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.     

Les traitements de maintenance dans les cancers bronchiques non à petites cellules métastatiques en 2012

Treatment of advanced non-smallcell lung cancer is usually based on several lines of therapy separated by treatment-free intervals, in which each new line is started when tumor progression is detected. The maintenance strategy consists of continuing an appropriate, well-tolerated treatment immediately after the end of first-line chemotherapy, in order to maintain the initial therapeutic benefit and to avoid rapid clinical deterioration that would rule out further treatment. Maintenance can use either a non-platinum component of induction chemotherapy defining ‘continuation maintenance’ or initiation of a new agent consisting in ‘switch maintenance’. Clinical trials show that maintenance therapy with pemetrexed or erlotinib provides a significant clinical benefit in terms of disease control and survival. Maintenance therapy is an important option in first-line treatment of non-small cell lung cancer but more reliable criteria is needed to identify the patientsmost likely to benefit from either continuation or switch maintenance.     

Comparaison de la survie et de la toxicité chronique gastro-intestinale chez les patientes atteintes de cancer du col de l’utérus localement évolué, traité par irradiation classique ou avec modulation d’intensité

Purpose

To evaluate prospectively chronic gastrointestinal toxicity in patients with cervical cancer treated with conventional irradiation or with intensity-modulated irradiation (IMRT).

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.     

Les contraintes du chirurgien dentiste sont compatibles avec les résultats d’une irradiation optimale avec modulation d’intensité dans les cancers de l’oropharynx de stade N0

PurposeWe compared intensity-modulated radiotherapy and 3D-conformal irradiation in oropharyngeal cancers according to the requirement of dentists.Material and methodsFrom the files of seven patients with cancer of the oropharynx, two dosimetry plannings for 3D-conformal radiotherapy and intensity-modulated radiotherapy with tomotherapy were performed. The dose distributions in the target volumes and organs at risk in relation to the dental sphere were compared.ResultsFor the planning target volume of the primitive tumour sites, average values of V_95%, D_2%, D_98% and of the conformal index were statistically in favour of tomotherapy. For the planning target volume of node areas, averages values of V_95%, D_2%, D_98% were statistically in favour of tomotherapy. For ipsi- and controlateral parotide glands, average values of V_15Gy, V_26Gy, V_30Gy, V_40Gy were significantly lower for tomotherapy. For the submaxillary glands, average values of mean doses and V_40Gy were statistically in favour of tomotherapy. For the buccal cavity, the average values of V_45Gy were statistically in favour of tomotherapy. For ipsi- and controlateral masseter muscles, the average values of mean doses were statistically in favour of tomotherapy. For the ipsi- and controlateral temporomandibular joints, average values of mean doses and V_60Gy were statistically in favour of tomotherapy. For mandibular bone, average values of mean doses and V_40Gy, V_50Gy, V_60Gy and V_70Gy were statistically in favour of tomotherapy. For maxillary bone, average values of V_40Gy, V_50Gy and V_60Gy were statistically in favour of tomotherapy.ConclusionThe radiation oncologist can constrain the intensity-modulated radiotherapy dosimetry to the needs of dentists to prevent or improve dental care and quality of life.     

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.     

Toxicité aiguë cutanée de l’irradiation mammaire avec modulation d’intensité avec technique de champ dans le champ (optimisation avec pré-segmentation)

PurposeThe optimization with presegmentation irradiation technique (Dosisoft™), used in treatment of breast carcinomas, facilitates the treatment delivery and improves radioprotection. The objective of our study was to evaluate the potential impact of this innovative technique on the acute skin toxicity especially on the rate of moist desquamation during irradiation of the whole breast after conservative surgery.Patients and methodsThe scores of acute skin toxicity observed at 50 Gy in 103 patients treated with the presegmentation technique were compared to those of 101 patients with similar breast size treated with a classic 3D technique. All patients received 50 Gy/2 Gy per fraction, 5 days a week using 4 MV photon beam. The boost on the tumoural bed was realized according to conventional technique. Using the NCI-CTCAE V4, the skin toxicity was recorded every week during the medical visit. Moreover, the following factors that could induce skin toxicity have been studied: breast size, body mass index, age, prior chemotherapy, concurrent administration of trastuzumab, hypertension, diabetes, smoking habits and statin uptake.ResultsThe incidence of moist desquamation observed in all sites, has been decreased to only 9.8% in the presegmentation group versus 16.8% in the test group, the difference being not statistically significant OR = 0.53 [0.23; 1.22] (P = 0.13). In univariate analysis the presegmentation technique enabled a significant decrease of 4.4 Gy in mean, of the value of maximum dose (P = 0.001). The other risk factors of skin toxicity are the increase of breast size (P < 0.001), a high body mass index (P < 0.001), hypertension (P = 0.03) and concurrent administration of trastuzumab (P = 0.07). In multivariate analysis, the two remaining significant factors are breast size (OR = 1.004 [1.002; 1.006]) and trastuzumab administration (OR = 4.95 [1.17; 20.79]).ConclusionThe comparison of the skin toxicity induced by the presegmentation or the reference technique shows a trend regarding the improvement of the skin tolerance when using the presegmentation technique, thus pleading in favour of its use considering its dosimetric interest and the improvement of radioprotection of the patient. The next step will consist to experiment the simultaneous boost on tumoural bed using this technique.     

