Dosimetric impact of MLC positional errors on dose distribution in IMRT.

Optimizing the positional accuracy of multileaf collimators (MLC) for radiotherapy is important for dose accuracy and for reducing doses delivered to normal tissues. This study investigates dose sensitivity variations and complexity metrics of MLC positional error in volumetric modulated arc therapy and determines the acceptable ranges of MLC positional accuracy in several clinical situations. Treatment plans were generated for four treatment sites (prostate cancer, lung cancer, spinal, and brain metastases) using different treatment planning systems (TPSs) and fraction sizes. Each treatment plan introduced 0.25-2.0 mm systematic or random MLC leaf bank errors. The generalized equivalent uniform dose (gEUD) sensitivity and complexity metrics (MU/Gy and plan irregularity) were calculated, and the correlation coefficients were assessed. Furthermore, the required tolerances for MLC positional accuracy control were calculated. The gEUD sensitivity showed the highest dependence of systematic positional error on the treatment site, followed by TPS and fraction size. The gEUD sensitivities were 6.7, 4.5, 2.5, and 1.7%/mm for Monaco and 8.9, 6.2, 3.4, and 2.3%/mm (spinal metastasis, lung cancer, prostate cancer, and brain metastasis, respectively) for RayStation. The gEUD sensitivity was strongly correlated with the complexity metrics (r = 0.88-0.93). The minimum allowable positional error for MLC was 0.63, 0.34, 1.02, and 0.28 mm (prostate, lung, brain, and spinal metastasis, respectively). The acceptable range of MLC positional accuracy depends on the treatment site, and an appropriate tolerance should be set for each treatment site with reference to the complexity metric. It is expected to enable easier and more detailed MLC positional accuracy control than before by reducing dose errors to patients at the treatment planning stage and by controlling MLC quality based on complexity metrics, such as MU/Gy.

Accelerated hypofractionated radiotherapy with 3 Gy per fraction for central/ultra-central lung tumors: toxicity to mediastinal organs.

BACKGROUND: Accelerated hypofractionated radiotherapy with 3 Gy per fraction is routinely performed for central lung tumors in Japan. However, the tolerable doses to mediastinal organs at risk during this procedure are unclear. This study aimed to clarify the rate of toxicities and tolerable doses to mediastinal organs. METHODS: Patients treated with accelerated hypofractionated radiotherapy using a total dose of 60-75 Gy, with 3 Gy per fraction, for central lung tumors (July 2009-April 2021) were retrospectively reviewed. We extracted patients who received ≥30 Gy irradiation to each mediastinal organ and analyzed dosimetric factors, including doses to 0.03, 0.5, 1, 4 and 10 mL of each organ, in relation to grade 3-5 toxicities, except for radiation pneumonitis. RESULTS: In total, 251 organs in 91 (ultra-central, 24) lesions were analyzed, with a median follow-up duration of 26 months (range, 4-94). The prescribed doses were 75/72/69/66/63/60 Gy for 52/14/16/3/2/4 lesions, respectively. Grade 3 bronchopulmonary hemorrhage was confirmed in two (2.2%) patients, whose tumors were located ultra-centrally. The two patients with toxicity received up to 74.5 and 71.6 Gy to the bronchus. Among patients who received 70 Gy or more to the bronchus, the incidence rate was 7% (2/28 patients). CONCLUSION: The rate of severe toxicities was low (2.2%). Although we did not identify the dose tolerance of the organs, because of the low incidence rate, we did note that doses of >70 Gy to the bronchus were likely to cause bronchopulmonary hemorrhage.

Evaluation of the MVCT-based radiomic features as prognostic factor in patients with head and neck squamous cell carcinoma.

BACKGROUND: Megavoltage computed tomography (MVCT) images acquired during each radiotherapy session may be useful for delta radiomics. However, no studies have examined whether the MVCT-based radiomics has prognostic power. Therefore, the purpose of this study was to examine the prognostic power of the MVCT-based radiomics for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 100 HNSCC patients who received definitive radiotherapy were analyzed and divided into two groups: training (n = 70) and test (n = 30) sets. MVCT images obtained using TomoTherapy for the first fraction of radiotherapy and planning kilovoltage CT (kVCT) images obtained using Aquilion LB CT scanner were analyzed. Primary gross tumor volume (GTV) was propagated from kVCT to MVCT images using rigid registration, and 107 radiomic features were extracted from the GTV in MVCT and kVCT images. Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to examine the association between overall survival (OS) and rad score calculated for each patient by weighting the feature value through the coefficient when features were selected. Then, the predictive values of MVCT-based and kVCT-based rad score and patient-, treatment-, and tumor-specific factors were evaluated. RESULTS: C-indices of the rad score for MVCT- and kVCT-based radiomics were 0.667 and 0.685, respectively. The C-indices of 6 clinical factors were 0.538-0.622. The 3-year OS was significantly different between high- and low-risk groups according to the MVCT-based rad score (50% vs. 83%; p < 0.01). CONCLUSIONS: Our results suggested that MVCT-based radiomics had stronger prognostic power than any single clinical factor and was a useful prognostic factor when predicting OS in HNSCC patients.

Impact of CT scan parameters on deformable image registration accuracy using deformable thorax phantom.

The purpose of this study was to evaluate the deformable image registration (DIR) accuracy using various CT scan parameters with deformable thorax phantom. Our developed deformable thorax phantom (Dephan, Chiyoda Technol Corp, Tokyo, Japan) was used. The phantom consists of a base phantom, an inner phantom, and a motor-derived piston. The base phantom is an acrylic cylinder phantom with a diameter of 180 mm, which simulates the chest wall. The inner phantom consists of deformable, 20 mm thick disk-shaped sponges with 48 Lucite beads and 48 nylon cross-wires which simulate the vascular and bronchial bifurcations of the lung. Peak-exhale and peak-inhale images of the deformable phantom were acquired using a CT scanner (Aquilion LB, TOSHIBA). To evaluate the impact of CT scan parameters on DIR accuracy, we used the four tube voltages (80, 100, 120, and 135 kV) and six reconstruction algorithms (FC11, FC13, FC15, FC41, FC44, and FC52). Intensity-based DIR was performed between the two images using MIM Maestro (MIM software, Cleveland, USA). Fiducial markers (beads and cross-wires) based target registration error (TRE) was used for quantitative evaluation of DIR. In case with different tube voltages, the range of average TRE were 4.44-5.69 mm (reconstruction algorithm: FC13). In case with different reconstruction algorithms, the range of average TRE were 4.26-4.59 mm (tube voltage: 120 kV). The TRE were differed by up to 3.0 mm (3.96-6.96 mm) depending on the combination of tube voltage and reconstruction algorithm. Our result indicated that CT scan parameters had moderate impact of TRE, especially for reconstruction algorithms for the deformable thorax phantom.

Experimental investigation of the effective point of measurement for plane-parallel chambers used in electron beam dosimetry.

In this study, the effective point of measurement (EPOM) for plane-parallel ionization chambers in clinical high-energy electron beams was determined experimentally. Previous studies have reported that the EPOM of plane-parallel chambers is shifted several tens of millimeters downstream from the inner surface of the entrance window to the cavity. These findings were based on the Monte Carlo (MC) simulation, and few experimental studies have been performed. Thus, additional experimental validations of the reported EPOMs were required. In this study, we investigated the EPOMs of three plane-parallel chambers (NACP-02, Roos and Advanced Markus) for clinical electron beams. The EPOMs were determined by comparing the measured percentage depth-dose (PDD) of the plane-parallel chambers and the PDD obtained using the microDiamond detector. The optimal shift to the EPOM was energy-dependent. The determined EPOM showed no chamber-to-chamber variation, thereby allowing the use of a single value. The mean optimal shifts were 0.104 ± 0.011, 0.040 ± 0.012, and 0.012 ± 0.009 cm for NACP-02, Roos, and Advanced Markus, respectively. These values are valid in the R50 range from 2.40 to 8.82 cm, which correspond to 6-22 MeV. Roos and Advanced Markus exhibited similar results to those of the previous studies, but NACP-02 showed a larger shift. This is probably due to the uncertainty of the entrance window of NACP-02. Therefore, it is necessary to carefully consider where the optimal EPOM is located when using this chamber.

Fracture risk following stereotactic body radiotherapy for long bone metastases.

BACKGROUND: Stereotactic body radiotherapy is a new treatment modality for long bone metastasis and has not been discussed in literature. We aimed to clarify stereotactic body radiotherapy outcomes for long bone metastases. METHODS: Data of patients receiving stereotactic body radiotherapy for long bone metastases (July 2016-November 2020) were retrospectively reviewed. The prescribed dose was 30 or 35 Gy in five fractions. The endpoints were local failure and adverse effects. Local failure was defined as radiological tumor growth within the irradiation field. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5. RESULTS: Nineteen osseous lesions in 17 patients were assessed. The target lesions included 13 femoral, 4 humeral and 2 radial lesions. The median follow-up duration was 14 (range, 3-62) months. The 12- and 18-month local failure rates were 0 and 11%, respectively. Following 2 and 46 months of stereotactic body radiotherapy, two lesions (11%) resulted in painful femoral fractures (grade 3). Both patients underwent bipolar hip arthroplasty and could walk normally after surgery. In the late phase, one patient developed radiculopathy (almost complete paralysis of grasp) and another developed grade 2 limb edema. Other grade 2 or more severe acute and late toxicities were not observed during the follow-up period. CONCLUSIONS: Stereotactic body radiotherapy for long bone metastases achieved excellent local control and caused two femoral fractures. We argue that stereotactic body radiotherapy for curative intent should not be contraindicated in long bone oligometastasis because fractures do not directly contribute to life expectancy.

Risk of radiculopathy caused by second course of spine stereotactic body radiotherapy.

OBJECTIVE: Stereotactic body radiotherapy is used to treat spinal metastases; however, 10% of patients experience local failure. We aimed to clarify the outcomes of the second course of stereotactic body radiotherapy for spinal metastases with a uniform fractionation schedule at our institution. METHODS: Data of patients treated with a second salvage stereotactic body radiotherapy course at the same spinal level or adjacent level from July 2018 to December 2020 were retrospectively reviewed. The initial prescribed dose was 24 Gy in two fractions, and the second dose 30 or 35 Gy in five fractions. The spinal cord dose constraint at the second course was 15.5 Gy at the maximum point dose. The endpoints were local failure and adverse effects. Local failure was defined as tumor progression using imaging. RESULTS: We assessed 19 lesions in 17 patients, with radioresistant lesions in 14 (74%) cases, the second stereotactic body radiotherapy to the same/adjacent spinal level in 13/6 cases, the median interval between stereotactic body radiotherapy of 23 (range, 6-52) months, and lesions compressing the cord in 5 (26%) cases. The median follow-up period was 19 months. The 12- and 18-month local failure rates were 0% and 8%, respectively. Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 0 (0%), 4 (21%) and 2 (11%) lesions, respectively. Three patients with radiculopathy experienced almost complete upper or lower limb paralysis. CONCLUSIONS: The second course of salvage stereotactic body radiotherapy for spinal metastases achieved good local control with a reduced risk of myelopathy. However, a high occurrence rate of radiation-induced radiculopathy has been confirmed.

Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis.

BACKGROUND: Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013-18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique. RESULTS: Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed. CONCLUSIONS: DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.

Efficacy and toxicity of re-irradiation spine stereotactic body radiotherapy with respect to irradiation dose history.

OBJECTIVE: We aimed to clarify the outcomes of re-irradiation stereotactic body radiotherapy for spinal metastases with a uniform dose fractionation schedule at our institution. METHODS: Data of patients treated with re-irradiation stereotactic body radiotherapy for spinal metastases (September 2013-March 2020) were retrospectively reviewed. The prescribed dose was 24 Gy in two fractions. The spinal cord dose constraint and dose for previously irradiated cases ≥50 Gy in 25 fractions were 12.2 Gy (maximum dose) and 11 Gy, respectively. The endpoints were pain control, local failure and adverse effects. Pain status was measured on a scale of 0-10 using the patients' self-reports and pain response was defined using international consensus criteria. Local failure was defined as tumor progression on imaging evaluations. RESULTS: We assessed 133 lesions in 123 patients, where 70 (52.6%) had three or more spinal levels treated, 58 (43.6%) had previous irradiation doses of 40 Gy or more and 53 (39.8%) had the targets compressing the cord. The median follow-up was 12 months and the 3-, 6- and 12-month pain response rate was 75, 64 and 59%, respectively. The 1-year local failure rate was 25.8%. Previous irradiation dose was not correlated with local failure rate (P = 0.13). Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 4 (3.0%), 2 (1.5%) and 17 (13.8%) lesions, respectively. A trend towards an association between any toxicity and previous irradiation dose was not observed. CONCLUSIONS: Re-irradiation spine stereotactic body radiotherapy achieved good local control and pain control, with reduced risk of radiation myelopathy.

High neutrophil-to-lymphocyte ratio is a predictor of short-term survival for patients with recurrent cervical cancer after radiation-based therapy.

AIM: Patients with recurrent cervical cancer after radiotherapy have poor prognoses because of the lack of effective treatment options. Biomarkers to predict survival outcomes for recurrent cervical cancer are warranted because patients with limited life expectancy sometimes benefit from less aggressive treatment in combination with early palliative care. Therefore, we aimed to explore a predictive biomarker for the outcomes of patients with recurrent cervical cancer. METHODS: We retrospectively investigated 231 patients initially treated with radiation-based therapy between January 2004 and December 2015. The associations between clinicopathological features at the time of relapse and overall survival after relapse were assessed. As factors which reflect patients' conditions, we particularly focused on C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-lymphocyte ratio (NLR) at the time of relapse. Additionally, we investigated biomarkers predictive of short-term survival. RESULTS: Among 231 patients, 91 patients experienced relapse and 74 patients died during the follow-up period. Multivariate analysis revealed that treatment after relapse, CAR, and NLR was significantly associated with overall survival. Among them, treatment after relapse significantly affected survival outcomes, and patients who received definitive local treatment had a better 3-year survival rate than those who received other treatments. Conversely, NLR was the most influential biomarker for short-term survival, and the prognosis of patients with high NLRs was much worse than those with low NLRs. CONCLUSIONS: This study thus demonstrated that, for the patients with recurrent cervical cancer who received radiation-based therapy, definitive local treatment can provide long-term survival and extremely high NLRs are predictive of short-term survival.

Development of a physical geometric phantom for deformable image registration credentialing of radiotherapy centers for a clinical trial.

PURPOSE: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions. METHODS AND MATERIALS: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies. CONCLUSIONS: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.

Radiation therapy and the risk of herpes zoster in patients with cancer.

BACKGROUND: The role and impact of radiation therapy (RT) on the development of herpes zoster (HZ) has not been well studied. The objective of this study was to investigate the association between RT and HZ. METHODS: A propensity score-matched, retrospective cohort study was conducted using institutional cancer registry data and medical records from 2011 to 2015. The risk of developing HZ in the RT and non-RT groups was compared using a Cox proportional hazards model. Associations also were explored between the RT field and the anatomic location of HZ in patients who developed HZ after RT. The expected number of HZ events within the radiation field was calculated according to the RT received by each patient; then, this number was compared with the observed number of in-field events. RESULTS: Of 17,655 patients, propensity score matching yielded 4350 pairs; of these, 3891 pairs were eligible for comparison. The cumulative incidence of HZ in the RT group (vs the non-RT group) during the first 5 years after the index date was 2.1% (vs 0.7%) at 1 year, 3.0% (vs 1.0%) at 2 years, 3.4% (vs 1.3%) at 3 years, 4.1% vs 1.7% at 4 years, and 4.4% vs 1.8% at 5 years. The RT group showed a significantly higher risk of HZ than the non-RT group (hazard ratio, 2.59, 95% CI, 1.84-3.66). In the 120 patients who developed HZ after RT, HZ events were observed significantly more frequently within the RT field than expected (74 vs 43.8 events; P < .001). CONCLUSIONS: Patients with cancer who received RT showed a significantly higher risk of HZ, which was commonly observed within the radiation field.

Stereotactic body radiotherapy for bone metastases in patients with colorectal cancer.

OBJECTIVE: To clarify the clinical outcomes of stereotactic body radiotherapy for colorectal cancer-derived bone metastases and identify factors predicting treatment failure. METHODS: Patients treated with stereotactic body radiotherapy for bone metastases from colorectal cancer between September 2013 and June 2019 were retrospectively reviewed. The prescribed dose for spine and non-spine bone metastases was 24 Gy in two fractions and 35 Gy in five fractions, respectively. The end point was local failure, which was defined as tumour progression on imaging evaluations. In addition, various treatment- and tumour-specific factors were evaluated to determine predictors of local failure. RESULTS: This study included 43 lesions in 38 patients, with solitary bone metastases in 18 lesions (42%), re-irradiation stereotactic body radiotherapy in 28 lesions (65%) and postoperative stereotactic body radiotherapy due to spinal cord compression in 10 lesions (23%). The median follow-up after stereotactic body radiotherapy was 12 (range, 2-60) months. The 1-year LF rate was 44%. In the univariate analysis, sacral metastases (P = 0.02) were found to be significantly correlated with LF, and multiple-course systemic therapy before stereotactic body radiotherapy (P= 0.06) and large target volume (P = 0.07) showed a trend towards an association with LF. However, these factors were not independent predictors of LF in the multivariate analysis. CONCLUSION: More than 40% of the lesions treated with stereotactic body radiotherapy for bone metastases from colorectal cancer showed LF within 1 year. No poor prognostic factors could be identified statistically. The poor outcomes in all groups indicate that the treatment intensity of the stereotactic body radiotherapy was insufficient to control colorectal cancer bone metastases.

Postradiotherapy persistent lymphopenia as a poor prognostic factor in patients with cervical cancer receiving radiotherapy: a single-center, retrospective study.

BACKGROUND: Radiotherapy (RT) is effective in cervical cancer; radiation-induced lymphopenia correlates with poor survival outcome in several cancer types. We investigated the association of total lymphocyte count (TLC) with survival outcomes in patients with cervical cancer. METHODS: We retrospectively reviewed 168 patients with cervical cancer initially treated with definitive RT. We obtained clinicopathological data and TLCs before RT and at the end and at 6 months after RT. Patient-, treatment-, and tumor-specific factors were evaluated to determine their predictive values for overall survival. The association of overall and progression-free survivals with lymphopenia at each point was evaluated. RESULTS: Median follow-up duration was 44 (interquartile range: 25-67) months. Median TLCs before RT and at the end and at 6 months after RT were 1625/mm3, 400/mm3, and 800/mm3 (interquartile range: 1270-1930/mm3, 290-550/mm3, and 600-1067/mm3), respectively. For overall survival, in addition to FIGO stage, body mass index, histology, treatment, and presence of para-aortic lymph node metastasis, lymphopenia at 6 months after RT was a poor prognostic factor in multivariate analysis (P = 0.0026; hazard ratio [HR], 3.06; 95% confidence interval [CI]: 1.48-6.33). For progression-free survival, TLCs before and at 6 months after RT were poor prognostic factors in univariate analysis (P = 0.0318 and 0.0081, respectively); however, the latter was the only independent prognostic factor in multivariate analysis (P = 0.0021; HR, 2.67; 95% CI: 1.43-4.99). CONCLUSION: Post-RT persistent lymphopenia could be a poor prognostic factor for patients with cervical cancer who receive RT.

Extreme skeletal muscle loss during induction chemotherapy is an independent predictor of poor survival in advanced epithelial ovarian cancer patients.

AIM: Skeletal muscle loss is often observed in advanced cancer patients. This study investigates whether skeletal muscle loss is associated with survival outcomes of advanced epithelial ovarian cancer (EOC) patients after induction chemotherapy (IC) in a Japanese cohort. Whether serum inflammatory markers are associated with skeletal muscle changes is also addressed. METHODS: We retrospectively reviewed 60 patients with stage III/IV EOC who underwent IC between 2010 and 2017. Skeletal muscle area (SMA) was measured at the third lumbar vertebrae level on a single axial computed tomography-scan image. Receiver operating curve analysis was used to determine cut-off values of pre- and post-IC SMA and SMA ratio (SMAR). Univariate and multivariate analyses of overall survival (OS) were conducted using the log-rank test and Cox proportional hazards regression model, respectively. RESULTS: The SMA decreased significantly after IC (P = 0.019). The cut-off value between low and high SMAR was 0.96. High or low SMAR was observed in 34 (57%) and 26 (43%) patients, respectively. Univariate analysis revealed that low SMAR was associated with poor OS (P = 0.025). Multivariate analysis showed that incomplete resection during interval debulking surgery (hazard ratio, 0.30; 95% CI, 0.11-0.80; P = 0.016) and a low SMAR (hazard ratio, 3.17; 95% CI, 1.18-9.06; P = 0.022) were independent predictors of poor OS. Of the serum inflammatory markers investigated, only post-IC absolute neutrophil count correlated significantly with SMAR (P = 0.012). CONCLUSION: Low SMAR can be used to predict poor prognosis in advanced EOC patients who have undergone IC.

Determining the recommended dose of stereotactic body radiotherapy boost in patients with cervical cancer who are unsuitable for intracavitary brachytherapy: a phase I dose-escalation study.

OBJECTIVE: Some patients are ineligible for intracavitary brachytherapy (ICBT) for locally advanced cervical cancer. Stereotactic body radiotherapy (SBRT) could be a good treatment option for such patients. This phase I clinical trial aimed to determine the recommended SBRT boost dose for ICBT-ineligible cervical cancer patients. METHODS: Patients with untreated uterine cervical cancer (clinical stages IB1-IIIB) who were ineligible for ICBT were enrolled. Radiotherapy consisted of whole-pelvis radiotherapy (45 Gy in 25 fractions) followed by SBRT. Three dose levels of SBRT (19.5/21/22.5 Gy in three fractions) were set; the treatment protocol began at 21 Gy (level 2). The 'rolling-six' design study was used to establish the recommended dose of SBRT. Each dose level covered three or six patients. The primary endpoint included dose-limiting toxicity (DLT), defined as the occurrence of grade 3 (or worse) non-hematologic adverse effects within 6 months after SBRT. RESULTS: The median follow-up after registration was 17 (range, 8-32) months. Three patients were enrolled in study level 2 (SBRT of 21 Gy); none of the patients exhibited DLT within 6 months after treatment completion. In study level 3 (SBRT of 22.5 Gy), three patients did not exhibit DLT. Although all six patients achieved locoregional control during follow-up, one patient treated with level 2 SBRT experienced distant metastases 14 months after registration. CONCLUSIONS: The recommended dose of SBRT boost was 22.5 Gy in three fractions. We plan to conduct a phase II multi-center clinical trial using the methodology obtained from the current study.

A low albumin to globulin ratio with a high serum globulin level is a prognostic marker for poor survival in cervical cancer patients treated with radiation based therapy.

OBJECTIVE: We investigated whether the pretreatment albumin to globulin ratio, serum albumin level, and serum globulin level can be used to predict survival among cervical cancer patients treated with radiation based therapy and assessed globulin fractions. METHODS: We retrospectively enrolled 128 patients with cervical cancer treated with radiation based therapy at our institution between 2010 and 2015. The associations of the pretreatment albumin to globulin ratio, and serum albumin and globulin levels with overall survival were assessed. Additionally, the associations of the globulin fractions with the serum globulin levels and overall survival were evaluated. RESULTS: Median follow-up duration was 30 months (IQR 16-44 months). A low albumin to globulin ratio (< 1.53) was found to be an independent prognostic factor for overall survival (HR= 3.07; 95% CI, 1.03 to 13.3; P=0.044). On evaluating serum globulin and albumin separately, a high serum globulin level was significantly associated with overall survival (cut-off value 2.9 g/dL; HR=3.74; 95% CI 1.08 to 23.6; P=0.036) whereas a low serum albumin level was not associated with overall survival (cut-off value 3.6 g/dL; HR=1.77; 95% CI 0.57 to 4.54; P=0.29). Electrophoresis data of the serum proteins revealed that the γ-globulin fraction was most strongly correlated with the globulin levels (P<0.001). Furthermore, a high γ-globulin level (≥1.28 g/dL) was significantly associated with poor overall survival (log rank test, P=0.034). CONCLUSIONS: A pretreatment low albumin to globulin ratio, which might be attributable to a high serum globulin level, can be used to predict poor prognosis in cervical cancer patients treated with radiation based therapy.

Left Ventricular T1 Mapping during Chemotherapy-Radiation Therapy: Serial Assessment of Participants with Esophageal Cancer.

Purpose To assess changes in left ventricular function and tissue composition by using MRI after chemotherapy-radiation therapy in participants with esophageal cancer. Materials and Methods Between January 2013 and April 2015, this prospective study enrolled 24 participants (42% women; mean age, 63 years; range, 49-73 years) scheduled for chemotherapy-radiation therapy. 3.0-T MRI examinations were performed before, at 0.5 year, and at 1.5 years after chemotherapy-radiation therapy. Myocardial native T1, postcontrast T1, and extracellular volume were measured in basal septum (as irradiated areas) and apical lateral wall (as nonirradiated areas). Left ventricular function, prevalence of late gadolinium enhancement, and T1 and extracellular volume values were compared over the follow-up period by using Friedman or Cochran Q tests, followed by Dunn test. Results In 14 participants who were followed up for 1.5 years, native T1 and extracellular volume in the septum were elevated at 0.5 year compared with baseline (1183 msec ± 46 [standard deviation] vs 1257 msec ± 35; 26% ± 3 vs 32% ± 3; adjusted P < .01 for both), but not in the lateral wall. Left ventricular stroke volume index and late gadolinium enhancement changed at 1.5 years compared with baseline (41 mL/m2 ± 11 vs 36 mL/m2 ± 9; P = .046; 7% [one of 14] vs 78% [11 of 14]; P < .01). Other measures of left ventricular function did not change during the follow-up period (P > .10 for all). Conclusion Native T1 and extracellular volume could detect early changes in myocardium at 0.5 year after chemotherapy-radiation therapy, whereas left ventricular stroke volume index and late gadolinium enhancement showed abnormality at 1.5 years. © RSNA, 2018 Online supplemental material is available for this article.

Phase II Clinical Trial of Second Course of Stereotactic Body Radiotherapy for Spinal Metastases.

PURPOSE: The optimal method for the second course of stereotactic body radiotherapy (SBRT) for spinal metastases remains poorly established. This single-center, single-arm, phase II trial was conducted to propose a safe and effective salvage spine SBRT. METHODS: The patients initially treated with SBRT for spine-targeted protocol treatment, or for areas adjacent to the spine, were enrolled. The second SBRT dose was 30 Gy delivered in five fractions; the spinal cord dose constraint was 15.5 Gy at the maximum point dose. The brachial or lumbosacral plexuses were dose-constrained to <30 Gy if the boundary between the nerves and tumors was detected. The primary endpoint was dose-limiting toxicity (DLT) (grade ≥ 3 severe radiation-related toxicity) within a year after the second SBRT. RESULTS: The second SBRT was administered to the same spinal level in 12 patients and to an adjacent spinal level in 8 patients. SBRT2 was performed for 14 painful lesions, 10 MESCC, and 6 oligometastases, with some lesions having multiple indications. The median interval between SBRT sessions was 21 months (range: 6-51 months). The median follow-up duration was 14 months. No radiation myelopathy or local failure was reported during the follow-up period. DLT was confirmed in two patients (10%) within a year, both of whom developed grade 3 lumbosacral plexopathy. These two patients received SBRT twice to the S1-2 and S1-5 vertebrae, respectively, and both experienced paralysis of the tibialis anterior muscle (L5 level). Grade 3 late adverse effects (including lumbosacral plexopathy and vertebral compression fracture) were observed in 25% of the patients throughout the entire follow-up period. CONCLUSIONS: The second spine SBRT achieved good local control without causing myelopathy. However, one-quarter of the patients experienced grade 3 late adverse effects, suggesting that the treatment protocol carries a risk of toxicity.

Phase I/II study of stereotactic body radiotherapy boost in patients with cervical cancer ineligible for intracavitary brachytherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).