Search Results (103)

Background/Objectives: The PACIFIC trial showed that immune checkpoint inhibitors (ICI) administered after concurrent chemoradiotherapy (cCRT) significantly improve survival in stage III unresectable non-small cell lung cancer (NSCLC). However, the optimal timing of ICI administration with cCRT is still debated, with concerns about increased risks of adverse effects, particularly radiation-induced pneumonitis (RP), from combining radiotherapy and immunotherapy. Methods: A search of multiple databases identified studies on stage III unresectable NSCLC patients receiving cCRT and ICI. A meta-analysis was performed utilizing the meta package in R software. Furthermore, data from 170 patients treated at Shandong Cancer Hospital and Institute between 2019 and 2023 were analyzed to assess RP following cCRT and ICI treatment. Results: The meta-analysis revealed that the incidences of ≥grade 2 RP were 25.3%, 24.3%, and 45.3% in the ICI following cCRT group, the ICI concurrent with cCRT group, and the ICI prior to cCRT group, respectively. The ICI prior to cCRT group exhibited significantly elevated rates. In the clinical retrospective study, ≥grade 2 RP was more prevalent in the ICI concurrent with cCRT group (HR: 2.258, 95% CI: 1.135–4.492, p = 0.020) and the ICI prior to cCRT group (HR: 2.843, 95% CI: 1.453–5.561, p = 0.002) compared with the ICI following cCRT group. Furthermore, a shorter interval between treatments correlates with an increased incidence of RP. Conclusions: Advancing the timing of ICI administration is associated with an increased incidence of ≥grade 2 RP following cCRT in patients with stage III unresectable NSCLC. Full article

Objectives: Extensive-stage small-cell lung cancer (SCLC) has a poor prognosis, but recently, the combination of immunotherapy and chemotherapy has improved treatment outcomes in some patients, and treatment plans may vary depending on the individual’s general condition and tumor response. In addition, intrathoracic tumor control remains a major challenge for this disease. In the current study, we aim to share our clinical experience and demonstrate that consolidative high-dose thoracic radiotherapy effectively reduces intrathoracic tumor recurrence while maintaining acceptable treatment-related toxicities. Materials and Methods: The medical records of 81 SCLC patients treated at Korea University Guro Hospital from January 2019 to December 2023 were reviewed retrospectively. Among them, 22 patients with extensive-stage SCLC who had a favorable tumor response after systemic therapy, including those with oligo-progressive disease limited to the thoracic region and suitable for curative local therapy, received consolidative radiotherapy. A total dose of 52.5 Gy in 25 fractions was administered over 5 weeks to all patients with extensive-stage SCLC. Results and Conclusions: The median follow-up time was 22 months (range: 8–59 months), with the median follow-up period after completing consolidative radiotherapy being 13 months (range: 4–35 months). In-field local recurrence occurred in only one patient after consolidative thoracic radiotherapy. Most importantly, 10 patients with oligo-progressive disease at the thoracic site, at the time of tumor response, remained stable without further intrathoracic in-field recurrence. Additionally, no severe cases of radiation pneumonitis or esophagitis were observed. Based on our institution’s experience, consolidative high-dose thoracic radiotherapy is well-tolerated and associated with fewer intrathoracic recurrences, leading to improved long-term survival in carefully selected patients with extensive-stage SCLC. Given these findings, we believe consolidative radiotherapy should be considered more proactively in clinical practice. Furthermore, these results may help guide the design of future clinical trials. Full article

