Robert Maki - Academia.edu (original) (raw)

Papers by Robert Maki

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 12, 2016

Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, the... more Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding the generation of toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with doxorubicin plus placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m(2) intravenously day 1 plus palifosfamide 150 mg/m(2)/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles. The primary end point was progression-free survival (PFS) by independent radiologic review. In all, 447 patients were randomly assigned to receive doxorubicin plus palifosfamide (n = 226) or doxorubicin plus placebo (n = 221). Median PFS was 6.0 months for doxorubicin plus palifosfamide and 5.2 months for doxorubicin plus placebo (hazard ratio, 0.86; 95% CI, 0.68 to 1.08; P = .19). Median overall survival was 15.9 months for doxorubicin plus pa...

The Lancet. Oncology, Jan 4, 2016

Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young.... more Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young. Outside rare syndromes, the nature, extent, and clinical significance of their genetic origins are not known. We aimed to investigate the genetic basis for bone and soft-tissue sarcoma seen in routine clinical practice. In this genetic study, we included 1162 patients with sarcoma from four cohorts (the International Sarcoma Kindred Study [ISKS], 966 probands; Project GENESIS, 48 probands; Asan Bio-Resource Center, 138 probands; and kConFab, ten probands), who were older than 15 years at the time of consent and had a histologically confirmed diagnosis of sarcoma, recruited from specialist sarcoma clinics without regard to family history. Detailed clinical, pathological, and pedigree information was collected, and cancer diagnoses in probands and relatives were independently verified. Targeted exon sequencing using blood (n=1114) or saliva (n=48) samples was done on 72 genes (selected du...

The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liv... more The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 1251-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 m M Mg2+ (EC5o = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 1251-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 m M Mg2+ or 5 m M EDTA diminishes receptor affinity for hormone (from KD = 1.2 f 0.1 nM to KD = 2.6 f 0.3 nM) and the fraction of '251-glucagon in high molecular weight receptor-N, complexes without affecting site number (Bmx = 1.8 f 0.1 pmol/mg of protein). Thus, while G T P promotes disaggregation of receptor-N, complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence

Cancer Research, Apr 15, 2006

J Clin Oncol, 2005

To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients wi... more To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Cancer, Feb 1, 2008

BACKGROUND. Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal ... more BACKGROUND. Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal tract and often shows constitutive activation of either the KIT or PDGFRA receptor tyrosine kinases because of gain-of-function mutation.

Http Dx Doi Org 10 4161 Cc 7 6 5569, Apr 1, 2008

The Wnt signal transduction pathway coordinates myriad activities, from development and different... more The Wnt signal transduction pathway coordinates myriad activities, from development and differentiation to proliferation and tumorigenesis. What is perhaps most remarkable is that Wnt signaling is able to accomplish this diverse set of activities in a cell-specific and differentiation stage-dependent manner. In this review, we will highlight the diverse effect of Wnt signaling on three types of tissue stem cells and their corresponding malignancies.

Cancer, Oct 1, 2008

BACKGROUND-Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a pro... more BACKGROUND-Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease.

Genome medicine, 2016

Personalized therapy provides the best outcome of cancer care and its implementation in the clini... more Personalized therapy provides the best outcome of cancer care and its implementation in the clinic has been greatly facilitated by recent convergence of enormous progress in basic cancer research, rapid advancement of new tumor profiling technologies, and an expanding compendium of targeted cancer therapeutics. We developed a personalized cancer therapy (PCT) program in a clinical setting, using an integrative genomics approach to fully characterize the complexity of each tumor. We carried out whole exome sequencing (WES) and single-nucleotide polymorphism (SNP) microarray genotyping on DNA from tumor and patient-matched normal specimens, as well as RNA sequencing (RNA-Seq) on available frozen specimens, to identify somatic (tumor-specific) mutations, copy number alterations (CNAs), gene expression changes, gene fusions, and also germline variants. To provide high sensitivity in known cancer mutation hotspots, Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2) was also employed. We integr...

