Leiomyosarcoma of the Prostate: Report of Two Cases and Review of the Literature.

Introduction: Leiomyosarcoma (LMS) of the prostate is an extremely rare and aggressive tumor that presents with nonspecific signs and symptoms. Treatment guidelines are not yet established. Case Presentation: We report two cases of LMS of the prostate. The presenting symptom was hematuria, and diagnosis was ascertained through a transurethral resection of the prostate for the 2 patients. The treatment course consisted of three courses of chemotherapy with gemcitabine and docetaxel, radical prostatectomy, and postoperative radiation therapy for the first patient and three courses of gemcitabine and radiation therapy of the prostate and the whole pelvis for the second patient. The follow-up of our 2 patients was 9 and 12 months, respectively. Recurrence occurred 10 months after treatment completion for the second case. No recurrence was noticed in the first case. Conclusion: These two cases highlight the importance of a multimodal approach to yield the best outcomes.

IROCA-TES: Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices. Materials and methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization). Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice. Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres.

[Uterin adenosarcoma: French Guidelines of the French Sarcoma Group and the Rare Gynecologic Tumor Group]. / Adénosarcomes mullériens de l'utérus ­ référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Uterine adenosarcoma is a very rare malignancy defined as a biphasic tumor composed of both benign epithelial component and a malignant sarcoma component. The stage of the disease is determined by the presence of myometrial invasion and the extent of extra-uterine disease. The most important histopronostic factors are the existence of a sarcomatous overgrowth defined by a sarcomatous contingent occupying more than 25 % of the volume of the tumor (directly correlated to the grade of the disease), the presence of a heterologous and/or a high-grade component. Stage I adenosarcomas without sarcomatous overgrowth have a good prognosis, with an overall 5-year survival of up to 80 %. In localized disease, complete surgical removal is recommended. The role of hormone therapy, chemotherapy and adjuvant radiotherapy is not established. If possible, relapses should be re-treated surgically, with the aim of achieving complete resection. In the advanced inoperable or metastatic setting, hormone therapy is an option for low-grade adenosarcomas with estrogen receptor (ER) and progesterone receptor (PR) overexpression. For high-grade tumors, the standard chemotherapies are doxorubicin-based combinations, although an integrated approach of surgery and medical treatment should also be considered in this setting.

[Uterine leiomyosarcoma - French guidelines from the GSF/NETSARC and TMRG groups]. / Léiomyosarcomes utérins ­ Référentiel de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Uterine leiomyosarcomas represent the most common uterine sarcomas. The prognosis is poor with metastatic recurrence in more than half of the cases. The purpose of this review is to make French recommendations for the management of uterine leiomyosarcomas within the framework of the French Sarcoma Group - Bone Tumor Study Group (GSF-GETO)/NETSARC+ and Malignant Rare Gynecological Tumors (TMRG) networks in order to optimize their therapeutic management. The initial assessment includes a MRI with diffusion perfusion sequence. The diagnosis is histological with a review in an expert center (Reference Network in Sarcoma Pathology (RRePS)). Total hysterectomy with bilateral salpingectomy, en bloc without morcellation, is performed when complete resection is possible, whatever the stage. There is no indication of systematic lymph node dissection. Bilateral oophorectomy is indicated in peri-menopausal or menopausal women. Adjuvant external radiotherapy is not a standard. Adjuvant chemotherapy is not a standard. It can be an option and consists in doxorobucin based protocols. In the event of local recurrence, the therapeutic options are based on revision surgery and/or radiotherapy. Systemic treatment with chemotherapy is most often indicated. In case of metastatic disease, surgical treatment remains indicated when resecable. In cases of oligo-metastatic disease, focal treatment of metastases should be considered. In the case of stage IV, chemotherapy is indicated, and is based on first-line doxorubicin-based protocols. In the event of excessive deterioration in general condition, management by exclusive supportive care is recommended. External palliative radiotherapy can be proposed for symptomatic purposes.

Magnetic Resonance-Guided Reirradiation for Local Recurrence within the Prostate or in the Prostate Bed: One-Year Clinical Results of a Prospective Registry Study.