Objectives: Identifying patients’ advantageous radiotherapy modalities prior to CT simulation is challenging. This study aimed to develop a workflow using deep learning (DL)-predicted synthetic CT (sCT) for treatment modality comparison based solely on a diagnostic CT (dCT). Methods: A DL network, U-Net, was trained utilizing 46 thoracic cases from a public database to generate sCT images predicting planning CT (pCT) scans based on the latest dCT, and tested on 15 institutional patients. The sCT accuracy was evaluated against the corresponding pCT and a commercial algorithm deformed CT (MdCT) based on Mean Absolute Error (MAE) and Universal Quality Index (UQI). To determine advantageous treatment modality, clinical dose-volume histogram (DVH) metrics and Normal Tissue Complication Probability (NTCP) differences between proton and photon treatment plans were analyzed on the sCTs via concordance correlation coefficient (CCC). Results: The AI-generated sCTs closely resembled those of the commercial deformation algorithm in the tested cases. The differences in MAE and UQI values between the sCT-vs-pCT and MdCT-vs-pCT were 19.38 HU and 0.06, respectively. The mean absolute NTCP deviation between sCT and pCT was 1.54%, 0.21%, and 2.36% for esophagus perforation, lung pneumonitis, and heart pericarditis, respectively. The CCC between sCT and pCT was 0.90 for DVH metrics and 0.97 for NTCP, indicating moderate agreement for DVH metrics and substantial agreement. Conclusions: Radiation oncologists can potentially utilize this personalized sCT based approach as a clinical support tool to rapidly compare the treatment modality benefit during patient consultation and facilitate in-depth discussion on potential toxicities at a patient-specific level. Full article

Background: The role of CDK4/6 inhibitors (CDK4/6i) has expanded from the treatment of advanced breast cancer to early-stage disease, as recent studies have demonstrated their therapeutic benefits. However, evidence regarding the safety of combining CDK4/6i with adjuvant radiation therapy (RT) in a curative setting remains limited. This study aims to present clinical experiences of pulmonary toxicity following the combined use of adjuvant RT and CDK4/6i. Case presentation: We report a case of an Asian female with left breast cancer who underwent a modified radical mastectomy followed by adjuvant chemotherapy, RT, endocrine therapy, and CDK4/6i (abemaciclib) treatment. Cancer therapy-induced grade 2 pneumonitis was impressed by clinical signs and image findings. A 57-year-old postmenopausal woman was diagnosed with left breast invasive lobular carcinoma, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−), K67 index of 5–10%, and classified as pT3N3aM0 (stage IIIC). She received adjuvant chemotherapy with FEC followed by docetaxel, endocrine therapy with letrozole, and adjuvant RT of 50.4 Gy in 28 fractions to the left chest wall and regional nodal irradiation. Abemaciclib was initiated after completing RT. Treatment-related pneumonitis developed five months after RT and abemaciclib use. Conclusions: In breast cancer patients receiving a combination of RT and CDK4/6i as curative adjuvant treatment, pulmonary toxicity is a concern and requires careful monitoring, particularly in Asian populations. Full article

Aims: This phase II study aimed to evaluate the impact of early nutritional intervention on the nutritional status and survival of locally advanced non-small cell lung cancer (LANSCLC) patients undergoing concurrent chemoradiotherapy (CCRT). Methods: LANSCLC patients treated with CCRT were enrolled in the study group and received early nutritional intervention, including individualized nutrition counseling and oral nutritional supplements, from the initiation of CCRT to 2 weeks after its completion. The primary endpoint was the incidence of weight loss ≥5% during the CCRT. For comparison with the study group, a matched control group was retrieved from previous trials by the 1:1 propensity score matching method. Results: Sixty-seven patients were enrolled in the study group with a median follow-up of 52.4 months. Compared with the control group, the study group exhibited a lower incidence of weight loss ≥5% (p = 0.032), higher body mass index (p = 0.034) and prealbumin levels (p = 0.014) at the end of CCRT, as well as lower patient-generated subjective global assessments scores at the end of CCRT (p < 0.001) and 6 months after CCRT (p = 0.007). The study group also had a lower incidence of grade 2+ radiation pneumonitis (p = 0.023) and longer progression-free survival (13.5 vs. 11.3 months, p = 0.032). Patients who responded well to oral nutritional supplements had a higher Firmicutes/Bacteroidetes ratio at baseline (p = 0.036). Conclusions: Early nutritional intervention in LANSCLC patients undergoing CCRT improved nutritional status and reduced radiation pneumonitis. Gut microbiota was associated with the response to oral nutritional supplements. Full article

