Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.

National trends and perioperative outcomes of robotic resection of thymic tumours in the United States: a propensity matching comparison with open and video-assisted thoracoscopic approaches†.

OBJECTIVES: Despite the recent increased rate of adoption of robotic approaches for the resection of thymic tumours, their use is still limited to large-volume academic centres. To date, a large-scale analysis of the robotic approach has not been performed. We assessed the recent trends and outcomes of robotic thymectomies in the United States compared to those of open and video-assisted thoracoscopic surgical (VATS) approaches. METHODS: The National Cancer Database was queried for patients who underwent resection for thymic tumours (2010-2014). Predictors of using the robotic approach were estimated by logistic regression analysis. Propensity matching analysis (robotic versus open and robotic versus VATS) was done (1:1-caliper 0.05), controlling for age, gender, comorbidity index, induction treatment, tumour size and tumour extension. RESULTS: A total of 2558 thymectomies were performed (robotic = 300, VATS = 280, open = 1978). The use of a robotic approach increased from 6% (2010) to 14% (2014). The number of hospitals performing at least 1 robotic thymectomy increased from 22 (2010) to 52 (2014). Independent predictors influencing the choice of a robotic approach included an academic research/integrated cancer programme [odds ratio (OR) 1.66, confidence interval (CI) 1.22-2.27], later year of diagnosis (2014; OR 2.23, CI 1.31-3.80) and a patient's race (Asian) (OR 1.68, CI 1.05-2.69). A robotic approach was less likely to be utilized in midwestern hospitals (OR 0.65, CI 0.42-0.99), in larger tumours (cm) (OR 0.85, CI 0.80-0.90), with invasion of adjacent organs (OR 0.55, CI 0.37-0.82), thymic carcinoma (OR 0.62, CI 0.40-0.97) and following induction chemotherapy (OR 0.22, CI 0.08-0.61). In a propensity-matched analysis, there were no differences in the incidence of positive margins, nodal dissection, 30-day readmission rates and 30-/90-day mortality rates between the groups. However, a robotic approach was associated with fewer conversions compared to VATS, with a trend towards a shorter length of stay compared to an open approach. There were no differences in the 5-year overall survival rate between the matched groups (robotic 93% vs VATS 94%; P = 0.571; robotic 91% vs open 80%; P = 0.094). CONCLUSIONS: Over a 4-year study period, there was a significant increase in robotic utilization for thymectomies and an increase in the number of hospitals performing the procedure. In a matched analysis, a robotic approach was comparable to a VATS or an open approach. Current trends demonstrate increased robotic utilization for small thymomas with excellent perioperative results.

Anatomical Segmentectomy and Wedge Resections Are Associated with Comparable Outcomes for Patients with Small cT1N0 Non-Small Cell Lung Cancer.

OBJECTIVES: Sublobar resection is advocated for patients with NSCLC and compromised cardiopulmonary reserve, and for selected patients with early stage disease. Anatomic segmentectomy (AS) has traditionally been considered superior to wedge resection (WR), but well-balanced comparative studies are lacking. We hypothesize that WR and AS are associated with comparable oncologic outcomes for patients with cT1N0 NSCLC. METHODS: A retrospective review of a prospective database was performed (2000-2014) for cT1N0 patients, excluding patients with multiple primary tumors, carcinoid tumors, adenocarcinoma in situ, and minimally invasive adenocarcinoma. Demographic, clinical, and pathological data were reviewed. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Multivariable analysis (MVA) of factors affecting DFS was performed by Cox regression analysis. For further comparison of the effect of resection type on survival, propensity score matching (i.e., by age, sex, Charlson comorbidity index, percent forced expiratory volume in 1 second (FEV1%), clinical tumor size, and tumor maximum standardized uptake value) was performed to obtain balanced cohorts of patients undergoing WR and AS (n = 76 per group). RESULTS: Two hundred eighty-nine patients met our selection criteria, including WR in 160 and AS in 129. Poor performance status and limited cardiopulmonary reserve were the primary indications for sublobar resection in 76% of WR patients and in 62% of AS patients (p = 0.011). Thirteen patients (4.5%) had pN1/2 disease. Patients undergoing AS were more likely to have nodal sampling/dissection [123 (95%) versus 112 (70%); p < 0.001], more stations sampled (3 versus 2; p < 0.001), and more total nodes resected (7 versus 4; p = 0.001). However, there was no difference between patients undergoing WR versus AS in local recurrence [15 versus 14; p = 0.68] or 5-year DFS (51% versus 53%; p = 0.7; median follow-up 34 months). Univariate analysis showed no effect of extent of resection on DFS [hazard ratio 1.07 (95% confidence interval 0.74-1.56); p = 0.696]. MVA showed that only tumor maximum standardized uptake value was associated with worse DFS [hazard ratio 1.07 (95% confidence interval 1.01-1.13); p = 0.016]. In the propensity-matched analysis of balanced subgroups, there was also no difference (p = 0.950) in 3- or 5-year DFS in cT1N0 patients undergoing WR (65% and 49%) or AS (68% and 49%). CONCLUSIONS: Our data show that WR and AS are comparable oncologic procedures for carefully staged cT1N0 NSCLC patients. Although AS is associated with a more thorough lymph node dissection, this did not translate to a survival benefit in this patient population with a low rate of nodal metastases.

Cesium-131 permanent seed brachytherapy: dosimetric evaluation and radiation exposure to surgeons, radiation oncologists, and staff.

PURPOSE: Cesium-131 ((131)Cs) radioactive seed is Food and Drug Administration approved for permanent seed implant for all cancers, including lung and head and neck (HN) cancers. We describe the first clinical report of (131)Cs dosimetry and exposure rates to treating physicians and staff. METHODS AND MATERIALS: Twenty-eight patients received (131)Cs implant for early stage lung and recurrent HN cancers. A nomogram was developed to calculate the number of seeds needed to cover the wedge line with the prescription dose (80 Gy). Final dosimetry was obtained after CT planning a few days following the surgical procedure. Radiation exposure to the treating physicians and staff was measured at the completion of the procedure. RESULTS: A nomogram was developed using the variseed software with source data from American Association of Physicists in Medicine TG-43 report. The total volume covered by the prescription isodose line of (131)Cs was measured and compared with (125)I. The prescription volume was smaller for (131)Cs. In addition, the exposure rate with (131)Cs was found to be acceptable. CONCLUSION: Our preliminary experience with (131)Cs lung and HN brachytherapy has been very encouraging with excellent dosimetric coverage and acceptable exposure to the treating physicians and staff.