Des Centres De Lutte Contre Research Articles

How Long Should We Follow Patients With Soft Tissue Sarcomas?

Guidelines suggest that followup for low-grade soft tissue sarcomas should be every 3 to 6 months for 2 to 3 years and then annually, and for high-grade sarcomas every 3 to 6 months for 2 to 5 years, then every 6 months for the next 2 years, and then annually. However, there is only very limited evidence to support these strategies. In a population of patients treated surgically for soft tissue sarcomas, we evaluated the (1) timing of diagnosis of local recurrences after sarcoma excision; (2) timing of diagnosis of distant metastases; and (3) the difference in those parameters based on tumor size and grade. Patients diagnosed with soft tissue sarcomas and who underwent surgical excision between 1978 and 2008 were retrospectively reviewed. Age, histologic diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, tumor location, and size were reviewed at a mean of 6 years (range, 1 month to 30 years). We met with patients every 3 months for 5 years, every 6 months for 10 years, and then annually until 15 years after surgery. Eight hundred sixty-seven patients with a median age at diagnosis of 52 years were eligible for analysis. The incidence of local recurrence and metastases was calculated for every 2-year period and presented per 1000 person-years. Ninety-eight patients (11%) developed local recurrence at a median time of 19 months; 90% of patients who had local recurrences had them within 7.1 years, and 95% occurred by 8.6 years. One hundred ninety-eight patients (23%) developed distant metastases at a median time of 12 months; 90% of patients who developed metastases developed them by 4.2 years and 95% did so by 7.3 years. High-grade tumors had a higher incidence of local recurrence and metastases in first 2 years, whereas low-grade tumors recurred at a constant rate throughout the followup period. Followup beyond 10 years does not yield a sufficient number of local recurrences or metastases to warrant further monitoring. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Prognostic Factors and Outcomes of Patients with Myxofibrosarcoma

Myxofibrosarcomas (MFS) are a historically heterogeneous group of tumors that exhibit a propensity for local recurrence. The objectives of this study were to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. We retrospectively reviewed the records of 69 consecutive patients with pathologically confirmed MFS of the extremities or superficial trunk who underwent surgery from August 1995 to November 2010. Clinicopathologic features, treatments, and patient outcomes were reviewed. Sixty-nine patients were identified, of whom 38 were men (55%). The median age was 62 years. Sixty-four patients (93%) presented with primary tumors, and 5 patients (7%) presented with locally recurrent tumors. Median tumor size was 6.0 cm, and 44 patients (64%) had grade 3 tumors (FNCLCC [Fédération Nationale des Centres de Lutte Contre le Cancer] classification). Margins were microscopically positive in 14 patients (20%) and negative in 55 patients (80%), including close margins (<1 mm) in 14 patients (20%). Fifty-three patients (77%) received radiotherapy. At a median follow-up of 41 months, there were 11 local (16%) and 11 distant (16%) recurrences. The local and distant 5-year recurrence-free survival rates were 72% and 82%, and the 5-year overall survival was 61%. Increased age (scaled by 0.1; hazard ratio [HR] 1.80, P=0.002) and tumor size (HR 1.12, P=0.004) were negatively correlated with overall survival. Positive/close (<1 mm) margin status (HR 4.34, P=0.030) predicted worsened local recurrence-free survival. MFS exhibit a propensity for local recurrence, which is predicted by resection with positive or close margins. Aggressive surgery combined with radiotherapy may contribute to more effective local control.

Chemotherapy Definitions and Policies for Thymic Malignancies

Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat.1 Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection, which is the mainstay of the curative-intent treatment.1 However, approximately 30% of patients present with an advanced tumor at the time of diagnosis, with invasion of neighboring organs, dissemination to the pleura, the pericardium, or less frequently extrathoracic organs. In such cases, chemotherapy has been used both to reduce the tumor burden—possibly allowing subsequent surgery or radiotherapy—and to achieve prolonged disease control. Recurrence after resection may be similarly treated with chemotherapy. Thymic carcinomas, although rare, are usually already advanced at the time of presentation, and systemic therapy is important for almost all of these patients. Knowledge regarding chemotherapy for thymic tumors has mainly been based on retrospective series,2–9 although several prospective trials have also been conducted.10–21 These studies have clearly demonstrated the chemosensitivity of thymoma, and to a lesser extent thymic carcinoma, to various cytotoxic agents and combinations. However, details of patient selection are often lacking (either disease extent or general condition), and the intent of the treatment sequence is often vague. Adoption of a common language and definition of terms is crucial for the International Thymic Malignancies Interest Group (ITMIG) effort to develop a international prospective database of thymic tumors. The article by Huang et al.22 provides definitions for survival and endpoints for recurrences assessment and discusses how to measure response to treatment. Herein, we discuss additional points with regard to chemotherapy, including treatment sequence, general modalities, and impact of corticosteroids.

