Perinatal Risk Factors Associated With Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000-2012): A Record Linkage Cohort Study.

BACKGROUND: Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions associated with childhood gastroenteritis-related hospitalizations. METHODS: We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia 2000-2012. We identified hospital admissions up to <15 years of age pertaining to these children, with a principal diagnosis code for infectious gastroenteritis. Cox regression was used to obtain the adjusted hazard ratios with 95% confidence intervals and the population attributable fractions associated with each risk factor in Aboriginal and non-Aboriginal children for their first gastroenteritis-related hospital admission. RESULTS: There were a total of 15,888 gastroenteritis-related hospital admissions (25.7% occurring among non-Aboriginal children). The overall gastroenteritis hospitalization rate for children <15 years of age was 4.6/1000 child-years for non-Aboriginal children and 21.5/1000 child-years for Aboriginal children. Male gender, <20 years of maternal age, preterm birth, low birth weight, residence in remote regions of Western Australia and birth in the pre-rotavirus vaccine era were significant independent risk factors for gastroenteritis hospitalization in both Aboriginal and non-Aboriginal children. Additionally, birth by caesarean section and low socioeconomic status were identified as being associated with gastroenteritis hospitalization in non-Aboriginal children. Population attributable fractions suggest that 39% of all gastroenteritis hospitalizations in non-Aboriginal children (38% in Aboriginal children) could be averted if all children receive the rotavirus vaccine. CONCLUSIONS: Given the beneficial effect of infant rotavirus vaccination in preventing all-cause gastroenteritis hospitalization, efforts should be taken to optimize rotavirus vaccine coverage in those at highest risk.

Manual vs. automated implantation of seeds in prostate brachytherapy: Oncologic results from a single-center study.

PURPOSE: The objective of this study was to study survival and tolerance of prostate cancer patients treated with 125I permanent interstitial brachytherapy by automated vs. manual implantation of seeds. METHODS AND MATERIALS: Between 2002 and 2010, 349 selected patients were treated with 125I brachytherapy by the same team: from 2002 to April 2005, 65 patients with linked seeds and then 284 patients treated using Nucletron First System automated implantation. We analyzed biochemical recurrence-free survival (bRFS) rates and toxicities (univariate and multivariate analyses). RESULTS: Two hundred seventy-seven (79.4%) and 69 patients (19.8%) with low- and intermediate-risk disease were treated, respectively (median follow-up: 64 months). The 5-year bRFS rate was 93.1% (95% confidence interval 89.3-95.6) for the entire cohort. The 5-year bRFS rates were 93.4% and 91.7% for patients with low- and intermediate-risk disease, respectively (p = 0.42). In univariate and multivariate analyses, there was no statistically significant difference in the 5-year bRFS rate depending on the implantation technique (93.1% vs. 91.8%, respectively, for automated and linked seeds; p = 0.53). In univariate analysis, only D90 prostate (dose delivered to 90% of the prostate) <140 Gy (p = 0.01), lack of prostate-specific antigen bounce (p = 0.008), and nadir prostate-specific antigen >0.11 (p = 0.01) were predictive factors for bRFS. We observed Grade 3 urethritis in 7 patients (2%), urinary incontinence in 2 patients (0.7%), and Grade 4 proctitis in 2 patients (0.7%). CONCLUSIONS: In this large single-center series, brachytherapy for selected localized prostate cancer achieved excellent rates of biochemical control at 5 years (93.1%) with an acceptable toxicity profile, irrespective of the implantation technique used.

Post-Prostatectomy Image-Guided Radiotherapy: The Invisible Target Concept.

In the era of intensity-modulated radiation therapy, image-guided radiotherapy (IGRT) appears crucial to control dose delivery and to promote dose escalation while allowing healthy tissue sparing. The place of IGRT following radical prostatectomy is poorly described in the literature. This review aims to highlight some key points on the different IGRT techniques applicable to prostatic bed radiotherapy. Furthermore, methods used to evaluate target motion and to reduce planning target volume margins will also be explored.

Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors.

PURPOSE: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. METHODS AND MATERIALS: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). RESULTS: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). CONCLUSIONS: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT after cytoreductive surgery and perioperative chemotherapy.

PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients.

PURPOSE: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. EXPERIMENTAL DESIGN: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. RESULTS: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). CONCLUSIONS: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.

Progress in survival outcomes in patients with advanced ovarian cancer treated by neo-adjuvant platinum/taxane-based chemotherapy and late interval debulking surgery.

BACKGROUND: Steady progress in outcomes has been observed after standard treatment by surgery and chemotherapy in patients with advanced ovarian cancer (AOC), but little is known about outcomes after alternative neoadjuvant chemotherapy (NAC) proposed to primary inoperable patients. We assessed whether NAC offers comparable survival to standard treatment, whether survival rates have progressed over time, and what the optimal extent of surgery at late interval debulking surgery (IDS) should be. METHODS: This was a retrospective data analysis of prospectively recorded patients with poor prognosis AOC treated by platinum/taxane NAC and late IDS (after six cycles). Independent prognostic factors for surgical morbidity and overall survival (OS) are determined and survival outcomes are compared to survival rates for a similar group of patients treated with platinum protocols. RESULTS: A total of 118 patients with stages IIIC-IV AOC (median age: 64 years, stage IV: 31%) received IDS (46% standard surgery and 54% radical, with 68% obtaining complete resection). Major morbidity was 18%. OS was 42 months across all patients (95% confidence interval 35.3-49.1) and 80 months in stage IIIC. This is higher by 15 months than after platinum-based treatment. Higher morbidity was associated with bowel resection. Longer OS was associated with ASA class I, stage IIIC, no bowel surgery, and no residual disease. CONCLUSIONS: The neoadjuvant approach with late IDS offers survival similar to that reported by standard treatment, with progress in outcomes compared with rates after platinum treatment. The goal of IDS surgery is complete resection, while sparing surrounding organs.

Pulsed-dose-rate brachytherapy for uterine cervix carcinoma: 10 years of experience with 226 patients at a single institution.

PURPOSE: To analyze the long-term results of pulsed-dose-rate (PDR) brachytherapy (BT) in cervical carcinoma patients treated at a single institution. METHODS AND MATERIALS: All patients with histopathologically proven Stages IB-IVA cervical carcinoma, treated at our institution with PDR intracavitary BT between April 1996 and November 2007, were included in this retrospective analysis. All patients underwent primary pelvic radiotherapy (45 Gy) with concomitant chemotherapy from 1999 and PDR intracavitary BT (16 Gy to the clinical target volume), followed by hysterectomy in 124 patients. RESULTS: Two hundred twenty-six patients received radiochemotherapy and BT. With a median followup of 81.7 months, the 5-year overall survival, disease-free survival, and local control (LC) were 67%, 65%, and 80%, respectively; seventy-seven relapses were observed including 38 local recurrences. Multivariate analysis showed earlier FIGO (International Federation of Gynecology and Obstetrics) stage and absence of nodal involvement to be associated with better overall and disease-free survivals. Use of three-dimensional image-guided BT planning and absence of nodal involvement were associated with better LC in the multivariate analysis. Late Grade ≥3 toxicity was experienced by 22 patients (9.7%), consisting of gastrointestinal toxicity for 6 patients, urinary tract for 10 patients, lymphatics for 3 patients, and vaginal toxicity for 3 patients. CONCLUSIONS: This study demonstrates excellent LC rates with few late side effects with PDR BT for cervix carcinoma, similar to those reported in the literature with historical standard low-dose-rate BT.

A large retrospective multicenter study of vaginal melanomas: implications for new management.

The outcome of patients presenting with vaginal melanoma has been assessed in a large multicentric retrospective study. The databases of 12 French institutions were searched for primary vaginal melanomas managed between 1990 and 2007. Among the 54 patients recorded, 46 were managed with a curative intent and included in the study. The clinical characteristics, treatments, and detection of c-KIT protein expression have been studied. The median age of the patients was 63.5 years (42-88). Twenty-eight patients were classified as International Federation of Gynecology and Obstetrics (FIGO) stage I, five as stage II, six as stage III, and one as stage IVA. c-KIT protein was overexpressed in 80% of the patients. Forty-two patients underwent surgical resection of the tumor, nine patients received local adjuvant treatment, and 10 received systemic adjuvant therapy. The median relapse-free survival was 10.9 months. c-KIT-negative status (P=0.01) and stage I (P=0.02) were associated with locoregional recurrence. The rate of metastasis was increased for advanced FIGO stages (P<0.01). The median overall survival (OS) was 28.4 months. The finding of lymph node metastasis adversely affected OS (P<0.01). Conservative surgery and radiotherapy were associated with a decrease in metastasis-free and OS (P<0.01) compared with surgery alone, this group of patients presenting with advanced FIGO stages (P=0.02). Despite the use of limited data, conservative surgery combined with a sentinel lymph node procedure, followed by adjuvant radiotherapy could be proposed to patients with early FIGO stage in the absence of validated management. c-KIT negativity by immunochemistry appears to be a poor prognosis marker in terms of locoregional recurrences but not for metastatic spread nor survival. Further assessment of the role of c-KIT expression in this disease is thus mandatory to select patients for targeted therapy.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

BACKGROUND AND PURPOSE: To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. MATERIALS AND METHODS: Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). RESULTS: The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(ß)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(ß)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. CONCLUSIONS: For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity.

Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: results of the French STIC prospective study.

PURPOSE: In 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis. PATIENTS AND METHODS: For the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed. PATIENTS AND METHODS: Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117). PATIENTS AND METHODS: The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0. RESULTS: The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK. RESULTS: Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2Gy(α/ß10), 63.2Gy(α/ß10) and 73.1Gy(α/ß10) for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5Gy(α/ß10), 57.3Gy(α/ß10) and 61.7Gy(α/ß10) for groups 1, 2 and 3. For the OARs, doses delivered to D2cc ranged 60-70Gy(α/ß3) for the bladder, 33-61Gy(α/ß3) for the rectum, and 44-58Gy(α/ß3) for the sigmoid according to the regimen. RESULTS: At 24 months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3-4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm. CONCLUSION: This multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity.

[Advanced endometrial carcinoma: primary debulking surgery or neoadjuvant chemotherapy?]. / Cancers de l'endomètre de stades avancés : chirurgie première ou chimiothérapie néoadjuvante ?

Endometrial cancers with peritoneal spread are stage IVB of FIGO classification. Their pattern is similar to that of ovarian cancer. Optimal debulking surgery and chemotherapy are predictor of better overall and disease free survival. Despite the poor outcome, there is a need for new treatment options. Recommended management for this group of patients should consist of surgical cytoreduction followed by chemotherapy. There may be a role for neoadjuvant chemotherapy followed by interval surgery in selected subgroups of patients.

Optimal timing of interval debulking surgery in advanced ovarian cancer: yet to be defined?

OBJECTIVES: Interval debulking surgery (IDS) following neo-adjuvant chemotherapy (NAC) is a treatment option in advanced ovarian cancer. It is recommended to perform IDS early, after 3 cycles of NAC, but late IDS (after 6 cycles) may yield better results. Delaying IDS, however, harbours the risk of loosing the opportunity for debulking surgery. STUDY DESIGN: Retrospective comparison of two groups of patients with advanced ovarian carcinoma (stages IIC-IV) treated by platinum-based chemotherapy (CT) having undergone early IDS (after 3.6 cycles, group 1, n=33) or late IDS (after 6.3 cycles, group 2, n=104). Contemporary patients who had undergone standard treatment by primary debulking surgery (PDS)+CT (group 3, n=446) and those treated by CT alone (group 4, n=64 patients) served as internal controls. RESULTS: Prognosis in IDS patients (groups 1+2) was comparable to that in PDS patients (group 3). Only a few patients in group 4 potentially had lost an opportunity for debulking surgery. Groups 1 and 2 were well-matched concerning usual prognostic factors. Surgery extent and post-operative outcomes were similar in both. In contrast, complete cytoreductions were significantly more frequent in late than in early IDS (group 2 vs.1: 58% vs. 36%, p=0.03) and survival was not inferior in the late IDS group compared to the early IDS group with 37 vs. 22 months, respectively (p=0.09). CONCLUSION: Late IDS yields higher complete resection rates than early IDS and should be evaluated prospectively for outcome in further trials.

Clinical practice guidelines for the management of patients with endometrial cancer in France: recommendations of the Institut National du Cancer and the Société Française d'Oncologie Gynécologique.

INTRODUCTION: Endometrial cancer is the most common gynecological malignancy in France, with more than 6500 new cases in 2010. The French National Cancer Institute has been leading a clinical practice guidelines (CPG) project since 2008. This project involves the development and updating of evidence-based CPG in oncology. OBJECTIVE: To develop CPG for diagnosis, treatment, and follow-up for patients with endometrial cancer. METHODS: The guideline development process is based on systematic literature review and critical appraisal by experts, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. RESULTS: Main recommendations include a routine pelvic magnetic resonance imaging in association with magnetic resonance imaging exploration of the para-aortic lymph nodes for locoregional staging, surgical treatment based on total hysterectomy with bilateral salpingo-oophorectomy with or without lymphadenectomy, and clinical examination for the follow-up. The initial laparoscopic surgical approach is recommended for stage I tumors. Lymphadenectomy and postoperative external radiotherapy are recommended for patients with high risk of recurrence but are restricted for patients with low or intermediate risk. If brachytherapy is indicated, it should be given at a high-dose rate rather than a low-dose rate. Routine imaging, biologic tests, and vaginal smears are not indicated for follow-up.

High-dose-rate brachytherapy for non-small-cell lung carcinoma: a retrospective study of 226 patients.

PURPOSE: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. METHODS AND MATERIALS: We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. RESULTS: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001). CONCLUSIONS: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma.

Lymph node involvement in epithelial ovarian cancer: sites and risk factors in a series of 355 patients.

OBJECTIVES: To perform a cartography of lymph node metastases in epithelial ovarian cancer and to determine predictive factors of lymph node metastases. METHOD: The charts of 355 patients with epithelial ovarian cancer who underwent lymphadenectomy during a primary (n = 252) or secondary debulking surgery (n = 103) were analyzed. The topography of the lymph node metastases was notified for the whole group according to the stage of the disease, the histological type, and the moment of surgery. In patients who underwent a primary surgery before chemotherapy, independent prognostic variables for the risk of lymph node involvement were tested with a multivariate analysis. Independent prognostic factors were combined to determine risk profiles in individual patients. RESULTS: The main area of the lymph node metastases was para-aortic. Isolated pelvic lymph node involvement was 10%. Three variables independently predicted lymph node invasion: advanced T stage, high-risk histological profile, and metastases. CONCLUSIONS: When lymphadenectomy is recommended, systematic lymph node dissections in the aortic and pelvic areas are warranted. An isolated pelvic lymph node assessment, particularly in the early stages, is inappropriate. By combining independent risk factors, a useful tool for individual risk assessment of lymph node involvement could be established, helping to decide whether to perform a lymph node dissection, especially at restaging surgery.

Prognostic factors in early-stage leiomyosarcoma of the uterus.

