Radiotherapy in the management of lung oligometastases.

In recent years, the development of both medical imaging and new systemic agents (targeted therapy and immunotherapy) have revolutionized the field of oncology, leading to a new entity: oligometastatic disease. Adding local treatment of oligometastases to systemic treatment could lead to prolonged survival with no significant impact on quality of life. Given the high prevalence of lung oligometastases and the new systemic agents coming with increased pulmonary toxicity, this article provides a comprehensive review of the current state-of-art for radiotherapy of lung oligometastases. After reviewing pretreatment workup, the authors define several radiotherapy regimen based on the localization and size of the oligometastases. A comment on the synergistic combination of medical treatment and radiotherapy is also made, projecting on future steps in this specific clinical setting.

Radiotherapy in the management of synchronous metastatic lung cancer.

Metastatic lung cancer classically portends a poor prognosis. The management of metastatic lung cancer has dramatically changed with the emergence of immune checkpoint inhibitors, targeted therapy and due to a better understanding of the oligometastatic process. In metastatic lung cancers, radiation therapy which was only used with palliative intent for decades, represents today a promising way to treat primary and oligometastatic sites with a curative intent. Herein we present through a literature review the role of radiotherapy in the management of synchronous metastatic lung cancers.

Quality/risk management system in radiotherapy: Changes afoot.

The French sanitary and regulatory context in which radiotherapy centres are comprised is evolving. Risk and quality management systems are currently adapting to these evolutions. The French nuclear safety agency (ASN) decision of July 1st 2008 on quality assurance obligations in radiotherapy has reached 10 years of age, and the French high authority of health (HAS) certification system 20 years now. Mandatory tools needed for the improvement of quality and safety in healthcare are now well known. From now on, the focus of healthcare policies is oriented towards evaluation of efficiency of these new organisations designed following ASN and HAS nationwide guidelines.

Radiotherapy for primary lung cancer.

Herein are presented the recommendations from the Société française de radiothérapie oncologique regarding indications and modalities of lung cancer radiotherapy. The recommendations for delineation of the target volumes and organs at risk are detailed.

[Lung dose constraints for normo-fractionated radiotherapy and for stereotactic body radiation therapy]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie stéréotaxique : les poumons.

Radiation-induced lung disease (RILD) is common after radiation therapy and represents cornerstone toxicities after treatment of thoracic malignancies. From a review of literature, the objective of this article was to summarize clinical and non-clinical parameters associated with the risk of RILD in the settings of normo-fractionated radiotherapy and stereotactic body radiation therapy (SBRT). For the treatment of lung cancers with a normo-fractionated treatment, the mean lung dose (MLD) should be below 15-20Gy. For a thoracic SBRT, V20Gy<10% and MLD<6Gy are recommended. One should pay attention to central tumors and respect specific dose constraints to the bronchial tree. The recent technological improvements may represent an encouraging way to decrease lung toxicities. Finally, our team developed a calculator in order to predict the risk of radiation pneumonitis.

[Respiratory synchronization and breast radiotherapy]. / Synchronisation respiratoire et radiothérapie mammaire.

Adjuvant radiation therapy following breast cancer surgery continues to improve locoregional control and overall survival. But the success of highly targeted-conformal radiotherapy such as intensity-modulated techniques, can be compromised by respiratory motion. The intrafraction motion can potentially result in significant under- or overdose, and also expose organs at risk. This article summarizes the respiratory motion and its effects on imaging, dose calculation and dose delivery by radiotherapy for breast cancer. We will review the methods of respiratory synchronization available for breast radiotherapy to minimize the respiratory impact and to spare organs such as heart and lung.

[Radiotherapy for small cell lung carcinoma]. / Radiothérapie des cancers bronchiques à petites cellules.

Radiotherapy for small cell lung carcinoma has known significant improvements over the past 10 years especially through routine use of PET-CT in the initial work-up and contouring before treatment. Prophylactic cranial irradiation remains a standard of care for locally advanced disease and is a subject of controversy for metastatic disease. A new indication for thoracic radiotherapy may soon arise for metastatic disease, still confirmation studies are ongoing.

[Quality and safety management for radiotherapy]. / Démarches d'amélioration de la qualité et gestion des risques en radiothérapie.

Quality and safety management have been implemented for many years in healthcare structures (hospitals treating cancer, private radiotherapy centres). Their structure and formalization have improved progressively over time. These recommendations aim at describing the link between quality and safety management through its organization scheme based on quality-safety policy, process approach, document management and quality measurement. Dedicated tools, such as experience feedback, a priori risk mapping, to-do-lists and check-lists are shown as examples and recommended as routine practice.

[Experience feedback committees (CREX) and beyond ]. / Les Crex et après .

