[Radiotherapy for oligometastatic non-small cell lung cancer patients]. / Place de la radiothérapie dans la prise en charge des patients atteints d'un cancer bronchique non à petites cellules oligométastatique.

The oligometastatic disease concept suggests that patients with a limited number of metastases have a favorable prognosis. Radical local treatment of oligometastatic patients has then increased given developments in imaging (mainly positron emission tomography and brain magnetic resonance imaging) and access to effective and better tolerated treatments. Stereotactic radiotherapy has the advantage of being noninvasive, allowing a good rate of local control and a limited number of side effects. A better definition of oligometastatic disease, particularly for non-small cell lung cancer (NSCLC), has recently been published. For patients with NSCLC, two randomized phase II trials also suggested that the addition of a radical local treatment results in encouraging survival data, with a good safety profile. A single-arm phase II finally showed a benefit when combining a radical local treatment with an anti-PD1 immunotherapy. This review describes the definitions of oligometastatic disease, the main prospective findings including radiation therapy, and prospects for oligometastatic NSCLC patients.

RADIORYTHMIC: Phase III, Opened, Randomized Study of Postoperative Radiotherapy Versus Surveillance in Stage IIb/III of Masaoka Koga Thymoma after Complete Surgical Resection.

INTRODUCTION: Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. PATIENTS AND METHODS: Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. RESULTS: The first patient will be enrolled in January 2021, with results expected in 2028.

[Role of immunotherapy in locally advanced non-small cell lung cancer]. / 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.

[Lung cancer and elective nodal irradiation: A solved issue?] / Cancer du poumon et irradiation ganglionnaire prophylactique : un débat clos ?

Lung cancer treatment is a heavy workload for radiation oncologist and that field showed many evolutions over the last two decades. The issue about target volume was raised when treatment delivery became more precise with the development of three-dimensional conformal radiotherapy. Initially based upon surgical series, numerous retrospective and prospective studies aimed to evaluate the risk of elective nodal failure of involved-field radiotherapy compared to standard large field elective nodal irradiation. In every setting, locally advanced non-small cell lung cancer, localized non-small cell lung cancer, localized small cell lung cancer, exclusive chemoradiation or postoperative radiotherapy, most of the studies showed no significant difference between involved-field radiotherapy or elective nodal irradiation with elective nodal failure rate under 5% at 2 years, provided staging had been done with modern imaging and diagnostic techniques (positron emission tomography scan, endoscopy, etc.). Moreover, if reducing irradiated volumes are safe regarding recurrences, involved-field radiotherapy allowed dose escalation while reducing acute and late oesophageal, cardiac and pulmonary toxicities. Consequently, major clinical trials involving radiotherapy initiated in the last two decades and international clinical guidelines recommended omission of elective nodal irradiation in favour of in-field radiotherapy.

[Therapeutic options for oligoprogressive non-small cell lung cancer]. / Prise en charge thérapeutique des cancers bronchiques non à petites cellules oligoprogressifs.

Lung cancer is the leading cause of cancer-related mortality and more than half of the cases are diagnosed at a metastatic stage. Major progress in terms of systemic treatments has been achieved in recent decades. Access to new anti-PD-(L) 1 immunotherapies and targeted therapies for non-small cell lung cancer (NSCLC) with oncogenic addiction such as EGFR mutation or ALK rearrangement have led to improved outcomes. Patients with limited progression of their disease during systemic treatment may be a particular subgroup. This oligoprogressive state is characterized by a limited number of sites in progression, implying that the other sites remain controlled and therefore sensitive to systemic treatments. The advent of non-invasive techniques such as stereotactic radiotherapy, radiofrequency, and mini-invasive surgery has led to a precise re-evaluation of local ablative treatments in this situation. Local treatment of the oligoprogressive lesion(s) may allow modification of the natural history of the disease, maintenance of effective systemic targeted treatment and, ultimately, to improved survival. Data validating an aggressive local therapeutic approach in oligoprogressive NSCLC patients are currently limited and essentially retrospective. Several international trials are underway that could confirm the clinical benefit of radical local treatment in oligoprogressive advanced NSCLC patients.

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? : A planning study.

BACKGROUND: After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation. MATERIALS AND METHODS: In all, 12 consecutive stage I-IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a "selective" PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an "elective" PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a "selective" pleural irradiation plan (SPI plan) and an "elective" pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]). RESULTS: In the SPI plans, the average median dose to the S­PTV was 53.6 Gy (range 41-63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S­PTV to >58 Gy. In the EPI plans, the average median doses to the E­PTV and to the S­PTV were 48.6 Gy (range 38.5-58.7) and 49 Gy (range 38.6-59.5 Gy), respectively. No significant dose escalation was achievable. CONCLUSION: The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.