Prognosis of Patients with Cutaneous Angiosarcoma After Surgical Resection with Curative Intent: Is There a Difference Between the Subtypes?

BACKGROUND: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes. PATIENTS AND METHODS: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS). RESULTS: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57-76 years), the median tumor size was 4.4 cm (IQR 2.5-7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12-60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373-0.840, p = 0.005 and HR 0.421, 95% CI 0.225-0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939-14.318 p < 0.001). CONCLUSION: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates.

Frailty in Very Elderly Patients is Not Associated with Adverse Surgical or Oncological Outcomes in Extremity Surgery for Soft Tissue Sarcoma.

BACKGROUND: While surgery remains the mainstay of treatment for limb sarcoma, extreme old age is a relative contraindication to oncological surgery. METHODS: Patients >80 years referred with primary extremity soft-tissue sarcoma (ESTS) between 2007 and 2016 were retrospectively reviewed. Prognostic variables, including ASA status and Clinical Frailty Scores, were collected. Endpoints were perioperative morbidity, locoregional (LRR) and distant recurrence (DR), disease-specific survival (DSS) adjusted using competing risk modelling, and overall survival (OS). RESULTS: A total of 141 primary tumours were identified, with 116 undergoing resections. Main motives for nonoperative management were severe frailty or significant comorbidity (56.0%). The operative group had a median age of 84 (range 80-96) years and median follow-up of 16 months (range 0-95). 45.7% of patients received radiotherapy. Median hospital stay was 7 (range 0-40) days, with frailty (p = 0.25) and ASA (p = 0.28) not associated with prolonged admission. 12.9% developed significant complications, with one perioperative mortality. 24.1% had LRR, occurring at a median of 14.5 months. All patients with reported DR (28.4%), except one, died of their disease. Frailty did not confer a significant difference in adjusted LRFS (p = 0.95) and DMFS (p = 0.84). One- and 5-year adjusted DSS and OS was 87.0% versus 74.9% and 62.3% versus 27.4%, respectively. Frailty (CFS ≥4) was associated with worse OS (hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.51-4.12; p < 0.001), however not with adjusted DSS (p = 0.16). Nonoperative management conferred a 1- and 5-year adjusted DSS was 58.3% and 44.4%, respectively. CONCLUSIONS: Extremity surgery for sarcoma is well tolerated in the frail very elderly population with low morbidity and comparable oncological outcomes.

Oncological Outcome After Diagnostic Biopsies in Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

OBJECTIVE: To analyze whether the route of preoperative biopsy influences oncological outcome in GIST patients. SUMMARY OF BACKGROUND DATA: Preoperative biopsies are widely used for diagnosing GIST. Little is known about the risk of tumor seeding after different routes of biopsy. METHODS: Patients who underwent resection of a primary GIST between 1996 and 2014 were identified from 2 databases from 2 tertiary referral centers. Survival data were obtained using the Kaplan-Meier method. Possible confounders were identified using Cox regression analysis. The primary endpoint was local recurrence free survival (RFS) and the secondary endpoint was DSS. RESULTS: A total of 228 patients were included, with a median age of 62 years (range 17-86) and a median follow-up time of 53 months (range 1-204). From these patients, 42 patients did not have a biopsy (18%), 70 underwent a transcutaneous biopsy (31%), and 116 a transluminal biopsy (51%). A total of 42 patients (19.0%) had a local and/or distant recurrence. From the 70 patients with a transcutaneous biopsy, only 1 patient developed a needle tract recurrence (1.4%). Local RFS and DSS were both significantly shorter in the transcutaneous biopsy group on univariate analysis compared to the other groups; however, in multivariate analysis the route of biopsy did not influence local RFS (P = 0.128) or DSS (P = 0.096). CONCLUSIONS: Transluminal or transcutaneous biopsies for diagnosing GIST do not significantly alter the risk of local recurrent disease or DSS in multivariate Cox regressions. The risk of needle tract seeding after transcutaneous biopsy was low.

Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website.

Less is more: A systematic review and meta-analysis of the outcomes of radical versus conservative primary resection in anorectal melanoma.

INTRODUCTION: Anorectal melanoma (ARM) is a rare disease with a poor prognosis. There is no consensus as to the optimal primary surgical treatment for ARM, with advocates for both radical (abdominoperineal resection [APR]) and conservative strategies (wide local excision [WLE]). Here, we report a systematic review of studies comparing outcomes between these strategies. METHODS: Studies comparing APR with WLE in patients with ARM were included, and a systematic review using the Grading of Recommendations, Assessment, Development and Evaluation methodology was performed. Outcomes deemed critical included overall survival, disease-free survival, local recurrence and quality of life. RESULTS: Forty studies were identified, of which 27 were suitable for inclusion. Twenty-three studies compared overall survival between WLE and APR, with no difference in outcomes noted (risk ratio [RR]: 0.80, 95% confidence interval [CI]: 0.60-1.07, p = 0.13). Seven studies compared disease-free survival, with no difference in outcomes noted (RR: 1.08, 95% CI: 0.61-1.91, p = 0.79). A total of 19 studies compared local recurrence rates, with again no significant difference in outcomes noted (RR: 0.71, 95% CI: 0.44-1.14, p = 0.16). None of the studies identified reported quality of life-related outcomes. CONCLUSION: There is no evidence to suggest that a radical primary surgical strategy improves outcomes in ARM. Therefore, given the well-documented morbidity associated with APR, WLE with regular surveillance for local recurrence should be the primary strategy in most patients.

Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance.

BACKGROUND: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. METHODS: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. RESULTS: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). CONCLUSIONS: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

Incidental Metastatic Melanoma Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer.

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.

Major Amputations for Extremity Soft-Tissue Sarcoma.

INTRODUCTION: With modern techniques facilitating limb conservation, amputation for extremity soft-tissue sarcoma (ESTS) is now rare. We sought to determine the indications and outcomes following major amputation for ESTS and whether amputation is prognostic of oncological outcomes in primary disease. PATIENTS AND METHODS: Patients undergoing major amputations for ESTS from 2004 to 2014 were identified from electronic patient records. RESULTS: The amputation rate in primary localized disease was 4.1%. Overall, 69 patients were identified, including 23 (33.3%) amputations for primary localized disease, 36 (52.2%) amputations for recurrent disease, and 10 (14.5%) amputations for metastatic disease. The local recurrence rate for localized disease at 3 years was 10.4%. Three-year overall survival (OS) was 50.3% following curative amputation, with a median survival of 41 months, and median OS following palliative amputation was 6 months. In the context of primary, localized disease, patients undergoing amputation had a greater proportion of high-grade tumors (69.6% vs. 41.1%; p = 0.009) of greater size (median 16.0 vs. 9.0 cm; p = 0.003) when compared with patients undergoing limb-conserving surgery. The rates of systemic relapse and disease-specific survival were poorer following amputation compared with limb-conserving surgery, however mode of surgery (amputation vs. limb conservation) was only prognostic for OS. CONCLUSIONS: Amputation maintains an important role in ESTS and achieves durable local control in those unsuitable for limb-conserving surgery. Survival following amputation in the presence of metastatic disease is poor and should be reserved for patients with significant symptoms.

Selective marginal resections in the management of aggressive angiomyxomas.