Since the late 2,000 years, under the incentive of the French agencies ANAP (previously MEAH) and HAS and following the decision DC-0103 of the ASN, experience feedback committees (known as 'Comité de retour d'expérience or Crex' in French) have widely been implemented within radiation oncology departments in France. Based on the declaration of error/near misses (precursor events) occurring during medical care to patients, an intuitive method of systematic analysis of these events is basically the aim of such committees (such as the Orion method(©) derived from the air transportation industry). Our article aims at summarizing the paths and pitfalls attached to this methodology, emphasizing what could be the next step, beyond the 'Crex' committees, in the long march to know how to secure care to patients within a radiotherapy medical team.

[Patient information duties in radiation oncology]. / Devoir d'information au patient en radiothérapie.

Patient information duties are a basic task of radiation oncologists in their daily practice. This article is essentially a factsheet on legal obligations, the value of written informed consent and information documents that ought to be given to patient.

[Target volume margins for lung cancer: internal target volume/clinical target volume]. / Marges dans le cancer pulmonaire : volume cible interne/volume cible anatomoclinique.

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned.

[FMEA applied to the radiotherapy patient care process]. / Analyse des risques a priori du processus de prise en charge des patients en radiothérapie : exemple d'utilisation de la méthode Amdec.

PURPOSE: Failure modes and effects analysis (FMEA), is a risk analysis method used at the Radiotherapy Department of Institute Sainte-Catherine as part of a strategy seeking to continuously improve the quality and security of treatments. PATIENTS AND METHODS: The method comprises several steps: definition of main processes; for each of them, description for every step of prescription, treatment preparation, treatment application; identification of the possible risks, their consequences, their origins; research of existing safety elements which may avoid these risks; grading of risks to assign a criticality score resulting in a numerical organisation of the risks. Finally, the impact of proposed corrective actions was then estimated by a new grading round. RESULTS: For each process studied, a detailed map of the risks was obtained, facilitating the identification of priority actions to be undertaken. For example, we obtain five steps in patient treatment planning with an unacceptable level of risk, 62 a level of moderate risk and 31 an acceptable level of risk. CONCLUSION: The FMEA method, used in the industrial domain and applied here to health care, is an effective tool for the management of risks in patient care. However, the time and training requirements necessary to implement this method should not be underestimated.

Cisplatin-docetaxel induction plus concurrent 3-D conformal radiotherapy and weekly chemotherapy for locally advanced non-small cell lung cancer patients: a phase II trial.

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study was to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m(2)) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). The primary endpoint was the response rate. Secondary objectives were toxicity, time to progression, and overall survival. Forty-four patients were included and 40 were eligible. The mean age was 60.5 years (range 40.7-72.1), and 75% had stage IIIB disease. Six patients underwent complete R0 resection including 2 pathologic complete responses after a planned intermediate evaluation. Thirty-three patients completed CHRT. The objective response rate was 65% (95% CI 50.2-79.8). Grade 3-4 hematologic and digestive toxicities were observed mainly during the induction phase. Grade 3 esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7 months, the median progression-free survival was 28.3 months (95% CI 11.0-35.0) and the median survival rate was 31.4 months. Cisplatin-docetaxel induction followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a feasible protocol associated with a promising response rate and acceptable toxicity.

[Image guidance for the evaluation of setup accuracy]. / Imagerie de contrôle de positionnement : quelle fréquence pour quel objectif ?

Information obtained by different methods of image-guided radiotherapy now allows us to reposition the target volume. This evolution causes a change in practice and positioning control. In order to control positioning errors, a systematic control during the first three to five sessions is required. Random repositioning errors and clinical target volume motions can be mastered only by performing a daily imaging. Finally, image-guided radiotherapy allows assessing anatomical changes occurring during treatment, and opens the field of adaptive radiotherapy.

[Dosimetric and clinical benefits of respiratory-gated radiotherapy for lung and breast cancers: results of the STIC 2003]. / Intérêts dosimétriques et cliniques de la radiothérapie asservie à la respiration des cancers du poumon et du sein : résultats du Stic 2003.

PURPOSE: To compare respiratory-gated conformal radiotherapy versus conventional conformal radiotherapy for the irradiation of non-small cells lung cancer and breast cancer. PATIENTS AND METHODS: The STIC 2003 project was a comparative, non-randomized, multicenter and prospective study that included in 20 French centers between April 2004 and June 2008, 634 evaluable patients, 401 non-small cells lung cancer and 233 breast cancers. RESULTS: The final results confirmed the feasibility and good reproducibility of the various respiratory-gated conformal radiotherapy systems regardless of tumour location. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity, especially for non-small cells lung cancer, as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold techniques (ABC and SDX), which markedly increased the total lung volume compared to the inspiration-synchronized system based on tidal volume (RPM). For non-small cells lung cancer, these theoretical dosimetric benefits were correlated with a significant reduction in clinically acute and late toxicities, especially the pulmonary. For breast cancer, although less clear due to the lower total dose, there was a decrease in the dose delivered to the heart, potentially reducing the risk of cardiac toxicity in the long-term, especially during the irradiation of the left breast, and a reduction in dose to the contra lateral breast. CONCLUSION: Respiratory-gated radiotherapy appears to be essential to reduce the risk of acute and late toxicities, especially for lungs and heart, during irradiation of non-small cells lung cancer and breast cancers.

