Sylvie Helfre

Conformal radiotherapy (CRT) planning for lung cancer: analysis of intrathoracic organ motion during extreme phases of breathing

PURPOSE Conformal radiotherapy beams are defined on the basis of static computed tomography acquisitions by taking into account setup errors and organ/tumor motion during breathing. In the absence of precise data, the size of the margins is estimated arbitrarily. The objective of this study was to evaluate the amplitude of maximum intrathoracic organ motion during breathing. METHODS AND MATERIALS Twenty patients treated for non-small-cell lung cancer were included in the study: 10 patients at the Institut Curie with a personalized alpha cradle immobilization and 10 patients at Tenon Hospital with just the Posirest device below their arms. Three computed tomography acquisitions were performed in the treatment position: the first during free breathing and the other two during deep breath-hold inspiration and expiration. For each acquisition, the displacements of the various intrathoracic structures were measured in three dimensions. RESULTS Patients from the two centers were comparable in terms of age, weight, height, tumor site, and stage. In the overall population, the greatest displacements were observed for the diaphragm, and the smallest displacements were observed for the lung apices and carina. The relative amplitude of motion was comparable between the two centers. The use of a personalized immobilization device reduced lateral thoracic movements (p < 0.02) and lung apex movements (p < 0.02). CONCLUSION Intrathoracic organ movements during extreme phases of breathing are considerable. Quantification of organ motion is necessary for definition of the safety margins. A personalized immobilization device appears to effectively reduce apical and lateral displacement.

Proton Therapy in Pediatric Skull Base and Cervical Canal Low-Grade Bone Malignancies

PURPOSE To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. PATIENTS AND METHODS Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n = 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. RESULTS With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). CONCLUSIONS High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.

Ovarian transposition in prepubescent and adolescent girls with cancer

Ovarian transposition was the first procedure proposed to preserve fertility in girls with cancer and is indicated for patients with tumours requiring pelvic radiation at doses of 42·0-58·4 Gy, much higher doses than those that can induce loss of ovarian function (4-20 Gy). Ovarian transposition is usually done after neoadjuvant chemotherapy and is completed by minimally invasive surgery or open surgery in case of concomitant resection of the abdominal tumour. According to the type of tumour, the ovaries are moved and placed in the paracolic gutters when the radiation field reaches the midline (for medulloblastoma or urogenital rhabdomyosarcoma), contralaterally to the tumour (for pelvic sarcomas), or in line with the iliac crests (for Hodgkins lymphoma). However, in 10-14% of cases the procedure can fail to protect the ovaries. Although few long-term results in adults are available, normal hormonal function and pregnancies have been reported in a few long-term follow-up studies. In view of the continued development of fertility preservation techniques, ovarian transposition should be discussed at a multidisciplinary meeting at the time of cancer diagnosis.

Radiation and chemotherapy combination for nasopharyngeal carcinoma in children: Radiotherapy dose adaptation after chemotherapy response to minimize late effects†

To retrospectively report the clinical and therapeutic features of children with nasopharyngeal carcinoma (NPC) treated by chemotherapy and doses adapted of radiotherapy.

Desmoid Fibromatosis in Pediatric Patients: Management Based on a Retrospective Analysis of 59 Patients and a Review of the Literature

Background. Only limited data are available concerning desmoid tumor in children. Methods. Fifty-nine children and adolescents with desmoid tumor treated in 2 French cancer centers with a very long followup were retrospectively reviewed. Results. Median age was 6 years (range, 0–15). Tumors mainly involved the limbs (42%). Five cases occurred in a context of genetic disorder. Surgery was first-line treatment in 80% of cases. Resection was microscopically complete in 3 patients (pts), with a microscopic residue in 19 pts and a macroscopic residue in 35 cases. Various adjuvant therapies were used. Overall response to all systemic therapies was 33%. Thirty-eight patients developed one or more recurrences or progressions. After a median followup of 8.5 years, 34 patients were alive in complete remission (CR), including 16 first CR. Seven patients died, 6 from refractory disease and 1 from colorectal carcinoma in a genetic context. Ten-year progression-free survival (PFS) and overall survival were 31% and 88%, respectively. In univariate analysis, age less than 10 years and head-neck site were favorable prognostic factors for PFS. Conclusions. When surgery is required, surgical margins must be negative. Low-dose chemotherapy can be proposed as adjuvant therapy. Prospective trials must be developed to evaluate long-term response and side effects.

Alveolar soft part sarcoma in childhood: Is Sunitinib‐Sutent® treatment an effective approach?

To the Editor: Alveolar soft part sarcoma (ASPS) is a rare, highly malignant, chemoand radio-resistant mesenchymal tumor. ASPS is characterized by an unbalanced recurrent translocation t(X;17)(p11;q25), which leads to a chimeric transcription factor ASPL-TFE3 [1,2]. Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), some of which are involved in tumor growth, tumor angiogenesis, and metastatic progression of cancer. The rationale is based on the fact that autophosphorylation of mesenchymal epithelial transition factor (MET), by fusion protein ASPSCR1-TFE3, activates cell signaling pathways governing angiogenesis, cell division and growth, and cell survival [3,4]. Sunitinib has also demonstrated an effect in Xp11 renal cell carcinoma, known to sometimes share the same transcript, with objective responses, and prolonged progression-free survival [5,6].

