomised phase III trials remain the gold standard, they usually require large numbers of patients. In this perspective, late single-arm phase II trials assessing treatment feasibility might prove a good alternative. However, it is essential to take into account the heterogeneity in an ageing population characterised by frailty. Standard parallel phase II studies in defined frail and non-frail populations also require a high number of patients. Used in molecular subtyping and treatment effect heterogeneity, stratified adaptive designs can improve statistical performance, but they have never been used in geriatric oncology. This report describes their potential benefits and useful applications as compared with standard designs.

Methods: In a heterogeneous population, stratified adaptive designs allowed us to select subgroups of interest in two stages. Operational characteristics were evaluated through simulations of clinical trials under different scenarios.

Results: Simulations showed that the use of stratified adaptive designs can efficiently minimise both the number of patients to be included and accrual duration with competitive statistical power and high heterogeneity detection rate at interim analysis.

Conclusion: Compared with classical phase II designs, stratified adaptive phase II trial methodology offers a promising approach to improve clinical research in geriatric oncology. These designs may also be efficient in other populations such as children or adolescents and young adults.
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http://dx.doi.org/10.1016/j.ejca.2018.07.136DOI Listing
November 2018

Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer.

Brachytherapy 2018 Nov - Dec;17(6):922-928. Epub 2018 Jul 27.

Unit of Biostatistics and Methodology, Paoli Calmettes Institute, Comprehensive Cancer Centre, Marseille, France.

Purpose: To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT).

Methods And Materials: Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method.

Results: One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9-5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70 and D5 (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78-0.88) and 0.89 (IQR, 0.85-0.93) at 2 and 5 years of followup, respectively.

Conclusions: A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70 and D5) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT.
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http://dx.doi.org/10.1016/j.brachy.2018.07.005DOI Listing
April 2019

[Impact of Her2 and BRCA1/2 status in high-dose chemotherapy and autologous stem cells transplantation in the treatment of breast cancer: The Institut Paoli Calmettes' experience].

Bull Cancer 2017 Apr 16;104(4):332-343. Epub 2017 Feb 16.

Institut Paoli-Calmettes (IPC), département d'oncologie médicale, 232, boulevard de Sainte-Marguerite, 13009 Marseille cedex 9, France; Centre de recherches en cancérologie de Marseille (CRCM), UMR Inserm 1068/CNRS 7258/AMU 105/IPC, 232, boulevard de Sainte-Marguerite, 13009 Marseille, France; Aix-Marseille université, Jardin du Pharo, 58, boulevard Charles-Livon, 13284 Marseille, France. Electronic address:

Introduction: Studies evaluating chemotherapy high dose chemotherapy with autologous haematopoietic stem cell transplantation (HDC-ACSH) in the treatment of metastatic (MBC), locally advanced (LABC) and inflammatory (IBC) breast cancer have in common lack of biomarker information, in particular the HER2 status.

Patients And Methods: All consecutive female patients treated for breast cancer with HDC and AHSCT at Institut Paoli Calmettes between 2003 and 2012 were included. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: luminal, (HR+/HER2-), HER2 (HER2+, any HR) and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the IHC subtypes.

Results: Three hundred and seventy-seven patients were included. For MBC, the TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95 % CI 11.76-44.4) compared to 44.64 months (95 % CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (P<0.01). For IBC, HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89 % (95 % CI 64-97) compared to 57 % (95 % CI 33-76) for the TN subgroup (HR 5.38, 95 % CI 1.14-25.44; P=0.034). For CSLA, luminal subgroup appeared to have the best prognosis with a 5-year OS of 92 % (95 % CI 71-98) against 75 % (95 % CI 46-90) for HER 2 subtype and 70 % (95 %CI 97-88) for TN subtype (P=0.301).

Conclusion: The HDC-ACSH does not change the prognosis value of IHC subtype in breast cancer patients.
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http://dx.doi.org/10.1016/j.bulcan.2016.12.007DOI Listing
April 2017

Prognostic impact of hormone receptor- and HER2-defined subtypes in inflammatory breast cancer treated with high-dose chemotherapy: a retrospective study.

J Cancer 2016 23;7(14):2077-2084. Epub 2016 Oct 23.

Aix-Marseille Université, Marseille, F-13284, France.; Centre de Thérapie Cellulaire, Département de Biologie du Cancer, Institut Paoli-Calmettes, Marseille, F-13273, France.; Centre d'Investigations Cliniques en Biothérapies, Inserm CBT-1409, Marseille, F-13009, France.