Significance of Microscopic Margin Status in Completely Resected Retroperitoneal Sarcoma

We determined whether microscopic margin status is an independent prognosticator in patients who underwent complete resection of retroperitoneal sarcoma. A total of 99 patients with a median age of 55.4 years (range 26.0 to 81.9) underwent complete surgical resection for primary (79) or recurrent (20) retroperitoneal sarcoma between September 1990 and January 2010. Median followup was 36.0 months (range 1.0 to 221.1). Microscopic involvement of the margins was detected in 24 patients and local recurrence developed in 69 (69.7%). Univariate analysis showed that pain, recurrent disease and higher Fédération Nationale des Centres de Lutte Contre le Cancer grade were associated with an increased risk of local recurrence. On multivariate Cox analysis presenting symptoms and grade were significantly associated with local recurrence-free survival, including pain vs other symptoms (HR 1.7, p = 0.035) and grade 3 vs 1 (HR 2.4, p = 0.028). A total of 25 patients (25.3%) died of retroperitoneal sarcoma. Histological subtype, grade and tumor margin status were prognostic for disease specific survival. Cox regression analysis revealed that certain factors were significantly associated with disease specific survival, including other sarcomas vs liposarcoma (HR 2.8, p = 0.030) and positive vs negative margins (HR 3.4, p = 0.005). Although complete surgical resection is possible in patients with retroperitoneal sarcoma, the procedure is associated with a high recurrence rate even in patients with negative margins. Microscopically clear margins reliably predict disease specific survival but not local control.

Atypical Intradermal Smooth Muscle Neoplasms

Atypical or mitotically active dermal smooth muscle neoplasms are uncommon lesions, which are most often termed "cutaneous leiomyosarcoma," although preexisting-mostly small-series suggest a low risk of aggressive behavior. To further investigate these tumors, 84 cases from consultation and institutional files were analyzed for pathologic and clinical characteristics. There was a striking male-to-female preponderance (4.3:1), with a mean age of 56 years (range, 6 to 82y). Nine patients had a history of malignancies (6 of the skin). Tumors measured 1.3 cm on average and were predominantly located on the trunk (32) and lower extremities (30). Histologically, all tumors were confined to the dermis or showed only very superficial, focal subcutaneous extension. The majority showed an infiltrative growth pattern with fascicles of atypical eosinophilic spindle cells ramifying between dermal collagen fibers. Primary tumors showed a mean mitotic rate of 4.7/10 high-power fields. By the Fédération Nationale des Centres de Lutte Contre le Cancer grading system, 97% of primary tumors were grade I lesions, with only 3% showing necrosis. All tumors were immunopositive for smooth muscle actin; 98% expressed desmin, 90% caldesmon, and 45% pankeratin (usually focal). Follow-up in 52 cases (mean, 51 mo) showed no metastases or tumor-related deaths. Eighteen tumors showed local recurrence at a mean interval of 43 months; 12 of the recurrent lesions showed positive margins in the primary excision and 1 showed margins <0.2 cm. Margin status was not available for the other 5 cases, which recurred locally. Recurrent tumors showed, on average, 13.7 mitoses/10 high-power fields. Of recurrences, 47% were grade I lesions, 35% were grade II, and 18% were grade III, and 28% showed necrosis. The primary excision of tumors, which later recurred, showed no difference in grade, presence of necrosis, or mitotic rate, compared with those that did not recur; there were no discernible clinical differences either. In summary, these tumors, when confined to the dermis or showing only minimal subcutaneous involvement, seem to carry no evident risk of metastasis; hence, the designation "sarcoma" is inappropriate. Margin status is the most important predictor of recurrence. On excision with clear margins, the risk of local recurrence is very low. Hence, we propose the term "atypical intradermal smooth muscle neoplasm" as being more appropriate.

