Elisabetta Pennacchioli

Aggressive Surgical Policies in a Retrospectively Reviewed Single-Institution Case Series of Retroperitoneal Soft Tissue Sarcoma Patients

PURPOSE To explore whether the adoption of a systematic attempt to perform wider resections may lead to prognostic improvements in retroperitoneal soft tissue sarcoma (RSTS). PATIENTS AND METHODS Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out. RESULTS Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years. CONCLUSION In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.

Chordoma: Natural History and Results in 28 Patients Treated at a Single Institution

Background: The natural history of chordoma is characterized by a high failure rate and a poor functional outcome. The purpose of this study was to review the long-term outcome of our institutional experience.Methods: The clinical features, type of treatment, pathologic assessment, and follow-up of 56 consecutive patients with chordoma were reviewed.Results: Fifty sacral and six mobile spine chordomas (median size, 13 cm; range, 2–30 cm) were treated at our center between January 1933 and December 2000. Twenty-eight patients affected by sacrococcygeal chordoma and operated on after 1977 form the basis of our study. Surgical margins were rated as wide in 11 cases, marginal in 13 cases, and intralesional in 4 cases. The median follow-up was 71 months (range, 15–200 months). Seventeen patients’ disease recurred. Ten patients died as a result of disease. Nine patients remained continuously free of disease. The estimated 5- and 10-year overall survival was, respectively, 87.8% and 48.9%; disease-free survival was 60.6% and 24.2%. Radiotherapy was considered for marginal and intralesional resections.Conclusions: High sacral amputation can achieve a good rate of wide-margin resections for sacrococcygeal chordomas. Adjuvant radiotherapy may offset the negative effect in the prognosis of marginal resections.

Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution.

Objective.To ascertain whether childhood melanoma presents any peculiar clinical features or differences in prognosis with respect to adults, we retrospectively analyzed the data from 33 patients who were up to 14 years of age and treated for cutaneous melanoma at the Istituto Nazionale Tumori, Milan, over a 25-year period. Methods.Primary lesions were amelanotic in half of the cases and raised in 73%. Lower extremities were the most common primary sites. Histologically, 9 cases were classified as nodular type, and median thickness was 2.5 mm. Nine children had nodal involvement at diagnosis, 2 in-transit metastases, and 1 distant spread. Surgery was the mainstay of treatment; 9 patients underwent lymph node dissection, 3 received chemotherapy, and 2 received radiotherapy. Results.With a median follow-up of 122 months, 5-year event-free survival and overall survival were 60% and 70%, respectively. Age seemed to correlate with survival, event-free survival being 90% in children under 10 and 47% in older patients, although the initial microstaging seemed worse in the former. Conclusion.By comparison with adult cases, childhood melanoma can have a higher percentage of atypical clinical features (amelanotic and raised lesions), nodular histotype, and thick lesions. Although we have no data to support any suggestion of biological differences between young children and adolescents or adults, our findings give the impression that melanoma behaves differently in the younger age group.

Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal stromal tumors (GIST)

AIM To explore the effect of preoperative imatinib mesylate (IM) in patients with unresectable or locally advanced primary gastrointestinal stromal tumor (GIST). METHODS From January 2003 to January 2008, all patients affected by bulky localized GIST who presented at our institution were considered for preoperative IM with cytoreductive intent. Clinical, pathological and molecular characteristics were assessed and the rate of response recorded. Progression-free survival (PFS) was calculated according to Kaplan-Meier analysis. RESULTS Fifteen patients (1 esophageal, 7 gastric, 3 duodenal, 4 rectal GISTs) received preoperative IM for a median of 9 months. All patients had tumor shrinkage, with a median size reduction of 34%. One patient had radiological complete response. In all cases an improvement of the originally planned surgical procedure was obtained: 3 patients initially considered unresectable underwent complete surgery; 7 patients with initial indication for extensive surgery were more conservatively operated on; 4 patients initially deemed at high perioperative risk underwent safe surgery. Due to the small sample size, no association between tumor shrinkage and tumor site, size, IM duration, mutational status and pathological response could be formally explored. PFS at 3 years from IM onset was 77%. CONCLUSIONS In unresectable or locally advanced GISTs, preoperative IM is a useful tool both to improve resectability and reduce surgical morbidity. It should be therefore always be considered before embarking on a major surgical procedure. The long-term impact of IM on PFS and survival is presently under investigation in multicenter prospective randomized trials.

A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-α in metastatic melanoma patients

The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage®) given with GM-CSF and IFN-α in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days –1, 0 and +1, while IFN-α (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-α is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with those recorded in a previous study investigating HSPPC-96 monotherapy.

Immunization of Stage IV Melanoma Patients with Melan-A/MART-1 and gp100 Peptides plus IFN-α Results in the Activation of Specific CD8+ T Cells and Monocyte/Dendritic Cell Precursors

The use of IFN-alpha in clinical oncology has generally been based on the rationale of exploiting its antiproliferative and antiangiogenic activities. However, IFN-alpha also exhibits enhancing effects on T-cell and dendritic cell functions, which may suggest a novel use as a vaccine adjuvant. We have carried out a pilot phase I-II trial to determine the effects of IFN-alpha, administered as an adjuvant of Melan-A/MART-1:26-35(27L) and gp100:209-217(210M) peptides, on immune responses in stage IV melanoma patients. In five of the seven evaluable patients, a consistent enhancement of CD8(+) T cells recognizing modified and native MART-1 and gp100 peptides and MART-1(+)gp100(+) melanoma cells was observed. Moreover, vaccination induced an increase in CD8(+) T-cell binding to HLA tetramers containing the relevant peptides and an increased frequency of CD45RA(+)CCR7(-) (terminally differentiated effectors) and CD45RA(-)CCR7(-) (effector memory) cells. In all patients, treatment augmented significantly the percentage of CD14(+) monocytes and particularly of the CD14(+)CD16(+) cell fraction. An increased expression of CD40 and CD86 costimulatory molecules in monocytes was also observed. Notably, postvaccination monocytes from two of the three patients showing stable disease or long disease-free survival showed an enhanced antigen-presenting cell function and capability to secrete IP10/CXCL10 when tested in mixed leukocyte reaction assays, associated to a boost of antigen and melanoma-specific CD8(+) T cells. Although further clinical studies are needed to show the adjuvant activity of IFN-alpha, the present data represent an important starting point for considering a new clinical use of IFN-alpha and new immunologic end points, potentially predictive of clinical response.

Myxoid/round cell and pleomorphic liposarcomas : Prognostic factors and survival in a series of patients treated at a single institution

The objective of this study was to investigate prognostic factors and clinical outcome of myxoid/round cell and pleomorphic liposarcoma.

Local and intralesional therapy of in-transit melanoma metastases.

Regional relapse of melanoma may occur as satellite or in‐transit metastases proximal to the primary tumor in the direction of the lymph flow. The management of in‐transit metastases is challenging because the efficacy of treatment is largely dictated by the biological behavior of the patients melanoma. This review examines local treatment modalities. J. Surg. Oncol. 2011; 104:391–396.

Epithelioid sarcoma: Prognostic factors and survival in a series of patients treated at a single institution

BackgroundEpithelioid sarcoma (ES) is a rare subtype of soft-tissue sarcoma of unknown histogenesis. Typically, it occurs superficially as single/multiple nodules (nodular ES), or in deeper tissues as a mass. The correlation between initial presentation and clinical outcome was investigated.MethodsFifty-four consecutive patients surgically treated at a single referral center were retrospectively reviewed. Thirty-six patients presented with a primary and 18 with a recurrent tumor. Potential prognostic clinicopathological variables, including macroscopic features at first presentation, were tested by univariable and multivariable analysis with respect to overall (OS), metastasis-free (MFS), and local recurrence-free survival (LRFS).ResultsThe 10-year OS was 61.8% for the whole series. Thirty patients relapsed; in detail, local and distant failure occurred in 14 (25.9%) and 24 (44.4%) patients, respectively. The lymph node involvement rate was 16/54 (29.6%). In both the whole series and the subset of patient with primary ES, single localized tumor correlated with increased OS at multivariable analysis; occurrence of nodal involvement during postoperative follow-up correlated to worse OS and MFS. Nodular ES was an independent predictor of worse LRFS. In univariable analysis, nodular ES was associated with smaller tumor size, distal limb locations, earlier classification of malignant tumor (TNM) stage, and higher amputation rate. A statistical difference in the pattern of failure between nodular and mass ES was found.ConclusionsPrimary tumor macroscopic features seem to correlate to different local aggressiveness and failure patterns. Better prognosis is associated with single localized disease stage and no occurrence of locoregional spread.

Treatment of melanoma metastases in a limb by isolated limb perfusion and isolated limb infusion

In‐transit melanoma metastases are often confined to a limb. In this circumstance, treatment by isolated limb perfusion or isolated limb infusion can be a remarkably effective regional treatment option. J. Surg. Oncol. 2011; 104:397–404.