Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma.

Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option.

Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector.

Volumetric-modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector "Delta4 Discover® (D4D)" was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance-to-agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta4 Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A-side and B-side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of -0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission-type detector "D4D" is thus suitable for detecting delivery errors during irradiation.

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer.

BACKGROUND: To evaluate the treatment outcomes of external-beam radiotherapy (EBRT) with or without radioactive iodine therapy (RAIT) for metastatic or recurrent lesions of differentiated thyroid cancer (DTC). METHODS: Between August 1997 and March 2018, 73 lesions (distant metastases, 50; regional lymph-node metastases, 17; postoperative tumor-bed recurrences, 6) in 36 patients that had received EBRT with or without RAIT were reviewed. Doses of EBRT were 8-70 Gy (median 40 Gy). Seventeen patients received RAIT after EBRT. RESULTS: Median follow-up time of imaging studies was 14 months (range 1-110 months). Two-year overall survival rates and control rates of EBRT sites were 71% and 62%, respectively. Two-year control rates for EBRT of < 30 Gy (n = 7), 30 Gy (n = 13), 31-49 Gy (n = 25), 50 Gy (n = 20), and > 50 Gy (n = 8) were 0%, 56%, 53%, 79%, and 100%, respectively. There were statistically significant differences in control rates between < 30 Gy and 30 Gy (p = 0.003), and between 50 Gy and > 50 Gy (p = 0.037). Control rates of > 50 Gy were significantly better compared to ≤ 50 Gy (p = 0.021). Two-year control rates with (n = 28) and without (n = 45) post-EBRT RAIT were 89% and 45%, respectively (p = 0.009). In multivariate analysis, EBRT of > 50 Gy and post-EBRT RAIT were significant independent factors for favorable control of EBRT sites (hazard ratio [HR], 5.72; 95% confidence interval [CI], 1.21-27.1; p = 0.028 and HR, 2.98; 95% CI, 1.28-6.98; p = 0.012, respectively). CONCLUSION: EBRT of > 50 Gy and post-EBRT RAIT appeared to be useful for long-term control of EBRT sites for metastatic or recurrent lesions of DTC.

[Tolerability of Definitive Chemoradiotherapy in Elderly Patients with Esophageal Cancer].

Definitive chemoradiotherapy(CRT)for esophageal cancer is the standard treatment and alternative to surgery. However, the tolerability of CRT in elderly patients is not well known. In this study, we retrospectively analyzed 60 patients with esophageal cancer who were treated with CRT(5-FU 700 mg/m2, cisplatin 70 mg/m2, radiation 60 Gy)at our hospital between January 2015 and September 2017. The patients were divided into 2 groups: an elderly group comprising 16 patients aged >75 years and a non-elderly group comprising 44 patients aged <74 years. The relative dose intensity of cisplatin in the elderly group was significantly lower than that in the non-elderly group. Radiotherapy was successfully executed in both groups. More patients in the elderly(25%)than the non-elderly group(7%)developed pneumonitis, and all patients who developed severe pneumonitis in the elderly group died. Application of definitive CRT and irradiation methods in elderly patients with a subpleural reticular shadow should be carefully considered before initiating therapy.

Tumor growth patterns on magnetic resonance imaging and treatment outcomes in patients with locally advanced cervical cancer treated with definitive radiotherapy.

BACKGROUND: To evaluate the prognostic value of tumor growth patterns on magnetic resonance (MR) images in patients with locally advanced cervical cancer (LACC) treated with definitive radiotherapy or concurrent chemoradiotherapy (RT/CCRT). METHODS: We retrospectively reviewed 102 patients with LACC who received definitive RT/CCRT and who underwent MR imaging before RT/CCRT. Growth patterns on pretreatment T2-weighted MR images were classified into expansive or infiltrative type according to tumor morphologic patterns in the myometrium and/or parametrial space. RESULTS: The median age was 60 years (range 26-90 years). The median follow-up time was 47.7 months (range 5.7-123 months). The numbers of patients with stages IB, II, III, and IVA were 17, 39, 43, and 3, respectively. The 3-year overall survival (OS) rates for stages IB, II, III, and IV were 87%, 76%, 74%, and 67%, respectively. Regarding growth patterns on MR images, 31 were of expansive type and 71 were of infiltrative type. The infiltrative type was significantly associated with lower OS and locoregional recurrence-free survival (LRRFS) than the expansive type (3-year OS, 70% vs. 93%, p = 0.003; 3-year LRRFS, 64% vs. 94%, p = 0.001). On multivariate analysis, infiltrative tumor growth patterns were a significant independent factor for low OS (hazard ratio [HR], 3.81; 95% confidence interval [CI] 1.26-16.7; p = 0.015) and low LRRFS (HR, 4.27; 95% CI 1.43-18.5; p = 0.007). CONCLUSION: Tumor growth patterns on MR images could be an indicator of survival and locoregional control in patients with LACC treated with definitive RT/CCRT.

The potential overdose of heart and left anterior descending coronary artery region during intensity-modulated radiation therapy in patients with esophageal cancer.

This study aimed to investigate the changes in dose distribution in the heart and left anterior descending coronary artery region (LADR) during intensity-modulated radiation therapy (IMRT) in patients with esophageal cancer (EC) treated at our institution. The heart and LADR were delineated on the initial and off-cord boost planning computed tomography (CT) images. Cardiac volume reduction (CVR) was defined as the reduction in cardiac volume between the initial CT and off-cord boost CT at the dose of 36 Gy irradiated. The involved field IMRT plan was created based on each initial and off-cord boost CT image and was analyzed based on the relationship between CVR and heart and LADR dose-volume parameters (Heart-Dmax, Heart-Dmean, Heart-V20, Heart-V30, Heart-V40, LADR-Dmax, LADR-Dmean, LADR-V15 and LADR-V30). Forty patients with EC were investigated between January 2016 and January 2022. The median CVR ratio during radiation therapy (RT) was 5.57% (range, -7.79 to 18.26%). Simple linear regression analysis revealed significant correlations between CVR during RT and changes in the heart and LADR dose-volume parameters. Some patients (>10%) experienced severe changes in the heart and LADR dose distribution. In three cases with reduced heart volume and primary tumor mass, the changes in LADR-V15 and LADR-V30 showed outliers. In conclusion, CVR during RT correlated with an increase in the heart and LADR dose. When both CVR and tumor volume reduction are large, a potential overdose of LADR during RT should be noted in the IMRT era.

Internal mammary node abnormality in imaging studies and treatment outcomes in patients with breast cancer.

The clinical significance of mild internal mammary node (IMN) enlargement (Mild-IMN) is uncertain. This study aimed to evaluate the relationship between treatment outcomes and IMN status in patients with breast cancer who underwent postmastectomy radiation therapy between January 2010 and December 2018. Overall, 250 patients were categorized based on IMN status: Clinically normal IMN (Normal-IMN; n=172), Mild-IMN (n=39) and clinically metastatic IMN (cMet-IMN; n=39). None of the patients in the Normal- or Mild-IMN groups received IMN irradiation. In the cMet-IMN group, 25 patients underwent IMN irradiation with an IMN boost (10 Gy in 5 fractions), while 14 patients did not. The median follow-up time was 80.0 months (range, 7.2-147.6 months). The 7-year overall survival (OS), disease-free survival (DFS) and IMN recurrence-free survival (IRF) rates were 80.2, 73.0 and 93.4%, respectively. Multivariate analyses indicated that only cMet-IMN had a significant impact on OS [hazard ratio (HR), 1.66; 95% CI, 1.01-3.68; P=0.05] and DFS (HR, 1.91; 95% CI, 1.08-3.39; P=0.03), while cMet-IMN did not have a significant impact on IRF (HR, 1.66; 95% CI, 0.41-6.78; P=0.48). Additionally, receiving an IMN boost had no influence on OS (HR, 1.11; 95% CI, 0.37-2.34; P=0.84), DFS (HR, 1.28; 95% CI, 0.51-3.22; P=0.60) or IRF (HR, 1.94; 95% CI, 0.22-17.47; P=0.55). In conclusion, the impact of Mild-IMN on clinical outcomes was small. Although irradiation for cMet-IMN is important, the impact of the cMet-IMN boost with 10 Gy in 5 fractions on clinical outcomes may also be limited.

Cardiac volume reduction during radiotherapy in patients with esophageal carcinoma.

The present study investigated the factors contributing to cardiac volume reduction (CVR) during radiotherapy (RT) in patients with esophageal carcinoma (EC). This retrospective study included patients with EC treated at National Hospital Organization Shikoku Cancer Center (Matsuyama, Japan). Cardiac delineation was based on initial and off-cord boost (spinal cord-sparing approach) planning computed tomography images. The relationship between CVR and other relevant parameters was analyzed. A total of 58 patients with EC were investigated between January 2016 and January 2022. Univariate and multiple regression analyses revealed a statistically significant association between CVR during RT and the change ratio of the inferior vena cava (IVC) volume and body mass index (BMI) loss. In multivariate analysis of CVR of >10%, only the change in IVC volume exhibited a significant association. Conversely, CVR during RT displayed no association with heart dose-volume parameters, laboratory data, or changes in blood pressure and pulse rate. Among the 12 cases with CVR of >10%, the median movement of the left anterior descending coronary artery region (LADR) was 1.35 cm (range, 0.0-2.7 cm). In conclusion, CVR during RT was most strongly associated with changes in IVC volume, suggesting dehydration as the primary cause, rather than radiation-induced heart damage. LADR movement due to a CVR of >10% may lead to LADR radiation overdose.

Association between tumor cell in air space and treatment outcomes in early-stage lung cancer treated with stereotactic body radiation therapy.

Background and purpose: Spread-through air space (STAS) is an unfavorable factor in patients with lung cancer treated with surgery. However, the relationship between the treatment outcomes of stereotactic body radiation therapy (SBRT) for lung cancer and STAS has not been adequately investigated. This study aimed to evaluate the impact of tumor cells in the air space (TCIAS), which show a STAS burden, on treatment outcomes in patients with early-stage lung cancer treated with SBRT. Materials and methods: Data of patients who underwent SBRT for early-stage lung cancer treated with SBRT were retrospectively reviewed. The influence of the TCIAS status on local progression-free (LPF), regional failure-free (RFF), distant failure-free (DFF), progression-free survival (PFS), and overall survival (OS) rates was assessed using univariate and multivariate analyses. Results: Overall, 68 patients were included. The median follow-up time was 24.3 months. For patients positive/negative for TCIAS, the 2-year LPF, RFF, DFF, PFS, and OS rates were 81.4 %/91.1 %, 73.7 %/96.2 %, 55.9 %/75.3 %, 55.0 %/84.6 %, and 67.8 %/92.2 %, respectively. In the multivariate analysis, TCIAS-positive was a significant unfavorable factor for RFF (hazard ratio [HR]: 4.10; 95 % confidence interval [CI]: 1.04-16.16, p = 0.04), DFF (HR: 2.61, 95 % CI: 1.03-6.57, p = 0.04), and PFS (HR: 2.36; 95 % CI: 1.05-5.30, p = 0.04). By contrast, TCIAS-positive was not a significant risk factor for LPF and OS. Conclusion: TCIAS-positive is an unfavorable factor for regional and distant failure after SBRT. TCIAS status may be useful in predicting the treatment outcome of SBRT for early-stage lung cancer.

The Japanese breast cancer society clinical practice guidelines for radiation treatment of breast cancer, 2022 edition.

The Breast Cancer Clinical Practice Guidelines, organized by the Japanese Breast Cancer Society (JBCS), were published in 2022. We present the English version of the Radiation Therapy (RT) section of the guidelines. The JBCS formed a task force to update the 2018 version of the JBCS Clinical Practice Guidelines. The Background Questions (BQs) contain the standard treatments for breast cancer in clinical practice, whereas the Clinical Questions (CQs) address daily clinical questions that remain controversial. Future Research Questions (FRQs) explore the subjects that are considered important issues, despite there being insufficient data for inclusion as CQs. The task force selected the 12 BQs, 8 CQs, and 6 FRQs for the RT section. For each CQ, systematic literature reviews and meta-analyses were conducted according to the Minds Manual for Guideline Development 2020, version 3.0. The recommendations, strength of recommendation, and strength of evidence for each CQ were determined based on systematic reviews and meta-analyses, and finalized by voting at the recommendation decision meeting.

Local control of bone metastasis treated with palliative radiotherapy in patients with lung cancer: An observational retrospective cohort study.

Bone metastasis is common in advanced lung cancer, with the incidence reported to be 30%, and radiotherapy (RT) is used for pain relief from bone metastasis. The present study aimed to identify factors affecting local control (LC) of bone metastasis from lung cancer and to assess the significance of moderate RT dose escalation. This was a retrospective cohort study, where LC of bone metastasis from lung cancer that had received palliative RT was reviewed. LC at RT sites was evaluated with follow-up computed tomography (CT). The influence of treatment-, cancer- and patient-related risk factors for LC was assessed. A total of 317 metastatic lesions in 210 patients with lung cancer were evaluated. The median RT dose (biologically effective dose calculated using an α/ß of 10 Gy; BED10) was 39.0 Gy (range, 14.4-50.7 Gy). The median follow-up time for survival and median radiographic follow-up time were 8 (range, 1-127) and 4 (range, 1-124) months, respectively. The 0.5-year overall survival and LC rates were 58.9 and 87.7%, respectively. The local recurrence rate in RT sites was 11.0%, and bone metastatic progression, except in RT sites, was observed in 46.1% at the time of local recurrence or the last follow-up CT of the RT sites. According to multivariate analysis, RT sites, pre-RT neutrophil to lymphocyte ratio (NLR), post-RT non-administration of molecular-targeting agents (MTs), and non-administration of bone modifying agents (BMAs) were significant unfavorable factors for LC of bone metastasis. Moderate RT dose escalation (BED10 >39 Gy) tended to improve the LC of RT sites. In cases without MTs, moderate dose escalation of RT dose improved the LC of RT sites. In conclusion, treatment (post-RT MTs and BMAs), cancer (RT sites) and patient (pre-RT NLR)-related risk factors had a large impact on improving the LC of RT sites. Moderate RT dose escalation seemed to have a small impact on improving the LC of RT sites.

Chemoradiotherapy for Small-Cell Prostate Carcinoma: A Case Report.

A 60-year-old male with small-cell prostate carcinoma (SCPC) received external-beam radiotherapy of 60 Gy in 30 fractions and chemotherapy (cisplatin (CDDP) 80 mg/m2 + etoposide (VP-16) 100 mg/m2, six courses). Although fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed a complete response, local recurrence occurred in the gross tumor volume after 12 months after the end of chemoradiotherapy. Although the standard treatment for SCPC is not established because SCPC is a rare disease, radiotherapy for SCPC is necessary to study the optimal dose and irradiation area for local control.

An easy tool to predict survival in patients with bone metastatic lung cancer treated with palliative radiotherapy.

BACKGROUND: This study aimed to devise a simple assessment system for bone metastases (BMs) from lung cancer (LC). METHODS: A total of 368 LC patients with BMs who underwent radiotherapy (RT) were retrospectively reviewed. Prognostic factors were evaluated using multivariate analysis, and a scoring system based on regression coefficients was devised. RESULTS: The median follow-up time for survival was 4.3 months, and the 0.5-year overall survival (OS) rate was 44.7%. In the multivariate analysis, the significant prognostic factors were performance status (PS), metastases to internal organs, and post-RT molecular-targeting therapies (MTs) (tyrosine kinase inhibitors, and/or immune checkpoint inhibitors). A scoring system aggregating points assigned to each risk factor was created (2 points; non-administration of post-RT MTs, 1 point; PS ≥3 and metastases to internal organs). The median OSs were 25.0 months, 12.8 months, and 2.5 months in patients with a total score of 0 (n = 22), 1-2 (n = 124), and 3-4 (n = 221), respectively (p < 0.01). CONCLUSION: This easy-to-use scoring system is useful for selecting patients who received comparatively high-dose fractionated RT for BMs from LC. Updates are required to follow the progress of systemic therapy.

Impact of palliative radiotherapy with or without lung irradiation in patients with interstitial lung disease.

BACKGROUND AND PURPOSE: Acute exacerbations or acute lung injury, including radiation pneumonitis (AE-ALI/RP) of interstitial lung disease (ILD), has a fatal prognosis. We evaluated the risk of palliative-intent radiotherapy (RT), with or without lung irradiation, for AE-ALI/RP of ILD. MATERIALS AND METHODS: The data of patients with ILD who received palliative-intent RT between January 2011 and January 2022 were retrospectively reviewed. Factors associated with AE-ALI/RP grade ≥ 3 were assessed using univariate and multivariate analyses. RESULTS: One hundred and three patients were examined, with median imaging and survival follow-up times of 88 (2-1440) and 144 (8-1441) days. The median time to onset of AE-ALI/RP grade ≥ 3 was 72 (5-206) days. In multivariate analysis, a higher pulmonary fibrosis score (PFS ≥ 3) (hazard ratio, HR: 2.16; 95% confidence interval, CI: 1.36-3.43; p < 0.01) and lung irradiation (lung-RT) (HR: 3.82; 95% CI: 1.01-15.73; p = 0.04) were significant factors for AE-ALI/RP grade ≥ 3. In patients who received lung-RT, the 100-day survival rate and cumulative incidence of AE-ALI/RP grade ≥ 3 were 56.8% and 13.7%, respectively. In patients with PFS ≥ 3 and who underwent lung-RT, the 100-day cumulative incidence of AE-ALI/RP grade ≥ 3 was 37.5%; all patients with AE-ALI/RP grade ≥ 3 had grade 5. In patients with PFS ≥ 3 without lung-RT, the 100-day cumulative incidence of AE-ALI/RP grade ≥ 3 was 4.8%. CONCLUSION: High PFS and lung-RT are significant risk factors for AE-ALI/RP grade ≥ 3. Even with relatively low doses, palliative-intent lung-RT carries an extremely high risk of AE-ALI/RP when PFS is high.

Relationship between seminal vesicle displacement and distribution of hydrogel spacer within the perirectal space in prostate radiotherapy.

The influence of a hydrogel spacer (HS) on seminal vesicle (SV) displacement in prostate radiotherapy was examined in the present study. A total of 20 patients with prostate cancer, who received intensity-modulated radiation therapy (IMRT), were enrolled. Computed tomography and magnetic resonance imaging were performed before and after HS insertion within the peripheral space for IMRT planning. Before and after HS insertion, The SV was delineated, and the amount of SV displacement was evaluated. Large SV cranial displacements (≥0.50 cm) were observed in 25% of patients. A HS lateral distribution of ≥1.00 cm in the upper two slices (midgland + superior) influenced the SV cranial displacements (P<0.01) and was associated with large SV cranial displacements (≥0.5 cm) (P<0.01). The HS cranial distribution in the upper slices did not influence SV cranial displacements (P=0.16). In addition, any HS lateral distribution of ≥1.00 cm in all slices did not induce the SV lateral and anterior-posterior displacements (P=0.50 and 0.70, respectively). In conclusion, SV cranial displacement was influenced by HS lateral distribution of ≥1.00 cm in the upper two slices. Therefore, when the sigmoid colon or small bowel is depressed in rectovesical excavation and SV needs to be included in the target volume, HS insertion should be performed carefully.

Factors Affecting Survival and Local Control in Patients with Bone Metastases Treated with Radiotherapy.

The aim of this study was to evaluate the expected prognosis and factors affecting local control (LC) of the bone metastatic sites treated with palliative external beam radiotherapy (RT). Between December 2010 and April 2019, 420 cases (male/female = 240/180; median age [range]: 66 [12-90] years) with predominantly osteolytic bone metastases received RT and were evaluated. LC was evaluated by follow-up computed tomography (CT) image. Median RT doses (BED10) were 39.0 Gy (range, 14.4-71.7 Gy). The 0.5-year overall survival and LC of RT sites were 71% and 84%, respectively. Local recurrence on CT images was observed in 19% (n = 80) of the RT sites, and the median recurrence time was 3.5 months (range, 1-106 months). In univariate analysis, abnormal laboratory data before RT (platelet count, serum albumin, total bilirubin, lactate dehydrogenase, or serum calcium level), high-risk primary tumor sites (colorectal, esophageal, hepatobiliary/pancreatic, renal/ureter, and non-epithelial cancers), no antineoplastic agents (ATs) administration after RT, and no bone modifying agents (BMAs) administration after RT were significantly unfavorable factors for both survival and LC of RT sites. Sex (male), performance status (≥3), and RT dose (BED10) (<39.0 Gy) were significantly unfavorable factors for only survival, and age (≥70 years) and bone cortex destruction were significantly unfavorable factors for only LC of RT sites. In multivariate analysis, only abnormal laboratory data before RT influenced both unfavorable survival and LC of RT sites. Performance status (≥3), no ATs administration after RT, RT dose (BED10) (<39.0 Gy), and sex (male) were significantly unfavorable factors for survival, and primary tumor sites and BMAs administration after RT were significantly unfavorable factors for LC of RT sites. In conclusion, laboratory data before RT was important factor both prognosis and LC of bone metastases treated with palliative RT. At least in patients with abnormal laboratory data before RT, palliative RT seemed to be focused on the only pain relief.

Prognostic assessment of patients who receive radiotherapy for bone metastases from breast cancer.

For prognostic assessment in women who receive radiotherapy (RT) for bone metastases (BMs) from breast cancer (BC), prognostic factors specific for BMs from BC were investigated in the present study. The prognostic assessment was performed by retrospectively reviewing 143 women who received first-time RT for BMs from BC between January 2007 and June 2018. The median follow-up time and median overall survival (OS) time from the first-time RT for BMs were 22 and 18 months, respectively. In the multivariate analysis, nuclear grade 3 (NG 3) [hazard ratio, 2.18; 95% confidence interval (CI), 1.34-3.53], brain metastases (hazard ratio, 1.96; 95% CI, 1.01-3.81), liver metastases (hazard ratio, 1.75; 95% CI, 1.17-2.63), performance status (PS) (hazard ratio, 1.63; 95% CI, 1.10-2.41) and previous systemic therapy (hazard ratio, 1.58; 95% CI, 1.03-2.42) were significant factors for OS, whereas age, hormone-receptor/human epidermal growth factor receptor 2 status, number of BMs and synchronous lung metastases were not significant factors. When points according to risk levels [unfavorable points (UFPs)] were assigned to each risk factor (1.5 points for NG 3 and brain metastases; and 1 point for PS ≥2, previous systemic therapy and liver metastases), the median OS times of patients with a total number of UFPs ≤1 (n=45), 1.5-3 (n=55) and ≥3.5 (n=43) were 36, 17 and 6 months, respectively. Overall, in patients who received first-time RT for BMs from BC, NG 3, brain/liver metastases, poor PS and previous systemic therapy were unfavorable prognostic factors. Comprehensive prognostic assessment using these factors seemed to be useful for the prediction of prognoses in patients with BMs from BC.

Factors affecting local control of bone metastases from radioresistant tumors treated with palliative external beam radiotherapy.

BACKGROUND: This study aimed to evaluate the factors that affect the local control (LC) of bone metastases from radioresistant carcinomas (renal cell carcinoma, hepatocellular carcinoma [HCC], and colorectal carcinoma [CRC]) treated with palliative external-beam radiotherapy (EBRT). METHODS AND MATERIALS: Between January 2010 and December 2020, 211 bone metastases in 134 patients were treated with EBRT in two hospitals (a cancer center and university hospital). Based on follow-up CT, these cases were reviewed retrospectively to evaluate LC at the EBRT site. RESULTS: The median EBRT dose (BED10) was 39.0 Gy (range, 14.4-66.3 Gy). The median follow-up time of the imaging studies was 6 months (range, 1-107 months). The 0.5-year overall survival and LC rates of the EBRT sites were 73% and 73%, respectively. Multivariate analysis revealed that the primary sites (HCC/CRC), low EBRT dose (BED10) (≤ 39.0 Gy), and non-administration of post-EBRT bone modifying agents (BMAs) and/or antineoplastic agents (ATs) were statistically significant factors that negatively affected the LC of EBRT sites. In the absence of BMAs or ATs, the EBRT dose (BED10) escalation from 39.0 Gy improved the LC of EBRT sites. Based on ATs administration, the LC of EBRT sites was significantly affected by tyrosine kinase inhibitors and/or immune checkpoint inhibitors. CONCLUSIONS: Dose escalation improves LC in bone metastases from radioresistant carcinomas. Higher EBRT doses are needed to treat patients for whom few effective systemic therapies remain available.

Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer.

AIMS: Durvalumab (Durva) administration after chemoradiation therapy (CRT) in locally advanced non-small-cell lung cancer (NSCLC) is the standard of care, associated with relatively prolonged progression-free (PFS) and overall survival. However, pneumonitis occurs in 73.6% of Japanese patients. This retrospective study aimed to identify factors associated with Durva efficacy and safety, specifically, the risk of pneumonitis. METHODS: This study included data from 26 consecutive patients with locally advanced NSCLC who underwent CRT followed by Durva. The rates of adverse events and PFS were examined. RESULTS: The median PFS time was 15.6 months (95% confidence interval [CI]: 8.7-not available). Patients developed pneumonitis of grade 1, 2, 3, and 4 at the rate of 62%, 27%, 12%, and 0%, respectively. The median PFS time was 6.4 months for patients with programmed death ligand 1 (PD-L1) expression level of <50% and not reached for patients with PD-L1 expression level of ≥50% (hazard ratio [HR], 0.19; 95% CI: 0.04-0.89), which was significantly prolonged. The cumulative incidence of pneumonitis grade 2 or above was significantly higher when the time between the last day of thoracic radiotherapy (TRT) and the start of Durva therapy was within 14 days compared to >14 days (HR: 0.19; 95% CI: 0.06-0.59). This association was statistically significant in multivariate analysis. CONCLUSIONS: The initiation of Durva therapy within 14 days after TRT may increase the risk of pneumonitis grade 2 or above. Careful observation and suitable treatment are recommended.

Impact of timing of radium­223 administration on the survival of patients with bone metastatic castration­resistant prostate cancer.

The present study aimed to evaluate the optimal timing of radium-223 chloride (Ra-223) administration among patients with bone metastasis from castration-resistant prostate cancer (BmCRPC). Patients, who were diagnosed with BmCRPC and treated with Ra-223 therapy between October, 2016 and January, 2022, were reviewed. The survival time was calculated from the initiation of Ra-223 administration. The time from the diagnosis of BmCRPC to the initiation of Ra-223 administration was identified as a potential prognostic factor. A total of 51 patients were examined in the present study. Ra-223 was administered as the first- and second-line therapy (earlier Ra-223 administration) in 32 patients and as the third- to fifth-line therapy (later Ra-223 administration) in 19 patients. In the multivariate analysis, which considered the potential prognosis, the difference in survival times between patients who received early and late Ra-223 administration was not significant [hazard ratio (HR), 2.67; 95% confidence interval (CI), 0.79-9.07; P=0.11]. By contrast, an incomplete Ra-223 administration (HR, 128.03; 95% CI, 10.59-1548.42; P<0.01) and higher levels of prostate-specific antigen prior to Ra-223 administration (HR, 7.86; 95% CI, 2.7-27.24; P<0.01) were independent factors, significantly associated with a poorer prognosis. The timing of Ra-223 administration did not significantly affect the survival of patients from the initiation of treatment. Further studies are thus required to determine the optimal timing for Ra-223 administration.