Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers.

BACKGROUND AND PURPOSE: Positron emission tomography (PET) with [(18)F]-fluoromisonidazole ([(18)F]-FMISO) provides a non-invasive assessment of hypoxia. The aim of this study is to assess the feasibility of a dose escalation with volumetric modulated arc therapy (VMAT) guided by [(18)F]-FMISO-PET for head-and-neck cancers (HNC). PATIENTS AND METHODS: Ten patients with inoperable stages III-IV HNC underwent [(18)F]-FMISO-PET before radiotherapy. Hypoxic target volumes (HTV) were segmented automatically by using the fuzzy locally adaptive Bayesian method. Retrospectively, two VMAT plans were generated delivering 70 Gy to the gross tumour volume (GTV) defined on computed tomography simulation or 79.8 Gy to the HTV. A dosimetric comparison was performed, based on calculations of tumour control probability (TCP), normal tissue complication probability (NTCP) for the parotid glands and uncomplicated tumour control probability (UTCP). RESULTS: The mean hypoxic fraction, defined as the ratio between the HTV and the GTV, was 0.18. The mean average dose for both parotids was 22.7 Gy and 25.5 Gy without and with dose escalation respectively. FMISO-guided dose escalation led to a mean increase of TCP, NTCP for both parotids and UTCP by 18.1, 4.6 and 8% respectively. CONCLUSION: A dose escalation up to 79.8 Gy guided by [(18)F]-FMISO-PET with VMAT seems feasible with improvement of TCP and without excessive increase of NTCP for parotids.

Potential of [18F]-fluoromisonidazole positron-emission tomography for radiotherapy planning in head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: Positron-emission tomography (PET) with [(18)F]-fluoromisonidazole (FMISO) permits consideration of radiotherapy dose escalation to hypoxic volumes in head and neck cancers (HNC). However, the definition of FMISO volumes remains problematic. The aims of this study are to confirm that delayed acquisition at 4 h is most appropriate for FMISO-PET imaging and to assess different methods of volume segmentation. PATIENTS AND METHODS: A total of 15 HNC patients underwent several FMISO-PET/computed tomography (CT) acquisitions 2, 3 and 4 h after FMISO injection. Three automatic methods of PET image segmentation were tested: fixed threshold, adaptive threshold based on the ratio between tumour-derived and background activities (R(T/B)) and the fuzzy locally adaptive Bayesian (FLAB) method. The hypoxic fraction (HF), which is defined as the ratio between the FMISO and CT volumes, was also calculated. RESULTS: The R(T/B) for images acquired at 2, 3 and 4 h differed significantly, with mean values of 2.5 (1.7-2.9), 3 (2-4.5) and 3.4 (2.3-6.1), respectively. The mean tumour volume, as defined manually using CT images, was 39.1 ml (1.2-116 ml). After 4 h, the mean FMISO volumes were 18.9 (0.1-81), 9.5 (0.9-33.1) and 12.5 ml (0.9-38.4 ml) with fixed threshold, adaptive threshold and the FLAB method, respectively; median HF values were 0.47 (0.1-1.93), 0.25 (0.11-0.75) and 0.35 (0.14-1.05), respectively. FMISO volumes were significantly different. CONCLUSION: The best contrast is obtained at the 4-hour acquisition time. Large discrepancies were found between the three tested methods of volume segmentation.

[Epithelioid sarcoma: a retrospective study of conservative treatment with initial surgery and radiotherapy]. / Sarcomes épithélioïdes: étude rétrospective après chirurgie conservatrice et radiothérapie.

INTRODUCTION: Epithelioid sarcoma is a rare type of soft tissue sarcomas with a high risk of recurrence both local and distant. The place of surgical conservative treatment and the role of radiation therapy remain controversial. PATIENTS AND METHODS: A serie of 9 consecutive patients treated with initial conservative surgery and postoperative radiotherapy (median dose of 52.8 Gy) from 1987 to 2006 in the same institution was analyzed. RESULTS: With a median follow-up of 40 months (range 15-153 months), the rate of local, nodal and distant relapse is respectively 56%, 11% and 33%. The rate of death is 44.5%. No imputation has been performed. CONCLUSION: Even with a high rate of local relapse observed, a conservative treatment doesn't seem to influence badly the overall survival (55.5% alive at 40 months). Indeed the rate of distant relapse and death are comparable with those found in the literature. Moreover relapse occurred almost within the irradiated volumes. An improvement of dose could be also discussed.