Background/Objectives: Pneumonitis caused by radiotherapy for lung cancer may be missed since it often occurs only several months later. In a previous trial including patients of any age, a scoring system was tested to facilitate the correct diagnosis of radiation pneumonitis. Since elderly lung cancer patients have a greater risk of developing this complication, a separate scoring system for this group appears useful. Our prospective multi-center trial (NCT06480734) investigates a specific tool for elderly patients irradiated for lung cancer. Methods: Patients aged ≥65 years with lung cancer will complete paper-based questionnaires and rate symptoms potentially caused by pneumonitis weekly during and up to 24 weeks following radiotherapy. The total score of this symptom-based scoring system ranging from 0 to 9 points is correlated to pneumonitis. The discriminative power of the scoring system is evaluated by calculating the area under the receiver operating characteristic curve. Optimality is defined as a cut-off score with sensitivity ≥90% and specificity ≥80%. Moreover, the Youden index will be applied. Fifty-nine patients are required for the full analysis set. Assuming 5% will not qualify for this set, 65 patients should be enrolled. Moreover, patient satisfaction with the scoring system is evaluated. If the dissatisfaction rate is >20%, the system needs modifications; if the dissatisfaction rate is >40%, it is considered not useful. An optimal cut-off score facilitating the diagnosis of pneumonitis and its discrimination from other lung diseases will contribute to a corresponding mobile application to be used by elderly lung cancer patients at home. Full article

Background/Objectives: ACEIs protect against radiation pneumonitis by reducing angiotensin II production, oxidative stress, and inflammation. This study highlights the significance of concurrent angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in radiotherapy by evaluating its impact on radiotherapy-related side effects and survival outcomes, addressing the gap in existing research and providing insights to guide clinical practice in oncology. Methods: The literature was retrieved from the MEDLINE, EMBASE, Web of Science, and Scopus databases from January 2000 to October 2024. Studies on adults (≥18 years) with histologically confirmed cancer, receiving ACEIs or ARBs during radiotherapy, were included. Radiotherapy-related side effects and clinical outcomes were analysed using odds ratios (ORs) and 95% confidence intervals (95%CIs), comparing ACEI/ARB users to non-users. Differences in the median survival time, recurrence, and death rates were also calculated. Results: Sixteen studies (14 cohort studies and two randomised trials) were included. ACEI users exhibited a 50% reduction in the risk of ≥grade 2 radiation pneumonitis (OR: 0.50, 95%CI: 0.32–0.77) in lung cancer and significant reductions in the odds of proctitis (80%, OR: 0.20, 95%CI: 0.12–0.33), haematuria (75%, OR: 0.25, 95%CI: 0.16–0.41), and rectal bleeding (61%, OR: 0.39, 95%CI: 0.30–0.51) in prostate cancer. ACEI/ARB users showed reduced symptomatic radiation necrosis in brain metastases and better 6-month functional independence in supratentorial glioblastoma. Among six studies reporting survival, ACEI/ARB users had longer median survival in early-stage non-small-cell lung cancer and glioblastoma but shorter survival in small cell lung cancer and brain metastases. ARB users had inconsistent survival rates for lung cancer. The varying survival outcomes suggest that ACEIs/ARBs have different effects depending on the cancer type and stage, potentially influenced by cancer-specific factors, treatment protocols, or disease progression. Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival outcomes remains inconsistent across cancer types and severities. Further research should carefully control for confounders. Full article

Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of aggressive B-cell lymphoma with a predominant onset in young patients. The minimization of potential (late) side effects is of cardinal interest for these patients. An anticipation of the individual risk profile is desirable to counsel the patient on the putative impact of radiotherapy (RT). Methods: RT plans for a cohort of 25 patients with PMBCL were prospectively designed. One plan with two parallel- opposing fields (APPA) and another with volume-modulated arc therapy (VMAT) technique with 40 Gy in 2 Gy fractions each. Normal The normal tissue complication probability (NTCP) was calculated using the Lyman-–Kutcher-–Burman model for heart, lung and oesophageal toxicity. Results: APPA planning resulted in lower median doses (Dmedian) for the heart and lungs, whereas all other dose metrics for heart, lungs and esophagus were lower in VMAT planning. A significant difference in the mean NTCPs when comparing the APPA to VMAT plans was seen for increased cardiac mortality, pneumonitis and esophagitis. PTV size correlated with increased cardiac mortality and esophagitis in both plan variations and with pneumonitis for VMAT plans. Dmean, Dmedian, and V20Gy correlated with the risk for pneumonitis, and Dmean, Dmedian, and V1% with the risk for esophagitis in both variants. Conclusions: We showed decreased risk of different NTCPs for VMAT and APPA planning for thoracic toxicities. The use of an IMRT technique like VMAT showed advantages for several DVH metrics in organs at risk and should therefore be recommended for radiation treatment of PMBCL. Full article

Background: Combining radiotherapy with targeted therapy benefits patients with advanced epidermal growth factor receptor-mutated non-small cell lung cancer (EGFRm NSCLC). However, the optimal strategy to combine EGFR tyrosine kinase inhibitors (TKIs) with radiotherapy for maximum efficacy and minimal toxicity is still uncertain. Notably, EVs, which serve as communication mediators among tumor cells, play a crucial role in the anti-tumor immune response. Methods To exploit the role of EVs in the delivery of tumor antigens, we formulated a therapeutic strategy that involves the use of radiation-induced tumor-derived EVs (TEXs) loaded onto dendritic cells (DCs) as a kind of vaccine in conjunction with EGFR TKIs and assessed the efficacy and safety of this approach in the treatment of EGFRm NSCLC. Results In our study, we characterized the release of immunogens as influenced by various modes of cell death, examining the impact of different levels of cell death under diverse irradiation modalities. Our results demonstrated that a radiation mode of 6Gy*3f exhibited the most promising potential to stimulate anti-tumor immune responses. This radiotherapy fraction, combined with TKIs, showed promising results in a tumor-bearing mouse model with an EGFR mutation, although there is a risk of radiation-associated pneumonitis. Furthermore, we found that 6Gy*3f-TEXs in vitro activate DCs and promote T cell proliferation as well as cytotoxic T lymphocyte-mediated tumor cell destruction. The administration of EGFR-TKIs combined DCs loaded with 6Gy*3f-TEXs exhibited the potential to inhibit tumor growth and mitigate the risk of pneumonitis. Together, the research shows that TEXs from high-dose fractionation radiation can mature DCs and boost the killing of cytotoxic T lymphocytes. Combining these DC vaccines with Osimertinib offers a promising and safe treatment for EGFRm NSCLC. Full article

Objectives: We aimed to develop imaging biomarkers to predict radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients undergoing thoracic radiotherapy. We hypothesized that measuring morphometric complexity in the lung using simulation computed tomography may provide objective imaging biomarkers for lung parenchyma integrity, potentially forecasting the risk of RP. Materials and Methods: A retrospective study was performed on medical records of 175 patients diagnosed with NSCLC who had received thoracic radiotherapy. Three indices were utilized to measure the morphometric complexity of the lung parenchyma: box-counting fractal dimension, lacunarity, and minimum spanning tree (MST) fractal dimension. Patients were dichotomized into two groups at median values. Cox proportional hazard models were constructed to estimate the hazard ratios for grade ≥ 2 or grade ≥ 3 RP. Results and Conclusions: We found significant associations between lung parenchymal morphometric complexity and RP incidence. In univariate Cox-proportional hazard analysis, patients with a lower MST fractal dimension had a significantly higher hazard ratio of 2.296 (95% CI: 1.348–3.910) for grade ≥ 2 RP. When adjusted for age, sex, smoking status, category of the underlying lung disease, category of radiotherapy technique, clinical stage, histology, and DLCO, patients with a lower MST fractal dimension showed a significantly higher hazard ratio of 3.292 (95% CI: 1.722–6.294) for grade ≥ 2 RP and 7.952 (95% CI: 1.722 36.733) for grade ≥ 3 RP than those with a higher MST fractal dimension. Patients with lower lacunarity exhibited a significantly lower hazard ratio of 0.091 (95% CI: 0.015–0.573) for grade ≥ 3 RP in the adjusted model. We speculated that the lung tissue integrity is captured by morphometric complexity measures, particularly by the MST fractal dimension. We suggest the MST fractal dimension as an imaging biomarker for predicting the occurrence of symptomatic RP after thoracic radiotherapy. Full article

