A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer

Introduction: For unresectable stage III non-small cell lung cancer (NSCLC), the standard therapy consists of chemoradiotherapy (CRT) followed by durvalumab maintenance for responding patients. The present study reports on the safety and outcome of durvalumab use after CRT in a real-world, multicenter, retrospective cohort. Methods: Two hundred thirty-eight patients have been included. We collected data on systemic therapy, radiation therapy, the timing between CRT and durvalumab, number of durvalumab cycles, reasons for non-starting or discontinuation, incidence and grade of adverse events (AEs), and progression-free survival (PFS) and overall survival (OS). Results: One hundred fifty-five patients out of 238 (65.1%) received at least one durvalumab dose: 91 (58.7%) after concomitant CRT (cCRT) and 64 (41.3%) after sequential CRT (sCRT). Programmed-death ligand 1 (PD-L1) status was unknown in 7/155 (4.5%), negative in 14 (9.1%), and positive ≥1% in 134/155 (86.4%). The main reasons for non-starting durvalumab were progression (10.1%), PD-L1 negativity (7.5%), and lung toxicity (4.6%). Median follow-up time was 14 months (range 2–29); 1-year PFS and OS were 83.5% (95%CI: 77.6–89.7) and 97.2% (95%CI: 94.6–99.9), respectively. No significant differences in PFS or OS were detected for cCRT vs. sCRT, but the median PFS was 13.5 months for sCRT vs. 23 months for cCRT. Potentially immune-related AEs were recorded in 76/155 patients (49.0%). Pneumonitis was the most frequent, leading to discontinuation in 11/155 patients (7.1%). Conclusions: Durvalumab maintenenace after concurrent or sequential chemoradiation for unresectable, stage III NSCLC showed very promising short-term survival results in a large, multicenter, restrospective, real-world study. Durvalumab was the first drug obtaining a survival benefit over CRT within the past two decades, and the present study contributes to validating its use in clinical practice

Intra-fraction setup variability: IR optical localization vs. X-ray imaging in a hypofractionated patient population

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to investigate intra-fraction setup variability in hypo-fractionated cranial and body radiotherapy; this is achieved by means of integrated infrared optical localization and stereoscopic kV X-ray imaging.</p> <p>Method and Materials</p> <p>We analyzed data coming from 87 patients treated with hypo-fractionated radiotherapy at cranial and extra-cranial sites. Patient setup was realized through the ExacTrac X-ray 6D system (BrainLAB, Germany), consisting of 2 infrared TV cameras for external fiducial localization and X-ray imaging in double projection for image registration. Before irradiation, patients were pre-aligned relying on optical marker localization. Patient position was refined through the automatic matching of X-ray images to digitally reconstructed radiographs, providing 6 corrective parameters that were automatically applied using a robotic couch. Infrared patient localization and X-ray imaging were performed at the end of treatment, thus providing independent measures of intra-fraction motion.</p> <p>Results</p> <p>According to optical measurements, the size of intra-fraction motion was (<it>median ± quartile</it>) 0.3 ± 0.3 mm, 0.6 ± 0.6 mm, 0.7 ± 0.6 mm for cranial, abdominal and lung patients, respectively. X-ray image registration estimated larger intra-fraction motion, equal to 0.9 ± 0.8 mm, 1.3 ± 1.2 mm, 1.8 ± 2.2 mm, correspondingly.</p> <p>Conclusion</p> <p>Optical tracking highlighted negligible intra-fraction motion at both cranial and extra-cranial sites. The larger motion detected by X-ray image registration showed significant inter-patient variability, in contrast to infrared optical tracking measurement. Infrared localization is put forward as the optimal strategy to monitor intra-fraction motion, featuring robustness, flexibility and less invasivity with respect to X-ray based techniques.</p

Hypofractionated proton therapy for non-small cell lung cancer: Ready for prime time? A systematic review and meta-analysis

Background: Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define indications, prescription doses and potential adverse events of protons in this clinical scenario. Hence, the present work aims to provide a critical literature revision, and to investigate associations between fractionation schedules/ biological effective doses (BEDs), oncological outcomes and toxicities. Materials and methods: This systematic review and meta-analysis complied with the PRISMA recommendations. Inclusion criteria were: 1) curative-intent hypofractionated PBT for ES-NSCLC (≥3 Gy(RBE)/fraction), 2) report of the clinical outcomes of interest, 3) availability of full-text written in English. The bibliographic search was performed on the NCBI Pubmed, Embase and Scopus in September 2021; no other limitations were applied. The BED was calculated for each included study (α/β = 10 Gy); the median BED for all studies was used as a threshold for stratifying selected evidence into "high" and "low"-dose subgroups. Heterogeneity was tested using chi-square statistics; inconsistency was measured with the I2 index. Pooled estimate was obtained by fitting both the fixed-effect and the DerSimonian and Laird random-effect model. Results: Eight studies and 401 patients were available for the meta-analysis; median follow-up was 32.8 months. The median delivered BED was 105.6 Gy(RBE). A BED ≥ 105.6 Gy(RBE) consistently provided superior OS, CSS, DFS and LC rates (i.e.: 4-year OS: 0.56 [0.34-0.76] for BED < 105.6 Gy(RBE) and 0.78 [0.64-0.88] for BED ≥ 105.6 Gy(RBE)). The meta-analysis of proportions showed a comparable probability of developing acute grade ≥ 2 toxicity between the two groups, while the probability of any late grade ≥ 2 event was almost three-times greater for BED ≥ 105.6 Gy(RBE), with rib fractures being more common in the high dose group. Conclusion: Hypofractionated PBT is a safe and effective treatment option for ES-NSCLC; the delivery of BED ≥ 105.6 Gy(RBE) with advanced techniques for uncertainty management has been associated with improved oncological outcomes across all considered time points. Keywords: Biological effective dose; Hypofractionation; Meta-analysis; Non-small cell lung cancer; Proton beam therapy

The Impact of Multidisciplinary Team Meetings on Patient Management in Oncologic Thoracic Surgery: A Single-Center Experience

Background: the aim of this paper is to quantify multidisciplinary team meeting (MDT) impact on the decisional clinical pathway of thoracic cancer patients, assessing the modification rate of the initial out-patient evaluation. Methods: the impact of MDT was classified as follows: confirmation: same conclusions as out-patient hypothesis; modification: change of out-patient hypothesis; implementation: definition of a clear clinical track/conclusion for patients that did not receive any clinical hypothesis; further exams required: the findings that emerged in the MDT meeting require further exams. Results: one thousand consecutive patients evaluated at MDT meetings were enrolled. Clinical settings of patients were: early stage lung cancer (17.4%); locally advanced lung cancer (27.4%); stage IV lung cancer (9.8%); mesothelioma (1%); metastases to the lung from other primary tumors (4%); histologically proven or suspected recurrence from previous lung cancer (15%); solitary pulmonary nodule (19.2%); mediastinal tumors (3.4%); other settings (2.8%). Conclusions: MDT meetings impact patient management in oncologic thoracic surgery by modifying the out-patient clinical hypothesis in 10.6% of cases; the clinical settings with the highest decisional modification rates are &ldquo;solitary pulmonary nodule&rdquo; and &ldquo;proven or suspected recurrence&rdquo; with modification rates of 14.6% and 13.3%, respectively

The Impact of Multidisciplinary Team Meetings on Patient Management in Oncologic Thoracic Surgery: A Single-Center Experience

Background: the aim of this paper is to quantify multidisciplinary team meeting (MDT) impact on the decisional clinical pathway of thoracic cancer patients, assessing the modification rate of the initial out-patient evaluation. Methods: the impact of MDT was classified as follows: confirmation: same conclusions as out-patient hypothesis; modification: change of out-patient hypothesis; implementation: definition of a clear clinical track/conclusion for patients that did not receive any clinical hypothesis; further exams required: the findings that emerged in the MDT meeting require further exams. Results: one thousand consecutive patients evaluated at MDT meetings were enrolled. Clinical settings of patients were: early stage lung cancer (17.4%); locally advanced lung cancer (27.4%); stage IV lung cancer (9.8%); mesothelioma (1%); metastases to the lung from other primary tumors (4%); histologically proven or suspected recurrence from previous lung cancer (15%); solitary pulmonary nodule (19.2%); mediastinal tumors (3.4%); other settings (2.8%). Conclusions: MDT meetings impact patient management in oncologic thoracic surgery by modifying the out-patient clinical hypothesis in 10.6% of cases; the clinical settings with the highest decisional modification rates are “solitary pulmonary nodule” and “proven or suspected recurrence” with modification rates of 14.6% and 13.3%, respectively

Unmet needs in the management of unresectable stage III non-small cell lung cancer: a review after the 'radio talk' webinars

Introduction Stage III non-small cell lung cancer (NSCLC) is a variable entity, encompassing bulky primary tumors, nodal involvement, or both. Multidisciplinary evaluation is essential to discuss multiple treatment options, to outline optimal management, and to examine the main debated topics and critical issues not addressed by current trials and guidelines that influence daily clinical practice. Areas covered From March to 5 May 2021 ,meetings were scheduled in a webinar format titled 'Radio Talk' due to the COVID-19 pandemic; the faculty was composed of 6 radiation oncologists from 6 different Institutions of Italy, all of them were the referring radiation oncologist for lung cancer treatment at their respective departments and were or had been members of AIRO (Italian Association of Radiation Oncology) Thoracic Oncology Study Group. The topics covered included: pulmonary toxicity, cardiac toxicity, radiotherapy dose, fractionation and volumes, unfit/elderly patients, multidisciplinary management. Expert opinion The debate was focused on the unmet needs triggered by case reports, personal experiences and questions; the answers were often not univocal; however, the exchange of opinion and the contribution of different centers confirmed the role of multidisciplinary management and the necessity that the most critical issues should be investigated in clinical trials

Treatment of uterine sarcoma at the University of Florence from 1980-2001

PURPOSE: To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed. PATIENTS AND METHODS: Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively. RESULTS: At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy. CONCLUSIONS: Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients