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Purpose: To evaluate the efficacy and toxicity of helical tomotherapy (HT) in the management of spine chordomas when proton therapy is unavailable or non-feasible., Methods and Materials: Between 2007 and 2013, 30 patients with biopsy-proven chordomas were treated by HT in five French institutions. Information regarding local control (LC), overall survival (OS), progression-free survival (PFS) and metastasis-free survival (MFS) was collected. Clinical efficacy, toxicity and treatment quality were evaluated., Results: Two-year actuarial LC, OS, PFS and MFS were 69.9%, 96.7%, 61.2% and 76.4%, respectively. HT treatments were well tolerated and no Grade 4-5 toxicities were observed. HT permitted the delivery of a mean dose of 68 Gy while respecting organ at risk (OAR) dose constraints, in particular in the spinal cord and cauda equina., Conclusions: This multicentric, retrospective study demonstrated the feasibility of HT in the treatment of spine chordomas, in the absence of hadron therapy.

During their follow-up, patients with cancer can experience several types of recurrent events and can also die. Over the last decades, several joint models have been proposed to deal with recurrent events with dependent terminal event. Most of them require the proportional hazard assumption. In the case of long follow-up, this assumption could be violated. We propose a joint frailty model for two types of recurrent events and a dependent terminal event to account for potential dependencies between events with potentially time-varying coefficients. For that, regression splines are used to model the time-varying coefficients. Baseline hazard functions (BHF) are estimated with piecewise constant functions or with cubic M-Splines functions. The maximum likelihood estimation method provides parameter estimates. Likelihood ratio tests are performed to test the time dependency and the statistical association of the covariates. This model was driven by breast cancer data where the maximum follow-up was close to 20 years.

Purpose: This single-arm phase I dose-escalation study determines the optimal dose of the non-platinum treatment pegylated liposomal doxorubicin (PLD) plus cyclophosphamide (CPM) every 4 weeks in early recurrent ovarian carcinoma., Methods: Twenty-one women with ovarian carcinoma relapsing within 12 months of first-line surgery and platinum-taxane chemotherapy received escalating doses of PLD (35-45 mg/m(2)) and CPM (500-600 mg/m(2)) every 4 weeks for at least two cycles. Primary objective was assessment of maximum-tolerated dose (MTD) over the first two cycles. Secondary objectives were to assess safety over 2 cycles, efficacy evaluated every two cycles (response evaluation criteria in solid tumours criteria) and overall survival (OS)., Results: The PLD-CPM MTD was 40/600 mg/m(2) with 2/3 patients treated at 45/500 mg/m(2), showing DLTs with Grade 3/4 oesophagitis, thrombopenia/neutropenia, leucopoenia, and Grade 3 stomatitis/asthenia during the first cycle of treatment. Four severe toxicities were reported by three patients during the two first cycles, namely Grade 4 anaemia, and Grade 3 stomatitis. The most common treatment-related toxicities were anaemia (71.4 %), nausea (61.9 %), neutropenia (57.1 %), asthenia (52.4 %), leucopoenia (47.6 %), stomatitis (42.9 %), skin (28.6 %) and palmar-plantar-erythrodysesthesia (19 %). No treatment-related deaths were reported. The overall response rate (complete and partial) was 31 %, and median OS was 8.2 months [95 % CI (3.3-13.2)]., Conclusions: The combination of PLD and CPM is feasible and may be considered particularly in cases where platinum-based treatment is not suitable. The recommended doses for a phase II trial are PLD 40 mg/m(2) plus CPM 600 mg/m(2) every 4 weeks.

Background: Liver metastases (LM) in close contact to hepatic veins (HV) are a frequent cause of unresectability. Reconstruction of hepatic veins is technically difficult and outcomes are poor. Intra-operative radiofrequency ablation (IRFA) with vascular exclusion (VE) may be a useful approach., Methods: Out of 358 patients operated for LM, 22 with LM close to a HV treated by IRFA under VE with at least one year of follow-up were included in this retrospective study. Technical success was evaluated at four months by CT scan of the ablated lesion. Complications; local, hepatic and extra-hepatic recurrence rates, and overall survival are reported., Results: The median number of metastases was 4.5 [range: 1-12]. Seventeen patients had bilateral metastases. The median size of ablated lesions was 2 cm [range: 1-5.5]. Seven complications occurred (1 Grade 1, 2 Grade 3b and 4 Grade IVa), with no mortality. No recurrence of ablated lesions was detected at four months or during follow-up. Seventeen patients had new or extra-hepatic lesions. Median overall survival for colorectal patients was 40 months 95%CI[17.5-not reached]., Conclusions: IRFA plus VE for LM in close contact to a HV is a novel approach, appearing to be a safe and effective technique which can extend the applications of liver metastases surgery., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to determine safety and efficacy of radiofrequency ablation (RFA) in the treatment of lung metastases arising from sarcoma., Methods: Between 2002 and 2009, 29 patients (mean age 51 years) treated for metastatic sarcoma with a maximum of 5 lung metastases treatable with RFA were followed prospectively. The end points were local efficacy (assessed by computed tomography during the follow-up period), complications, and survival (overall and disease-free)., Results: A total of 47 metastases were treated with RFA. Median follow-up time was 50 months (range 28-72 months). Pneumothorax was the most frequent complication and occurred in 68.7% of the procedures. The 1- and 3-year survival rates were 92.2% (95% confidence interval [CI] 0.73-0.98) and 65.2% (95% CI 0.42-0.81), respectively. Disease-free survival was 7 months (95% CI 3.5-10). Five recurrences on RFA sites were noted during follow-up., Conclusions: RFA is safe and efficient in the treatment of lung metastasis originating from sarcomas. RFA may provide a low-morbidity alternative to surgery, being less invasive and preserving the patient's ability to undergo possible repeat operations.

Background: The objective of this retrospective study was to identify prognostic, diagnostic, and therapeutic disparities between younger (≤ 40 years) and older (> 40 years) women with ductal carcinoma in situ (DCIS) of the breast., Methods: From 1971 to 2001, all patients treated for DCIS at Institut Bergonié were included in our analyses. Follow-up data was collected over 10 years. We used univariate and multivariate analyses to investigate patient-, disease-, and treatment-related factors predictive of diagnostic, histological, therapeutic, and prognostic DCIS criteria., Results: A total of 812 patients were eligible including 731 women aged >40 years and 81 women ≤40 years. Younger women with DCIS were more likely to receive a mastectomy and less likely to receive radiotherapy. Young age and initial surgical treatment (lumpectomy and especially nonfree margins) were revealed as predictive of recurrence in multivariate analyses., Conclusions: Young age represents a recurrence risk independent of histological and clinical characteristics of the tumor. Initial treatment, especially for nonfree margins, is also a predictive factor. Appropriate initial surgery with particularly wide margins appears essential for the treatment of young women with DCIS.

Background: Current adjuvant hormone therapy in postmenopausal women with breast cancer is debatable between upfront aromatase inhibitors (AIs) and sequential treatment with tamoxifen. A major concern is the higher rate of early recurrences observed with sequential treatment. The authors conducted a retrospective analysis to identify risk factors of early recurrences in hormone receptor (HR)-positive, postmenopausal women within the first 3 years of adjuvant tamoxifen., Methods: Between 1986 and 2000, operable breast cancer patients who received exclusively adjuvant tamoxifen for at least 3 years were selected from the authors' institutional database. Age, histology, pathologic tumor size, modified Scarff-Bloom-Richardson (mSBR) grade, mitotic index, tumor necrosis, peritumoral vascular emboli (PVE), HR status, and the number of involved axillary lymph-node were considered as prognostic factors of recurrence., Results: Among 715 patients who met the inclusion criteria, a distant recurrence occurred in 38 patients (5.3%) within the first 3 years of tamoxifen therapy. Significant prognostic factors of early recurrence were mSBR, axillary lymph node involvement, tumor necrosis, mitotic index, PVE, and pathologic tumor size. Grade 1 and/or lymph node-negative tumors were excluded from the multivariate analysis (1 recurrence in 208 patients). In this model, mSBR grade 3 was the only significant predictive factor of early recurrence (hazard ratio, 3.72; P<.001)., Conclusions: In this study, a subset of patients was identified that was at low-risk of early recurrence (mSBR grade 1 and/or negative lymph node status). Women in that subset could be treated using sequential hormone therapy with tamoxifen and AIs. In women with mSBR grade 3 or lymph node-positive tumors, an upfront treatment with AIs seemed to be the current optimal strategy., ((c) 2007 American Cancer Society.)

Objective: To determine the reliability of pretherapeutic laparoscopic pelvic lymphadenectomy in cervical cancer as a function of lymph node recurrences according to initial lymph node status: 1) to establish the false negative rate by analyzing lymph node recurrence in patients N-, 2) to verify treatment adequacy in patients N+ by comparing the rate of node recurrence to initial node positivity., Patients and Methods: Retrospective analysis of a prospectively registered patient database. One hundred and ninety patients treated by a combination of radiotherapy and surgery for cervical cancer stages 1b to 2b in 95% of cases had undergone, from March 1992 to June 2003, a previous laparoscopic pelvic lymphadenectomy. Median follow-up was 40 months (range: 3-126 months)., Results: Initial lymph node positivity (N+) was found in 79 patients (42%). Fourteen patients (7.4%) presented with lymph node recurrence, all of whom have died from disease. Lymph node recurrence was found in 4/111 patients N- (3.6%) and in 10/79 patients N+ (12.7%), of whom 8/10 occurred outside the radiation fields., Conclusion: With a very low false negative rate, accuracy of the laparoscopic pelvic lymphadenectomy in the determination of lymphatic spread in cervical cancer is confirmed. It can still be considered the gold standard despite recent developments (e.g. sentinel lymph node determination) to which they should be compared. Treatment adequacy in patients N+ is confirmed.