Ejc Suppl, 2009

abstr LBA6006) G4 ASCO ABSTRACT First results of a phase III multicenter randomized controlled tr... more abstr LBA6006) G4 ASCO ABSTRACT First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer (PARSPORT: ISRCTN48243537; CRUK/03/005)

Cancer Research, Apr 15, 2006

Biochemistry Usa, 1988

The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liv... more The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 1251-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 m M Mg2+ (EC5o = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 1251-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 m M Mg2+ or 5 m M EDTA diminishes receptor affinity for hormone (from KD = 1.2 f 0.1 nM to KD = 2.6 f 0.3 nM) and the fraction of '251-glucagon in high molecular weight receptor-N, complexes without affecting site number (Bmx = 1.8 f 0.1 pmol/mg of protein). Thus, while G T P promotes disaggregation of receptor-N, complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence

Rare Tumors, May 21, 2015

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extrao... more We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

Journal of the National Comprehensive Cancer Network Jnccn, Apr 1, 2010

The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly c... more The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at

Asco Meeting Abstracts, May 20, 2014

Asco Meeting Abstracts, May 20, 2012

Annals of Surgical Oncology, Feb 1, 2011

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically prese... more Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically presents with local invasion but rarely metastasizes. We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy. Patients treated for DFSP were identified in a prospectively maintained database. Clinicopathologic factors associated with DFS were analyzed using univariate and multivariate analysis. A total of 244 patients with DFSP were identified. Median follow-up was 50 months. A total of 14 patients had local recurrence (LR), and 2 patients had distant recurrence (DR), with a median time to recurrence of 35 months. At time of last follow-up, 70% and 47% of patients showed no evidence of disease (NED) in the primary (n = 197) and recurrent groups (n = 47), respectively. On univariate analysis, tumor location and depth were associated with DFS in the primary group, while margin status (R1 vs. R0) was associated with DFS in the LR group. On multivariate analysis, only depth (primary group) and margin status (LR group), remained significant. Also, 22 patients had therapy other than surgical resection: 14 radiotherapy, 4 tyrosine kinase inhibitor (TKI) only, 2 conventional chemotherapy only, and 2 chemotherapy plus TKI. Responses to other therapies were variable. DFS after treatment for DFSP is strongly predicted by tumor depth in the primary setting and margin status in recurrent tumors. The treatment for DFSP in the primary or recurrent setting is excision with negative margins, resulting in low recurrence rates and infrequent metastatic spread. Multimodality treatment, especially TKI use, can be effective, but is not curative.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 12, 2016

Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, the... more Palifosfamide is the active metabolite of ifosfamide and does not require prodrug activation, thereby avoiding the generation of toxic metabolites. The PICASSO III trial compared doxorubicin plus palifosfamide with doxorubicin plus placebo in patients who had received no prior systemic therapy for metastatic soft tissue sarcoma. Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m(2) intravenously day 1 plus palifosfamide 150 mg/m(2)/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles. The primary end point was progression-free survival (PFS) by independent radiologic review. In all, 447 patients were randomly assigned to receive doxorubicin plus palifosfamide (n = 226) or doxorubicin plus placebo (n = 221). Median PFS was 6.0 months for doxorubicin plus palifosfamide and 5.2 months for doxorubicin plus placebo (hazard ratio, 0.86; 95% CI, 0.68 to 1.08; P = .19). Median overall survival was 15.9 months for doxorubicin plus pa...

The Lancet. Oncology, Jan 4, 2016

Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young.... more Sarcomas are rare, phenotypically heterogeneous cancers that disproportionately affect the young. Outside rare syndromes, the nature, extent, and clinical significance of their genetic origins are not known. We aimed to investigate the genetic basis for bone and soft-tissue sarcoma seen in routine clinical practice. In this genetic study, we included 1162 patients with sarcoma from four cohorts (the International Sarcoma Kindred Study [ISKS], 966 probands; Project GENESIS, 48 probands; Asan Bio-Resource Center, 138 probands; and kConFab, ten probands), who were older than 15 years at the time of consent and had a histologically confirmed diagnosis of sarcoma, recruited from specialist sarcoma clinics without regard to family history. Detailed clinical, pathological, and pedigree information was collected, and cancer diagnoses in probands and relatives were independently verified. Targeted exon sequencing using blood (n=1114) or saliva (n=48) samples was done on 72 genes (selected du...

The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liv... more The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 1251-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 m M Mg2+ (EC5o = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 1251-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 m M Mg2+ or 5 m M EDTA diminishes receptor affinity for hormone (from KD = 1.2 f 0.1 nM to KD = 2.6 f 0.3 nM) and the fraction of '251-glucagon in high molecular weight receptor-N, complexes without affecting site number (Bmx = 1.8 f 0.1 pmol/mg of protein). Thus, while G T P promotes disaggregation of receptor-N, complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence

Cancer Research, Apr 15, 2006

J Clin Oncol, 2005

To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients wi... more To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

Cancer, Feb 1, 2008

BACKGROUND. Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal ... more BACKGROUND. Gastrointestinal stromal tumor (GIST) is the most frequent sarcoma of the intestinal tract and often shows constitutive activation of either the KIT or PDGFRA receptor tyrosine kinases because of gain-of-function mutation.

