La chimiothérapie et la chimioradiothérapie préopératoires des cancers bronchiques non à petites cellules

The very disappointing results obtained by surgery in resectable non-small-cell lung cancer have led to a high active clinical research concerning pre- or postoperative treatment. Preoperative treatment has several distincts goals: to increase survival for patients suitable for surgery, to limit surgery or transform borderline or non resectable cancer into resectable tumors. Available datas on preoperative treatments for non-small-cell lung cancer provide from three types of therapeutics trials: 1/ Some phase II studies of neoadjuvant chemotherapy have demonstrated that the neoadjuvant approach was feasible, and didn’t compromise surgery. 2/ Phase II trials of neoadjuvant chemoradiotherapy, performed for the majority on more extensive cancers, have demonstrated that this approach was also feasible at the expense of higher but still tolerable toxicity. 3/ Phase III randomised published trials exclusively deal with preoperative chemotherapy with different results: two of them concerned a small number of patients presenting with non-small-cell lung stage IIIA cancer: they are positive. The third concerned 373 patients presenting with stage I, II, IIIA cancer: the three-year survival was increased by 11%, but this difference is not yet significant. The benefit essentially appeared for stage I and II. One trial comparing preoperative chemotherapy and radiochemotherapy has been reported, concluding to the superiority of the association. These observations suggest that the clinical research should now be different for stages I and II, and stage IIIA.     

Facteurs de récidive après radiothérapie stéréotaxique des cancers bronchiques non à petites cellules

Lung cancer is the fourth most common cancer in France with a prevalence of 30,000 new cases per year. Lobectomy surgery with dissection is the gold standard treatment for T1-T2 localized non-small cell lung carcinoma. A segmentectomy may be proposed to operable patients but fragile from a respiratory point of view. For inoperable patients or patients with unsatisfactory pulmonary function tests, local treatment with stereotactic radiotherapy may be proposed to achieve local control rates ranging from 85 to 95% at 3–5 years. Several studies have examined prognostic factors after stereotaxic pulmonary radiotherapy. We conducted a general review of the literature to identify factors affecting local control.     

Radiothérapie postopératoire des cancers bronchiques non à petites cellules : efficacité, volume cible,dose

The rate of local failure of stage IIIA-N2 non-small cell lung cancer is 20 to 40%, even if they are managed with surgery and adjuvant chemotherapy. Postoperative radiotherapy improves local control, but its benefit on global survival remains to be demonstrated. Considered for many years as an adjuvant treatment option for pN2 cancers, it continues nevertheless to be deemed too toxic. What is the current status of postoperative radiotherapy? The Lung Adjuvant Radiotherapy Trial (Lung ART) phase III trial should give us a definitive, objective response on global survival, but inclusion of patients is difficult. The results are consequently delayed. The aim of this review is to show all the results about efficacy and tolerance of postoperative radiotherapy and to define the target volume and dose to prescribe.     

Radiothérapie conformationnelle avec modulation d’intensité dans les carcinomes bronchiques non à petites cellules

Intensity modulated radiotherapy is increasingly used in non-small-cell lung cancers despite a low level of evidence. A literature review was conducted. Several critical physical and dosimetric uncertainties are however unsolved. Methods to circumvent these limitations are being developed. In several retrospective studies, survival rates were at least similar with intensity-modulated radiotherapy as those reported with three-dimensional irradiation. To date, intensity modulated radiotherapy might be authorized in complex anatomical situations such as tumours close to the spinal cord (such as Pancoast Tobias, paraspinal and paracardiac tumours) or with limited motion amplitudes. Dosimetric benefits should also account for 4D dose distribution issues. The reduction of intermediate and high doses in the organs at risk with intensity modulated radiotherapy is advantageous. However, the effect of low doses in large volumes (lung, bone, unspecified tissues along beam paths) and the effect of increasing integral dose are still poorly known. In conclusion, dose–volume correlations need to be better documented and prospective randomized trials should be encouraged.     

Radiothérapie hypofractionnée des cancers ORL chez le sujet âgé

Thirty percent of patients with head and neck cancer are over 70 years. Radiotherapy approach in elderly is a challenge. On one hand, radiotherapy side effects, as well as the number of sessions required, could be a burden. On the other hand, omission of local treatment is not an option due to the symptoms of the tumor. Patients in good general condition may receive standard fractionnated radiotherapy. For frail patients unsuitable for standard fractionated radiotherapy, more convenient shorter course of radiotherapy are commonly used. Physicians have to choose the best radiotherapy schedule according to the objective of the treatment. In case of palliative intend: hypofractionated radiotherapy delivered with a single short course could be recommanded. This course could be followed by other subsequent courses if the patient's condition improves during the treatment. For patients treated in curative intend, the choice of hypofractionation schedule depends on the general condition: split course hypofractionated radiotherapy for unfit patients, or accelerated radiotherapy with concomitant boost for fit patients. In all cases, a high-quality radiotherapy technique and appropriate supportive care are mandatory to minimize the side effects. The ELAN RT trial, soon to be completed, will rule on the non-inferiority of hypofractionated radiotherapy compared to standard radiotherapy for unfit patients.     

Résections carcinologiques limitées des cancers non à petites cellules du poumon

It has been proved that lobectomy for lung cancer of less than 3 cm is superior to sublobar resection (segmentectomy and wedge resection) in the Lung Cancer Study Group trial published in 1995. Lobectomy is therefore recommended, with lymph node resection. Nevertheless, some publications have shown identical or close results after segmentectomy for tumors of less than 2 cm, and after wedge resection for tumors of less than 1 cm. It is likely that local recurrences are avoided by respecting a macroscopic margin of more than 2 cm around the tumor. A new trial comparing lobectomy and sublobar resection has been ongoing since 2007 for tumors of less than 2 cm. Persistent ground glass opacities are now often discovered after screening, either pure or with a small solid component, and correspond to an in situ or a micro-invasive adenocarcinoma, that can be removed with sublobar resection without recurrence.     

Radiothérapie hypofractionnée des cancers du rectum chez le sujet âgé

Rectal cancer is a common pathology in the elderly. The standard for advanced rectal tumors is a chemoradiotherapy regimen combined 50 Gy with concomitant chemotherapy followed by a surgery. This treatment induces interruptions of chemoradiotherapy and toxicities G3–4 more important in people over 70 years of age. Hypofractionated radiotherapy 5 × 5 Gy with surgery following week is an alternative. All retrospective studies on this fractionation report an excellent immediate and chronic tolerance. The randomized phase III NACRE trial, comparing these 2 radiotherapy, followed by surgery at 6–8 week, established a standard in the management of the elderly patients.     

Radiothérapie en conditions stéréotaxiques des cancers bronchiques de stade I

Stereotactic body radiotherapy (SBRT) is an innovative irradiation technique which delivers high dose per fraction in a highly accurate way. It allows to treat medically inoperable patients with non-small cell lung cancer, with impressive local control rates and a very little toxicity. The different SBRT techniques available are presented in this article. Results from literature studies of SBRT for stage I non-small cell lung cancer are reviewed.     

Traitements systémiques des métastases cérébrales (MC) des cancers bronchiques à petites cellules (CPC)

Patients with small cell lung cancer present initially with brain metastases in 10 to 24 % of the cases when detected respectively by CT scan or Gadolinium-enhanced MRI of the brain. The aim of this review is to evaluate the effectiveness of systemic chemotherapy for the treatment of brain metastases from small cell lung cancer in first and second line: in fact, there are only case reports, small phase II studies and one phase III study. In spite of the scarcity of these data, the efficacy of the systemic treatment is shown and the guidelines recommend the use of chemotherapy, particularly in asymptomatic patients.     

Radiothérapie axillaire prophylactique des cancers du sein

Adjuvant radiotherapy, after breast conserving surgery or mastectomy for breast cancer, improves overall survival while decreasing the risk of recurrence. However, prophylactic postoperative radiotherapy of locoregional lymph nodes for breast cancer, particularly of the axillary region, is still controversial since the benefits and the risks due to axillary irradiation have not been well defined. To begin with, when performing conformal radiotherapy, volume definition is crucial for the analysis of the risk–benefit balance of any radiation treatment. Definition and contouring of the axillary lymph node region is discussed in this work, as per the recommendations of the European Society for Radiotherapy and Oncology (ESTRO). Axillary recurrences are rare, and the recent trend leads toward less aggressive surgery with regard to the axilla. In this literature review we present the data that lead us to avoid adjuvant axillary radiotherapy in pN0, pN0i+ and pN1mi patients even without axillary clearance and to perform it in some other situations. Finally, we propose an update about the potential toxicity of adjuvant axillary irradiation, which is essential for therapeutic decision-making based on current evidence, and to guide us in the evolution of our techniques and indications of axillary radiotherapy.     