The risk of postoperative complications and functional impairment after multimodality treatment for limb and trunk wall soft-tissue sarcoma: Long term results from a monocentric series.

BACKGROUND AND OBJECTIVES: Conservative surgery for soft-tissue sarcoma (STS) within multimodality treatment attempts to reconcile two contradictory requirements: assuring a good oncological outcome through a wide resection and preserving the function. The aim of our study is to verify whether our conservative approach to STS met these objectives. METHODS: A retrospective database analysis was performed in adults with primary limb or trunk wall STS operated in a single center from 1989 to 2012. Predictive factors for postoperative complications and functional impairment were tested in a multivariate analysis. RESULTS: 728 patients were operated (resection R0: 68%). Neoadjuvant chemotherapy (NAC) was given to 28%, postoperative radiotherapy to 70% of patients. Median follow-up was 103 months. At five years, overall survival was 80% and local recurrences 11%. Major postoperative complications occurred in 8% and functional impairment in 13% of the patients. Independent predictive factors for postoperative complications were American Society of Anesthesiologist classes 2 and 3 (OR: 2.3, CI: 1.2-4.5 and 4.0 CI: 1.7-9.3), tumor size >80 mm (OR: 2.5, CI: 1.3-4.9), tumor site (trunk wall/lower limb, OR: 4.1, CI: 1.3-13.6) and multifocal/multicompartmental spread (OR: 2, CI: 1.1-3.6). Independent predictive factors for function impairment were postoperative complications (OR: 5.3, CI: 2.8-10.1), NAC (OR: 3.6, CI: 2.2-5.8), and bone or neurovascular involvement (OR 3.3, CI 2.0-5.3), whereas Early Rehabilitation after Surgery (ERAS) improved outcome (OR: 0.5, CI: 0.3-0.9). CONCLUSION: Postoperative complications induced functional impairment. They may be reduced by acting on comorbidity factors and careful tumor evaluation prior to surgery. Furthermore, ERAS measures improved function.

[Radiotherapy for retroperitoneal sarcomas]. / Place de la radiothérapie dans la prise en charge des sarcomes rétropéritonéaux.

The management of retroperitoneal sarcoma can be very challenging, and the quality of initial treatment strategy appears to be a crucial prognostic factor. En bloc surgery is currently the standard of care for these rare tumours and perioperative treatments such as chemotherapy or radiotherapy have not been validated yet. However, local-regional relapse constitutes the most common disease course. While adjuvant radiotherapy is less and less common due to gastrointestinal toxicities, preoperative radiation therapy offers numerous advantages and is being evaluated as part of a national multicentre phase II study (TOMOREP trial) and is the subject of a European randomized phase III study (STRASS trial). The objective of this article is to present data on preoperative irradiation in terms of dose, volumes and optimal radiotherapy techniques for the treatment of this rare disease.

Long-term update of the 24954 EORTC phase III trial on larynx preservation.

The long-term results of the EORTC 24954 trial comparing sequential versus alternating chemotherapy and radiotherapy (RT) for patients with locally advanced laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin-5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy and post-operative RT for the non-responders) and an alternating arm (AA = cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with functional larynx (primary end-point) and overall survival were similar in both arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also similar; however, a trend for higher larynx preservation and better laryngeal function was observed in AA.

Local treatment of metastases from differentiated thyroid cancer.

OBJECTIVES: To study the various local treatments available for thyroid cancer metastases, investigate techniques and assess their advantages and limitations and roles in the overall treatment strategy for metastatic disease. RESULTS: We investigated metastases surgery, external radiation therapy, embolization, chemoembolization, cementoplasty, radiofrequency ablation and cryotherapy, describing techniques, advantages and drawbacks and possible complications. Indications were reviewed according to metastases location, and the roles of the various techniques are discussed in the overall treatment strategy for thyroid cancer metastases. Despite the advent of new targeted therapies, local treatment still has an important role to play: either palliative or, in oligometastatic involvement, curative. Even in extensive disease, it may allow postponement of tyrosine kinase inhibitor therapy, which, once initiated, has to be continued life-long, is expensive and is not free of side-effects.