Http Dx Doi Org 10 4161 Cc 7 6 5569, Apr 1, 2008

The Wnt signal transduction pathway coordinates myriad activities, from development and different... more The Wnt signal transduction pathway coordinates myriad activities, from development and differentiation to proliferation and tumorigenesis. What is perhaps most remarkable is that Wnt signaling is able to accomplish this diverse set of activities in a cell-specific and differentiation stage-dependent manner. In this review, we will highlight the diverse effect of Wnt signaling on three types of tissue stem cells and their corresponding malignancies.

Cancer, Oct 1, 2008

BACKGROUND-Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a pro... more BACKGROUND-Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease.

Genome medicine, 2016

Personalized therapy provides the best outcome of cancer care and its implementation in the clini... more Personalized therapy provides the best outcome of cancer care and its implementation in the clinic has been greatly facilitated by recent convergence of enormous progress in basic cancer research, rapid advancement of new tumor profiling technologies, and an expanding compendium of targeted cancer therapeutics. We developed a personalized cancer therapy (PCT) program in a clinical setting, using an integrative genomics approach to fully characterize the complexity of each tumor. We carried out whole exome sequencing (WES) and single-nucleotide polymorphism (SNP) microarray genotyping on DNA from tumor and patient-matched normal specimens, as well as RNA sequencing (RNA-Seq) on available frozen specimens, to identify somatic (tumor-specific) mutations, copy number alterations (CNAs), gene expression changes, gene fusions, and also germline variants. To provide high sensitivity in known cancer mutation hotspots, Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2) was also employed. We integr...

Ejc Suppl, 2009

abstr LBA6006) G4 ASCO ABSTRACT First results of a phase III multicenter randomized controlled tr... more abstr LBA6006) G4 ASCO ABSTRACT First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer (PARSPORT: ISRCTN48243537; CRUK/03/005)

Cancer Research, Apr 15, 2006

Biochemistry Usa, 1988

The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liv... more The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 1251-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 1251-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 m M Mg2+ (EC5o = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 1251-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 m M Mg2+ or 5 m M EDTA diminishes receptor affinity for hormone (from KD = 1.2 f 0.1 nM to KD = 2.6 f 0.3 nM) and the fraction of '251-glucagon in high molecular weight receptor-N, complexes without affecting site number (Bmx = 1.8 f 0.1 pmol/mg of protein). Thus, while G T P promotes disaggregation of receptor-N, complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence

Rare Tumors, May 21, 2015

We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extrao... more We report a response to pazopanib in a 69-year-old man with heavily pre-treated metastatic extraosseous Ewing sarcoma in addition to molecular profiling of his tumor. To our knowledge, this case is the earliest to demonstrate activity of an oral multi-targeted kinase inhibitor in Ewing sarcoma. This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371). This national multi-institutional study is ongoing.

Journal of the National Comprehensive Cancer Network Jnccn, Apr 1, 2010

The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly c... more The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at

Asco Meeting Abstracts, May 20, 2014

Asco Meeting Abstracts, May 20, 2012

Annals of Surgical Oncology, Feb 1, 2011

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically prese... more Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically presents with local invasion but rarely metastasizes. We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy. Patients treated for DFSP were identified in a prospectively maintained database. Clinicopathologic factors associated with DFS were analyzed using univariate and multivariate analysis. A total of 244 patients with DFSP were identified. Median follow-up was 50 months. A total of 14 patients had local recurrence (LR), and 2 patients had distant recurrence (DR), with a median time to recurrence of 35 months. At time of last follow-up, 70% and 47% of patients showed no evidence of disease (NED) in the primary (n = 197) and recurrent groups (n = 47), respectively. On univariate analysis, tumor location and depth were associated with DFS in the primary group, while margin status (R1 vs. R0) was associated with DFS in the LR group. On multivariate analysis, only depth (primary group) and margin status (LR group), remained significant. Also, 22 patients had therapy other than surgical resection: 14 radiotherapy, 4 tyrosine kinase inhibitor (TKI) only, 2 conventional chemotherapy only, and 2 chemotherapy plus TKI. Responses to other therapies were variable. DFS after treatment for DFSP is strongly predicted by tumor depth in the primary setting and margin status in recurrent tumors. The treatment for DFSP in the primary or recurrent setting is excision with negative margins, resulting in low recurrence rates and infrequent metastatic spread. Multimodality treatment, especially TKI use, can be effective, but is not curative.