Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. Aim: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT. Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis. Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively). In LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.

Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. Materials and methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3–5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery. Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. Materials and methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3–5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery.