Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study.

INTRODUCTION: ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program. METHODS: Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival. RESULTS: Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data. CONCLUSIONS: Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.

[Interest of robotic stereotactic radiosurgery in the management of brain metastases: Results of a retrospective, single center analysis]. / Place de la radiochirurgie stéréotaxique robotisée dans la prise en charge des métastases cérébrales : résultats d'une analyse rétrospective monocentrique.

PURPOSE: The management of malignant brain metastases becomes a main issue for the treatment of patients, because of the survival extension related to the improvement in systemic treatments. Robotic stereotactic radiosurgery (RSR) is a new approach in this indication. The purpose of this analysis was to define the efficacy of RSR, in order to determine prognostic factors of survival and factors of response. PATIENTS AND METHODS: It was a retrospective, single center (polyclinique de Bordeaux Nord Aquitaine) analysis performed from 2012 to 2015, involving patients with malignant brain metastases treated by RSR using the Cyberknife® technique. We analyzed the following parameters: response to RSR, prognostic and predictive factors of response, and survival. RESULTS: A total of 72 RSRs were performed among 55 analyzed patients; 62 treatments were assessable with a median follow-up of 9.4 months. The main delivered dose on the 80%-isodose was 20Gy. A complete response was achieved in 40.3% of patients (stability or regression=83.9%). The overall survival was 13 months. The risk of failure was significantly correlated with the increase in metastasis size and non-adenocarcinoma histology. A performance status<2 was the main prognostic factor of survival. CONCLUSIONS: The RSR allowed treating 3 to 5 brain metastases, avoiding an entire brain irradiation, and maintaining survival and quality of life.

Hypoxia imaging with [18F]-FMISO-PET for guided dose escalation with intensity-modulated radiotherapy in head-and-neck cancers.

BACKGROUND AND PURPOSE: Positron emission tomography (PET) with [(18)F]-fluoromisonidazole ([(18)F]-FMISO) provides a non-invasive assessment of hypoxia. The aim of this study is to assess the feasibility of a dose escalation with volumetric modulated arc therapy (VMAT) guided by [(18)F]-FMISO-PET for head-and-neck cancers (HNC). PATIENTS AND METHODS: Ten patients with inoperable stages III-IV HNC underwent [(18)F]-FMISO-PET before radiotherapy. Hypoxic target volumes (HTV) were segmented automatically by using the fuzzy locally adaptive Bayesian method. Retrospectively, two VMAT plans were generated delivering 70 Gy to the gross tumour volume (GTV) defined on computed tomography simulation or 79.8 Gy to the HTV. A dosimetric comparison was performed, based on calculations of tumour control probability (TCP), normal tissue complication probability (NTCP) for the parotid glands and uncomplicated tumour control probability (UTCP). RESULTS: The mean hypoxic fraction, defined as the ratio between the HTV and the GTV, was 0.18. The mean average dose for both parotids was 22.7 Gy and 25.5 Gy without and with dose escalation respectively. FMISO-guided dose escalation led to a mean increase of TCP, NTCP for both parotids and UTCP by 18.1, 4.6 and 8% respectively. CONCLUSION: A dose escalation up to 79.8 Gy guided by [(18)F]-FMISO-PET with VMAT seems feasible with improvement of TCP and without excessive increase of NTCP for parotids.

[Guidelines for delineation of pelvic lymph nodes in anal cancer treatment]. / Recommandations pour la délinéation des aires ganglionnaires pelviennes dans le cancer du canal anal.

Squamous cell anal cancer is a rare malignancy, its incidence increases due to higher exposure of the young adults to risk factors. The current management is based on chemoradiotherapy, which is highly effective and achieves locoregional control but causes important morbidity. Improvement of radiation technique such as intensity modulated radiation therapy has led to reduce acute toxicities, but also requires an accurate delineation of the target volumes in order not to underestimate potential and pathological sites resulting in an increase of the locoregional failures. PET scanner has an important place in the pretreatment work-up for staging and targeting the delineation of the volumes, allowing to select patients with localized disease, avoid geographic miss and appropriately boost nodal disease. The study of recurrences sites has not yet provided a real mapping of the recurrences depending on the treatment volumes. Different radiation oncologist cooperative groups have published guidelines and tools for delineation, in order to provide homogeneity but also customize the management of anal carcinoma.