Around 33% of patients treated by EBRT or brachytherapy will present a biochemical recurrence. SBRT is a new option for the treatment of patients with local-only recurrence. MRgRT seems to be interesting for the treatment of these recurrences. This article presents the one-year late tolerance and biochemical recurrence-free survival results of a prospective registry study. Patients with intraprostatic (or in the prostate bed) recurrence were treated with 5 to 9 fractions (median dose of 30 Gy in 5 fractions) with the MRIdian® system. PSA level and toxicities were evaluated before treatment and at three, six and 12 months after treatment. Thirty-seven patients with a median age of 74.5 years old were treated between 21 October 2019 and 7 December 2020. Acute tolerance was excellent with no grade >2 toxicities. Twelve months after treatment, we observed an increase of grade 1−2 dysuria (46% vs. 13% before treatment) and grade 1 polyuria (73% vs. 7%). The six, nine and 12-months biochemical-recurrence free survival were 97.3%, 86.5% and 65.0%. Fifteen patients (40%) presented a biochemical recurrence. Nine of these 15 patients (60%) had a persistent disease within the treated volume. In conclusion, MRgRT is safe and has promising survival results.

Long-term follow-up experience in anal canal cancer treated with Intensity-Modulated Radiation Therapy: Clinical outcomes, patterns of relapse and predictors of failure.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of patients with squamous cell carcinoma of the anal canal (SCCAC) treated with Intensity-Modulated Radiation Therapy (IMRT). MATERIAL AND METHODS: From 2007 to 2015, 193 patients were treated by IMRT for SCCAC. Radiotherapy delivered 45 Gy in 1.8 Gy daily-fractions to the primary tumor and elective nodal areas, immediately followed by a boost of 14.4-20 Gy to the primary tumor and involved nodes. Concurrent chemotherapy with 5-FU-mitomycin (MMC) or cisplatin was added for locally advanced tumors. Survivals were estimated by Kaplan-Meier method. Locoregional (LR) relapses were precisely assessed. Prognostic factors were evaluated by uni- and multivariate analyses. Late toxicity was scored according to the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: Median follow-up was 70 months (range, 1-131). Forty-nine men (25%) and 144 women (75%) were analyzed. Median age was 62 years. Tumor stages were I, II, III and IV in 7%, 24%, 63% and 6% of cases, respectively. Chemotherapy was delivered in 167 patients (87%), mainly MMC (80%). Five-year OS, DFS, CFS and LR control rates were 74%, 68%, 66% and 85%, respectively. Forty-one patients (21%) had a relapse: 22 were LR, mostly in-field (68%). Predictors for LR failure were exclusive radiotherapy, chemotherapy lacking MMC and treatment breaks >3 days. Overall late toxicity ≥grade 2 occurred in 43% of patients, with 24% grade 3 and one case of grade 4 (hematuria). CONCLUSION: CRT with IMRT assures excellent local control in locally advanced SCCAC with manageable long-term toxicity. Multicentric prospective trials are required to reinforce those results.

SBRT planning for liver metastases: A focus on immobilization, motion management and planning imaging techniques.

AIM: To evaluate the different techniques used for liver metastases Stereotactic Body Radiation Therapy (SBRT) planning. We especially focused on immobilization devices, motion management and imaging used for contouring. BACKGROUND: Although some guidelines exist, there is no consensus regarding the minimal requirements for liver SBRT treatments. MATERIALS AND METHODS: We reviewed the main liver metastases SBRT publications and guidelines; and compared the techniques used for immobilization, motion management, margins and imaging. RESULTS: There is a wide variety of techniques used for immobilization, motion management and planning imaging. CONCLUSIONS: We provide a subjective critical analysis of minimal requirements and ideal technique for liver SBRT planning.

Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results.

BACKGROUND: Motion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment. MATERIALS AND METHODS: Between May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5 mm from the ITV. Dose prescription ranged from 40 to 50 Gy in 5-10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients. RESULTS: With a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes. In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved "in field". 12 patients had an intrahepatic progression "out of field". Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91 mm (0-6 mm). CONCLUSION: The clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating.