Objective: Radiotherapy, which is commonly used for the local control of thoracic cancers, also induces chronic inflammatory responses in the microvasculature of surrounding normal tissues such as the lung and heart that contribute to fatal radiation-induced lung diseases (RILDs) such as pneumonitis and fibrosis. In this study, we investigated the potential of cannabidiol (CBD) to attenuate the irradiation damage to the vasculature. Methods: We investigated the ability of CBD to protect a murine endothelial cell (EC) line (H5V) and primary lung ECs isolated from C57BL/6 mice from irradiation-induced damage in vitro and lung ECs (luECs) in vivo, by measuring the induction of oxidative stress, DNA damage, apoptosis (in vitro), and induction of inflammatory and pro-angiogenic markers (in vivo). Results: We demonstrated that a non-lethal dose of CBD reduces the irradiation-induced oxidative stress and early apoptosis of lung ECs by upregulating the expression of the cytoprotective mediator heme-oxygenase-1 (HO-1). The radiation-induced increased expression of inflammatory (ICAM-2, MCAM) and pro-angiogenic (VE-cadherin, Endoglin) markers was significantly reduced by a continuous daily treatment of C57BL/6 mice with CBD (i.p. 20 mg/kg body weight), 2 weeks before and 2 weeks after a partial irradiation of the lung (less than 20% of the lung volume) with 16 Gy. Conclusions: CBD has the potential to improve the clinical outcome of radiotherapy by reducing toxic side effects on the microvasculature of the lung. Full article

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle’s biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered. Full article

Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy. Full article

A 54-year-old female patient diagnosed with Stage IIIb squamous cell carcinoma (cT2aN3M0) initially received chemoradiotherapy. Two years after initial treatment, cancer relapse led to the administration of nivolumab, which was halted due to the development of drug-induced pneumonitis. Subsequent management with prednisolone and eight different cytotoxic agents failed to prevent metastasis to the cervical lymph nodes. The tumor’s programmed death-ligand 1 (PD-L1) expression rate was recorded at 10%. Four years after her diagnosis, the patient received a ninth-line therapy combining cisplatin, gemcitabine, and necitumumab, followed by palliative neck radiation due to increasing lymph node size. Remarkable tumor regression occurred three months after introducing atezolizumab as the tenth-line treatment, suggesting that previous treatments, particularly radiotherapy and cisplatin, might have enhanced PD-L1 expression, aligning with the existing literature. This case highlights the urgent need for further research to elucidate the intricate interplay between treatment history and PD-L1 expression in squamous cell carcinoma, emphasizing the importance of accumulating case studies to inform therapeutic strategies. Full article

The lung is a major dose-limiting organ for radiation therapy (RT) for cancer in the thoracic region, and the clarification of radiation-induced lung damage (RILD) is important. However, there have been few reports containing a detailed comparison of radiographic images with the pathological findings of radiation pneumonitis (RP)/radiation fibrosis (RF). We recently reported the upregulated expression of tenascin-C (TNC), an inflammation-associated extracellular matrix molecule, in surgically resected lung tissue, and elevated serum levels were elevated in a RILD patient. Therefore, we have developed a novel mouse model of partial lung irradiation and studied it with special attention paid to the computed tomography (CT) images and immunohistological findings. The right lungs of mice (BALB/c) were irradiated locally at 30 Gy/1fr, and the following two groups were created. In Group 1, sequential CT was performed to confirm the time-dependent changes in RILD. In Group 2, the CT images and histopathological findings of the lung were compared. RP findings were detected histologically at 16 weeks after irradiation; they were also observed on the CT images from 20 weeks. The immunostaining of TNC was observed before the appearance of RP on the CT images. The findings suggest that TNC could be an inflammatory marker preceding lung fibrosis. Full article