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.     

Cancer bronchique non à petites cellules localement évolué : place de la chimioradiothérapie exclusive

Lung cancer is the most frequent form of malignant tumours. The prognosis is poor with a 5-year cure rate which increased from approximately 6% in the sixties to only 15% in the nineties. Surgery remains the reference treatment but only a small minority of patients (about 25%) present with operable disease. The post-surgical 5-year survival is only 25%, providing the rationale for the current research on adjuvant treatments for control of both local and metastatic disease. In that context, the combination of radiotherapy and chemotherapy, commonly referred to as chemo-radiotherapy, has assumed considerable importance : either exclusively in inoperable patients (inoperable tumour or patients inoperable for medical reasons), or pre-operatively. This article reviews the results of the pivotal definitive chemoradiotherapy studies in non-metastatic non-small-cell lung cancer. With exclusive chemoradiation, the concomitant scheme seems to be the most favourable, results issued from randomised studies are expected to confirm that point. An increased toxicity is observed, and the advent of conformal therapy may allow another survival gain. Optimal treatments integration will be necessary.     

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 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.     

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.     

Association des thérapeutiques ciblées anti-EGFR avec la radio-chimiothérapie chez les patients présentant un cancer bronchique non à petites cellules localement avancé

The current standard of care for patients with locally advanced non-small cell lung cancer (NSCLC) is the concomitant administration of radiotherapy and platinum-based chemotherapy. Treatment combinations with molecular targeted agents represent a promising line of research and a chance of improving patient management. There is indeed a well-grounded preclinical rationale suggesting the existence of a synergistic action of targeted drugs and ionizing radiation, and there is extensive experimental evidence of a radiosensitizing effect of targeted therapies that inhibit EGFR activation (anti-EGFR). The preliminary clinical data currently available only demonstrate the feasibility of combining anti-EGFR treatments and radiotherapy. Nevertheless, the promising results of phase II studies testing cetuximab, a humanized monoclonal antibody targeting EGFR, and concomitant radiotherapy have led to the development of phase III studies with this agent in this setting. In this article, we briefly review the experimental data and the pre-clinical rationale for treatment strategies combining radiation and targeted chemotherapies, and then we summarize the major ongoing clinical trials.     

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.     

Préservation par chimioradiothérapie des cancers de vessie

When localized, the reference treatment of urothelial, muscle-invasive bladder tumours relies on radical cystectomy with reconstruction by enterocystoplasty if possible or Bricker bypass. Trimodal therapy combining transurethral resection of the tumour followed by concomitant chemotherapy may be considered as a therapeutic alternative to radical cystectomy in well-selected patients with unifocal tumours, stage T2, non-diverticular location, without in situ carcinoma or hydronephrosis and with macroscopically complete transurethral resection. The functional prognosis of the bladder and quality of life should be discussed with the patient as well as the need for salvage surgery for persistent tumour at a 45-Gy dose level, the latter being a highly unfavourable prognosis factor. On the other hand, this trimodal treatment is the reference in case of surgical contraindication. This article details the methods and results of the main series available in the literature in terms of local control, survival, bladder preservation rates and complications, as well as study prospects.     

Immunothérapie : un nouveau paradigme dans la prise en charge du cancer bronchique non à petites cellules

Immunotherapy, in particular immune response checkpoint inhibitors, has shown to be extremely effective in terms of survival in locally advanced or metastatic nonsmall cell lung cancer, as a second line treatment in PS 0 or PS 1 patients who have progressed following platinumbased first line chemotherapy. In squamous cell cancers, nivolumab, a PD1 antibody, enables an overall survival of 9.2 months vs 6 months to be achieved, HR = 0.59; P < 0.001; in non-squamous cell carcinoma, the benefit is of the same order (12.2 months vs 9.4 months, HR = 0.73; P = 0.002), but clearly correlated to the PDL1 expression rate by the tumour cells, with no benefit for patients without expression, and a considerable benefit for those patients with strong expression. This is confirmed through trials using pembrolizumab, another PD1 antibody, with an increase in survival over docetaxel (HR = 0.71; P = 0.0008), with a more considerable benefit seen in the sub-group of patients who have PDL1 expression > 50% and, more recently, with a PDL1 antibody, atezolizumab, which in a phase II randomised study showed an increase in survival of 12.6 vs 9.7 months compared with docetaxel, HR = 0.73; P = 0.04, which correlated with the PDL1 expression rate from the tumour and immune cells. The tolerance of these drugs is good; however, with rare, but often serious immune type events, they require specific management. Numerous questions remain unanswered regarding specific populations: the elderly, those with co-morbidities, those who are PS 2 and those with brain metastases. Finally, numerous trials are ongoing, evaluating the use of these second line immunotherapies, given concomitantly or not with chemotherapy.     

Place de la chimiothérapie et de la chimioradiothérapie dans le cancer de l’estomac localement évolué

Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. Three approaches exist abroad continents. In France and Europe, perioperative chemotherapy and gastrectomy with D1.5 lymph-node dissection is the current standard. In Japan and South Korea, postoperative adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. In the United States, where limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In France, postoperative chemoradiotherapy indications are discussed in limited settings: patients with locally advanced gastric cancer or lymph node involvement discovered on the pathologic report of the gastrectomy without preoperative chemotherapy delivery or in case of non-carcinologic resection (R1). Exclusive chemoradiotherapy can be proposed in patients unfit for surgery.     

Conséquences des traitements des cancers et préservation de la fertilité

Cancer prognosis has considerably improved over recent decades and increasing numbers of young adults live with the long-term consequences of their treatment. Their quality of life is often serious compromised by the inability to conceive a child. As such the recent and rapidly evolving practice of fertility preservation needs to become a standard option in cancer care. Embryos, oocytes, spermatozoa, and germinal tissue can be cryopreserved without damage until such time that the patient, freed from their illness can envisage starting a family. Fertility can be persevered prior to initiation of gonadotoxic treatments by different methods. Some options, in particular in prepubescent boys (and even in adolescents and young adults), though a high research priority and a source of great hope, remain highly experimental. Since the available options combine both validated and experimental methods, it is necessary that care teams are multidisciplinary and that they discuss these choices with the patient and (for children) their family. Even though some patients, through choice or otherwise, are not candidates for Fertility Preservation, their decision, taken in the light of complete, correct and understandable information about the available options, must be respected in accordance with their rights to determine their own reproductive future. The current situation in France needs improvement and multidisciplinary structures are forming where cancer specialists work closely with specialists in reproductive medicine and biology to provide rapid and coordinated patient care. The national cancer institute (INCA) with the Agence de la biomédecine have co-published a report that brings the knowledge of all involved in the care of these patients up to date and makes a series of propositions to improve the situation and notably to guarantee equitable access to quality care for all concerned persons. The principal areas of improvement are:

• — Equitably improve cancer patients’ access to fertility preservation across the country through the regional planning and establishment of multidisciplinary teams, supported by targeted funding and the authorisation of centres.
• — Publish and disseminate professional guidelines and verify that they are taken into account during multidisciplinary decision making.
• — Systematically inform patients and their families about the consequences of cancer therapy on reproductive function.
• — Set up longitudinal cohorts of patients.
• — Promote research into how to prevent or reduce the risk of the attenuation of fertility and into how to restore it.