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Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease.Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide.Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established.Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

Background: The primary aim of this study was to investigate the prognostic value of peripheral blood lymphocyte subsets in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods: From 2018 to 2019, 82 patients diagnosed with stage IIIB-IV NSCLC at Zhejiang Cancer Hospital were recruited for this study. Peripheral blood lymphocyte subsets of NSCLC patients were analyzed using flow cytometry before and after ICI treatment. The relationship between the percentage of peripheral blood lymphocyte subsets, clinicopathological features, progression-free survival (PFS), and overall survival (OS) was identified by correlation heat map, Kaplan-Meier curve, log-rank test, and Cox regression analysis. Results: The CD4/CD8 ratio and the percentage of B cells was decreased after ICI treatment. Furthermore, the percentage of CD3(+) T cells, natural killer (NK) cells, and natural killer T (NKT) cells before ICI treatment was associated with brain metastases, the proportion of CD3(+)CD4(+) T cells before ICI treatment was related to epidermal growth factor receptor (EGFR) status, the CD4/CD8 ratio before ICI treatment was correlated to pathology, the ratio of B cells before ICI treatment was related to therapeutic regimen, and the percentage of NKT cells before ICI treatment was associated with use of radiotherapy. Furthermore, univariate survival analysis revealed that low percentage of B cells forecasted a poor OS for NSCLC patients with ICI treatment. In addition, the nomogram developed by percentages of peripheral blood lymphocyte subsets could determine survival probability and survival time of NSCLC patients with immunotherapy. Conclusions: ICI treatment induced changes in the percentage of peripheral blood lymphocyte subsets, which had prognostic value for brain metastases, radiotherapy, EGFR status, pathology, and therapeutic regimen, along with prognostic value, for NSCLC patients treated with ICIs.

Prophylactic cranial irradiation (PCI) has well established place in therapy for patients with limited-disease small cell lung cancer who responded to treatment. The data from randomized trials document that PCI reduces brain metastases rate from approximately 60% to 30%, and increases 3-year overall survival by approximately 5%. Currently, the dose of 25 Gy in 10 fractions is considered as standard. In attempt to reduce neuropsychological sequelae attributable to PCI hippocampal sparing techniques are employed. The existing studies suggest the benefit of hippocampal sparing in limiting memory and higher neurocognitive function losses, but with a risk of failures in the spared region. Ongoing studies will further validate the role of hippocampal sparing, both in terms of toxicity reduction and metastases prevention. PCI for patients who have undergone resection for stage I small cell lung cancer (SCLC) is not recommended, PCI may be, however, associated with a favourable outcome in SCLC patients who have undergone complete surgery in stages II-III. The role of PCI in extensive-disease (ED) SCLC has been evolving. Most recent evidence indicate that PCI is controversial in ED patients with response to initial chemotherapy and absence of brain metastases confirmed by contrast-enhanced MRI. The patients who do not receive PCI, must, however, receive periodic MRI examination during follow-up, i.e., remain under active surveillance with access to radiotherapy at brain relapse. The assessment of safety and effectiveness of hippocampal-sparing PCI, with or without drug neuroprotection in consideration of diverse combinations of radiotherapy, chemotherapy and immunotherapy create a background for future directions of research.

It was commonly assumed in the past that blood-brain barrier could efficiently prohibit penetration of large peptide molecules, such as monoclonal antibodies, including programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. This belief has been recently revised by studies that demonstrate the presence of functional lymphatic vessels lining the dural sinuses. Furthermore, the activated circulating T cells have been shown to cross the blood-brain barrier. Such observations created strong rationale for attempts of immunotherapy for patients with brain metastases, used either alone or in combination with radiotherapy. The expected benefit from immunotherapy particularly refers to patients without targetable "driver" mutations who are not considered as candidates for novel targeted therapies. Current inference on efficacy and safety of combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) origins, in most, from the retrospective studies. The existing data suggest that use of immune checkpoint inhibitors (ICIs) with brain radiotherapy improves patients outcome, compared to brain radiotherapy alone. The available data also suggest that concurrent use of ICI and stereotactic radiation therapy (SRT) for brain metastases from NSCLC is tolerable and appears more effective than sequential combination of radiotherapy and ICI. Use of steroids appeared detrimental. Since a dependence between the risk of adverse events and type of ICI therapy as well as tumor pathology was found, further studies are required to establish optimal dosage, selection of drugs and sequence of ICI and brain radiotherapy in patients with brain metastases from NSCLC.

Item does not contain fulltext BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. METHODS: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. FINDINGS: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0.94, 95% CI 0.90-0.98; p=0.0033), with an absolute difference at 5 years of 3.1% (95% CI 1.3-4.9) and at 10 years of 1.2% (-0.8 to 3.2). We found a significant interaction (p=0.051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0.83, 0.74-0.92), with absolute differences at 5 years of 8.1% (3.4 to 12.8) and at 10 years of 3.9% (-0.6 to 8.4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1.22, 1.05-1.42; p=0.0098), with absolute differences at 5 years of -5.8% (-11.9 to 0.3) and at 10 years of -5.1% (-13.0 to 2.8). INTERPRETATION: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. FUNDING: Institut National du Cancer; and Ligue Nationale Contre le Cancer.

Objective The primary outcome was sphincter preservation. No benefit was found with chemoradiation. The aim of this report is to analyse postoperative complications, which were the secondary outcome. Material and methods Patients with resectable T3–4 low rectal carcinoma were randomised to receive either pre-operative 5 × 5 Gy irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation (50.4 Gy, 1.8 Gy per fraction plus bolus 5-fluorouracil and leucovorin) followed by TME after 4–6 weeks. Results Three hundred and five patients (153 in 5 × 5 Gy group and 152 in chemoradiation group) were analysed. The rates of patients with postoperative complications for the 5 × 5 Gy group and for the chemoradiation group were 27 vs 21%, respectively (P = 0.27). If the values were expressed in terms of number of complications, the rates were 31 vs 22%, respectively (P = 0.06). The corresponding values for severe complications were 10 vs 11% (P = 0.85) of patients with complications and 12 vs 11% (P = 0.85) of events. Conclusion The study did not demonstrate a statistically significant difference in the rate of postoperative complications after short-course pre-operative radiotherapy compared with full course chemoradiation.