[Adaptive radiotherapy in routine: The radiation oncologist's point of view]. / Radiothérapie adaptative en routine : point de vue de l'oncologue radiothérapeute.

Adaptive radiotherapy is defined as all processes leading to the modification of a treatment plan on the basis of patient-specific variations observed during the course of a treatment. This concept is currently of particular relevance due to the development of onboard volumetric imaging systems, which allow for daily viewing of variations in both tumour and organs at risk in terms of position, shape or volume. However, its application in routine clinical practice is limited due to the demanding nature of the processes involved (re-delineation and replanning) and increased dependence on available human resources. Even if "online" strategies, based on deformable image registration (DIR) algorithms, could lead to a reduction in both work and calculation time, for the moment their use is limited to the research field due to uncertainties surrounding the validity of results gathered. Other strategies without DIR can be used as "offline" or "hybrid offline-online" strategies that seem to offer a compromise between time consumption and therapeutic gain for the patient.

French multicentre clinical evaluation of helical TomoTherapy for anal cancer in a cohort of 64 consecutive patients.

PURPOSE/OBJECTIVES: To assess feasibility and toxicity of Helical TomoTherapy for treating anal cancer patients. METHODS: From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7%) had T2, 16 patients (25.0%) T3, and 27 patients (42.2%) T4 tumours. Thirty-nine patients (60.9%) had nodal involvement. Median tumour size was 45 mm (range, 10-110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6% (95 %CI [71.1%-93.0%]), and the one-year disease-free survival, and colostomy-free survival were 68.7% (95 %CI [54.4%-79.4]), and 75.5% (95 %CI [60.7%-85.3%]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9% of patients), gastrointestinal (20.3%), and hematologic (17.2%) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed. CONCLUSIONS: TomoTherapy for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement.

[Thermoplastic mask in radiotherapy: a source of anxiety for the patient?]. / Le masque de contention en radiothérapie : une source d'anxiété pour le patient ?

PURPOSE: The thermoplastic mask often used to immobilize patients in radiotherapy can cause varying levels of stress and anxiety. This study aimed at evaluating the anxiety related to the use of radiotherapy masks and the coping strategies adopted by patients. PATIENTS AND METHODS: Nineteen patients treated with radiotherapy mask for head and neck cancer, a brain tumour or a lymphoma, were met twice by a psychologist, either after the making of the mask and the first course of radiotherapy, or in the middle and at the end of treatment. Thirty-four semi-structured interviews were treated using a thematic content analysis and 13 patients answered to anxiety (STAI-YB) and coping (WCC) scales. RESULTS: The STAI-YB anxiety scores related to wearing the masks were low during the radiotherapy treatment period, and were confirmed by the remarks of patients recorded during the semi-structured interviews. Most patients had a positive perception of the mask, and considered it as a friend or protection. Twelve out of the 13 patients admitting to anxiety benefited from problem focused coping strategies. CONCLUSIONS: Thermoplastic mask-related anxiety is low and possibly lies in the positive representation patients have about the mask. The explanations provided by health professionals on the radiotherapy mask possibly have a very positive effect on this perception.

[Postoperative radiation therapy for a patient with osteogenesis imperfecta: case report]. / Radiothérapie chez une patiente atteinte d'un cancer du sein et d'ostéogenèse imparfaite : à propos d'un cas.

Osteogenesis imperfecta is an unusual disease also called Lobstein disease. Characterized by abnormalities of collagen biosynthesis, a possible mutation on 17th chromosome is described. On the other hand, 29% of breast cancers present a mutation on the same chromosome. Nevertheless, the association of osteogenesis imperfecta and breast cancer is at the moment unknown. Therapeutic management is very difficult because of a loss in dihydropyrimidine dehydrogenase for patients having osteogenesis imperfecta, generating some toxicity by default in catabolism of 5-fluorouracil. We report the case of a 49-year-old woman with a breast cancer in the context of osteogenesis imperfecta. Dosimetric considerations permitting to reduce chess dose level have been performed for this patient. With a follow-up of 6 months, no imaging fracture has been revealed after radiotherapy. No evident conclusion about radiation injury from a case report could be described in case of osteogenesis imperfecta. To our knowledge, this is the first case which take into account potential radiation induced toxicities.

