Evaluation of the usefulness of non-weight-bearing tunnel view using X-ray in the short term after medial meniscus posterior root tear onset: a retrospective study.

BACKGROUND: This study aimed to examine whether the non-weight-bearing tunnel view X-ray is effective for short-term evaluation of medial meniscus posterior root tear (MMPRT) by assessing the X-ray characteristics at the initial and follow-up visits. METHODS: This was a retrospective longitudinal study of 26 enrolled knees diagnosed with MMPRT on magnetic resonance imaging. The distance between the medial tibial eminence and medial femoral condyle (MTE-MFC distance) and medial tibiofemoral joint (MTFJ) width were measured by obtaining non-weight-bearing tunnel view and frontal view X-ray radiographs. The initial and follow-up values at a median interval of 17 days were compared. Additionally, the correlations between the MTE-MFC distance increase rate and body mass index (BMI), age, femorotibial angle (FTA), and posterior tibial slope (PTS) were evaluated using linear regression analysis. RESULTS: The tunnel view images of the initial and follow-up X-rays showed a significant increase in the MTE-MFC distance and a significant decrease in the MTFJ width. Furthermore, a moderate correlation was observed between the change in the MTE-MFC distance and the time interval between X-rays. However, no substantial correlation was observed for the change in the MTFJ width over time. Moreover, no significant correlation was observed between the change in the MTE-MFC distance in the non-weight-bearing tunnel view and BMI, age, FTA, and PTS. CONCLUSIONS: The non-weight-bearing tunnel view is highly beneficial for evaluating MMPRT progression in the short term.

Type V Tibial Tubercle Avulsion Fracture with Suspected Complication of Anterior Cruciate Ligament Injury: A Case Report.

Background and Objectives: Type V tibial tubercle avulsion fractures are extremely rare; therefore, information on them remains limited. Furthermore, although these fractures are intra-articular, to the best of our knowledge, there are no reports on their assessment via magnetic resonance imaging (MRI) or arthroscopy. Accordingly, this is the first report to describe the case of a patient undergoing detailed evaluation via MRI and arthroscopy. Case Presentation: A 13-year-old male adolescent athlete jumped while playing basketball, experienced discomfort and pain at the front of his knee, and fell down. He was transported to the emergency room by ambulance after he was unable to walk. The radiographic examination revealed a Type Ⅴ tibial tubercle avulsion fracture that was displaced. In addition, an MRI scan revealed a fracture line extending to the attachment of the anterior cruciate ligament (ACL); moreover, high MRI intensity and swelling due to ACL were observed, suggesting an ACL injury. On day 4 of the injury, open reduction and internal fixation were performed. Furthermore, 4 months after surgery, bone fusion was confirmed, and metal removal was performed. Simultaneously, an MRI scan obtained at the time of injury revealed findings suggestive of ACL injury; therefore, an arthroscopy was performed. Notably, no parenchymal ACL injury was observed, and the meniscus was intact. The patient returned to sports 6 months postoperatively. Conclusion: Type V tibial tubercle avulsion fractures are known to be extremely rare. Based on our report, we suggest that MRI should be performed without hesitation if intra-articular injury is suspected.

8-Nitro-cGMP suppresses mineralization by mouse osteoblasts.

Nitric oxide and reactive oxygen species regulate bone remodeling, which occurs via bone formation and resorption by osteoblasts and osteoclasts, respectively. Recently, we found that 8-nitro-cGMP, a second messenger of nitric oxide and reactive oxygen species, promotes osteoclastogenesis. Here, we investigated the formation and function of 8-nitro-cGMP in osteoblasts. Mouse calvarial osteoblasts were found to produce 8-nitro-cGMP, which was augmented by tumor necrosis factor-α (10 ng/ml) and interleukin-1ß (1 ng/ml). These cytokines suppressed osteoblastic differentiation in a NO synthase activity-dependent manner. Exogenous 8-nitro-cGMP (30 µmol/L) suppressed expression of osteoblastic phenotypes, including mineralization, in clear contrast to the enhancement of mineralization by osteoblasts induced by 8-bromo-cGMP, a cell membrane-permeable analog of cGMP. It is known that reactive sulfur species denitrates and degrades 8-nitro-cGMP. Mitochondrial cysteinyl-tRNA synthetase plays a crucial role in the endogenous production of RSS. The expression of osteoblastic phenotypes was suppressed by not only exogenous 8-nitro-cGMP but also by silencing of the Cars2 gene, indicating a role of endogenous 8-nitro-cGMP in suppressing the expression of osteoblastic phenotypes. These results suggest that 8-nitro-cGMP is a negative regulator of osteoblastic differentiation.

Impact of early tumor reduction on outcome differs by histological subtype in stage III non-small-cell lung cancer treated with definitive radiotherapy.

