Lymphopenia after palliative radiotherapy for vertebral metastases.

Lymphopenia is a well-known side effect of radiotherapy and has been shown to have a negative impact on patient outcomes. However, the extent of lymphopenia caused by palliative radiotherapy and its effect on patient prognosis has not been clarified. The aim of this study was to determine the incidence and severity of lymphopenia after palliative radiotherapy for vertebral metastases and to determine their effects on patients' survival outcomes. We conducted a retrospective analysis for patients who underwent palliative radiotherapy for vertebral metastases and could be followed up for 12 weeks. Lymphocyte counts were documented at baseline and throughout the 12-week period following the start of radiotherapy and their medians and interquartile ranges (IQRs) were recorded. Exploratory analyses were performed to identify predictive factors for lymphopenia and its impact on overall survival (OS). A total of 282 cases that met the inclusion criteria were analyzed. The median baseline lymphocyte count was 1.26 × 103/µl (IQR: 0.89-1.72 × 103/µl). Peak lymphopenia occurred at a median of 26 days (IQR: 15-45 days) with a median nadir of 0.52 × 103/µl (IQR: 0.31-0.81 × 103/µl). Long-term analysis of patients surviving for 1 year showed that lymphopenia persisted at 1 year after radiotherapy. The main irradiation site, radiation field length and pretreatment lymphocyte count were significantly related to grade 3 or higher lymphopenia. Lymphopenia was identified as a significant predictor of OS by multivariate Cox regression analysis. This study demonstrated the incidence of lymphopenia after palliative radiotherapy for vertebral metastases and its effect on patients' OS.

Beginning of clinical treatment using the 1.5 Tesla MR-Linac system in Japan: a narrative review.

Background and Objective: In the field of radiation therapy, image-guided radiotherapy (IGRT) technology has been gradually improving and highly accurate radiation treatment has been possible. Research on IGRT using 1.5 Tesla magnetic resonance imaging (MRI) began in 1999, and a radiation therapy device called 1.5 Tesla magnetic resonance linear accelerator (MR-Linac), which combines a linear accelerator with 1.5 Tesla MRI, was developed in Europe. The aim of this review is to present an overview of 1.5 Tesla MR-Linac with a review of the literature and our experience. Methods: Reports related to 1.5 Tesla MR-Linac were searched for in PubMed and are discussed in relation to our experience. Key Content and Findings: The 1.5 Tesla MR-Linac enables IGRT using 1.5 Tesla MRI, further enhancing the precision of radiation therapy. Position verification by cone-beam computed tomography (CBCT) is performed in many institutions, but soft tissue contrast is often unclear in CBCT images of the abdomen and mediastinal organs. Since the 1.5 Tesla MR-Linac allows position verification using MRI, position verification can be performed using clear MRI even in regions where CBCT is unclear. With the 1.5 Tesla MR-Linac, it is possible to perform online adaptive radiotherapy (ART) using 1.5 Tesla MRI. Online ART is a method in which images are acquired while the patient is on the treatment table. The method is based on the current condition of the organs in the body on that day and an optimal treatment field is recreated. Additionally, it allows monitoring of tumor motion using cine images obtained by 1.5 Tesla MRI during the delivery of X-ray radiation. A previous report showed that patients with prostate cancer who received radiotherapy by MR-Linac had fewer side effects than those in patients who received conventional CBCT radiation therapy. Conclusions: The 1.5 Tesla MR-Linac obtained CE-mark certification in Europe in August 2018 and it has been used for clinical treatment. In Japan, clinical treatment using this device started in 2021. By using 1.5 Tesla MR-Linac, patients can be provided with higher precision radiotherapy. In this review, we provide an overview of 1.5 Tesla MR-Linac.

VMAT with DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery: results of a non-inferiority clinical study.

The purpose of this study was to show the safety of volumetric modulated arc therapy (VMAT) with deep inspiration breath-hold (DIBH) in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery in a clinical setting. Twenty-five Japanese women, aged 20-59 years, who were enrolled in this prospective non-inferiority study received VMAT under the condition of DIBH with 42.4 Gy/16 fractions for whole-breast irradiation (WBI) ± boost irradiation for the tumor bed to show the non-inferiority of VMAT with DIBH to conventional fractionated WBI with free breathing. The primary endpoint was the rate of occurrence of radiation dermatitis of Grade 3 or higher or pneumonitis of Grade 2 or higher within 6 months after the start of radiotherapy. This study was registered with UMIN00004321. All of the enrolled patients completed the planned radiotherapy without interruption. The evaluation of adverse events showed that three patients (12.0%) had Grade 2 radiation dermatitis. There was no other Grade 2 adverse event and there was no patient with an adverse event of Grade 3 or higher. Those results confirmed our hypothesis that the experimental treatment method is non-inferior compared with our historical results. There was no patient with locoregional recurrence or metastases. In conclusion, VMAT under the condition of DIBH in hypofractionated radiotherapy for left-sided breast cancer after breast-conserving surgery can be performed safely in a clinical setting.

Glasgow prognostic score for assessing the efficacy of whole-brain radiation therapy in cases of recursive partitioning analysis class 2 and class 3 multiple brain metastases: a retrospective study.

PURPOSE: Whole-brain radiotherapy (WBRT) may not be beneficial for patients with brain metastases (BMs). The Glasgow Prognostic Score (GPS) is a suggested prognostic factor for malignancies. However, GPS has never been assessed in patients with BMs who have undergone WBRT. The purpose of this study was to determine whether GPS can be used to identify subgroups of patients with BMs who have a poor prognosis, such as recursive partitioning analysis (RPA) Class 2 and Class 3, and who will not receive clinical prognostic benefits from WBRT. MATERIALS AND METHODS: A total of 180 Japanese patients with BMs were treated with WBRT between May 2008 and October 2015. We examined GPS, age, Karnofsky Performance Status (KPS), RPA, graded prognostic assessment (GPA), number of lesions, tumor size, history of brain surgery, presence of clinical symptoms, and radiation doses. RESULTS: The overall median survival time (MST) was 6.1 months. seventeen patients (9.4%) were alive more than 2 years after WBRT. In univariate analysis, KPS ≤ 70 (p = 0.0066), GPA class 0-2 (p = 0.0008), > 3 BMs (p = 0.012), > 4 BMs (p = 0.02), patients who received ≥ 3 Gy per fraction (p = 0.0068), GPS ≥ 1 (p = 0.0003), and GPS ≥ 2 (p = 0.0009) were found to significantly decrease the MST. Patients who had brain surgery before WBRT (p = 0.036) had a longer survival. On multivariate analysis, GPS ≥ 1 (p = 0.008) was found to significantly decrease MST. CONCLUSION: Our results suggest that GPS ≥ 1 indicates a poor prognosis in patients undergoing WBRT for intermediate and poor prognosis BMs.

Acute hematologic toxicity of radiation therapy - a comprehensive analysis and predictive nomogram.

To investigate radiation-induced cytopenia and establish predictive nomograms for hematological toxicity, we reviewed 3786 patients aged 18 or older who received radiation monotherapy between 2010 and 2021 for non-hematologic malignancies. We collected data on patient background, treatment content and hematologic toxicities for 12 weeks after the start of radiotherapy. The patients were randomly divided into training and test groups in 7:3 ratio. In the training group, we conducted ordered logistic regression analysis to identify predictive factors for neutropenia, lymphocytopenia, anemia and thrombocytopenia. Nomograms to predict Grade 2-4 cytopenia were generated and validated in the test group. Grade 3 or higher hematologic toxicities were observed in 9.7, 44.6, 8.3 and 3.1% of patients with neutropenia, lymphocytopenia, anemia and thrombocytopenia, respectively. We identified six factors for neutropenia grade, nine for lymphocytopenia grade and six for anemia grade with statistical significance. In the analysis of thrombocytopenia, the statistical model did not converge because of a small number of events. Nomograms were generated using factors with high predictive power. In evaluating the nomograms, we found high area under the receiver operating characteristic curve values (neutropenia; 0.75-0.85, lymphopenia; 0.89-0.91 and anemia; 0.85-0.86) in predicting Grade 2-4 cytopenia in the test group. We established predictive nomograms for neutropenia, leukocytopenia and anemia and demonstrated high reproducibility when validated in an independent cohort of patients.

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel.

BACKGROUND: The purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. METHODS: From 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. RESULTS: Forty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). CONCLUSIONS: In BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

Clinical significance of completion of radium-223 treatment and acute adverse events in patients with metastatic castration-resistant prostate cancer.

Objectives: In the treatment of castration-resistant prostate cancer (CRPC) with bone metastases, radium-223 dichloride (Ra-223) is the only bone-targeted drug that shows survival benefits. Completing six courses of Ra-223 treatment is thought to be associated with better patient survival, but this treatment has a relatively high rate of acute adverse events. Methods: This retrospective study included 85 patients from 12 institutions in Japan to investigate the clinical significance of the completion of Ra-223 treatment and acute adverse events in CRPC patients. Results: Six courses of Ra-223 treatment were completed in 65.9% of the patients. Grade 3 or higher acute adverse events were observed in 27.1% of patients. The prostate specific antigen and alkaline phosphatase declined at 26.9% and 87.9%, respectively. The overall survival rates at 12 and 24 months were 80.7% and 63.2%, respectively. Both completion of six courses of Ra-223 treatment and absence of grade 3 or higher acute adverse events were associated with longer overall survival. In univariate analysis, factors related to the history of treatment (five or more hormone therapy agents and cytotoxic chemotherapy) and hematological parameters (Prostate specific antigen (PSA) doubling time, alkaline phosphatase, hemoglobin, albumin, and serum calcium) were associated with completing six courses of Ra-223 treatment without experiencing grade 3 or higher acute adverse events. Multivariate analysis showed that a history of chemotherapy, PSA doubling time, hemoglobin, and serum calcium showed statistical significance. We built a predictive score by these four factors. Patients with lower scores showed higher rates of treatment success (p<0.001) and longer overall survival (p<0.001) with statistical significance. Conclusions: Accomplishing six courses of Ra-223 treatment without grade 3 or higher acute adverse events was a prognostic factor in patients with mCRPC treated with Ra-223. We built a predictive score of treatment success and need future external validation.

Survival prediction nomogram for patients with vertebral bone metastases treated with palliative radiotherapy.

Background: In the treatment of vertebral bone metastases, estimating patient prognosis is important to select the optimal treatment strategy. The purpose of this study was to identify prognostic factors for vertebral bone metastases treated with palliative radiotherapy and to establish a nomogram for predicting patient survival. Materials and methods: We analyzed patients who underwent palliative radiotherapy for vertebral bone metastasis between January 2010 and December 2020 at a single institution. Exclusion criteria were as follows: (1) primary bone malignancy, (2) stereotactic body radiotherapy, (3) concurrent radiotherapy to sites other than the vertebral bone, (4) radiotherapy to other sites within 12 weeks before or after the current radiotherapy, and (5) lack of more than half of blood test data before radiotherapy. Results: A total of 487 patients met the inclusion criteria. Clinical and hematologic data were collected from the patient record system. Patients were divided into training and test groups in a 7:3 ratio. Multivariate Cox regression analysis in the training cohort revealed six significant factors, including a history of chemotherapy, primary site (breast cancer, prostate cancer, or hematologic malignancy), use of analgesics, neutrophil-lymphocyte ratio, serum albumin, and lactate dehydrogenase. A prognostic nomogram was developed and validated in the test cohort. The area under the curve (AUC) values in predicting survival at 6, 24, and 60 months were 0.83, 0.88, and 0.88 in the training cohort and 0.85, 0.81, and 0.79 in the test cohort, respectively. Conclusions: This nomogram may help to select the treatment strategy for vertebral bone metastases.

Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer.

BACKGROUND AND PURPOSE: The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy. MATERIALS AND METHODS: Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r). RESULTS: Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively). CONCLUSIONS: The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.

Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis: A case report.

BACKGROUND: There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm (IPMN), who are surgically intolerant and require less invasive treatment options, which are limited. In the present study, we report a case of IPMN presenting with acute recurrent pancreatitis (ARP), in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume. CASE SUMMARY: An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst. Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas, with dilated pancreatic ducts and mural nodules. The patient was diagnosed with mixed-type IPMN, and five years later, he developed ARP. Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks. Surgery was considered clinically inappropriate because of his old age and comorbidities. He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy. An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation. Fourteen months later, he remains symptom-free from ARP. CONCLUSION: This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study.

PURPOSE: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. MATERIALS AND METHODS: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1-5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. RESULTS: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3-22.2%), 20.1% (95% CI: 6.0-40.2%), 59.2% (95% CI: 34.4-77.3%), and 78.2% (95% CI: 51.4-91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. CONCLUSIONS: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.

The benefit of concurrent chemotherapy with radiotherapy for esophageal cancer is limited in Asian patients aged 80 years or older: a SEER database analysis.

PURPOSE: To evaluate the benefit of concurrent chemotherapy with radiotherapy (RT) for esophageal cancer in Asian patients aged ≥ 80 years using the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Among more than 7000 patients with squamous cell carcinoma or adenocarcinoma who were treated by RT without surgery for esophageal cancer in the SEER database, 2047 patients aged ≥ 80 years were analyzed. Patients who received chemoradiotherapy (CRT group) and patients who received RT alone (RT alone group) were matched with a propensity score. RESULTS: The median observation period for survivors was 57 months. The 3-year and 5-year overall survival rates in all patients were 15.2% and 8.5%, respectively. The 3-year and 5-year cause-specific survival rates in all patients were 20.8% and 14.5%, respectively. After propensity score matching, the overall survival rate in the CRT group was significantly higher than that in the RT alone group (5-year overall survival rates: 11.9% and 3.2%, respectively, p < 0.001). In 108 Asian or Pacific Islander patients, there was no significant difference (5-year overall survival rates: 13.5% and 0%, respectively, p = 0.291), although the overall survival rate in the CRT group was significantly higher than that in the RT alone group in any other race. CONCLUSIONS: It is controversial whether CRT is beneficial for Asian or Pacific Islander patients aged 80 years or older with esophageal cancer based on Analysis of data in SEER database.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan.

PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.