Characterization of prostate neuroendocrine cancers and therapeutic management: a literature review.

OBJECTIVES: Neuroendocrine prostate cancers (NEPCs) are rare. The current lack of consensus for clinical, biological and pathological characterization as well as therapeutic approach makes the management of those tumors a clinical challenge. This literature review aims to summarize available data on the characterization and management of patients with prostate cancer with a neuroendocrine element. We try to identify major controversies and uncertainties in order to understand all aspects of this particular entity. METHODS: We searched for all articles published and registered in the MEDLINE database before 31 November 2013 with the following search terms: (('prostatic neoplasms' (MeSH Terms)) AND ('carcinoma, neuroendocrine' (MeSH Terms)) OR ('carcinoma, small cell' (MeSH Terms))) AND (English (Language)). RESULTS: Case reports, letters or comments were excluded. We then selected relevant articles from titles and abstracts. Overall, 278 articles published between 1976 and November 2013 were identified. No definition of NEPC seems to be clearly established. Natural history of the disease reveals poor prognosis with median survival of up to 10 to 13 months. Histological characterization appears difficult. Serum markers could be helpful with some controversies in terms of prognostic significance. Concerning management, the majority of patients received local treatment combined with chemotherapy in case of early and localized disease. Few clinical trials described strategy for metastatic disease. CONCLUSIONS: The exploration of the different pathways implicated in the neuroendocrine differentiation of prostate cancers is essential for the comprehension of castration-resistance mechanisms. It will enable the identification of optimal therapeutic strategies for which no recommendation is currently established. Inclusion in prospective clinical trials appears necessary to identify the adequate strategy.

[Radiotherapy after testicular-sparing surgery for bilateral or monorchide testicular tumours: an innovative approach]. / Radiothérapie testiculaire après chirurgie conservatrice des tumeurs germinales bilatérales ou sur testicule unique: une stratégie innovante.

Testicular-sparing surgery may avoid definitive testosterone supplementation and preserve fertility in selected cases of men presenting with bilateral testicular tumours or in case of monorchidia. Testicular-sparing surgery may enable the conservation of both endocrine function and spermatogenesis in selected young men in order to preserve natural fatherhood, avoid definitive androgen replacement therapy and probably improve quality of life by reducing psychosexual consequences of anorchia. The tumorectomy must be followed by an external irradiation of the remaining testicle to eradicate testicular intratubular neoplasia revealed in 82% of cases after per-surgery biopsy. This approach concerns some rare indications. Dose level and technical consideration are still debated.

Therapeutic strategies in elderly and very elderly patients.

Management of the elderly with lymphoma needs specific attention. This means supplementary evaluation as regards to younger patients. The objective is to identify specific weaknesses of the patients and thus to foresee potential unexpected toxicities which may endanger patients' outcome. With this information, the hematologist will be able to propose an optimized treatment strategy i.e. with an adapted efficacy/toxicity ratio. These general principles are consensual but it remains to determine what the practical content of this approach is. Recent results suggest some specific tools for the pre-treatment evaluation. Some specific indexes have been proposed to categorize patients but the ultimate approach remains to be outlined. Finally, while geriatric intervention has demonstrated its capacity to improve survival in the general elderly population, no such demonstration has been made in cancer patients including lymphoma.

[Helical tomotherapy for axial and paraspinal tumours: experience of Institut Bergonié (14 cases)]. / Expérience de l'institut Bergonié à propos de 14 cas de tomothérapie hélicoïdale de tumeurs axiales et para-axiales.