Localized Resectable Genitourinary Sarcoma in Adult Korean Patients: Experiences at a Single Center

PurposeTo evaluate the clinicopathological characteristics and prognosis of localized resectable genitourinary sarcomas in adults.Materials and MethodsBetween September, 1996 and November, 2008, 18 consecutive cases of adults (12 men and 6 women; median age 48.8 years) who were treated for primary genitourinary sarcomas were identified. The following variables were analyzed: patient age, gender, body mass index, American Society of Anesthesiologists (ASA) score, primary organ, tumor histology, size, necrosis, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, and surgical margin positivity. Recurrence-free survival and disease-specific survival were the study end-points.ResultsThe most common presenting symptom was a palpable mass (six cases, 33.3%), the most common site was the kidney (six cases, 33.3%), and the most common histological subtype was leiomyosarcoma (eight patients, 44.4%). Complete resection with negative surgical margins was achieved in 13 patients (72.2%). The median follow-up period was 49.9 months (range 6.4 to 147.6). The recurrence-free survival rates at 1, 3, and 5 years were 81.6%, 66.5%, and 66.5%, respectively. Recurrence-free survival only associated significantly with ASA score (p=0.018). The disease-specific survival rate at 1, 3, and 5 years was 88.9%, 76.2%, and 67.7%, respectively. Disease-specific survival was associated significantly only with FNCLCC grade (p=0.042).ConclusionAlthough genitourinary sarcomas in adults are a rare group of tumors with a poor prognosis, some patients may have a favorable prognosis. Our findings suggest that FNCLCC grade is the most important prognostic factor for these patients.

Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database

BackgroundThe predictive value of grade for benefit from adjuvant chemotherapy (AC) in soft tissue sarcoma (STS) patients has never been explored. Patients and methodsFrom 1980 to 1999, 1513 adult patients with non-metastatic STS were included prospectively in the French Sarcoma Group database. Grade was assessed according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system after central review. ResultsAC was delivered to 13 grade 1 patients (3%), 145 grade 2 patients (35%) and 262 grade 3 patients (62%). Young age, non-well-differentiated liposarcoma histology, deep location, bone and/or neurovascular invasion and grade 2 or 3 were significantly associated with a higher likelihood to receive AC. Median follow-up was 9 years. On multivariate analysis, AC was significantly associated with improved metastasis-free survival (MFS) [5-year MFS: 58% versus 49%, hazard ratio (HR) 0.7 (95% confidence interval (CI) 0.6–0.9), P = 0.01] and overall survival (OS) [5-year OS: 58% versus 45%, HR 0.6 (95% CI 0.5–0.8), P = 0.0002] in grade 3 patients. This was not observed in grade 2 patients [5-year MFS: 76% versus 73%, HR 0.8 (95% CI 0.5–1.2), P = 0.27; 5-year OS: 75% versus 65%, HR 0.8 (95% CI 0.6–1.1), P = 0.15]. ConclusionsThis large cohort-based analysis with long-term follow-up indicates that patients with FNCLCC grade 3 disease may benefit from AC.

Initial McGill Experience with Fluorodeoxyglucose pet/ct Staging of Soft-Tissue Sarcoma

Soft-tissue sarcoma spreads predominantly to the lung. The frequency with which positron-emission tomography (pet) detects metastases not already obvious by chest computed tomography (ct) or clinical examination is currently unclear. We retrospectively identified cases of soft-tissue sarcoma. Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumour were excluded, as were cases in which patients underwent imaging for follow-up, response assessment, or recurrence. Patients all had undergone diagnostic chest ct as part of their staging. Directed studies were requested to follow up on abnormal findings in the clinical history or physical examination. All charts and pre-treatment imaging were reviewed retrospectively. From 2004 to 2008, 75 patients met the criteria for the present review. Their median age was 51 years. In 21% of cases, the primary tumour had been removed (by excisional biopsy or unplanned excision) before staging. Of the previously unresected primary tumours, 97% were avid for fluorodeoxyglucose. Of all tumours, 81% were intermediate or high grade (Fédération Nationale des Centres de Lutte Contre le Cancer grades 2-3). The primary tumour was stage T2b in 69% of cases. The most common primary site was a lower extremity (55%). The most common pathologic diagnoses were leiomyosarcoma (21%), liposarcoma (19%), and synovial sarcoma (17%). At the end of staging, 17% of patients were considered to have metastatic disease. Imaging by pet was negative for distant disease in 64 of the 75 cases. In 7 of the 64 cases, metastatic disease was evident on chest ct (negative predictive value: 88%). Imaging by pet was positive in 8 cases, with 5 of those already known to have metastases, 2 having pathologically proven false positives, and 1 being a new finding of a pulmonary metastasis (positive predictive value: 75%). The pet imaging was indeterminate in 3 patients (none of whom subsequently developed metastatic disease). Two incidental benign parotid tumours were found. Overall, only 1 patient was upstaged as a result of pet imaging (1.3%). In addition, pet did not alter the management of patients already know to have M1 disease (no new organ sites identified). Although pet may be helpful in specific circumstances, routine use of fluorodeoxyglucose pet imaging for detection of metastatic disease as part of the initial staging of soft-tissue sarcoma added little to imaging by chest ct and was unlikely to alter management in our series.