Cancers bronchiques non à petites cellules : amélioration des chances de survie par la radiothérapie conformationnelle ?

The conformal radiotherapy approach, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT), is based on modern imaging modalities, efficient 3D treatment planning systems, sophisticated immobilization devices and demanding quality assurance and treatment verification. The main goal of conformal radiotherapy is to ensure a high dose distribution tailored to the limits of the target volume while reducing exposure of healthy tissues. These techniques would then allow a further dose escalation increasing local control and survival. Non-small cell lung cancer (NSCLC) is one of the most difficult malignant tumors to be treated. It combines geometrical difficulties due to respiratory motion, and number of low tolerance neighboring organs, and dosimetric difficulties because of the presence of huge inhomogeneities. This localization is an attractive and ambitious example for the evaluation of new techniques. However, the published clinical reports in the last years described very heterogeneous techniques and, in the absence of prospective randomized trials, it is somewhat difficult at present to evaluate the real benefits drawn from those conformal radiotherapy techniques. After reviewing the rationale for 3DCRT for NSCLC, this paper will describe the main studies of 3DCRT, in order to evaluate its impact on lung cancer treatment. Then, the current state-of-the-art of IMRT and the last technical and therapeutic innovations in NSCLC will be discussed.

Role of palliative radiotherapy in the management of metastatic pediatric neuroblastoma: a retrospective single-institution study.

PURPOSE Neuroblastoma is the most common extracranial solid tumor of childhood, and metastatic disease occurs in a majority of patients. Although radiotherapy (RT) plays an important role in the management of metastatic disease, data on the effectiveness of palliative RT, in this setting, is scarce. METHODS AND MATERIALS A retrospective review of the outcome of palliative RT in children with metastatic neuroblastoma was conducted at the Institut Curie. RESULTS Thirty-four children with 69 metastatic sites received palliative RT between 2000 and 2009. Sites of disease were grouped according to location, and there were 19 soft tissue, 38 bone, 9 central nervous system (CNS), and 3 hepatic metastases. Mean RT doses for the four groups were 19.6 Gy, 17.6 Gy, 17 Gy, and 5 Gy, respectively. Median survivals after RT were 27 days, 43 days, 29 days, and 27 days, respectively, for an overall median survival of 29.5 days. For the soft tissue metastases, good response was defined as a decrease >25% in the tumor mass or any decrease in pain; the response rate was 84.2%. Furthermore, a dose 15 Gy or more significantly increased response rate (100% vs. 57%; p = 0.038), compared with a dose smaller than 15 Gy. For the bone group and CNS metastases group, the overall response rates were 63.2% and 44%, respectively. A trend toward dose-response relationship was seen for the bone but not the CNS group. CONCLUSION Good response rates are achieved with palliative RT for symptomatic metastatic pediatric neuroblastoma, but survival is dismal.

Cancers des voies aérodigestives supérieures : bénéfices cliniques de la radiothérapie conformationnelle et de la modulation d'intensité

The conformal radiotherapy approach, three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT), is based on modern imaging modalities, efficient 3D treatment planning systems, sophisticated immobilization systems and rigorous quality assurance and treatment verification. The central objective of conformal radiotherapy is to ensure a high dose distribution tailored to the limits of the target volume while reducing exposure of normal tissues. These techniques would then allow further tumor dose escalation. Head-and-neck tumors are some of the most attractive localizations to test conformal radiotherapy. They combine ballistic difficulties due to particularly complex shapes (nasopharynx, ethmoid) and problems due to the number and low tolerance of neighbouring organs like parotids, eyes, brainstem and spinal cord. The therapeutic irradiation of head-and-neck tumors thus remains a challenge for the radiation oncologist. Conformal radiotherapy does have a significant potential for improving local control and reducing toxicity when compared to standard radiotherapy. However, in the absence of prospective randomized trials, it is somewhat difficult at present to evaluate the real benefits drawn from 3DCRT and IMRT. The published clinical reports on the use of conformal radiotherapy are essentially dealing with dosimetric comparisons on relatively small numbers of patients. Recently, a few publications have emphasized the clinical experience of several precursor teams with a suitable follow-up. This paper describes the current state-of-the-art of 3DCRT and IMRT in order to evaluate the impact of these techniques on head-and-neck cancers irradiation.

Clinical applications of proton therapy. Experiences and ongoing studies.

Proton therapy offers potentially considerable advantages in the management of slow-growing, poorly resectable or non-resectable tumors resistant to x-rays and located close to critical radiosensitive anatomical structures, such as the brain stem of the spinal cord. Among over 13 000 irradiated patients in the USA, Europe, and Japan, two major clinical indications have been documented: 1. The conservative management of choroidal melanomas, in which 98% 5-year local control can be expected at the price of low toxicity and visual preservation in approximately half of them. 2. The curative management of low-grade chondrosarcomas and chordomas of the base of the skull and cervical spine, leading to, in combination with maximal tumor resection, 84%–94% long-term survival. Other ongoing studies concern prostate, head and neck carcinomas as well as various intracranial tumors. Radiosurgical programs are being conducted generally with single fractions and under stereotactic conditions.