for the Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung (SAFRON) II Study Investigators IMPORTANCE Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases.OBJECTIVE To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases.DESIGN, SETTING, AND PARTICIPANTS This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cm from any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years.INTERVENTIONS Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis. MAIN OUTCOMES AND MEASURESThe main outcome was grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale).RESULTS Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P = .13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P = .44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P > .99). There were no significant differences observed in patient-reported outcomes. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies.

Background: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. Patients and methods: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) !35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n ¼ 31) or DCF þ 45 Gy radiotherapy (DCFRT, n ¼ 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). Results: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. Conclusions: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. Trial registration: ACTRN12609000665235.

In this study no differences between nCT and nCRT were seen in postoperative complications and in-hospital mortality in patients treated for EAC. Inspite of improved complete resection and pathological response there was no difference in the overall survival between the treatment modalities.

BackgroundStereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases.Methods/DesignThe TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study.DiscussionFractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR.Trials registrationACTRN12613001157763, registered 17th October 2013

Extension of very long baseline interferometry (VLBI) to observing wavelengths shorter than 1.3mm provides exceptional angular resolution (~20 μas) and access to new spectral regimes for the study of astrophysical phenomena. To maintain phase coherence across a global VLBI array at these wavelengths requires that ultrastable frequency references be used for the heterodyne receivers at all participating telescopes. Hydrogen masers have traditionally been used as VLBI references, but atmospheric turbulence typically limits (sub) millimeter VLBI coherence times to ~1-30 s. Cryogenic Sapphire Oscillators (CSO) have better stability than Hydrogen masers on these time scale and are potential alternatives to masers as VLBI references. Here, We describe the design, implementation and tests of a system to produce a 10 MHz VLBI frequency standard from the microwave (11.2 GHz) output of a CSO. To improve long-term stability of the new reference, the CSO was locked to the timing signal from the Global Positioning System satellites and corrected for the oscillator aging. The long-term performance of the CSO was measured by comparison against a hydrogen maser in the same laboratory. The superb short-term performance, along with the improved long-term performance achieved by conditioning, makes the CSO a suitable reference for VLBI at wavelengths less than 1.3mm.

SBRT compared to 20.2 months in the combined group (HR¼1.3; p<0.001; CI: 1.22-1.44). Conclusion: SBRT should be the sole modality treatment for patients with inoperable stage I NSCLC. However, patients with stage II disease appear to benefit from adjuvant chemotherapy. Randomized trials are needed in this area to answer this question conclusively.

In our SCLC cohort, median OS following PCI in LS-SCLC and ES-SCLC is comparable to published data. PCI use at our institution was lower than utilization rates in large meta-analyses, predominately due to poor chemotherapy tolerance and patient suitability. This may be more representative of patients treated in clinical practice rather than those recruited into large phase III trials.

IntroductionThe aim of this study was to compare various coplanar and non‐coplanar 3‐dimensional conformal radiation therapy (3DCRT) beam arrangements for the delivery of stereotactic ablative radiation therapy (SABR) to patients with early stage lung cancer, based on the dosimetric criteria from the Radiation Therapy Oncology Group (RTOG) 1021 protocol.MethodsTen medically inoperable lung cancer patients eligible for SABR were re‐planned using three different coplanar and three different non‐coplanar beam arrangements. The plans were compared by assessing planning target volume (PTV) coverage, doses to normal tissues, the high‐dose conformity (conformity index) and intermediate dose spillage as defined by the D2cm, (the dose at any point 2 cm away from the PTV), and the R50% (the ratio of the volume of half the prescription dose to the volume of the PTV).ResultsSixty plans in total were assessed. Mean PTV coverage with the prescription isodose was similar between coplanar (95.14%) and non‐coplanar (95.26%) techniques (P = 0.47). There was significant difference between all coplanar and all non‐coplanar fields for the R50% (P < 0.0001) but none for the D2cm (P = 0.19). The seven and nine field beam arrangements with two non‐coplanar fields had less unacceptable protocol deviations (10 and 7) than the seven and nine field plans with only coplanar fields (13 and 8). The 13 field coplanar fields did not improve protocol compliance with eight unacceptable deviations. The 10 field non‐coplanar beam arrangement achieved best compliance with the RTOG 1021 dose criteria with only one unacceptable deviation (maximum rib dose).ConclusionA 3DCRT planning technique using 10 fields with ≥6 non‐coplanar beams best satisfied high and intermediate dose constraints stipulated in the RTOG 1021 trial. Further investigations are required to determine if minor protocol deviations should be balanced against efficiency with the extended treatment times required to deliver non‐coplanar fields and if treatment times can be improved using novel intensity modulated techniques.