Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

[Report of Multidisciplinary Treatment for Sisters with Li-Fraumeni Syndrome].

Li-Fraumeni syndrome(LFS)is a hereditary cancer disorder caused by germline variant in TP53 and characterized by various malignancies. Multidisciplinary treatment is needed for tumors of LFS, however, radiation therapy is a relative contraindication because of frequent development of secondary malignancy such as sarcoma in the irradiated field. Case 1: A 22- year-old woman who was diagnosed with LFS by genetic test when she developed upper rectal cancer. Her rectal tumor with marked bilateral lateral lymph node dissection was successfully removed by low anterior resection with extensive lateral lymph node dissection. She underwent resection for ovarian metastasis followed by chemotherapy and radiotherapy but subsequently died by the disease 32 months postoperatively. Case 2(elder sister of Case 1): A brain tumor was identified in the left high frontal lobe to the parietal lobe because of consciousness disorder, after the genetic diagnosis of LFS. The brain tumor was successfully resected. Histological examination revealed diffuse astrocytoma(WHO grade Ⅱ). Local recurrence was observed 46 months later, and radiation therapy was performed. Six months have passed since radiation therapy, no exacerbation of local recurrence has been observed.

Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan.

BACKGROUND: International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. METHODS: Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. RESULTS: Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. CONCLUSIONS: Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Algorithm for an automatic treatment planning system using a single-arc VMAT for prostate cancer.

Optimization process in treatment planning for intensity-modulated radiation therapy varies with the treatment planner. Therefore, a large variation in the quality of dose distribution is usually observed. To reduce variation, an automatic optimizing toolkit was developed for the Monaco treatment planning system (Elekta AB, Stockholm, Sweden) for prostate cancer using volumetric-modulated arc therapy (VMAT). This toolkit was able to create plans automatically. However, most plans needed two arcs per treatment to ensure the dose coverage for targets. For prostate cancer, providing a plan with a single arc was advisable in clinical practice because intrafraction motion management must be considered to irradiate accurately. The purpose of this work was to develop an automatic treatment planning system with a single arc per treatment for prostate cancer using VMAT. We designed the new algorithm for the automatic treatment planning system to use one arc per treatment for prostate cancer in Monaco. We constructed the system in two main steps: (1) Determine suitable cost function parameters for each case before optimization, and (2) repeat the calculation and optimization until the conditions for dose indices are fulfilled. To evaluate clinical suitability, the plan quality between manual planning and the automatic planning system was compared. Our system created the plans automatically in all patients within a few iterations. Statistical differences between the plans were not observed for the target and organ at risk. It created the plans with no human input other than the initial template setting and system initiation. This system offers improved efficiency in running the treatment planning system and human resources while ensuring high-quality outputs.

[Idea of Treatment Method for Upper and Lower Rectal Cancer Avoiding Irradiation to Internal and External Sphincter].

BACKGROUND: Preoperative chemoradiotherapy(CRT)followed by total mesorectal excision(TME)is used for locally advanced rectal cancer, but it can induce postoperative anorectal function. The primary objective of this study is to confirm the efficacy and safety of preoperative CRT and TME without irradiation to the internal and external sphincter muscles. SUBJECTS AND METHODS: Patients were eligible for this study if they met the following inclusion criteria: histologically proven rectal cancer, clinical T3T4N0-2 disease, and a distance between anal margin of tumor and the rental line is more than 2 cm. Twelve patients who underwent preoperative CRT and TME between 2013 and 2017 were enrolled. The primary endpoint was completion rate of sphincter-preserving surgery. RESULTS: All patients completed preoperative CRT without Grade 3 or higher adverse effect. Sphincter-preserving surgery was performed in all cases. The 5-year disease-free survival rate was 46.7%, and the local recurrence-free survival rate was 75%, and the overall survival rate was 90.9%. CONCLUSION: It is suggested that preoperative CRT and TME without irradiation to the internal and external sphincter muscles is effective and safe therapy for locally advanced rectal cancer.

Evaluation of geometrical uncertainties on localized prostate radiotherapy of patients with bilateral metallic hip prostheses using 3D-CRT, IMRT and VMAT: A planning study.

OBJECTIVE: Since most radiation treatment plans are based on computed tomography (CT) images, which makes it difficult to define the targeted tumor volume located near a metal implant, this study aims to evaluate and compare three treatment plans in order to optimally reduce geometrical uncertainty in external radiation treatment of localized prostate cancer. METHODS: Experimental subjects were three prostate patients with bilateral hip prosthesis who had undergone radical radiotherapy. The treatment plans were five-field three-dimensional conformal radiation therapy (3D-CRT), fixed 5-field intensity-modulated radiation therapy (IMRT) using similar gantry angles, and single-arc volumetric modulated arc therapy (VMAT). The monitor units (MUs), dose volume histograms (DVHs), the dose indices of planning target volume (PTV), clinical target volume (CTV) and rectum were compared among the three techniques. The geometrical uncertainties were evaluated by shifting the iso-center (2- 10 mm in the anterior, posterior, left, right, superior, and inferior directions). The CTV and rectum dose indexes with and without the iso-center shifts were compared in each plan. RESULTS: The Conformity Index of PTV were 1.35 in 3D-CRT, 1.12 in IMRT, and 1.04 in VMAT, respectively. The rectum doses in 3D-CRT are also higher than those in IMRT and VMAT. The iso-center shift little affected the CTV dose when smaller than the margin size. The rectum dose increased especially after a posterior shift. Additionally, this dose increase was larger in the VMAT plan than in the 3D- CRT plan. However, the VMAT achieved a superior rectum DVH to that of 3D- CRT, and this effect clearly exceeded the rectum-dose increase elicited by the iso-center shift. CONCLUSION: For radiotherapy treatment of localized prostate cancer in patients with hip prosthesis, the dose distribution was better in the VMAT and Metal Artifact Reduction (MAR)-CT image methods than the conventional methods. Because the anatomical structure of the male pelvic region is relatively constant among individuals, we consider that VMAT is a valid treatment plan despite analyzing just three cases.

Commissioning of the Mobius3D independent dose verification system for TomoTherapy.

In radiation therapy, a secondary independent dose verification is an important component of a quality control system. Mobius3D calculates three-dimensional (3D) patient dose using reference beam data and a collapsed cone convolution algorithm and analyzes dose-volume histogram automatically. There are currently no published data on commissioning and determining tolerance levels of Mobius3D for TomoTherapy. To verify the calculation accuracy and adjust the parameters of this system, we compared the measured dose using an ion chamber and film in a phantom with the dose calculated using Mobius3D for nine helical intensity-modulated radiation therapy plans, each with three nominal field widths. We also compared 126 treatment plans used in our institution to treat prostate, head-and-neck, and esophagus tumors based on dose calculations by treatment planning system for given dose indices and 3D gamma passing rates with those produced by Mobius3D. On the basis of these results, we showed that the action and tolerance levels at the average dose for the planning target volume (PTV) at each treatment site are at µ ± 2σ and µ ± 3σ, respectively. After adjusting parameters, the dose difference ratio on average was -0.2 ± 0.6% using ion chamber and gamma passing rate with the criteria of 3% and 3 mm on average was 98.8 ± 1.4% using film. We also established action and tolerance levels for the PTV at the prostate, head-and-neck, esophagus, and for the organ at risk at all treatment sites. Mobius3D calculations thus provide an accurate secondary dose verification system that can be commissioned easily and immediately after installation. Before clinical use, the Mobius3D system needs to be commissioned using the treatment plans for patients treated in each institution to determine the calculational accuracy and establish tolerances for each treatment site and dose index.

Structural development of non-secosteroidal vitamin D receptor (VDR) ligands without any asymmetric carbon.

Non-secosteroidal VDR ligands without any assymmetric carbon were designed and synthesized based on the structure of the previously reported non-secosteroidal VDR agonist LG190178. The VDR-agonistic activity of all synthesized compounds was evaluated, and 7b emerged as a potent agonist activity with an EC50 value of 9.26 nM. Moreover, a docking simulation analysis was also performed to determine the binding mode of 7b with VDR-LBD.

Palliative radiotherapy for breast cancer patients with skin invasion: a multi-institutional prospective observational study.

PURPOSE: To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer. MATERIALS AND METHODS: We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy. RESULTS: Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178). CONCLUSION: Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.

Simple index for validity of the evaluation point for dosimetric verification results of intensity-modulated radiation therapy using a Farmer-type ionization chamber.

PURPOSE: Based on a retrospective analysis, this study aims to develop a simple index for validity of the evaluation point for the dosimetric verification of intensity-modulated radiation therapy (IMRT). METHODS: The results for the dosimetric verifications of a total of 69 IMRT plans were analyzed in this study. A Farmer-type ion chamber was used as a dose detector, and a solid water-equivalent phantom was used. Index values were obtained by dividing the difference between the maximum and minimum dosages by the mean dosage of the 69 plans, and the values were classified into five groups with index value <4, 4-8, 8-12, 12-16, and >16. A t-test was used to assess the statistical significance of the mean differences of the absolute values of the relative errors among these groups. RESULTS: We found that there was no significant difference between the groups with index value <4 and 4-8 (p = 0.152); however, there were significant differences between the other groups (p < 0.01). In addition, when the index values were smaller than 8, the pass ratio of 3% tolerance was 96.2% and the pass ratio of 5% tolerance was 99.9%. We observed that the smaller the index value, the smaller the uncertainty of the dose measurement. CONCLUSIONS: The results obtained in this study may prove to be useful for accurate dosimetric verifications of IMRTs when ion chambers are used.

Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.

Output-limiting symptoms induced by radiofrequency hyperthermia. Are they predictable?

BACKGROUND: During radiofrequency (RF) hyperthermia treatment, hot-spot phenomena may occur and prevent treatment continuation if the output is not lowered. We previously reported a significant correlation between the initial energy output at which output-limiting symptoms occurred and patient status. Patients with a complete clinical response had significantly increased temperature, while some patients with partial clinical response and stable disease had increased temperature, depending on the occurrence of output-limiting symptoms. To predict the initial energy output at which output-limiting symptoms occur, we performed multiple regression analysis with the parameters of patients' physical status. MATERIALS AND METHODS: Hyperthermia alone or concomitant with chemotherapy and/or radiotherapy was applied in 62 patients with malignant disease for a total of 310 treatments with a Thermotron RF-8 between December 2011 and April 2014. RESULTS: No output-limiting symptoms were shown in 65.5% of 310 treatments. Pain (29.7%), micturition desire (1.9%), skin discomfort (0.6%), subcutaneous induration (1.6%), cold sensation (0.6%), and nausea (0.3%) were reported in the 310 treatments. A good predictive equation for initial energy output at which output-limiting symptoms occur was determined with two parameters, initial time of an output-limiting symptom onset, and thickness of the fat of the abdominal wall. Multiple regression analysis showed an adjusted R(2 )= 0.99 and variance inflation factor < 2. CONCLUSIONS: We present a good predictive equation for initial energy output at which output-limiting symptoms occur. It is critical to prevent RF hyperthermia-induced output-limiting symptoms and establish new prevention strategies.

Quality of palliative radiotherapy assessed using quality indicators: a multicenter survey†.

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.

Dual-color-emitting green fluorescent protein from the sea cactus Cavernularia obesa and its use as a pH indicator for fluorescence microscopy.

We isolated and characterized a green fluorescent protein (GFP) from the sea cactus Cavernularia obesa. This GFP exists as a dimer and has absorption maxima at 388 and 498 nm. Excitation at 388 nm leads to blue fluorescence (456 nm maximum) at pH 5 and below, and green fluorescence (507 nm maximum) at pH 7 and above, and the GFP is remarkably stable at pH 4. Excitation at 498 nm leads to green fluorescence (507 nm maximum) from pH 5 to pH 9. We introduced five amino acid substitutions so that this GFP formed monomers rather than dimers and then used this monomeric form to visualize intracellular pH change during the phagocytosis of living cells by use of fluorescence microscopy. The intracellular pH change is visualized by use of a simple long-pass emission filter with single-wavelength excitation, which is technically easier to use than dual-emission fluorescent proteins that require dual-wavelength excitation.

Carbonylation of propargyl carbamates with palladium(II) bisoxazoline catalysts: efficient synthesis of 5-methoxy-3(2H)-furanones.

Palladium and CO: Carbonylation of 1 with [Pd(tfa)2(±)-L1] (tfa = trifluoroacetate) affords the spirofuranone 2 with inversion of the stereochemistry at C17 in 96 % yield. C17-epi-1 also gave the same product 2 with retention of the stereochemistry at C17. Labelling studies show that (13)CO was incorporated into the C5' position of the furanone ring. The first asymmetric version of this new reaction was achieved.

A Retrospective Study of Patients Undergoing Palliative Radiotherapy for Airway Obstruction due to Lung Cancer.

BACKGROUND/AIM: In advanced stage lung cancer, bulky tumors can cause serious symptoms such as malignant airway obstruction (MAO). Prompt response to airway obstruction might be essential to improve quality of life and prolong life expectancy. Palliative external beam radiotherapy (EBRT) is a less invasive and highly safe treatment method that can alleviate symptoms and at the same time treat lung cancer. However, there are few reports on the results of palliative radiotherapy performed for improving airway obstruction and obstructive pneumonia. Therefore, this study retrospectively examined the effectiveness of palliative radiotherapy. PATIENTS AND METHODS: We reviewed 38 lung cancer patients with MAO who underwent EBRT. Patients were treated with a median dose of 37.5 Gy (range=30-40 Gy) in 10-20 fractions. Whether a patient was a responder or non-responder was assessed by whether the bronchus that was obstructed before EBRT reopened or improvement of obstructive pneumonia was observed on follow-up chest X-ray or computed tomography after EBRT. RESULTS: The median survival time was 135 days (range=31-469 days) for the responders to EBRT and 45 days (range=23-355 days) for non-responders; this difference was statistically significant (p=0.03). One-year overall survival rate was 18.5% and 0% for the responders to EBRT and non-responders, respectively. CONCLUSION: Palliative EBRT might be an important option for non-curative lung cancer patients with MAO.

Who should receive single-fraction palliative radiotherapy for gastric cancer bleeding?: An exploratory analysis of a multicenter prospective observational study (JROSG 17-3).

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer. Materials and methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival. Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival. Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

Factors associated with quality of life in patients receiving palliative radiotherapy for bone metastases: a secondary cross-sectional analysis of data from a prospective multicenter observational study.

OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.

Evaluation of prediction and classification performances in different machine learning models for patient-specific quality assurance of head-and-neck VMAT plans.

PURPOSE: The purpose of this study is to evaluate the prediction and classification performances of the gamma passing rate (GPR) for different machine learning models and to select the best model for achieving machine learning-based patient-specific quality assurance (PSQA). METHODS: The measurement verification of 356 head-and-neck volumetric modulated arc therapy plans was performed using a diode array phantom (Delta4 Phantom), and GPR values at 2%/2 mm with global normalization and 3%/2 mm with local normalization were calculated. Machine learning models, including ridge regression (RIDGE), random forest (RF), support vector regression (SVR), and stacked generalization (STACKING), were used to predict the GPR. Each machine learning model was trained using 260 plans, and the prediction accuracy was evaluated using the remaining 96 plans. The prediction error between the measured and predicted GPR was evaluated. For the classification evaluation, the lower control limit for the measured GPR and lower control limit for predicted GPR (LCLp ) was defined to identify whether the GPR values represent a "pass" or a "fail." LCLp values with 99% and 99.9% confidence levels were calculated as the upper prediction limits for the GPR estimated from the linear regression between the measured and predicted GPR. RESULTS: There was an overestimation trend of the low measured GPR. The maximum prediction errors for RIDGE, RF, SVR, and STACKING were 3.2%, 2.9%, 2.3%, and 2.2% at the global 2%/2 mm and 6.3%, 6.6%, 6.1%, and 5.5% at the local 3%/2 mm, respectively. In the global 2%/2 mm, the sensitivity was 100% for all the machine learning models except RIDGE when using 99% LCLp . The specificity was 76.1% for RIDGE, RF, and SVR and 66.3% for STACKING; however, the specificity decreased dramatically when 99.9% LCLp was used. In the local 3%/2 mm, however, only STACKING showed 100% sensitivity when using 99% LCLp . The decrease in the specificity using 99.9% LCLp was smaller than that in the global 2%/2 mm, and the specificity for RIDGE, RF, SVR, and STACKING was 61.3%, 61.3%, 72.0%, and 66.8%, respectively. CONCLUSIONS: STACKING had better prediction accuracy for low GPR values than other machine learning models. Applying LCLp to a regression model enabled the consistent evaluation of quantitative and qualitative GPR predictions. Adjusting the confidence level of the LCLp helped improve the balance between the sensitivity and specificity. We suggest that STACKING can assist the safe and efficient operation of PSQA.