Time interval between surgery and start of adjuvant radiotherapy in patients with soft tissue sarcoma: A retrospective analysis of 1131 cases from the French Sarcoma Group.

PURPOSE: The aim of this study was to evaluate the impact of the time interval (TI) between surgery and adjuvant radiotherapy (RT) in soft tissue sarcoma (STS). METHODS AND MATERIALS: Data from 1131 patients treated between 1990 and 2014 were retrospectively reviewed. Inclusion criteria were: limb or superficial trunk wall STS (R0 or R1 resection) and adjuvant RT. The impact of TI on 10-year local relapse-free survival (LRFS) and 10-year overall survival (OS) was analyzed using a Log-rank test and then Cox Model. RESULTS: The median TI was 82days (range, 18-346). With a median follow-up of 235months (range, 2-296months), the 10-year LRFS was 57.5% (±2%) and the 10-year OS was 64.2% (±2%). With a TI of 19-39days, 40-79days, 80-119days, and ⩾120days, 10-year LRFSs were 65.3%, 55.5%, 56.9% and 61.2% (p=0.465), and 10-year OSs were 72.8%, 60.7%, 66.4% and 62.1% (p=0.347), respectively. After adjustment for the factors significantly (p⩽0.05) associated with LRFS and OS, TI did not alter LRFS (p=0.182) either OS (p=0.335). CONCLUSIONS: In this retrospective STS database study, the TI between surgery and start of adjuvant RT did not seem to affect outcomes.

Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial.

BACKGROUND: Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer. METHODS: We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1:1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094. FINDINGS: 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25·3 months (IQR 15·9-36·4). Median progression-free survival was 9·7 months (95% CI 8·1-14·5) in the FOLFOX group and 9·4 months (8·1-10·6) in the fluorouracil and cisplatin group (HR 0·93, 95% CI 0·70-1·24; p=0·64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0·066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p<0·0001), sensory neuropathy (24 [18%] vs one [1%], p<0·0001), increases in aspartate aminotransferase concentrations (14 [11%] vs two [2%], p=0·002), and increases in alanine aminotransferase concentrations (11 [8%] vs two [2%], p=0·012) were more common in the FOLFOX group, whereas serum creatinine increases (four [3%] vs 15 [12%], p=0·007), mucositis (35 [27%] vs 41 [32%], p=0·011), and alopecia (two [2%] vs 12 [9%], p=0·005) were more common in the fluorouracil and cisplatin group. INTERPRETATION: Although chemoradiotherapy with FOLFOX did not increase progression-free survival compared with chemoradiotherapy with fluorouracil and cisplatin, FOLFOX might be a more convenient option for patients with localised oesophageal cancer unsuitable for surgery. FUNDING: UNICANCER, French Health Ministry, Sanofi-Aventis, and National League Against Cancer.

Implementing intensity modulated radiotherapy to the prostate bed: dosimetric study and early clinical results.

Salvage intensity modulated radiotherapy (IMRT) to the prostate bed has hardly been studied so far. We present here a feasibility study and early clinical results for 10 patients. These patients were selected on the basis of having either a biochemical relapse or high risk histology after prostatectomy. They were treated using "sliding-window" IMRT to 68 Gy in 34 fractions. Three-dimensional conformal radiotherapy (3D-CRT) plans were generated using the same planning computed tomography data set. Dose coverage of planning target volumes (PTVs) and of organs-at-risk (OAR, namely: rectum, bladder, and femoral heads) were compared. Acute toxicity and chronic toxicity were measured using the Common Toxicity Criteria for Adverse Events version 3.0 scale. IMRT significantly reduces the dose above the prescription dose given to the PTV1 (mean dose: IMRT 67.2 Gy vs 3D-CRT 67.7 Gy (p = 0.0137)), without altering dose coverage for PTV2 (mean dose: IMRT 68.1 Gy vs 3D-CRT 68.0 Gy (p = 0.3750)). Doses to OAR were lower with IMRT and differences were statistically significant (mean dose: IMRT 51.4 Gy vs 3D-CRT 56.6 Gy for rectum (p = 0.002), IMRT 45.1 Gy vs 3D-CRT 53.1 Gy for bladder (p = 0.002), and IMRT 26.1 Gy vs 3D-CRT 28.4 Gy for femoral heads (p = 0.0059)). There was no acute or chronic genitourinary or gastrointestinal toxicity >1 with a median follow-up of 38 months. IMRT to the prostatic fossa is feasible and reduces dose to OAR, with consequential limited toxicity.

