The aim of this study was to present current research trends on the synergistic use of radiotherapy and immunotherapy (IRT) for cancer treatment. On March 1, 2023, we conducted a literature search for IRT papers using the Web of Science database. We extracted information and constructed two databases - the Core Database (CD) with 864 papers and Generalized Database (GD) with 6344 papers. A bibliometric analysis was performed to provide insights into the research landscape, to identify emerging trends and highly cited papers and journals in the field of IRT. The CD contained 864 papers that were collectively cited 31,818 times. Prominent journals in this area included the New England Journal of Medicine, Lancet Oncology, and the Journal of Clinical Oncology. Corresponding authors from the USA contributed the most publications. In recent years, lung cancer, melanoma, stereotactic radiotherapy, immune checkpoint inhibitors, and the tumor microenvironment emerged as hot research areas. This bibliometric analysis presented quantitative insights into research concerning IRT and proposed potential avenues for further exploration. Moreover, researchers can use our findings to select appropriate journals for publication or identify prospective collaborators. In summary, this bibliometric analysis provides a comprehensive overview of the historical progression and recent advancements in IRT research that may serve as inspiration for future investigations.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%-50%. Additionally, only approximately 40%-50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25-40 Gy/5 Fx irradiation or 15-30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients.
UNASSIGNED: https://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.

UNASSIGNED: Currently, the prognosis for metastatic colorectal cancer (mCRC) still remains poor. The management of mCRC has become manifold because of the varied advances in the systemic and topical treatment approaches. For patients with limited number of metastases, radical local therapy plus systemic therapy can be a good choice to achieve long-term tumor control. In this study, we aimed to explore the efficacy and safety of the combination of fruquintinib, tislelizumab, and stereotactic ablative radiotherapy (SABR) in mCRC (RIFLE study).
UNASSIGNED: RIFLE was designed as a single-center, single-arm, prospective Phase II clinical trial. A total of 68 mCRC patients who have failed the first-line standard treatment will be recruited in the safety run-in phase (n = 6) and the expansion phase (n = 62), respectively. Eligible patients will receive SABR followed by fruquintinib (5 mg, d1-14, once every day) and tislelizumab (200 mg, d1, once every 3 weeks) within 2 weeks from completion of radiation. The expansion phase starts when the safety of the treatment is determined (dose limiting toxicity occur in no more than one-sixth of patients in the run-in phase). The primary end point is the objective response rate. The secondary end points include the disease control rate, duration of response, 3-year progression-free survival rate, 3-year overall survival rate, and toxicity.
UNASSIGNED: The results of this trial will provide a novel insight into SABR in combination with PD-1 antibody and vascular endothelial growth factor receptor inhibitor in the systematic treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients.
UNASSIGNED: NCT04948034 (ClinicalTrials.gov).

UNASSIGNED: radiotherapy is one of the major treatments for lung cancer and has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer radiotherapy.
UNASSIGNED: On August 31, 2022, the authors identified 9868 articles on lung cancer radiotherapy by the Web of Science (Science Citation Indexing Expanded database) and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top-papers) as well as top-journals on lung cancer radiotherapy. After that, the authors analyzed the recent research hotspots based on the latest publications in top-journals.
UNASSIGNED: These 9868 papers were cited a total of 268,068 times. \"Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer\" published in 2017 by Antonia et al.was the most cited article (2110 citations). Among the journals, New England Journal of Medicine was most influential. Moreover, J. Clin. Oncol. and Int. J. Radiat. Oncol. Biol. Phys. was both influential and productive. Corresponding authors represented the USA (2610 articles) and China mainland (2060 articles) took part in most publications and articles with corresponding authors from Netherlands were most cited (46.12 citations per paper). Chemoradiotherapy was the hottest research area, and stereotactic body radiotherapy has become a research hotspot since 2006. Radiotherapy plus immunotherapy has been highly focused since 2019.
UNASSIGNED: This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 9868 relevant articles, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive picture of the research landscape, historical development, and recent hotspots in lung cancer radiotherapy and can provide inspiration for future research.

Stereotactic ablative radiotherapy (SABR) is a novel radiation treatment method that delivers an intense dose of radiation to the treatment targets with high accuracy. The excellent local control and tolerance profile of SABR have made it become an important modality in cancer treatment. The radiobiology of SABR is a key factor in understanding and further optimizing the benefits of SABR. In this review, we have addressed several issues in the radiobiology of SABR from the perspective of clinical oncologists. The appropriateness of the linear-quadratic (LQ) model for SABR is controversial based on preclinical data, but it is a reliable tool from the perspective of clinical application because the biological effective dose (BED) calculated with it can represent the tumor control probability (TCP). Hypoxia is a common phenomenon in SABR in spite of the relatively small tumor size and has a negative effect on the efficacy of SABR. Preliminary studies indicate that a hypoxic radiosensitizer combined with SABR may be a feasible strategy, but so far there is not adequate evidence to support its application in routine practice. The vascular change of endothelial apoptosis and blood perfusion reduction in SABR may enhance the response of tumor cells to radiation. Combination of SABR with anti-angiogenesis therapy has shown promising efficacy and good tolerance in advanced cancers. SABR is more powerful in enhancing antitumor immunity and works better with immune checkpoint inhibitors (ICIs) than conventional fractionation radiotherapy. Combination of SABR with ICIs has become a practical option for cancer patients with metastases.

