Effect of preparation method for radioactive iodine therapy on serum electrolytes.

PURPOSE: Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT. MATERIALS AND METHODS: From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L). RESULTS: Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019). CONCLUSION: THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.

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.

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 value of human epidermal growth factor receptor 2 status and systemic therapy in breast cancer with brain metastases treated with radiotherapy.

PURPOSE: To evaluate the prognostic value of human epidermal growth factor receptor 2 (HER2) status and how to use HER2-targeted therapy in breast cancer (BC) with brain metastases (BM) treated with radiotherapy. METHODS: We retrospectively reviewed the data of 103 BC patients with parenchymal BM treated with radiotherapy. We collected data on the hormone receptor (HR), HER-2 amplification status, and systemic therapy after treatment for BM. The primary outcome was overall survival (OS), which was calculated from the diagnosis of BM to death. RESULTS: The median follow-up time from the diagnosis of the first BM was 9.1 months (range, .7-88 months). The 2-year OS of the HR-positive and HER2-positive (HR+HER2+) BC (31.3 mo) was significantly better than those of the HR-HER2+ (9,5 mo, p=.002), HR+HER2- (9.9mo, p=.003), and triple-negative BC (3.9 mo, p<.001) ( . Of the 36 HER2-positive patients, 31 patients treated with HER2-targeted therapy after radiotherapy for BM had a significantly better 2-year OS than those who did not receive HER2-targeted therapy (43% vs. 0%; p < .001). Among the 31 patients treated with HER2-targeted therapy, the 2-year OS for those treated with multiple anti-HER2 agents during the entire course of treatment was significantly higher than that for patients treated with a single agent (60% vs. 24%; p = .006). CONCLUSIONS: HR+HER2+ BC patients with BM treated with radiotherapy show a better prognosis than other subtypes. For HER2-positive patients with good prognosis, it may be important to continue HER2-targeted therapy appropriately after radiotherapy for BM.

Local control after palliative external beam radiotherapy for bone metastases in patients with favorable prognosis.

Advancement in systemic therapy has increased the importance of local control (LC) of bone metastatic sites treated with radiotherapy in intermediate-term survivors (surviving ≥1 year). To establish individualized radiotherapy for bone metastases, factors affecting LC of bone metastases treated with traditional fractionated moderate dose palliative radiotherapy (FMRT) in intermediate-term survivors were evaluated. Between January 2010 and December 2019, 317 lesions in 240 patients treated with FMRT for bone metastases surviving for at least 1 year and followed-up with CT for at least 6 months were reviewed retrospectively. The median survival and radiographic follow-up times were 24 months (range, 12-123 months) and 20 months (range, 1-119 months), respectively. The median FMRT dose [biologically effective dose (BED)10] was 39.0 Gy (range, 28.0-71.7 Gy). Multivariate analysis revealed that age (≥70 years), non-vertebral bone metastasis, bone metastasis from moderate and unfavorable primary tumor sites (esophageal, colorectal, hepatobiliary/pancreatic, kidney/ureter and sarcoma/melanoma cancers), and no administration of post-FMRT bone-modifying agents (BMAs) were unfavorable factors for LC of bone metastasis. The 2-year LC rates for FMRT doses (BED10) ≤39.0 Gy and >39.0 Gy were 90 and 87%, respectively. The 2-year LC rates of patients administered and not administered post-FMRT antineoplastic agents (ATs) were 91 and 78%, respectively. The sites of bone metastasis and primary tumors, and post-FMRT BMAs were factors associated with LC of bone metastasis in long-term survivors. However, a FMRT dose (BED10) ≥39.0 Gy and post-FMRT ATs were not significant factors.

Local control of bone metastases treated with external beam radiotherapy in recent years: a multicenter retrospective study.

BACKGROUND: Over the past decades, remarkable advancements in systemic drug therapy have improved the prognosis of patients with bone metastases. Individualization is required in external beam radiotherapy (EBRT) for bone metastases according to the patient's prognosis. To establish individualized EBRT for bone metastases, we investigated factors that affect the local control (LC) of bone metastases. METHODS: Between January 2010 and December 2019, 536 patients received EBRT for 751 predominantly osteolytic bone metastases. LC at EBRT sites was evaluated with a follow-up computed tomography. The median EBRT dose was biologically effective dose (BED10) (39.0) (range of BED10: 14.4-71.7 Gy). RESULTS: The median follow-up time and median time of computed tomography follow-up were 11 (range 1-123) months and 6 (range 1-119) months, respectively. The 0.5- and 1-year overall survival rates were 73% and 54%, respectively. The 0.5- and 1-year LC rates were 83% and 79%, respectively. In multivariate analysis, higher age (≥ 70 years), non-vertebral bone metastases, unfavorable primary tumor sites (esophageal cancer, colorectal cancer, hepatobiliary/pancreatic cancer, renal/ureter cancer, sarcoma, melanoma, and mesothelioma), lower EBRT dose (BED10 < 39.0 Gy), and non-administration of bone-modifying agents (BMAs)/antineoplastic agents after EBRT were significantly unfavorable factors for LC of bone metastases. There was no statistically significant difference in the LC between BED10 = 39.0 and BED10 > 39.0 Gy. CONCLUSIONS: Regarding tumor-related factors, primary tumor sites and the sites of bone metastases were significant for the LC. As for treatment-related factors, lower EBRT doses (BED10 < 39.0 Gy) and non-administration of BMAs/antineoplastic agents after EBRT were associated with poor LC. Dose escalation from BED10 = 39.0 Gy did not necessarily improve LC.

Usefulness of albumin-globulin ratio as a clinical prognostic factor in patients with thyroid cancer treated with radioiodine.

OBJECTIVE: Albumin-globulin ratio (AGR), which is calculated by dividing serum albumin by serum globulin, is considered as a cancer-related inflammation biomarker. Although the prognosis of many solid cancers has been shown to be associated with AGR, there are no studies to demonstrate the association between the prognosis of thyroid cancer and AGR. The purpose of this study is to reveal the relationship between AGR and overall survival (OS) in patients with thyroid cancer who received radioactive iodine therapy (RIT). METHODS: Eighty-eight patients with thyroid cancer who had received RIT for the first time in our institution were included. The values before RIT were adopted as initial measurements for serum albumin, globulin, and thyroglobulin (Tg) and used for analysis. Patients were divided into two groups based on the AGR value. We analyzed the relationship between clinical factors and treatment outcome. RESULTS: The median follow-up period was 92.4 months (range: 30.1-173.9 months). The 5-year OS and progression-free survival (PFS) were 94% and 54%, respectively. Seventeen patients (< 65 years, 8; and ≥ 65 years, 9) died during the follow-up period. Low AGR was significantly associated with OS in both univariate and multivariate analyses (p = 0.0059 and p = 0.0120, respectively). As the 5-year OS was as high as 94%, there was no significant difference in survival rate between the two groups during the first 5 years. However, there seemed to be a remarkable difference in 10 years after the first RIT. On the other hand, Tg was significantly associated with PFS in both univariate and multivariate analyses (p = 0.0016 and p = 0.0441, respectively). In patients under the age of 65, the PFS rate was significantly lower in the low AGR group (p < 0.0001), while there was no difference in PFS rate between the two AGR groups in patients aged 65 years or older. CONCLUSIONS: AGR may be used as a prognostic factor in relatively younger patients with thyroid cancer treated with radioiodine, while it may be less useful in the older. Overall, it may be an independent prognostic factor for long-term survival in those with thyroid cancer.

Prognostic significance of inflammatory response markers for locally advanced squamous cell carcinoma of the external auditory canal and middle ear.

We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4-70.0) Gy, with daily fractions of 1.8-2.0 Gy. The median follow-up period was 25 months (range, 6-137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.

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.

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.

Risk factors for pericardial effusion after chemoradiotherapy for thoracic esophageal cancer-comparison of four-field technique and traditional two opposed fields technique.

Pericardial effusion is an important late toxicity after concurrent chemoradiotherapy (CCRT) for locally advanced esophageal cancer. We investigated the clinical and dosimetric factors that were related to pericardial effusion among patients with thoracic esophageal cancer who were treated with definitive CCRT using the two opposed fields technique (TFT) or the four-field technique (FFT), as well as the effectiveness of FFT. During 2007-2015, 169 patients with middle and/or lower thoracic esophageal cancer received definitive CCRT, and 94 patients were evaluable (51 FFT cases and 43 TFT cases). Pericardial effusion was observed in 74 patients (79%) and appeared at 1-18.5 months (median: 5.25 months) after CCRT. The 1-year incidences of pericardial effusions were 73.2% and 76.7% in the FFT and TFT groups, respectively (P = 0.6395). The mean doses to the pericardium were 28.6 Gy and 31.8 Gy in the FFT and TFT groups, respectively (P = 0.0259), and the V40 Gy proportions were 33.5% and 48.2% in the FFT and TFT groups, respectively (P < 0.0001). Grade 3 pericardial effusion was not observed in patients with a pericardial V40 Gy of <40%, or in patients who were treated using the FFT. Although the mean pericardial dose and V40 Gy in the FFT group were smaller than those in the TFT group, the incidences of pericardial effusion after CCRT were similar in both groups. As symptomatic pericardial effusion was not observed in patients with a pericardial V40 Gy of <40% or in the FFT group, it appears that FFT with a V40 Gy of <40% could help minimize symptomatic pericardial effusion.

Observation of intrafraction prostate displacement through the course of conventionally fractionated radiotherapy for prostate cancer.

PURPOSE: Intrafraction prostate displacement (IFPD) through the course of conventionally fractionated radiotherapy was observed by real-time tracking. MATERIALS AND METHODS: IFPD was observed by using a CyberKnife real-time tracking system over 39 serial fractions in two patients. Stereoscopic X-ray images tracking the implanted fiducial markers were obtained with mean intervals of 58 s. In preparation for treatment, urination was performed routinely 1 h before treatment and rectal gas was evacuated if necessary. Patients were immobilized by a thermoplastic body shell. RESULTS: The maximal absolute values of IFPD in all 78 fractions were 7.9, 2.1, and 11.5 mm in cranio-caudal (CC), left-right (LR), and antero-posterior (AP) direction, respectively. Only in 5 % of fractions (4/78 fractions), the maximal absolute values of IFPD were 5.0 mm or larger. In these fractions, large IFPD was temporary or persistent. IFPD of ≥3 mm was detected in only ~2-3 % of all obtained tracking images. CONCLUSIONS: Daily maximal IFPD changed day by day. Although maximal IFPD was more than 10 mm, IFPD of ≥3 mm was observed in a comparatively small proportion of treatment time. Through the course of conventionally fractionated radiotherapy, fractions with IFPD of ≥5 mm were infrequent.