A new method for predicting metastasis in sarcomas

Treatment decisions for soft-tissue sarcomas are dependent on a number of factors, including tumor size, location, grade, and stage. Histological grading has been considered the best predictor of metastasis-free survival and the Federation Nacionale des Centres de Lutte Contre le Cancer (FNCLCC) grading system—defined over 20 years ago—is the most commonly used method.

Leiomyosarcoma of the urinary bladder: a clinicopathological study of 34 cases

BackgroundLeiomyosarcomas of the urinary bladder (LMS-UB) are rare, usually aggressive neoplasms. Owing to their rarity, only a limited number of cases with clinical follow-up information have been published. There is...

Correlation Between Glycolytic Phenotype and Tumor Grade in Soft-Tissue Sarcomas by 18F-FDG PET

Tumor glycolytic phenotyping can be accomplished with (18)F-FDG PET. Tumor (18)F-FDG uptake correlates with tumor grade in several cancers. However, the role of (18)F-FDG PET for the grading of soft-tissue sarcomas (STSs) warrants further research. One hundred two patients (48 men and 54 women; mean age +/- SD, 50 +/- 17 y) with 12 STS subtypes underwent (18)F-FDG PET/CT before treatment. Tumor (18)F-FDG uptake, expressed as maximum standardized uptake value (SUVmax), was compared among subtypes and correlated with histopathologic grade. Two frequently used sarcoma grading systems--the 3-tier system of the French Federation of Cancer Centers Sarcoma Group (Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC]) and a 2-tier system (low grade vs. high grade)--were used. More than 90% of STSs (93/102) exhibited a strong glycolytic phenotype (SUVmax, 2.7-52.2 g/mL). Tumor SUVmax differed significantly among tumor grades (P < 0.001 for the 3- and 2-tier grading systems). The FNCLCC and 2-tier grading systems predicted tumor grade with similar accuracy (area under the curve, 0.83 and 0.85, respectively; P = 0.35). SUVmax differed significantly among histologic subtypes (P = 0.03) in the entire population but not when high-grade STSs were analyzed separately (P = 0.31). The tumor glycolytic phenotype correlated significantly with histologic grade as determined by both the FNCLCC and 2-tier (high vs. low) grading systems. (18)F-FDG PET cannot be used to reliably distinguish among grade 2 and 3 STSs (by FNCLCC) and the various subtypes.

Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity

Sarcomas are heterogeneous and aggressive mesenchymal tumors. Histological grading has so far been the best predictor for metastasis-free survival, but it has several limitations, such as moderate reproducibility and poor prognostic value for some histological types. To improve patient grading, we performed genomic and expression profiling in a training set of 183 sarcomas and established a prognostic gene expression signature, complexity index in sarcomas (CINSARC), composed of 67 genes related to mitosis and chromosome management. In a multivariate analysis, CINSARC predicts metastasis outcome in the training set and in an independent 127 sarcomas validation set. It is superior to the Fédération Francaise des Centres de Lutte Contre le Cancer grading system in determining metastatic outcome for sarcoma patients. Furthermore, it also predicts outcome for gastrointestinal stromal tumors (GISTs), breast carcinomas and lymphomas. Application of the signature will permit more selective use of adjuvant therapies for people with sarcomas, leading to decreased iatrogenic morbidity and improved outcomes for such individuals.