Évaluation monocentrique de la tolérance de l’association concomitante de trastuzumab et de radiothérapie

PurposeProspective monocentric study of the skin and heart tolerance of a concurrent administration of trastuzumab (T) and radiotherapy (RT) for breast cancer (BC).Patients and methodsFrom February 2004 to January 2007, 57 patients (pts), were treated by a concomitant administration of T and normo-fractionated RT of either whole breast (± boost) or chest. The perfusion of T started either with or after chemotherapy (CT). Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT, after completion of RT and then every four to six months with either echocardiography or multiple gated acquisition scanning, were considered normal if greater or equal to 50% or stated so by the cardiologist. Inclusion criteria included a normal LVEF at baseline. Skin toxicity was evaluated using CTCAEV3. Median age was 49 years (25–80). CT with anthracycline was administered in 84% (total dose 300 mg/m²). All but one patient (treated weekly) received T every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (6–33). The internal mammary chain was irradiated in 88% of cases. Median follow-up for LVEF assessment was 13 months (2–33).ResultsLVEF at pre-RT were normal in 54 pts (100%, three Missing Data [MD]), at post-RT in 56 pts (98%, no MD) and at last follow-up in 53 pts (95%, one MD). There were two grade 0, 44 grade I and 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after six months, late skin toxicity was grade 0 in 22 pts, grade 1 in four, grade 2 in one.ConclusionProvided that the technique is adapted, the acute skin and heart toxicities of the concomitant administration of T-RT appeared satisfactory. More patients and longer follow-up are still mandatory.     

Radiothérapie conformationnelle avec modulation d’intensité dans les cancers de la sphère ORL : éthique et sélection des patients

PurposeIntensity modulated radiotherapy (IMRT) allows a better coverage of the target volume and a better saving of organs at risk with a decrease of toxicity in head and neck cancers. It requires more human labor and materials compared to conformational radiotherapy. If they are insufficient, a selection of the patients receiving IMRT may be necessary, raising an ethical problem.Material and methodsWe collected the motives guiding the choice of the technique of radiotherapy for head and neck cancers during a month of physicists’ shortage.ResultsNineteen patients received IMRT and eight conformational radiotherapy. Conformational irradiation was chosen in palliative and postsurgery treatments, to reduce delay, in laryngeal tumors and re-irradiation. IMRT was preferred for complex target volumes and the localizations at risk of important xerostomia following conformational radiotherapy. These choices were confronted with the bioethics criteria of Beauchamp and Childress. The beneficence justified the use of IMRT or conformational radiotherapy depending on the circumstances. The non-maleficence attempted to decrease the toxicity with IMRT. Justice was questioned by the selection. The autonomy of patients was not totally respected in the choice.ConclusionTo help in the choice of the patients receiving an IMRT in a crisis situation, we proposed a hierarchical organization of selection criteria: complex volumes close to critical organs at risk, localization with high risk of xerostomia, long life expectancy and postoperative delay constraints.     

Actualités en pathologie moléculaire dans les cancers du poumon non à petites cellules

Lung cancer is the leading cause of death by cancer worldwide. The vast majority of lung tumors are non-small cell lung carcinomas (NSCLC), and surgical resection remains the only effective treatment. According to the new WHO histological classification of lung cancer, NSCLC comprise three major histological subgroups; squamous cell carcinoma, adenocarcinoma, and large cell carcinoma and its variants. The recent discovery of EGFR tyrosine kinase inhibitor-sensitive mutations in a subset of adenocarcinomas has raised hopes toward the identification of new druggable molecular alterations in all subtypes of NSCLC.     

Dose de tolérance à l’irradiation des tissus sains : les glandes salivaires

Xerostomia is one of the most a common complication of radiotherapy for head and neck cancers, affecting quality of life. Parotid glands produce approximately 60% of saliva and submandibular glands 20% of saliva while the rest is secreted by sublingual and accessory salivary glands. Methods of measuring the salivary output are collection of unstimulated or stimulated saliva or 99mTc-pertechnate scintigraphy. Several studies demonstrated that late salivary dysfunction after radiotherapy has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia could be avoided if at one parotid gland is spared to a mean dose of less than approximately 25–30 Gy. Clinical benefit of submandibular gland sparing is more controversial. A mean dose less than 39 Gy could preserve submandibular gland function. This paper aims to review main studies evaluating tolerance dose of salivary glands.     

Complément de dose de protons pour les cancers du nasopharynx localement évolués : une expérience de l’institut Curie

PurposeThe aim of this study was to assess the treatment outcome and toxicity for patients with locally advanced nasopharyngeal carcinoma treated with a complementary dose with proton.Patients and methodsBetween November 1999 and September 2016, 17 patients have been treated for a stage III–IVa nasopharyngeal carcinoma in the proton therapy centre of Curie Institute. Bilateral lymph node in the neck (I–V levels) received from 40 to 54 Gy with photon beam. The primary tumor volume including microscopically extensions received a complementary dose with proton in order to reach the dose of 70 to 78 Gy. All the patients received a concomitant chemotherapy. The end-points of the study were loco-regional control, survival, and treatment-related toxicity.ResultsPatients characteristics were: median age 49, 71 % male, 88% stage IVa, with a majority (82%) of T4N0M0. The median follow-up was 99 months. The 2-, 5- and 10-year actuarial locoregional free survival and overall survival were 94% and 88%, 86% and 74%, and 86% and 66%, respectively. The grade ≥ 3 late adverse events were sphenoid bone radionecrosis (5.9%) and hearing loss (23.5%).ConclusionThis study showed that a complementary dose with proton seems to be a good option for the treatment of locally advanced nasopharyngeal carcinoma, particularly for T4N0M0.