[Radiation-related heart toxicity]. / Toxicité cardiaque de la radiothérapie.

The radiotherapy of thoracic cancers exposes the heart to late radiation-induced complications. The physiopathological and clinical consequences of heart irradiation have been mostly studied in patients with Hodgkin lymphoma and breast cancer. The main cause of cardiac morbidity is radiation-induced coronaropathy with a relative risk estimated between 2 and 3 in earlier studies. Preexisting factors of cardiovascular risk, including chemotherapy, potentalize the cardiotoxicity of radiotherapy. Conformational radiotherapy, adapting the ballistics and the energy to the delineated volumes while carefully evaluating the dose-volume distribution in the organs at risk, allowed a drastic reduction in cardiac mortality. This toxicity no longer seems to be significant if the cardiac volume has received less than 30 Gy. Nevertheless, the prolonged life expectancy of cancer patients and the expanding use of new cardiotoxic anticancer drugs underline the persistent need to further reduce the dose delivered to the heart. Indeed, 1 Gy added to the mean heart dose would increase the cardiotoxic risk by 4% (IC 95%: 2-6%, P=0.0002). A strengthened collaboration between the radiation oncologist and the cardiologist aims at detecting and treating long-term complications after thoracic radiotherapy.

[A phase II study of weekly cisplatine plus oral vinorelbine with concomittant radiotherapy in non-dependent elderly patients with localized inoperable non small cell lung carcinoma (Essai GFPC 08-06, Raccosa)]. / Radio-chimiothérapie concomitante chez le sujet âgé indépendant (Essai GFPC 0806 RACCOSA).

UNLABELLED: A phase II study of weekly cisplatine plus oral vinorelbine with concomittant radiotherapy in non-dependent elderly patients with localized inoperable non small cell lung carcinoma (Essai GFPC 08-06, Raccosa). BACKGROUND: Non small cell lung cancer (NSCLC) in elderly patients is an important problem because of the increasing incidence of NSCLC and the aging of the population. Elderly patients constitute a heterogeneous population including a significant group of relatively fit patients who ought to benefit from the conventional treatment. The standard treatment for a locally advanced NSCLC (inoperable IIIA and IIIB) is concomitant radiochemotherapy, however studies evaluating this treatment to the old subject are few. METHODS: This phase II study aims to evaluate tolerance of concomitant radiochemotherapy in fit elderly patients (more than 70 years old) with locally advanced NSCLC (inoperable IIIAN2 or IIIB). The treatment is oral vinorelbine (30 mg/m(2) per week) and intravenous cisplatine (30 mg/m(2) per week) during 6 weeks in conjunction with radiotherapy (66 Gy, 33 fraction, six and a half weeks). The main criterion of evaluation is acute toxicity. Late toxicity, quality of life, global response, time to progression and overall survival will also be estimated. With a Simon's optimal plan in two steps, the total number of patients to be included is 59 with an intermediate analysis after the inclusion of 19 patients. EXPECTED RESULTS: Our study aims to demonstrate that fit elderly patients can benefit from concomitant radiochemotherapy. It will permit an improvement in the care available for fit elderly patients with locally advanced NSCLC by allowing them to benefit from the reference treatment.

Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20-year experience.

BACKGROUND: This is a retrospective analysis of a series of meningiomas treated by radiotherapy. MATERIALS AND METHODS: From 1978 to 1997, 45 patients with intracranial meningiomas were referred for external fractionated radiotherapy at Centre Alexis Vautrin. All patients were given 50-70Gy to the tumor bed (median: 56Gy), 1.8-2Gy per fraction. RESULTS: Evaluation was performed in June 1999 using the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1-166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years; overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5 and 8 years. One major radiation-induced complication occurred in this series (decline of cognitive function). According to the indication of radiotherapy, we divided the series into four groups: postoperative irradiation after a first subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (+/-salvage surgery, 14 patients), 73%; after further recurrence (+/-salvage surgery, 11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients but one died before 42 months. Age at the time of irradiation (> or =60 vs. <60 years) and radiotherapy dose (> or =60 vs. <60Gy) did not influence local control or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a worse outcome than benign lesions (WHO grade I, P<0.01). CONCLUSIONS: These results compare favorably with previously published data. External fractionated radiotherapy is well tolerated and effective. There is still a debate about the place of radiotherapy in the treatment of meningiomas: after subtotal resection, should radiotherapy be given postoperatively or at the time of progression? Should radiotherapy replace surgery when the risk of postoperative sequellae is high? Prospective randomized trials would be required to address these issues.

[Management of mucositis following radiotherapy for head and neck cancers]. / Prise en charge des mucites après radiothérapie des cancers des voies aérodigestives supérieures.

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Glutamide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotéricine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformal radiotherapy and intensity-modulated radiation therapy).