Studies examining high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC-AHSCT) strategies in inflammatory breast cancer (IBC), showed encouraging results in terms of disease-free survival (DFS), and overall survival (OS). The lack of data regarding HER2 status in all of these studies prevented any prognostic analysis involving breast cancer subtypes. All consecutive female patients treated for IBC with HDC and AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. Since 2005, trastuzumab was included in initial treatment. Patient, tumor and treatment characteristics were collected. Patients were categorized in three subtypes based on hormonal receptor (HR) and HER2 status of the primary tumor: Luminal, (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The main objective was the analysis of OS according to the IHC subtypes. Sixty-seven patients were included. Eleven patients received trastuzumab. Median follow up was 80.04 months (95% CI 73.2-88.08). Five-year OS and DFS for the whole population patients were 74% (95% CI 61-83) and 65 % (95% CI 52-75), respectively. OS differed across subtypes (p=0.057) : HER2 subgroup appeared to have the best prognosis with a 5-year OS of 89% (95% CI 64-97) compared to 57% (95% CI 33-76) for the TN subgroup (HR 5.38, 95% CI 1.14-25.44; p=0.034). In IBC patients receiving HDC-AHSCT, OS favorably compares with data available in the literature on similar groups of patients. TN patients carried the least favourable OS and HER2 patients, half of them also receiving trastuzumab, had the best outcome. These findings provide additional information and options for patients with IBC and who could potentially benefit of HDC-AHSCT.
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http://dx.doi.org/10.7150/jca.15797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118671PMC
October 2016

Corrigendum to "Immunohistochemical subtypes predict survival in metastatic breast cancer receiving high-dose chemotherapy with autologous haematopoietic stem cell transplantation" [Eur J Cancer 57 (April 2016) 118-126].

Eur J Cancer 2016 11 24;67:223. Epub 2016 Sep 24.

Département d'Oncologie Médicale, Institut Paoli-Calmettes (IPC), Marseille, F-13273, France; Centre de Recherches en Cancérologie de Marseille (CRCM), UMR Inserm 1068/CNRS 7258/AMU 105/IPC, Marseille, F-13009, France; Aix-Marseille Université, Marseille, F-13284, France. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2016.09.002DOI Listing
November 2016

Immunohistochemical subtypes predict survival in metastatic breast cancer receiving high-dose chemotherapy with autologous haematopoietic stem cell transplantation.

Eur J Cancer 2016 04 23;57:118-26. Epub 2016 Feb 23.

Département d'Oncologie Médicale, Institut Paoli-Calmettes (IPC), Marseille, F-13273, France; Centre de Recherches en Cancérologie de Marseille (CRCM), UMR Inserm 1068/CNRS 7258/AMU 105/IPC, Marseille, F-13009, France; Aix-Marseille Université, Marseille, F-13284, France. Electronic address:

Introduction: The objective of this study was to evaluate the outcome of patients affected with different subtypes of metastatic breast cancer (MBC) following treatment with high-dose chemotherapy (HDC) and autologous haematopoietic progenitor cell transplantation (AHSCT).

Methods: All consecutive female patients treated for MBC with HDC and AHSCT at the Institut Paoli-Calmettes between 2003 and 2012 were included. Patient, tumour and treatment characteristics were collected. Patients were categorised in three subtypes based on hormonal receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of the primary tumour: luminal (L), (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The main objective was the analysis of overall survival (OS) according to the immunohistochemical (IHC) subtypes.

Results: A total of 235 patients were included, median age was 46 (range 21-62). Median follow up was 53.28 months (95% confidence interval [CI] 45.12-57.6). The TN subtype appeared to have the worst prognosis with a median OS of 19.68 months (95% CI 11.76-44.4) compared to 44.64 months (95% CI 40.32-67.56) for the luminal subtype and a median OS not reached for the HER2 subtype (p < 0.01). In the multivariate analysis, the TN subtype retained an independent poor prognosis value compared to the luminal subtype, with a hazard ratio of 2.03 (95% CI 1.26-3.29, p = 0.037).

Conclusion: HDC-AHSCT does not change the prognostic value of IHC subtypes in MBC patients. OS favourably compares with data available in the literature on similar groups of patients. These findings provide additional information and options for patients with MBC and who could potentially benefit of HDC-AHSCT.
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http://dx.doi.org/10.1016/j.ejca.2016.01.005DOI Listing
April 2016

Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era.

Urol Oncol 2016 Apr 3;34(4):167.e17-23. Epub 2015 Dec 3.

Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France.

Background: Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs.

Patients And Methods: Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression.

Results: In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P<0.02; HR = 1.4; 95% CI = 1.1-1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P<0.004).

Conclusions: This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies.
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http://dx.doi.org/10.1016/j.urolonc.2015.10.015DOI Listing
April 2016