Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy ...(SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749 ; ROSEL: NCT00687986 ). Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0–47·3) for the SABR group and 35·4 months (18·9–40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio HR 0·14 95% CI 0·017–1·190, log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0·69 95% CI 0·21–2·29, log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three 10% chest wall pain, two 6% dyspnoea or cough, and one 3% fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four 15% patients), chest pain (four 15% patients), and lung infections (two 7%). Interpretation SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Funding Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.
Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit.
Dutch scientific and ...health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment.
By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results.
Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.
Clinical validation and quantitative evaluation of computed tomography (CT) image autosegmentation using Smart Probabilistic Image Contouring Engine (SPICE).
CT images of 125 treated patients (32 ...head and neck HN, 40 thorax, 23 liver, and 30 prostate) in 7 independent institutions were autosegmented using SPICE and computational times were recorded. The number of structures autocontoured were 25 for the HN, 7 for the thorax, 3 for the liver, and 6 for the male pelvis regions. Using the clinical contours as reference, autocontours of 22 selected structures were quantitatively evaluated using Dice Similarity Coefficient (DSC) and Mean Slice-wise Hausdorff Distance (MSHD). All 40 autocontours were evaluated by a radiation oncologist from the institution that treated the patients.
The mean computational times to autosegment all the structures using SPICE were 3.1 to 11.1 minutes per patient. For the HN region, the mean DSC was >0.70 for all evaluated structures, and the MSHD ranged from 3.2 to 10.0 mm. For the thorax region, the mean DSC was 0.95 for the lungs and 0.90 for the heart, and the MSHD ranged from 2.8 to 12.8 mm. For the liver region, the mean DSC was >0.92 for all structures, and the MSHD ranged from 5.2 to 15.9 mm. For the male pelvis region, the mean DSC was >0.76 for all structures, and the MSHD ranged from 4.8 to 10.5 mm. Out of the 40 autocontoured structures reviews by experts, 25 were scored useful as autocontoured or with minor edits for at least 90% of the patients and 33 were scored useful autocontoured or with minor edits for at least 80% of the patients.
Compared with manual contouring, autosegmentation using SPICE for the HN, thorax, liver, and male pelvis regions is efficient and shows significant promise for clinical utility.
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