Protocol of a phase II study to evaluate the efficacy and safety of deep-inspiration breath-hold daily online adaptive radiotherapy for centrally located lung tumours (PUDDING study).

BACKGROUND: Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. METHODS: Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). DISCUSSION: Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. TRIAL REGISTRATION: Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/ ); registration number: jRCT1052230085 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085 ).

Usefulness of pro-gastrin-releasing peptide as a predictor of the incidence of brain metastasis and effect of prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer.

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.

Symptomatic Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Multiple Pulmonary Oligometastases or Synchronous Primary Lung Cancer.

Purpose: Stereotactic body radiation therapy (SBRT) can be easily used for patients with tumors in various organs and is a promising local therapy for eradicating tumors in cancer patients. There is a rising clinical need for increasing knowledge of oligometastases in the treatment of multiple pulmonary tumors. This study aimed to explore the predictive factors for symptomatic radiation pneumonitis (RP) after SBRT for multiple pulmonary oligometastases or synchronous primary lung cancer (SPLC). Methods and Materials: A total of 38 consecutive patients who had 2 or more pulmonary oligometastases (n = 21) or SPLC (n = 17) and who were treated with SBRT were investigated. Patient characteristics, tumor characteristics, and details of radiation therapy were retrospectively collected from a clinical database. The association between RP of grade 2 or worse (grade 2+ RP) and clinical or dosimetric factors was assessed using logistic regression analyses. Results: The tumors presented ipsilaterally in 24 patients and bilaterally in 14 patients. During the median follow-up period of 4.9 years, grade 2+ RP, grade 2 RP, and grade 3 RP were observed in 9 patients (23.7%), 7 patients (18.4%), and 2 patients (5.3%), respectively. The mean lung dose (MLD) and the volume of the normal lung receiving ≥5 Gy (lung V5Gy) were significantly associated with grade 2+ RP (P = .023 and P = .012, respectively). The logistic model showed that 20% and 50% of the predicted probability of grade 2+ RP were 6.1 Gy and 9.1 Gy for MLD and 31.6 % and 42.8% for lung V5Gy, respectively. Conclusion: Although further investigation is required to validate the metrics and establish reliable dose constraints, the dose-volume metrics for the normal lung could be predictive of the development of grade 2+ RP after SBRT for multiple pulmonary oligometastases or SPLCs.