•Real world data showed 55.3 % of patients did not meet the criteria of the PACIFIC study.•The incidence of grade 3 radiation pneumonitis was 18.2 % in durvalumab versus 2.5 % in observation.•Active ...surveillance and treatment for radiation pneumonitis were required.
The PACIFIC study demonstrated the benefits of durvalumab consolidation on progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). However, in real-world practice, patients with unresectable LA-NSCLC are heterogeneous with diverse tumor burdens and clinical factors; thus, it is important to examine the effectiveness and side effects of durvalumab when used in real clinical practice.
We investigated the efficacy of durvalumab consolidation and the incidence of radiation pneumonitis in patients who received concurrent chemo-radiotherapy (CCRT) for unresectable LA-NSCLC in a single institute.
Overall, 55.3 % of patients did not meet the criteria of the PACIFIC study; however, they still received consolidation durvalumab in real-world practice. Durvalumab consolidation was associated with favorable PFS in the total population as well as in the subgroup of patients who did not meet the criteria of the PACIFIC study. However, radiation pneumonitis occurred more frequently in the durvalumab group, especially within 3–6 months after CCRT. The incidence of grade 3 radiation pneumonitis was 14.3 % in the durvalumab group versus 2.5 % in the observation group.
Durvalumab consolidation was associated with favorable PFS in patients with LA-NSCLC in clinical practice. However, careful selection of candidates for durvalumab treatment and active surveillance and appropriate management for radiation pneumonitis are needed.
This study aimed to predict stress in patients using artificial intelligence (AI) from biological signals and verify the effect of stress on respiratory irregularity. We measured 123 cases in 41 ...patients and calculated stress scores with seven stress-related features derived from heart-rate variability. The distribution and trends of stress scores across the treatment period were analyzed. Before-treatment information was used to predict the stress features during treatment. AI models included both non-pretrained (decision tree, random forest, support vector machine, long short-term memory (LSTM), and transformer) and pretrained (ChatGPT) models. Performance was evaluated using 10-fold cross-validation, exact match ratio, accuracy, recall, precision, and F1 score. Respiratory irregularities were calculated in phase and amplitude and analyzed for correlation with stress score. Over 90% of the patients experienced stress during radiation therapy. LSTM and prompt engineering GPT4.0 had the highest accuracy (feature classification, LSTM: 0.703, GPT4.0: 0.659; stress classification, LSTM: 0.846, GPT4.0: 0.769). A 10% increase in stress score was associated with a 0.286 higher phase irregularity (p < 0.025). Our research pioneers the use of AI and biological signals for stress prediction in patients undergoing radiation therapy, potentially identifying those needing psychological support and suggesting methods to improve radiotherapy effectiveness through stress management.
The optimal radiotherapy (RT) dose for tracheobronchial adenoid cystic carcinoma (ACC) remains unclear due to its scarcity. This retrospective study evaluated the efficacy of dose-escalated RT for ...primary tracheobronchial ACC by dividing patients into groups of either low (<70.0 Gy EQD2) or high (≥70.0 Gy EQD2) RT doses. In the definitive RT group, the high-dose group showed better local control and survival rates compared to the low-dose group. The treatment related toxicities were the trachea or main bronchus stenosis. Dose-escalated RT may be effective for the definitive treatment of tracheobronchial ACC. Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim.
Idiopathic pulmonary fibrosis (IPF) is associated with fatal complications after radiotherapy (RT) for lung cancer patients; however, the role of proton therapy to reduce the incidence of ...life-threatening complications is unclear. Herein, we present the preliminary results of early-stage lung cancer patients having IPF and treated with RT, with a focus on the comparison between X-ray and proton therapy.
From January 2010 to October 2017, we retrospectively reviewed the medical records of 264 patients with stage I-II non-small cell lung cancer (NSCLC) treated with definitive RT alone. Ultimately, 30 patients (11.4%) who had underlying IPF were analyzed. Among these, X-ray and proton RT were delivered to 22 and 8 patients, respectively. Treatment-related complications and survival outcomes were compared between X-ray and proton therapy.
The median follow-up duration was 11 months (range, 2 to 51 months). All living patients were followed-up at least 9 months. Treatment-related death occurred in four patients (18.2%) treated with X-ray but none with proton therapy. Most patients died within one month after the onset of pulmonary symptoms in spite of aggressive treatment. In addition, the 1-year overall survival (OS) rate in patients treated with X-ray and proton was 46.4 and 66.7%, respectively, and patients treated with proton therapy showed a tendency of better survival compared to X-ray (p = 0.081). Especially, in GAP stage II and III subgroups, patients treated with proton therapy showed significantly increased survival outcomes compared to X-ray (1-year OS rate; 50.0% versus 26.4%, p = 0.036) in univariate analysis.
RT is associated with serious treatment-related complications in patients with IPF. Proton therapy may be helpful to reduce these acute and fatal complications.
retrospectively registered.
To assess clinical outcomes and complications in patients with non-small-cell lung cancer (NSCLC) treated with helical tomotherapy (HT) with or without chemotherapy.
Data from 37 NSCLC patients ...treated between January 2007 and August 2008 were analyzed retrospectively. Twenty-eight patients had Stage III disease. Concurrent and neoadjuvant chemotherapy was given to 24 and 14 patients, respectively. Radiotherapy was delivered to a total dose of 60-70.4 Gy at 2.0-2.4 Gy per fraction to the gross tumor volume and 50-64 Gy at 1.8-2.0 Gy per fraction to the planning target volume.
With a median follow-up of 18 months (range, 6-27 months), 2-year local control and overall survival rates were 63% and 56% for all 37 patients, respectively, and were 78% and 75% for the patients with Stage III disease who received concurrent chemoradiotherapy alone. Acute esophagitis and treatment-related pneumonitis (TRP) ≥Grade 3 occurred in 5 and 7 patients, respectively. Four patients died of treatment-related death (TRD) after HT. In univariate analysis, poor performance status, total lung V(5), contralateral lung (CL) V(5), and V(10) were associated with TRD. Only CL V(5) remained significant in the multivariate analysis (p = 0.029).
HT with chemotherapy has shown promising clinical outcomes, esophagitis, and TRPs. However, HT has produced a somewhat high rate of fatal pulmonary complications. Our data suggest that CL V(5) should be considered and kept as low as possible (<60%) in addition to the conventional dosimetric factors.
The COHORT trial was conducted to compare the efficacy of androgen deprivation therapy (ADT) alone versus combined with radiation therapy (ADT + RT) for clinically node-positive prostate cancer. We ...reported adverse events and quality of life between the two treatment groups. Fifty-nine patients were randomized to receive ADT alone or ADT + RT and analyzed as per-protocol. Patients allocated to the ADT alone arm received ADT for at least 2 years. Patients in the ADT + RT arm received additional pelvic RT. Higher rates of grade ≥ 2 acute genitourinary (0% vs. 7.1%) and late gastrointestinal adverse events (0% vs. 14.3%) were reported in the ADT + RT arm compared with the ADT alone. However, grade ≥ 2 late genitourinary toxicity was more common in the ADT alone than the ADT + RT arm (9.7% vs. 3.6%). No grade ≥ 3 adverse events were reported. There was no statistically significant difference in EPIC scores between two treatment arms. However, the urinary and bowel domains tended to decrease and recover in the ADT + RT arm. In conclusion, ADT + RT demonstrated higher rates of adverse events compared to ADT alone. However, the addition of RT did not significantly impact the quality of life.
We aimed to report the clinical outcomes following stereotactic body radiation therapy (SBRT) using photon or proton equipment in early-stage lung cancer. We retrospectively reviewed 202 cT1-2N0M0 ...lung cancer patients who underwent SBRT with 60 Gy in four consecutive fractions between 2010 and 2019 at our institution: 168 photon SBRT and 34 proton SBRT. Patients who underwent proton SBRT had relatively poor baseline lung condition compared to those who underwent photon SBRT. Clinical outcomes were comparable between treatment modalities: 5-year local control (90.8% vs. 83.6%, p = 0.602); progression-free survival (61.6% vs. 57.8%, p = 0.370); overall survival (51.7% vs. 51.9%, p = 0.475); and cause-specific survival (70.3% vs. 62.6%, p = 0.618). There was no statistically significant difference in grade ≥ 2 toxicities: radiation pneumonitis (19.6% vs. 26.4%, p = 0.371); musculoskeletal (13.7% vs. 5.9%, p = 0.264); and skin (3.6% vs. 0.0%, p = 0.604). In the binary logistic regression analysis of grade ≥3 radiation pneumonitis, poor performance status and poor baseline diffusion capacity of lung for carbon monoxide were significant. To summarize, though patients with high risk of developing lung toxicity underwent proton SBRT more frequently, the SBRT techniques resulted in comparable oncologic outcomes with similar toxicity profiles. Proton SBRT could be considered for patients at high risk of radiation pneumonitis.
To report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection.
Data from 27 adult patients, who were ...diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity.
The median follow-up was 28.9 months (range, 1.1-62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months' post-PBT (p=0.047) and was maintained until 13 months (p=0.028).
Hypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.
This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung ...cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.
We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared ...pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT).
After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs.
The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT.
The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.
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