R. Dendale

Anatomical, clinical and radiological delineation of target volumes in breast cancer radiotherapy planning: individual variability, questions and answers

The purpose of the study was to evaluate the individual variability of anatomical and radiological delineation for breast cancer radiotherapy (RT) in preparation for new techniques and to propose practical solutions to improve delineation in everyday practice. In the first phase, a patient with stage T3N3M0 breast cancer and complete response after neoadjuvant chemotherapy was assessed by CT scan in the treatment position before RT. 11 radiation oncologists (5 breast cancer specialists and 6 residents) independently delineated the breast and lymph node (LN) regions before definition of target volumes. Organs at risk (heart, lung, thyroid and brachial plexus) were also delineated. All regions (breast, axilla, supraclavicular LN, infraclavicular LN and internal mammary chain) were delineated and compared in terms of volume. Comparative analysis was performed with Aquilab software. Differences in the clinical and radiological assessment were observed between the various radiation oncologists. Simplified rules of delineation were developed in the department. Using these rules, the second patients CT was delineated by the same physicians and better results were observed. Simplified rules of delineation were developed. In conclusion, major differences in anatomical and radiological delineation for breast cancer RT were observed among the physicians. This study led to the development of written delineation protocols. The study is ongoing with evaluation of the dosimetric impact and definition of different target volumes.

Combined Proton Beam Radiotherapy and Transpupillary Thermotherapy for Large Uveal Melanomas: A Randomized Study of 151 Patients

Introduction: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. Patients and Method:Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas ≧7 mm thick or ≧15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. Results: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). Discussion: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.

Proton beam therapy for iris melanomas

AimsTo describe the results in terms of local control, eye preservation and systemic evolution of iris melanomas treated by proton beam irradiation.MethodsRetrospective review of the charts of patients with iris melanoma treated by proton beam therapy between April 1998 and September 2002. Ciliary body melanomas with iris involvement or tumours with extrascleral invasion were excluded. Treatment consisted of 60 Gy of proton beam irradiation delivered in four fractions to the tumour volume.ResultsA total of 21 patients were treated, median follow-up of 33 months (8–72 months). 15 patients presented a lesion with documented growth. The median clinical diameter was 5 mm (2–8 mm), the median ultrasound diameter 4.8 mm (2–7.7 mm) The patients were 6% T1, 57.1% T2, and 14.3% T3 all N0M0. The iridocorneal angle was invaded by the tumour in 71.4% of patients. At the end of follow-up, all patients were alive with no proven metastatic disease except one patient with suspicious liver lesions. None of the patients showed tumour progression or ocular relapse. The tumour response at 2 years was a flat lesion for 6.3% of cases, partial regression in 75% and stable in 18.8%. None of the patients required secondary enucleation. The main complication was cataract (45% within 24 months of treatment). Raised intraocular pressure was observed in 15% of patients but no neovascular glaucoma.ConclusionsProton beam therapy shows potential utility for selected cases of localised iris melanomas allowing excellent local tumour control and eye preservation. Further follow-up on larger series is needed to confirm these results.

High rates of breast conservation for large ductal and lobular invasive carcinomas combining multimodality strategies

The literature reports low rates of breast conservation after neoadjuvant chemotherapy for operable breast cancers not amenable to initial breast-conserving surgery. This study aims to compare the outcome of lobular vs ductal carcinomas after neoadjuvant chemotherapy. Between 1989 and 1999, 750 patients with clinical stage II/IIIA ductal (672) or lobular (78) invasive breast carcinomas were treated at the Institut Curie with primary anthracycline-based polychemotherapy followed by either breast conservation (surgery and/or radiotherapy) or mastectomy. Median follow-up was 10 years. Clinical response to primary chemotherapy was significantly worse for lobular than for ductal carcinomas (47 vs 60%; P=0.04), but only histological grade remained predictive in multivariate analysis. Breast conservation was high for both ductal and lobular carcinomas (65 and 54%; P=0.07), due, in part, to the use of radiotherapy, either exclusive or preoperative, for respectively 26 and 40% of patients. The lobular type had no adverse effect, neither on locoregional control nor on overall survival, even in the group of patients treated with breast conservation.

Dose de tolérance à l’irradiation des tissus sains : l’œil☆

The radiation dose received by the eye depends on the pathology, tumour location (ocular globe, orbit, neighboring structures) and the radiation technique. The major complication is the complete loss of vision, which is often multifactorial. This article, based on a literature review, describes the radiation effects and the tolerance doses for all eye structures: cornea, lens, retina, optic nerves, orbit and ocular adnexa.

Prise en charge des tumeurs phyllodes malignes du sein : l’expérience de l’institut Curie

PURPOSE Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices. PATIENTS AND METHODS Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7-257 months). RESULTS Median age at diagnosis was 52 years (20-64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12-250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, post-tumorectomy; five patients, post-mastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80-100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy). CONCLUSION Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

Management of advanced non-melanoma skin cancers using helical tomotherapy.

Helical tomotherapy (HT) is a relatively new method of radiotherapy, the main advantages of which are an increase of irradiation dose on the target tumour volume and best protection of adjacent organs at risk.

Évaluation monocentrique de la tolérance de l’association concomitante de trastuzumab et de radiothérapie

PURPOSE Prospective monocentric study of the skin and heart tolerance of a concurrent administration of trastuzumab (T) and radiotherapy (RT) for breast cancer (BC). PATIENTS AND METHODS From February 2004 to January 2007, 57 patients (pts), were treated by a concomitant administration of T and normo-fractionated RT of either whole breast (+/-boost) or chest. The perfusion of T started either with or after chemotherapy (CT). Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT, after completion of RT and then every four to six months with either echocardiography or multiple gated acquisition scanning, were considered normal if greater or equal to 50% or stated so by the cardiologist. Inclusion criteria included a normal LVEF at baseline. Skin toxicity was evaluated using CTCAEV3. Median age was 49 years (25-80). CT with anthracycline was administered in 84% (total dose 300 mg/m(2)). All but one patient (treated weekly) received T every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (6-33). The internal mammary chain was irradiated in 88% of cases. Median follow-up for LVEF assessment was 13 months (2-33). RESULTS LVEF at pre-RT were normal in 54 pts (100%, three Missing Data [MD]), at post-RT in 56 pts (98%, no MD) and at last follow-up in 53 pts (95%, one MD). There were two grade 0, 44 grade I and 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after six months, late skin toxicity was grade 0 in 22 pts, grade 1 in four, grade 2 in one. CONCLUSION Provided that the technique is adapted, the acute skin and heart toxicities of the concomitant administration of T-RT appeared satisfactory. More patients and longer follow-up are still mandatory.

Article originalPrise en charge des tumeurs phyllodes malignes du sein : l’expérience de l’institut CurieManagement of malignant phyllodes tumors of the breast: The experience of the Institut Curie

PURPOSE Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices. PATIENTS AND METHODS Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7-257 months). RESULTS Median age at diagnosis was 52 years (20-64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12-250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, post-tumorectomy; five patients, post-mastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80-100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy). CONCLUSION Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

La protonthérapie : bases, indications et nouvelles technologies

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.