Radiomics-based prediction of recurrence for head and neck cancer patients using data imbalanced correction.

OBJECTIVES: To propose a radiomics-based prediction model for head and neck squamous cell carcinoma (HSNCC) recurrence after radiation therapy using a novel data imbalance correction method known as Gaussian noise upsampling (GNUS). MATERIALS AND METHODS: The dataset includes 97 HNSCC patients treated with definitive radiotherapy alone or concurrent chemoradiotherapy at two institutions. We performed radiomics analysis using nine segmentations created on pretreatment positron emission tomography and computed tomography images. Feature selection was performed by the least absolute shrinkage and selection operator analysis via five-fold cross-validation. The proposed GNUS was compared with seven conventional data-imbalance correction methods. Classification models of HNSCC recurrence were constructed on oversampled features using the machine learning algorithms of linear regression. Their predictive performance was evaluated based on accuracy, sensitivity, specificity, and the area under the curve (AUC) of the receiver operating performance characteristic curve via five-fold cross-validation using the same combinations as for feature selection. RESULT: The prediction model without data imbalance correction shows sensitivity, specificity, accuracy, and AUC values of 83 %, 96 %, 92 %, and 0.96, respectively. The conventional model with the best performance is the random over-sampler model, which shows sensitivity, specificity, accuracy, and AUC values of 93 %, 91 %, 92 %, 0.97, respectively, whereas the GNUS model shows values of 93 %, 94 %, 94 %, 0.98, respectively. CONCLUSION: Oversampling methods can reduce sensitivity and specificity bias. The proposed GNUS can improve accuracy as well as reduce sensitivity and specificity bias.

A nomogram based on pretreatment radiomics and dosiomics features for predicting overall survival associated with esophageal squamous cell cancer.

OBJECTIVES: To propose a nomogram-based survival prediction model for esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy using pretreatment computed tomography (CT), positron emission tomography (PET) radiomics and dosiomics features, and common clinical factors. METHODS: Radiomics and dosiomics features were extracted from CT and PET images and dose distribution from 2 institutions. The least absolute shrinkage and selection operator (LASSO) with logistic regression was used to select radiomics and dosiomics features by calculating the radiomics and dosiomics scores (Rad-score and Dos-score), respectively, in the training model. The model was trained in 81 patients and validated in 35 patients at Center 1 using 10-fold cross validation. The model was externally tested in 26 patients at Center 2. The predictive clinical factors, Rad-score, and Dos-score were identified to develop a nomogram model. RESULTS: Using LASSO Cox regression, 13, 11, and 19 CT, PET-based radiomics, and dosiomics features, respectively, were selected. The clinical factors T-stage, N-stage, and clinical stage were selected as significant prognostic factors by univariate Cox regression. In the external validation cohort, the C-index of the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were 0.74, 0.82, and 0.92, respectively. Significant differences in overall survival (OS) in the combined model of CT-based radiomics, PET-based radiomics, and dosiomics features with clinical factors were observed between the high- and low-risk groups (P = 0.019, 0.038, and 0.014, respectively). CONCLUSION: The dosiomics features have a better predicter for OS than CT- and PET-based radiomics features in ESCC treated with radiotherapy. CLINICAL RELEVANCE STATEMENT: The current study predicted the overall survival for esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. The dosiomics features have a better predicter for overall survival than CT- and PET-based radiomics features.

Postoperative Lymph Node Recurrence in Esophageal Cancer After Surgery and Prognosis of Chemoradiotherapy.

