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The relevance of the initial observational approach for desmoid tumors (DTs) remains unclear. We investigated a new conservative management treatment for primary abdominal wall DTs. Data were collected from 147 patients between 1993 and 2012. The initial therapeutic approaches were categorized as front-line surgery [surgery group (SG), n = 41, 28 %] and initial observation or medical treatment [nonsurgery group (NSG), n = 106, 72 %]. The cumulative incidence of the last strategy modification was estimated using competing risk methods with variable censoring times. Of the 147 patients, 143 were female (97 %). In the SG, 27 patients (66 %) required full-thickness abdominal wall mesh repair. In the NSG, 102 patients (96 %) underwent initial observation and four received medical treatment. In the NSG, the 1- and 3-year incidences of changing to medical treatment (no further changes during the follow-up) were 19 % [95 % confidence interval (CI) 11–28] and 25 % (95 % CI 17–35), respectively, and the 1- and 3-year incidences of a final switch to surgery were 14 % (95 % CI 8–22) and 16 % (95 % CI 9–24), respectively. An initial tumor size of >7 cm was associated with a higher strategy modification risk (p = 0.004). Of the 102 patients initially observed, 29 experienced spontaneous regression over a median follow-up period of 32 months. All second-intent resections were macroscopically completed, with R0 resections achieved in 82 % of patients. This study supports an initial nonsurgical approach to abdominal wall DTs ≤7 cm, followed by surgery based on tumor growth in select cases.

This study was designed to evaluate the impact of multimodal management on a series of epithelioid sarcoma (ES) patients treated with curative intent. Data were collected on 69 consecutive patients treated from 1982 to 2012. Univariate and multivariate analyses were performed for tumor control and overall survival (OS). In total, 54 (78 %) patients had localized ES (M0 group). In the M0 group, 85 % of patients received multimodal management (surgery n = 50, radiotherapy n = 37, chemotherapy n = 30). Among 42 patients with limb ES, 9 (21 %) underwent amputation, and isolated limb perfusion (ILP) was required in 17 (40.5 %) to allow conservative management. Among the 45 patients who underwent conservative surgery, flap reconstructions were required in 13 (28.8 %). The median follow-up was 5.7 years. The 5-year actuarial OS rates were 54, 62, and 24 % in the entire group and the M0 and M1 groups, respectively. In the M0 group, the 5-year actuarial distant control, local control (LC), and locoregional control rates were 67, 75, and 66 %, respectively. Prognostic factors for poor OS in the multivariate analysis were tumors that were deep to the fascia (p = 0.04) and grade 3 (p = 0.005). In the univariate analysis, age

We sought to assess morbidity and mortality in primary retroperitoneal soft tissue sarcomas (RSTS) treated by a frontline aggressive surgical approach.A total of 249 consecutive patients with primary RSTS were treated by a frontline aggressive surgical approach at two major European institutions. Multivariable models were used for exploring the relationship between postsurgical morbidity and the number of organs resected, with adjustment for clinical variables. The impact of morbidity on local and distant recurrence-free survival was explored by multivariable models, adjusting for the main known prognostic factors.Median follow-up was 37 months (interquartile [IQ] range, 16-61 months). Median tumor size was 17 cm (IQ range, 11-26 cm). The median number of organs resected en bloc with the tumor was 2 (IQ range, 1-3). Complete macroscopic resection was achieved in 232 cases (93%). At 5 years, overall survival was 65.4% (95% confidence interval [95% CI], 56.8-72.7); local and distant recurrence crude cumulative incidences were 22.3% (95% CI, 16.5-30.2) and 24.2% (95% CI, 18.4-31.9), respectively. Postsurgical morbidity requiring at least one invasive therapeutic procedure was observed in 45 patients (18%; 95% CI, 14-23). Surgical reintervention was necessary in 30 patients (12%; 95% CI, 8-17). Eight patients died of postoperative complications (3%; 95% CI, 1-6). No statistically significant association between postsurgical morbidity and any clinical variable was detected. For number of resected organs, we documented an increased risk of morbidity for more than three organs (P = 0.007). Postsurgical morbidity did not affect oncologic outcome.Frontline aggressive surgical approach to primary RSTS is safe when carried out at high-volume centers. It could be systematically considered in primary RSTS.

In a prior randomized phase II trial comparing hyperthermic isolated limb perfusion (HILP) with four different doses of tumor necrosis factor alpha (TNF-alpha), no dose effect was detected for response, but systemic toxicity was far lower with low-dose TNF-alpha. The objective of the present study was to confirm these data on a larger sample size of locally advanced or recurrent extremity soft tissue sarcomas with low-dose TNF-alpha.We assessed a prospective database comprising 100 HILP (38-40 degrees C) with melphalan (10 mg/L) and TNF-alpha (1 mg). The remnant tumor was resected 2 months later.Among 52 recurrences, 18 were in a previously irradiated field. Stages according to the American Joint Committee on Cancer classification were II (19 patients), III (78 patients), and IV (3 patients). The site/size were: 30 patients/57 mm and 70 patients/86 mm for the upper and lower limbs, respectively. Tumor grades (FNCLCC) were 1 (23 patients), 2 (34 patients), and 3 (43 patients). Fifty-one patients had received systemic chemotherapy before HILP. Responses on magnetic resonance imaging were 30% complete, 49% partial, 9% no change, and 12% progression. No mortality or systemic toxicity occurred. Local toxicity (Wieberdink) attained grade 2 (16 patients), 3 (5 patients), and 4 (1 patient). Limbs were able to be saved in 87% patients. Three-year overall survival and the local recurrence rate were 89% and 18%, respectively. Age, sex, tumor size, recurrence, uni- or multifocality, grade, preoperative chemotherapy, and a previously irradiated field were not predictive of response or local toxicity.We confirm that 1 mg of TNF-alpha is as effective as the standard dose and results in no systemic toxicity.