Uterine leiomyosarcomas (LMSs) are rare cancers representing less than 1% of all uterine malignancies. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage is the most important prognostic factor. Other significant prognostic factors, especially for early stages, are difficult to establish because most of the published studies have included localized and extra-pelvian sarcomas. The aim of our study was to search for significant prognostic factors in clinical stage I and II uterine LMS. The pathologic features of 108 uterine LMS including 72 stage I and II lesions were reviewed using standardized criteria. The prognostic significance of different pathologic features was assessed. The median follow-up in the whole group was 64 months (range, 6-223 months). The 5-year overall survival (OS) and metastasis-free interval and local relapse-free interval rates in the whole group and early-stage group (FIGO stages I and II) were 40% and 57%, 42% and 50%, 56% and 62%, respectively. Clinical FIGO stage was the most important prognostic factor for OS in the whole group (P = 4 x 10). In the stage I and II group, macroscopic circumscription was the most significant factor predicting OS (P = 0.001). In the same group, mitotic score and vascular invasion were associated with metastasis-free interval (P = 0.03 and P = 0.04, respectively). Uterine LMSs diagnosed using standardized criteria have a poor prognosis, and clinical FIGO stage is an ominous prognostic factor. In early-stage LMS, pathologic features such as mitotic score, vascular invasion, and tumor circumscription significantly impact patient outcome.

Treatment of squamous cell anal canal carcinoma (SCACC) with pulsed dose rate brachytherapy: a retrospective study.

BACKGROUND AND PURPOSE: To evaluate the results of pulsed dose rate brachytherapy (PDR) in SCACC. MATERIAL AND METHODS: From 1996 to 2002, 71 patients (pts) with SCACC were treated with PDR brachytherapy. The median age was 61.2 years (35-88), with a sex ratio of 1 M/6.5 F. The TNM classification was: 14 T1, 41 T2, 15 T3 and 1 T4, 52 N0, 13 N1, 3 N2 and 3 N3. All the pts were M0. Treatment started with external beam irradiation to the posterior pelvis (mean dose: 45.5 Gy). Forty-seven patients received chemotherapy (neoadjuvant/concomitant or both). After an interval of 2-6 weeks, PDR interstitial brachytherapy was performed. The mean dose was 17.8 Gy to the 85% reference isodose of the Paris system. RESULTS: Treatment was interrupted in only one pt. With a median follow-up of 28.5 months, 2-year actuarial overall survival was 90%. Fourteen relapses occurred (four distant, three regional, and seven local). Ten patients developed a grade III complication (Lent Soma scale) and two a grade IV complication (colostomy or abdominal perineal resection for necrosis). CONCLUSION: PDR appears to be an effective treatment for SCACC. It is capable of reproducing the results usually observed with continuous LDR.

Low-dose intraoperative brachytherapy in soft tissue sarcomas involving neurovascular structure.

BACKGROUND AND PURPOSE: To evaluate intraoperative brachytherapy in the management of soft tissue sarcomas involving neurovascular structures, its impact on local control and complications. PATIENTS AND METHODS: Between 01/1989 and 12/2002, 98 patients received an intraoperative implant in conjunction with conservative surgery. Brachytherapy was part of the initial treatment (79 cases) or performed in recurrent disease (19 cases). We studied primary sarcomas involving neurovascular structures treated with conservative surgery and intraoperative brachytherapy (n = 6) or intraoperative brachytherapy and external irradiation (n = 73). Conservative surgery was performed as first treatment (51 cases), after chemotherapy (21 cases) and after primary external radiation (seven cases). Brachytherapy was performed according to Paris system rules. Patients were loaded with Iridium 192 (64 cases) or connected to a Microselectron PDR (15 cases). Mean dose given by brachytherapy was 20 Gy. Mean dose given of external radiotherapy was 46 Gy. RESULTS: With a median follow-up of 58 months, 5-year actuarial survival was 69% and local free disease at 5 years was 90%. Acute side-effects occurred in 22/79 requiring surgical repair in 10 patients. Late side-effects occurred in 35/79. No patient required amputation for complications. Prognostic factors were studied for the occurrence of acute and late side-effects and local control. CONCLUSIONS: Intraoperative brachytherapy is efficient with excellent local control rates in soft tissue sarcomas presenting with neurovascular involvement and offers an acceptable conservative option.

Management of soft tissue sarcomas (STS) in first isolated local recurrence: a retrospective study of 83 cases.

PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field.