PURPOSE: To evaluate the feasibility of helical tomotherapy intensity-modulated radiotherapy for the treatment of axial and paraspinal tumours. PATIENTS AND METHODS: Fourteen consecutive patients with axial and paraspinal tumours at the Bergonié Institute between June 2007 and June 2009 were analysed. Various localisations were observed: four paravertebral tumours, five primitive vertebral tumours and six iliosacral or sacral tumours. RESULTS: The dose prescribed to the median of the planning target volume (PTV) varied from 45 to 68Gy depending on histology. The maximum dose delivered to the PTV (Dnear max or D2%) was 60.6Gy (range 46.3-69.1). In the five cases where the tumour was located close to the spinal cord, the median value of Dnear max was 40.1Gy (range 37.8-45.4). In the seven where the tumour was situated close to the cauda equina, the median value of Dnear max was 46.5Gy (range 39.2-60). For two cases in whom the sciatic nerve was the nervous structure at risk, the Dnear max was 64.4 and 67Gy. Six patients were in complete remission, six patients suffered a relapse at a median follow-up of 14.5 months (4-24), two died following local tumour progression and metastasis, tumoral stabilisation had been obtained in two patients. Treatment was well tolerated and was never interrupted in all patients. CONCLUSIONS: Results from this preliminary series are encouraging, particularly concerning the good tolerance of this new intensity-modulated radiotherapy presently more available than proton therapy.

[Multifocal Langerhans cell histiocytosis of bone: indications for radiotherapy]. / Histiocytose langerhansienne osseuse multifocale: place de la radiothérapie. gaundong@yahoo.fr

Langerhans cell histiocytosis is a non-malignant proliferative disease of unknown etiology that can affect one or more organs. This is a rare disease, 1 to 2/100,000, affecting mainly children with a male predominance. The osseous lesions are the most frequent (60 to 90%). There is however no consensus treatment for the management of these sites. We report the cases of two patients successfully treated with radiotherapy after primary chemotherapy, at doses of 15 Gy in ten sessions of 1.5 Gy for one patient and 18 Gy in ten fractions of 1.8 Gy for the other. Single or multifocal bone Langerhans cell histiocytosis without visceral involvement is a benign, self-limiting affection in most cases. Some bone lesions could be treated by radiotherapy alone. But the high variability of doses currently given in the literature does not allow determining the lowest effective dose limiting the risk of secondary neoplasia or impaired growth in children, in whom lower doses of 6 to 8 Gy are recommended. The decision of radiotherapy must be weighed against the risk of the disease. Caution should be the rule in this non-malignant tumour pathology.

[Postoperative radiotherapy of prostate cancer]. / Radiothérapie postopératoire des cancers de la prostate.

After radical prostatectomy, the risk of biological recurrence at 5 years varies from 10 to 40 % and this natural evolution of the disease has led radiation therapy being proposed as a supplement to surgery. When the recurrence risk is essentially local, supplementary radiotherapy is justified in the aim of improving biological recurrence-free survival, local control, metastasis-free survival and specific and global survival, while respecting patient quality of life. Three recent studies, EORTC 22911, ARO 9602 and SWOG 8794 found a similar advantage for biological recurrence-free survival without higher major additional toxicity. However, only the SWOG 8794 study found a significant improvement for metastasis-free survival and global survival. In an adjuvant setting, the optimal moment to propose this postoperative radiotherapy remains uncertain: should it be proposed systematically to all pT3 R1 patients, running the risk of pointlessly treating patients who will never recur, or should it only be proposed at recurrence? The GETUG AFU 17 trial will provide answers to the question of the optimal moment for postoperative radiotherapy for pT3-4 R1 pN0 Nx patients with the objective of comparing an immediate treatment to a differed early treatment initiated at biological recurrence.

[Normal tissue tolerance to external beam radiation therapy: peripheral nerves]. / Dose de tolérance à l'irradiation des tissus sains: les nerfs périphériques.

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy...) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications.

[Helical tomotherapy: description and clinical applications]. / Tomothérapie hélicoïdale : aspects techniques et applications cliniques.

Helical tomotherapy is an innovative device combining with the same linac on board-imaging and IMRT facilities. The first national French evaluations, supported by National Institut of Cancer (INCa) are presented. Dosimetric characteristics as quality of homogeneity, cut-off outside target volumes allow IMRT treatments for large and complex volumes and a good organ at risk sparing. First comparative dosimetric studies are discussed.