Leiomyosarcoma of the Inferior Vena Cava: Clinicopathologic Study of 40 Cases

This report details the clinicopathologic features and follow-up data on 40 cases of inferior vena cava leiomyosarcoma, a rare sarcoma with a poor prognosis. Study cohort consisted of 31 females and 9 males (mean age, 53 y), whose material was accessioned to the Armed Forces Institute of Pathology between 1976 and 2008. Inferior vena cava leiomyosarcomas ranged in size from 3.5 to 15.0 (median, 8.5) cms, and most involved the middle segment of the vessel and grew extraluminally. Eleven leiomyosarcomas were French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histologic grade I; 21, grade II; and 5 were grade III. Eleven of 33 patients managed by complete or radical resection had involved surgical margins. Twenty of the 34 patients (59%) with clinical follow-up data (mean, 33.5; median, 51 mo) died of sarcoma-related complications and 9 (26%) of unknown causes. The 5-year and 10-year survival rates after resection without documented residual macroscopic disease were 50% and 22%, respectively. Two patients are alive without disease 9 and 18 years after last surgical intervention. Suprahepatic vena caval and right atrial involvement by tumor, predominant intraluminal tumor growth, and residual postsurgical macroscopic disease were factors that statistically correlate with death within 2 years. By univariate analysis, intraluminal tumor (P=0.03), liver injury or failure (compromised liver) (P=0.01), and moderate to poor tumor differentiation (P=0.03) were associated with increased tumor-related mortality, whereas a compromised liver (P=0.01) was the only factor correlated with mortality by multivariate analysis. Our study concludes that a macroscopic resection of localized inferior vena cava leiomyosarcoma provides the best chance for long-term survival, suprahepatic tumors often result in early death, and a compromised liver correlates with overall poor survival, but French Federation Nationale des Centres de Lutte Contre le Cancer grading does not affect prognosis.

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study

The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy. Patients were recruited to the trial between July 21, 1997, and November 30, 2006, at nine centres in Europe and North America. Patients with localised high-risk STS (> or = 5 cm, Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep to the fascia) were randomly assigned to receive either neo-adjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin (EIA) alone, or combined with regional hyperthermia (EIA plus regional hyperthermia) in addition to local therapy. Local progression-free survival (LPFS) was the primary endpoint. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT 00003052. 341 patients were enrolled, with 169 randomly assigned to EIA plus regional hyperthermia and 172 to EIA alone. All patients were included in the analysis of the primary endpoint, and 332 patients who received at least one cycle of chemotherapy were included in the safety analysis. After a median follow-up of 34 months (IQR 20-67), 132 patients had local progression (56 EIA plus regional hyperthermia vs 76 EIA). Patients were more likely to experience local progression or death in the EIA-alone group compared with the EIA plus regional hyperthermia group (relative hazard [RH] 0.58, 95% CI 0.41-0.83; p=0.003), with an absolute difference in LPFS at 2 years of 15% (95% CI 6-26; 76% EIA plus regional hyperthermia vs 61% EIA). For disease-free survival the relative hazard was 0.70 (95% CI 0.54-0.92, p=0.011) for EIA plus regional hyperthermia compared with EIA alone. The treatment response rate in the group that received regional hyperthermia was 28.8%, compared with 12.7% in the group who received chemotherapy alone (p=0.002). In a pre-specified per-protocol analysis of patients who completed EIA plus regional hyperthermia induction therapy compared with those who completed EIA alone, overall survival was better in the combined therapy group (HR 0.66, 95% CI 0.45-0.98, p=0.038). Leucopenia (grade 3 or 4) was more frequent in the EIA plus regional hyperthermia group compared with the EIA-alone group (128 of 165 vs 106 of 167, p=0.005). Hyperthermia-related adverse events were pain, bolus pressure, and skin burn, which were mild to moderate in 66 (40.5%), 43 (26.4%), and 29 patients (17.8%), and severe in seven (4.3%), eight (4.9%), and one patient (0.6%), respectively. Two deaths were attributable to treatment in the combined treatment group, and one death was attributable to treatment in the EIA-alone group. To our knowledge, this is the first randomised phase 3 trial to show that regional hyperthermia increases the benefit of chemotherapy. Adding regional hyperthermia to chemotherapy is a new effective treatment strategy for patients with high-risk STS, including STS with an abdominal or retroperitoneal location. Deutsche Krebshilfe, Helmholtz Association (HGF), European Organisation of Research and Treatment of Cancer (EORTC), European Society for Hyperthermic Oncology (ESHO), and US National Institute of Health (NIH).