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.     

Radiothérapie postopératoire des cancers de la prostate

Between 10 and 40% of patients who have undergone a radical prostatectomy may have a biologic recurrence. Local or distant failure represents the possible patterns of relapse. Patients at high-risk for local relapse have extraprostatic disease, positive surgical margins or seminal vesicles infiltration or high Gleason score at pathology. Three phase-III randomized clinical trials have shown that, for these patients, adjuvant irradiation reduces the risk of tumoral progression without higher toxicity. Salvage radiotherapy for late relapse allows a disease control in 60–70% of the cases. Several research in order to improve the therapeutic ratio of the radiotherapy after prostatectomy are evaluate in the French Groupe d’Étude des Tumeurs Urogénitales (Gétug) and of the French association of urology (Afu). The Gétug-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. The Gétug-Afu 22 questions the place of a short hormonetherapy combined with image-guided, intensity-modulated radiotherapy (IMRT) in adjuvant situation for a detectable prostate specific antigen (PSA). The implementation of a multicenter quality control within the Gétug-Afu in order to harmonize a modern postoperative radiotherapy will allow the development of a dose escalation IMRT after surgery.     

Guide de bonne pratique pour la radiothérapie thoracique exclusive ou postopératoire des carcinomes non à petites cellules

The objective was the drafting of a practical document intended for radiotherapists and radiophysicists, describing the technique of irradiation of a non small cell bronchial cancer. The good practices concern the care of patients affected by bronchial cancer localized in the thorax and inoperable or patients who must undergo postoperative irradiation. The document has been developed according to a methodology aiming to join the current scientific data from an analysis of the literature on the subject and the assessment of radiotherapists, radiophysicists, lung specialists and methodologists from Rhône-Alpes area. From the stages necessary for the good progress of a radiotherapy, the writers of this document proposed common definitions concerning the centering and the location of the zone to be treated, the calculation of the dose distribution, the preparation of the patient for the treatment, the treatment and the surveillance during the treatment. The recommendations of this guide took into account the peculiarities bound to the nature of the treated region and more particularly the lung heterogeneity, respiratory movements and the radiosensibility of healthy lung tissue. Even if the technical aspect of the radiotherapy was particularly developed, the interest accorded to patient information takes on all its importance for a therapeutic coverage of quality. The authors of the document wished that this Guide of Good Practices, which will be regularly updated, helps the radiotherapists and allows them to harmonize their practices.     

Place de l’immunothérapie dans le cancer bronchique non à petites cellules localement avancé

Concomitant radiochemotherapy has been the standard of care for unresectable stage III non-small cell lung cancer (NSCLC), irrespective of histological sub-type or molecular characteristics. Currently, only 15–30 % of patients are alive five years after radiochemotherapy, and this figure remains largely unchanged despite multiple phase III randomised trials. In recent years, immune-checkpoint blockades with anti-PD-(L)1 have revolutionised the care of metastatic NSCLC, becoming the standard front- and second-line strategy. Several preclinical studies reported an increased tumour antigen release, improved antigen presentation, and T-cell infiltration in irradiated tumours. Immunotherapy has therefore recently been evaluated for patients with locally advanced stage III NSCLC. Following the PACIFIC trial, the anti-PD-L1 durvalumab antibody has emerged as a new standard consolidative treatment for patients with unresectable stage III NSCLC whose disease has not progressed following concomitant platinum-based chemoradiotherapy. Immunoradiotherapy therefore appears to be a promising association in patients with localised NSCLC. Many trials are currently evaluating the value of concomitant immunotherapy and chemoradiotherapy and/or consolidative chemotherapy with immunotherapy in patients with locally advanced unresectable NSCLC.