AIM: Aggressive angiomyxomas (AA) are rare tumors, most commonly presenting in the pelvis of women of childbearing age. This study presents the results of selective marginal resection of this disease in patients managed at a single institution. METHODS: Patients diagnosed with AA from July 2001 to July 2015 were identified from a prospectively maintained histopathology database. RESULTS: Seventeen patients were diagnosed with AA in the study period. The median age at diagnosis was 48 years. Females were more commonly affected with a M:F of 1:8.5. The most common differential diagnoses were an ischiorectal abscess or Bartholin's cyst. Fifteen cases occurred in the pelvis, with two cases at other sites. Median maximum tumor diameter was 10 cm. Of the pelvic cases, 12 were managed operatively via perineal, abdominal, or abdominoperineal approaches. Excision was performed in a marginal fashion with minimal morbidity. Local recurrence developed in 58.3% with a median local recurrence free survival of 25 months. No patients developed metastatic disease or died from disease. CONCLUSION: AA are rare tumors with a propensity for local recurrence. Atypical presentations of other perineal pathologies should prompt further investigation. Surgery should be reserved for symptomatic patients and is associated with low rates of morbidity. J. Surg. Oncol. 2016;114:828-832. © 2016 2016 Wiley Periodicals, Inc.

Combined management of retroperitoneal sarcoma with dose intensification radiotherapy and resection: long-term results of a prospective trial.

BACKGROUND: Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS. METHODS: From June 1996 to October 2000, eligible patients with resectable RPS were entered onto a phase II trial of preoperative XRT (45-50 Gray) plus postoperative BT (20-25 Gray). Kaplan Meier survival curves were constructed and compared by log rank analysis (SPSS 21.0). RESULTS: All 40 patients had preoperative XRT and total gross resection as part of the prospective trial, nineteen received BT (48%). Median follow-up was 106 months. For the entire cohort, OS at 5 and 10 years was 70% and 64%, respectively; RFS at 5 and 10 years was 69% and 63%. RFS was significantly reduced in high versus low grade RPS at 5 years (53% vs. 88%, p=0.016), but not at 10 years (53% vs. 75%, p=0.079). RFS and OS at 10 years were reduced in patients who presented with recurrent compared to primary disease (RFS 30% vs. 74%, p=0.015; OS 36% vs. 76%, p=0.036). At 10 years, neither RFS nor OS was improved in patients who received BT compared to those who did not (RFS 56% vs. 69%, p=0.54; OS 52% vs.76%, p=0.23). CONCLUSIONS: In this prospective trial with mature follow-up, long-term OS and RFS in patients who underwent combined preoperative XRT plus resection of RPS compare favourably with those reported in retrospective institutional and population-based series. Postoperative BT was associated with unacceptable toxicity and did not contribute to disease control. CONDENSED ABSTRACT: In a prospective trial with mature follow-up, preoperative radiation combined with complete resection of retroperitoneal sarcoma resulted in favourable long-term RFS and OS compared to historical controls. Dose escalation with postoperative brachytherapy was not associated with better disease control.

Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemy.

Tumor removal remains the principal treatment modality in the management of solid tumors. The process of tumor removal may potentiate the resurgent growth of residual neoplastic tissue. Herein, we describe a novel murine model in which flank tumor cytoreduction is followed by accelerated local tumor recurrence. This model held for primary and recurrent tumors generated using a panel of human and murine (LS174T, DU145, SW480, SW640, and 3LL) cell lines and replicated accelerated tumor growth following excisional surgery. In investigating this further, epithelial cells were purified from LS174T primary and corresponding recurrent tumors for comparison. Baseline as well as tumor necrosis factor apoptosis-inducing ligand (TRAIL)-induced apoptosis were significantly reduced in recurrent tumor epithelia. Primary and recurrent tumor gene expression profiles were then compared. This identified an increase and reduction in the expression of p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits in recurrent tumor epithelia. These changes were further confirmed at the protein level. The targeting of PI3K ex vivo, using LY294002, restored sensitivity to TRAIL in recurrent tumor epithelia. In vivo, adjuvant LY294002 prolonged survival and significantly attenuated recurrent tumor growth by greatly enhancing apoptosis levels. Hence, PI3K plays a role in generating the antiapoptotic and chemoresistant phenotype associated with accelerated local tumor recurrence.