Grading of nonrhabdomyosarcoma soft tissue sarcoma in children and adolescents

AbstractBACKGROUND:Two systems for grading soft tissue sarcoma are widely used currently: the National Cancer Institute (NCI) and the Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) systems. Both were developed using cohorts of predominantly adult patients. The Pediatric Oncology Group (POG) system, based on the NCI system, was adapted for grading pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). The applicability and prognostic utility of the FNCLCC system in pediatric NRSTS has not been assessed or compared with the POG system.METHODS:Tumors from 130 patients with malignant NRSTS enrolled on 3 completed multi‐institutional clinical trials were assessed. Of 130 tumors, 102 (78%) were localized and 28 (22%) metastatic. Of the localized tumors, 55 of 102 (54%) were &gt;5 cm. The estimated 5‐year event‐free survival (EFS) for the entire group was 47%.RESULTS:As expected, stage and tumor sizes were predictive of EFS (P &lt; .001). Both systems were predictive of 5‐year EFS (POG, P = .0095 and FNCLCC, P = .0075). Patients whose tumors received discrepant grades (POG‐G3 vs FNCLCC‐G2/G1) (n = 44) had an intermediate outcome between those with concordant (G3 [n = 44] or G1/G2 [n = 42]) grades on both systems (P = .0018). By multivariate analysis, the mitotic index was predictive of EFS, using a cutoff of 10 mitotic figures per 10 high‐power fields (P &lt; .001).CONCLUSIONS:In conclusion, both FNCLCC and POG systems provide an adequate prognostic measure of outcome for pediatric NRSTS; albeit, a sizeable subset of cases with apparently intermediate prognosis was graded differently by the 2 systems. The mitotic index appears to be a key parameter in grading pediatric NRSTS. Cancer 2010. © 2010 American Cancer Society.

Long Term Persistent Alopecia and Suboptimal Hair Regrowth after Adjuvant Chemotherapy for Breast Cancer: Alert for an Emerging Side Effect: ALOPERS Observatory.

Abstract Background: Since 2003, through the impetus given by Pr Erick Gamelin and the Regional Health Agency in Western France (Bretagne, Pays de Loire), a network called OMIT (Drugs and Emerging Therapeutics Observatory) has been created, including the Breast Cancer Forum. Anthracyclins and taxanes are the cornerstones of adjuvant chemotherapy for breast cancer. In France, since the PACS 01 publication1, FEC 100 followed by docetaxel 100 has been the standard adjuvant chemotherapy regimen in breast cancer. Long term toxicities like persistent alopecia or suboptimal hair regrowth have been observed.Methods: Over the last year, the first cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy have been reported to the Breast Cancer Forum. Consequently, OMIT quickly drew up a case report form and mailed it to every oncologist in Western France to collect data.Results: From May 2008 to April 2009, 66 cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy from 15 different institutions were declared to OMIT: median age: 60 years (35-78), hypothyroidia: 11, fine hair before treatment: 2. Alopecia was localized: 13, diffuse: 49, complete: 4. The time lapse between the end of chemotherapy and persisting alopecia has been more than 3 months: 5 patients, more than 6 months: 10, more than 12 months: 22, more than 24 months: 29. The chemotherapy regimens were various: schedule FEC (epirubicin 100 mg/msq), 3 courses followed by docetaxel 100 mg/msq, 3 courses: 54, docetaxel 100 mg/msq: 3, TCH (docetaxel-carboplatin-trastuzumab) or TH: 2, FEC 100: 2, epirubicin 75 mg/msq in association with docetaxel 75 mg/msq: 2. Hormonotherapy: letrozole: 13, anastrozole: 18, exemestane: 3, tamoxifene: 14, LH-RH agonist: 3. No hormonotherapy: 13. In some institutions, according to the ECOG trial2, some oncologists quickly decided to change their standard regimen from FEC 100 - docetaxel 100, to EC 100 4 courses followed by weekly paclitaxel for 12 weeks: forthcoming data on persistent alopecia, suboptimal hair regrowth or neuropathy after this ECOG adjuvant chemotherapy regimen will be presented at the symposium.Conclusion: For the first time in France, Western OMIT offers us data about persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy: it is an important side effect and must be considered by oncologists as optimal information to give to curable patients. The next step is to evaluate the real incidence of this phenomen on the population of patients treated by adjuvant chemotherapy for breast cancer: OMIT is currently working with the Federation Nationale des Centres de Lutte contre le Cancer (FNCLCC) to collect data from prospective trials such as PACS 01 (FEC versus FEC-docetaxel), PACS 04 (FEC versus epirubicin-docetaxel) and PACS 05 (FEC 6 courses versus 4 courses), to create the ALOPACS database.1- Roché H. Sequential Adjuvant Epirubicin-based Regimen and Docetaxel Chemotherapy for node-positive Breast Cancer Patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 dec 20; 24 (36) 5664-71.2- Sparano JA.Weekly Paclitaxel in the Adjuvant Treatment in Breast Cancer. N Engl J Med. 2008 Apr 17; 358(16): 1663-71. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3174.