Surgery is still the standard treatment for desmoid-type fibromatosis (DF). Recently, the Institut Gustave Roussy (IGR), Villejuif, France, reported a series of patients treated with a front-line conservative approach (no surgery and no radiotherapy). The disease remained stable in more than half of patients. This study was designed to evaluate this approach on the natural history of the disease in a larger series of patients.A total of 142 patients presenting to the IGR or Istituto Nazionale Tumori (INT), Milan, Italy, were initially treated using a front-line deliberately conservative policy. Their progression-free survival (PFS) was observed and a multivariate analysis was performed for major clinical variables.Seventy-four patients presented with primary tumor, 68 with recurrence. Eighty-three patients received a "waitsee" policy (WS), whereas 59 were initially offered medical therapy (MT), mainly hormonal therapy and chemotherapy. A family history of sporadic colorectal cancer was present in 8% of patients. The 5-year PFS was 49.9% for the WS group and 58.6% for the medically treated patients (P = 0.3196). Similar results emerged for primary and recurrent DF. Multivariate analysis identified no clinical variables as independent predictors of PFS. In the event of progression, all patients were subsequently managed safely.A conservative policy could be a safe approach to primary and recurrent DF, which could avoid unnecessary morbidity from surgery and/or radiation therapy. Half of patients had medium-term stable disease after WS or MT. A multidisciplinary, stepwise approach should be prospectively tested in DF.

The objective of this study was to evaluate the adequate margin in the local treatment of extremity soft tissue sarcomas (ESTS) and understand the relationship between local control and overall survival (OS).All consecutive patients treated for a primary ESTS at a single center from 1993 to 2012 were reviewed.In all, 531 patients were included. Twelve (2 %) underwent a first-line amputation. The resections were R0/R1/not available in 434 (82 %), 92 (17 %), and 5 patients (1 %). The median tumor size was 8 cm, and the tumor grades were 1 (n = 132), 2 (n = 201), and 3 (n = 195). The median size of the minimal margin was 2 mm on fixed specimen. Preop or postop chemotherapy was administered to 222 patients, and 414 received radiotherapy. With a median follow-up period of 7 years, the 5-year actuarial local recurrence (LR) rate and OS were 8 % (95 % CI, 6-11 %) and 80 % (95 % CI, 76-83 %). Predictors of worse OS were grade 3, leiomyosarcoma, male gender, and age60 years, whereas tumor size, margin status, and LR were not. Among patients requiring re-excision (n = 252), the presence of residual cells correlated with OS but not LR. After preoperative treatment, a percentage of residual cells ≥10 % correlated with OS but not LR. In the multivariate analysis, specific subtypes (epithelioid sarcoma and myxofibrosarcoma) and margin size1 mm correlated with LR, whereas grade and the tissue constituting the surgical margins did not.Specific subtypes and surgical margin size1 mm were correlated with a higher LR. Neither the margin status nor LR affect OS.

To explore patterns of failure and postrelapse outcome of patients with retroperitoneal sarcoma primarily treated by extended resection. All consecutive patients with primary retroperitoneal sarcoma, treated between January 2002 and December 2011 at two European sarcoma centers were included. Five-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastases (DM) were calculated. Multivariate analyses for OS and CCI of LR and DM were performed. Postrelapse OS was investigated. A total of 377 patients were identified. Median follow-up from the time of primary surgery was 44 months [interquartile range (IQR) 27–82]. Five-year OS was 64 % [95 % confidence interval (CI) 0.588, 0710]. CCI of LR and DM were 23.6 % (95 % CI 18.9, 29.4) and 21.9 % (95 % CI 17.6, 27.3), respectively. OS, CCI of LR and DM were 87, 18 % and 0 for well-differentiated liposarcoma; 54, 44 and 9 % for grade II dedifferentiated liposarcoma; 41,33, and 44 % for grade III dedifferentiated liposarcoma; 58, 5, and 55 % for leiomyosarcoma; and 85, 4, and 17 % for solitary fibrous tumor, respectively. Seventy-six patients developed LR. Median postrelapse follow-up was 27 months (IQR 10–58). Twenty-one patients (27 %) underwent a second surgical resection (complete in 18), while 55 (73 %) did not (22 multifocal, 17 inoperable, 16 other causes). Median postrelapse OS was 17 months (IQR 7–31). Well-differentiated liposarcoma histology and disease-free interval predicted postrelapse OS, while surgical resection did not. When primary extended surgery limits LR, histologic subtype and grade determine the outcome. At recurrence, a second surgery is of limited benefit.

Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd-line sunitinib are limited.Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed.The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.5%), sorafenib n = 55 (24.5%), and imatinib n = 40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd-line treatment were 3.6 months [95% confidence interval (95% CI), 3.1-4.1] and 9.2 months (95% CI, 7.5-10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC.In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib.