Carlo Greco

Stereotactic radiotherapy in metastatic breast cancer

The treatment of metastatic breast cancer is largely focused on systemic therapy. However, over the past decades, there has been growing interest in the use of metastasis-directed therapy in selected cases presenting with an oligometastatic phenotype, i.e. low disease burden with a more indolent biology. Identification of the oligometastatic breast cancer population has, so far, proven elusive. Stereotactic radiotherapy offers an effective, non-invasive approach to ablate metastatic disease both in the brain and in extra-cranial settings. The advent of advanced imaging techniques for target definition, along with the ability to achieve highly conformal dose deposition with steep dose fall-off, enable safe implementation of extreme hypofractionated and single fraction regimens with ablative intent. There is growing evidence that radiation-based treatments are more cost-effective when compared to other ablative modalities. This article provides preliminary evidence that metastasis-direct ablation, with advanced radiotherapy techniques, may play an important role in the management of metastatic breast cancer patients, potentially improving clinical outcomes with minimal toxicity. However, prospective randomized controlled trials are needed to further the understanding of the interaction between systemic therapy and ablative irradiation. Additionally, research in genomic and molecular profiling is needed to characterize metastatic breast cancer patients who will most likely benefit from such combined treatment approaches.

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

Phase II Study of Neoadjuvant Modified FOLFOXIRI in Locally Advanced Pancreatic Cancer

Context FOLFIRINOX has shown high activity in metastatic pancreatic cancer patients and therefore the regimen could be of interest also for patients with inoperable locally advanced disease. Our group had developed a very similar schedule in colorectal cancer named FOLFOXIRI with no bolus 5-fluorouracil and a slight lower dose of irinotecan with good tolerance and activity. Objective We have performed a phase II trial in order to prospectively evaluate the activity of a modified (m)FOLFOXIRI regimen in locally advanced pancreatic cancer. Methods mFOLFOXIRI consisted of: oxaliplatin 85 mg/m 2 , irinotecan 150 mg/m 2 and folinic acid 200 mg/m 2 on day 1, plus infusional 5-fluorouracil 2,800 mg/m 2 administered in 48 hours on days 1 to 3, with cycle repeated every 14 days. The study enrolled patients with diagnosis of pancreatic cancer, stage III locally advanced disease without evidence of metastatic disease, ECOG performance status (PS) 0 or 1, age 18-75 years. The primary end-point of the study was the percentage of patients who achieve radical surgical resection after chemotherapy; the trial was designed with a percentage of low activity of 30% and a percentage of interest of 50% with an α and β errors of 0.05 and 0.20, respectively. Results Twenty-five patients have been so far enrolled; M/F: 8/17; PS 0/1: 10/15. Median age was 60 years (range: 44-75 years). Celiac axis was involved in 9 patients, superior mesenteric artery in 11 cases, both arteries in 5 patients. Baseline computer tomography showed pathological nodes in 21 patients. Twenty-one patients have been evaluated, with 9 partial responses (43%) and 12 stable disease (57%). A local treatment after chemotherapy was received by 13 patients until now: 8 (38%) underwent to radical surgery; 1 had an explorative laparotomy with evidence of liver metastases; 4 received concomitant chemo-radiotherapy with gemcitabine. Median progression-free survival was 24.5 months and median overall survival was 30.1 months. Conclusion Chemotherapy with mFOLFOXIRI seems active in locally advanced pancreatic cancer patients and may allow to obtain a downstaging of disease leading some patients to achieve a curative surgical resection. Longer follow-up is needed to better evaluate long-term outcome of this strategy.