Breast Cancer Prevention by Letrozole in Post Menopausal BRCA1/2 Mutations Carriers: The Onco-03/LIBER Trial.

Abstract Women carrying germline BRCA1/2 deleterious mutations are an extreme risk population for developing breast cancer, with a cumulative life-time risk of 56-80%. Prophylactic bilateral mastectomy provides a valid option for reducing the risk of breast cancer by nearly 90 %. Although it greatly affects the quality of life, breast prophylactic surgery in BRCA1/2 mutation carriers have increased in Europe and in US over the last decade.The major breast cancer prevention trials using tamoxifen and raloxifen showed an approximately 50% risk reduction in high risk women. The contralateral risk reduction in current adjuvant trials comparing aromatase inhibitors (AI) to tamoxifen therapies reveals a higher preventive efficacy of AI after menopause. Two ongoing randomized studies using exemestane (MAP3) or anastrozole (IBIS2) are assessing the risk reduction of breast cancer in menopausal women but none are designed for BRCA1/2 carriers.The French federation of cancer centres, "FNCLCC" (Federation Nationale des Centres de Lutte Contre le Cancer) has developed a randomized phase III study to determine the efficacy of the aromatase inhibitor letrozole to reduce the incidence of invasive breast cancer in post menopausal BRCA1/2 carriers. The ONCO-03 (LIBER) study is a double-blind, letrozole versus placebo, controlled study involving 28 centres in France. The study opened for recruitment in march 2008. The study design, procedures and first analysis of patients enrolment are presented.Based on the known preclinical and clinical profile of AI, a greater reduction in breast cancer incidence with fewer side effects is hypothesized with this class of agents than with tamoxifen or raloxifen. For postmenopausal women bearing a BRCA1/2 genetic predisposition, prevention of breast cancer risk by letrozole could provide a precious alternative to bilateral mastectomy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1048.

Coordinate Expression of Colony-Stimulating Factor-1 and Colony-Stimulating Factor-1-Related Proteins Is Associated with Poor Prognosis in Gynecological and Nongynecological Leiomyosarcoma

Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.

Prognostic implication of SYT–SSX fusion type and clinicopathological parameters for tumor‐related death, recurrence, and metastasis in synovial sarcoma

The present study aimed to describe the distribution and features of the SYT-SSX fusion gene in Chinese patients with synovial sarcoma (SS), and to analyze the prognostic value of SYT-SSX fusion type and clinicopathological parameters for tumor-related death, recurrence, and metastasis in SS. SYT-SSX1 and SYT-SSX2 fusion transcripts were tested by reverse transcription-polymerase chain reaction in 141 formalin-fixed, paraffin-embedded SS. The prognostic implication of SYT-SSX fusion type and clinicopathological parameters were analyzed by univariate and multivariate survival analyses. SYT-SSX1 and SYT-SSX2 were detected in 50 (34.5%) and 91 (64.5%) tumors, respectively. SYT-SSX1 (risk ratio [RR] = 2.032, P = 0.004), larger tumor size (RR = 1.859, P = 0.008), and aggressive Fédération Nationale des Centers de Lutte Contre le Cancer grade (RR = 2.094, P = 0.001) were adverse predictors for disease-specific survival. However, SYT-SSX fusion type was not associated with local recurrence-free survival (P = 0.216). Patients with larger tumors (RR = 2.071, P = 0.005) and those who received marginal excision (RR = 2.556, P = 0.005) had poor local recurrence-free survival. Besides, SYT-SSX1 (RR = 1.859, P = 0.037), older age (RR = 1.799, P = 0.040), and aggressive International Union Against Cancer stage (RR = 3.690, P < 0.001) proved to be adverse prognostic factors for metastasis-free survival. In conclusion, compared to SYT-SSX1, SYT-SSX2 was more frequent in Chinese patients with SS. Moreover, SYT-SSX1 was an adverse predictor for disease-specific survival and metastasis-free survival, but had no relation to local recurrence-free survival. In addition, histological grade and tumor size were also important prognostic factors for SS.