BACKGROUND: We retrospectively investigated the impact on survival of early tumor reduction during definitive radiotherapy for inoperable stage III non-small cell lung cancer (NSCLC) patients, according to their histological subtypes. METHODS: Between November 2006 and December 2012, 152 consecutive patients with inoperable stage III NSCLC who underwent definitive radiotherapy were reviewed retrospectively. Forty-one patients were excluded for not satisfying the inclusion criteria. Forty-five (40.5 %) and 48 (43.2 %) patients were diagnosed with squamous cell carcinoma (SQC) and adenocarcinoma (ADC), respectively. The tumor reduction rate (TRR) was defined as follows: TRR = 1-[gross tumor volume (GTV) on computed tomography at shrinking irradiation field planning]/(GTV on computed tomography at the initial treatment planning). The Cox proportional hazard model was used to identify significant prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: We evaluated 111 patients, with a median follow-up time of 52.2 months in surviving patients. The median TRR was 45.9 %. In all patients, there were significant associations between TRR and PFS (P = 0.036) on multivariate analysis, although TRR had no correlation with OS (P = 0.141). With respect to histological subtype, multivariate analyses revealed that a higher TRR showed significant associations with better OS and PFS in the SQC group (P = 0.013 and 0.040, respectively). In contrast, a higher TRR was associated with poorer OS in the ADC group (P = 0.030); there was no association between TRR and PFS. CONCLUSION: We found that a higher TRR is a promising prognostic factor for better survival and disease control in SQC patients.

Kinetics differences between PSA bounce and biochemical failure in patients treated with 125I prostate brachytherapy.

OBJECTIVE: To determine the helpful factors to distinguish prostate-specific antigen failure from prostate-specific antigen bounce with large magnitude. METHODS: From October 2004 to December 2009, 242 patients with prostate cancer treated with (125)I brachytherapy were analyzed, 88 patients were excluded because the follow-up durations were shorter than 5 years. Their median follow-up was 80.4 months (60.0-123.9). Prostate-specific antigen failure was determined using the Phoenix definition. Prostate-specific antigen bounce was defined as an increase ≥0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Prostate-specific antigen bounce +2 was defined as a prostate-specific antigen rise by 2.0 ng/ml or more above the nadir. RESULTS: The 5-year biochemical relapse-free survival rate was 90.2%. Prostate-specific antigen failure and prostate-specific antigen bounce +2 were seen in 23 patients (14.9%) and 12 patients (7.8%), respectively. On univariate analysis, age at implant (P = 0.028), T stage (P = 0.020), time to prostate-specific antigen failure or prostate-specific antigen bounce (time to onset) (P = 0.0008), prostate-specific antigen velocity (P = 0.0003) and prostate-specific antigen doubling time (P = 0.0004) were significant for the distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2. On multivariate analysis, no factor was the statistically significant factor. On receiver operating characteristic curve analysis, time to onset with a cutoff value of 29.8 months, prostate-specific antigen velocity of 0.18 ng/ml/month and prostate-specific antigen doubling time of 6.3 months had the highest accuracy of 82.9, 82.9 and 82.9% for prostate-specific antigen failure, respectively. CONCLUSIONS: Time to onset, prostate-specific antigen velocity and prostate-specific antigen doubling time would be helpful for distinction between prostate-specific antigen failure and prostate-specific antigen bounce +2.

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.

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.

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.

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.

Medial Meniscus Posterior Root Reconstruction and Open-Wedge High-Tibial Osteotomy for Medial Meniscus Posterior Root Tear With Varus Knee Alignment: A Retrospective Study on Short-Term Outcomes.

PURPOSE: We describe 13 cases of medial meniscus posterior root tear (MMPRT) with varus knee alignment treated with medial meniscus posterior root reconstruction (MMPR-R) and open-wedge high-tibial osteotomy (OWHTO) to identify an optimal MMPRT treatment. METHODS: We retrospectively reviewed 13 patients (mean age: 66.3 ± 8.0 years) who underwent MMPR-R and OWHTO. The Knee Injury and Osteoarthritis Outcome Score (KOOS), femorotibial angle (FTA), percentage mechanical axis (%MA) on radiography, and medial meniscus extrusion (MME) on magnetic resonance imaging (MRI) between the preoperative period and last follow-up were compared. Moreover, meniscus healing status and the International Cartilage Repair Society (ICRS) classification of the medial femoral condyle and medial tibial plateau on arthroscopy between the initial surgery and second-look arthroscopy were compared. RESULTS: The mean follow-up duration was 12.8 ± 2.2 months. At the last follow-up, the KOOS significantly improved (P < 0.01). Based on the FTA and %MA, the varus alignment was predominantly corrected at the last follow-up (P < 0.01). The MME was increased in nine (62.9%) patients, and the mean MME significantly increased at the last follow-up (P = 0.04). Second-look arthroscopy revealed improvements in the ICRS grade for the medial femoral condyle and medial tibial plateau in six (46.2%) patients. However, the results did not significantly differ. Regarding meniscus healing, four (30.8%) patients presented with complete healing, eight (57.1%) with partial healing, and one (7.7%) with failed healing. CONCLUSIONS: The MMPRT with varus knee alignment significantly improved with MMPR-R and OWHTO. However, the MME and meniscus healing were unsatisfactory.

Kielin/chordin-like protein enhances induction of osteoblast differentiation by Bone Morphogenetic Protein-2.

Bone morphogenetic proteins (BMPs) play a key role in embryonic differentiation for osteoblast and bone formation. Kielin/chordin-like protein (Kcp) is known to enhance the effects of BMP signaling. Here, we present ALP activity, gene expression, and calcification data demonstrating that Kcp affects the differentiation of C2C12 myoblasts into osteoblasts. We report that the presence of Kcp enhances the ability of BMP-2 to induce the differentiation of C2C12 myoblasts into osteoblasts. Additionally, BMP-2-mediated stimulation of phosphorylated Smad1/5 was apparently enhanced in the presence of Kcp. The present findings may contribute to progression toward the clinical use of BMPs for treatment of bone fracture, osteoarthritis, and other similar conditions.

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.

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.

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.

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.

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.