Radiotherapy produces immune-promoting effects, which may be blunted by the delivery of corticosteroids (CS). We thus aimed to evaluate the impact of CS use on recurrence and survival outcomes of patients with early stage non-small-cell lung cancer treated with stereotactic ablative radiotherapy (SABR).
A prospectively registered database of patients with stage I to II (T1-3N0M0) stage non-small-cell lung cancer treated with SABR from 2004 to 2015 was queried. Concurrent CS administration was defined as receipt of CS within 2 days of the SABR course. Statistics included Kaplan-Meier survival analysis, Cox proportional hazards modeling, and cumulative incidence analysis utilizing death as a competing risk.
Of 912 patients, 87 (9.5%) received CS with their SABR course. The most common agent was prednisone (64.4%). Indications for CS use were chronic obstructive pulmonary disease in 53 cases (60.9%), chemotherapy in 7 (8.0%), arthritis in 7 (8.0%), chronic pain in 4 (4.6%), transplant-related in 3 (3.4%), and \"others\" in 13 (14.9%; pneumonia, asthma, anemia, etc.). The median follow-up time was 59.3 months. Compared with patients who did not receive CS, receipt of CS was associated with poorer overall survival (P = .004). However, CS administration was not associated with worse time to progression (P = .766) or any recurrence when using death as a competing risk (local P = .119, regional P = .449, distant P = .847, and any recurrence P = .708). Toxicity rates were not statistically different between cohorts.
These data do not suggest increased recurrence rates when patients undergoing SABR are administered corticosteroids. However, owing to limitations of retrospective analyses, individualized judgment is still recommended.

Stereotactic ablative radiotherapy (SABR) has been recognized as a standard alternative treatment to surgery for inoperable early stage non-small cell lung cancer (NSCLC). Guaranteed local control rates over 90% makes oncologists wonder whether SABR is qualified enough to challenge surgery in operable patients. The role of SABR for centrally located lesions would be another question because of the increased risk of severe toxic effect. Plenty of studies suggest that optimization of dose regimen and appropriate case selection would be helpful. Additionally, the effect of adjuvant therapy following SABR in selected patients is worth looking forward, given that it significantly reduced risk of recurrence after complete resection. A consensus about salvage treatment after SABR also needs, given the current diversity of options. Finally, witnessing the emergence of proton therapy and immunotherapy, we believe that the future of SABR lay behind these novel forms of treatment.

Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-β) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions. As a result, radiation therapy may involve the use of large treatment volumes, often encompassing nodal regions that may not be irradiated with more conformal techniques. Traditional forms of radiation in particular pose challenges for combination trials with immunotherapy. This chapter explores these issues in more detail and provides insights as to how radiation therapy can be optimized to combine with immunotherapy.

Out-of-field tumor response, which is also called abscopal effect, bystander effect, or non-target effect, can be regarded as localized irradiation induced systemic antitumorigenic effects, indicating shrinkage of a tumor distant from the irradiated site. Although abscopal effect has been documented in several tumor types, it is a very rare phenomenon which is clinically reported in non-small-cell-lung carcinoma (NSCLC). Herein, we present a rare case of patient with NSCLC with 2 lesions in the upper lobe of left lung who, after receiving stereotactic ablative radiation therapy (SABR) to one of the tumors, had an apparent spontaneous regression of the other mass in the lung, suggestive of a radiation-induced abscopal effect.

OBJECTIVE: We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury.
METHODS: ADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation. Dose responses were tested at doses of 0-90 Gy in C57BL/6 and C3H/HeJCr mice at 6 weeks after irradiation. The volume effect was evaluated with 1-, 3-, and 5-mm diameter collimators at 1-4 weeks after 90-Gy irradiation.
RESULTS: ADFIR caused gross local lung injury of the inflated lung in just 1 week, with extensive hyaline material visible in the irradiated area. The fibrosing process was initiated as early as 2 weeks after irradiation. C3H and C57 mice did not show significant differences in dose response. Six weeks after irradiation, the radiation dose-response curve had a sigmoidal shape, where the lag, log, and stationary phases occurred at <40, 50-70, and >80 Gy, respectively. ADFIR induced substantial volume-dependent structural and functional damage to the lungs, and the volume changes of lung consolidation on micro-CT correlated inversely with lung fibrosis over time.
CONCLUSIONS: We determined the time, dose, and volume responses in our established small animal model, and found that lung injury was substantially accelerated and phenotypically different from that of prior studies using non-ablative hemi-thorax and complete thorax irradiation schemes.