Three Years of Salvage IMRT for Prostate Cancer: Results of the Montpellier Cancer Center.

Background. To assess the feasibility of salvage intensity-modulated radiation Therapy (IMRT) and to examine clinical outcome. Patients and Methods. 57 patients were treated with salvage IMRT to the prostate bed in our center from January, 2007, to February, 2010. The mean prescription dose was 68 Gy in 34 fractions. Forty-four patients received concomitant androgen deprivation. Results. Doses to organs at risk were low without altering target volume coverage. Salvage IMRT was feasible without any grade 3 or 4 acute gastrointestinal or urinary toxicity. With a median follow-up of 21 months, one grade 2 urinary and 1 grade ≥2 rectal late toxicities were reported. Biological relapse-free survival was 96.5% (2.3% (1/44) relapsed with androgen suppression and 7.7% (1/13) without). Conclusion. Salvage IMRT is feasible and results in low acute and chronic side-effects. Longer follow-up is warranted to draw conclusions in terms of oncologic control.

Feasibility study of volumetric modulated arc therapy for the treatment of retroperitoneal sarcomas.

BACKGROUND: Radiotherapy for retroperitoneal sarcomas remains controversial and a technical challenge considering the threshold of contiguous critical organs tolerance. We performed consecutive RapidArc dosimetric plans in preoperative or postoperative setting. METHODS: A dosimetric study was carried out from six preoperative (group A) and four postoperative (group B) CT-scans, performed in 7 patients.Prescribed dose was 45 and 50 Gy for groups A and B, respectively. The planning target volume (PTV) was defined as the clinical target volume (CTV) plus 5 mm. The CTV encompassed the gross tumor volume (GTV) plus 10 mm or the tumoral bed. The dosimetric plans were optimized on a RapidArc Eclipse console using the progressive resolution algorithm, PRO version 8.8. Normalization method allowed the coverage of 99% of the PTV by 95% of the dose. RESULTS: Mean PTV were 2318.5 ± 2223.9 cc [range 348-6198 cc] and 698.3 ± 216.6 cc [range 463 -933 cc] for groups A and B, respectively. Plans were optimized for single arcs in group B and for single or two arcs in group A. The contralateral kidney volume receiving 5 Gy (V5Gy) was 21.5 ± 23.3% [range 0-55%] and 3.1 ± 2.6% [range 0-7.3%] for groups A and B, respectively. The mean dose received by 1% of the kidney (D1%) was 5.6 ± 2.4 Gy [range 3.6 -7.6 Gy] for group A and 5.4 ± 0.7 Gy [range 4.3-6 Gy] for group B. The volume of small bowel excluding the PTV (small bowel-PTV) that received 40 Gy and 30 Gy (V40Gy and V30Gy) in group A were 7.5 ± 4.4% [range 5.4-14.1%] and 18.5 ± 7.1% [range 10-30.4%], respectively.In group B, small bowel-PTV V40Gy and V30Gy were 4.7 ± 3.3% [range 3.3-8%] and 21.6 ± 7.5% [range 9.4-30%] respectively. In a second step, we treated two patients in the postoperative group. Treatment time delivery with one arc was 74 seconds. No severe acute toxicity was observed. CONCLUSION: RapidArc technology for retroperitoneal sarcomas showed acceptable dosimetric results in preoperative or postoperative clinical situation. From the first treated patients, acute tolerability was good to excellent.