Background/Aim: This study aimed to evaluate the long-term prognosis of definitive chemoradiotherapy and clinical features of postoperative lymph node (LN) recurrence after curative resection of thoracic esophageal squamous cell cancer (ESCC). Patients and Methods: A total of 586 patients who underwent radical resection of ESCC at the Hiroshima University Hospital from January 2000 to December 2019 were reviewed retrospectively. This study analyzed the clinical characteristics of 54 patients who developed recurrence in a solitary LN by comparing them to 182 patients who experienced total recurrence. Additionally, we analyzed the prognostic factors of 50 patients who received chemo-radiotherapy (CRT). Results: The results revealed a tendency for a higher incidence of solitary LN recurrence in cases of early esophageal cancer and upper thoracic esophageal cancer among all recurrence cases. The 3-, 5-, and 7-year overall survival (OS) rates were 40.5%, 37.8% and 34.6%, respectively, with a median survival time of 27.9 months. Univariate analysis of OS factors, such as age, depth of the primary tumor at the initial surgery, time to LN recurrence after surgery, site of LN recurrence, and the number of the regional LNs with recurrence showed no significant impact on OS. Conclusion: Approximately 35% of patients with ESCC who experienced LN recurrence after curative resection achieved long-term survival through CRT. Despite the absence of identifiable prognostic factors, CRT proves to be a valuable initial treatment option for LN recurrence.

Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

OBJECTIVE: This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. METHODS: A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. RESULTS: The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). CONCLUSION: The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. ADVANCES IN KNOWLEDGE: The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Radiomics and dosiomics for predicting complete response to definitive chemoradiotherapy patients with oesophageal squamous cell cancer using the hybrid institution model.

OBJECTIVES: To develop a multi-institutional prediction model to estimate the local response to oesophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy based on radiomics and dosiomics features. METHODS: The local responses were categorised into two groups (incomplete and complete). An external validation model and a hybrid model that the patients from two institutions were mixed randomly were proposed. The ESCC patients at stages I-IV who underwent chemoradiotherapy from 2012 to 2017 and had follow-up duration of more than 5 years were included. The patients who received palliative or pre-operable radiotherapy and had no FDG PET images were excluded. The segmentations included the GTV, CTV, and PTV which are used in treatment planning. In addition, shrinkage, expansion, and shell regions were created. Radiomic and dosiomic features were extracted from CT, FDG PET images, and dose distribution. Machine learning-based prediction models were developed using decision tree, support vector machine, k-nearest neighbour (kNN) algorithm, and neural network (NN) classifiers. RESULTS: A total of 116 and 26 patients enrolled at Centre 1 and Centre 2, respectively. The external validation model exhibited the highest accuracy with 65.4% for CT-based radiomics, 77.9% for PET-based radiomics, and 72.1% for dosiomics based on the NN classifiers. The hybrid model exhibited the highest accuracy of 84.4% for CT-based radiomics based on the kNN classifier, 86.0% for PET-based radiomics, and 79.0% for dosiomics based on the NN classifiers. CONCLUSION: The proposed hybrid model exhibited promising predictive performance for the local response to definitive radiotherapy in ESCC patients. CLINICAL RELEVANCE STATEMENT: The prediction of the complete response for oesophageal cancer patients may contribute to improving overall survival. The hybrid model has the potential to improve prediction performance than the external validation model that was conventionally proposed. KEY POINTS: • Radiomics and dosiomics used to predict response in patients with oesophageal cancer receiving definitive radiotherapy. • Hybrid model with neural network classifier of PET-based radiomics improved prediction accuracy by 8.1%. • The hybrid model has the potential to improve prediction performance.

Unbiased evaluation of predicted gamma passing rate by an event-mixing technique.

BACKGROUND: Predicting models of the gamma passing rate (GPR) have been studied to substitute the measurement-based gamma analysis. Since these studies used data from different radiotherapy systems comprising TPS, linear accelerator, and detector array, it has been difficult to compare the performances of the predicting models among institutions with different radiotherapy systems. PURPOSE: We aimed to develop unbiased scoring methods to evaluate the performance of the models predicting the GPR, by introducing both best and worst limits for the performance of the GPR prediction. METHODS: Two hundred head-and-neck VMAT plans were used to develop a framework. The GPRs were measured using the ArcCHECK device. The predicted GPR [p] was generated using a deep learning-based model [pDL ]. The predicting model was evaluated using four metrics: standard deviation (SD) [σ], Pearson's correlation coefficient (CC) [r], mean squared error (MSE) [s], and mean absolute error (MAE) [a]. The best limit [ σ m ${\sigma _m}$ , r m ${r_m}$ , s m ${s_m}$ , and a m ${a_m}$ ] was estimated by measuring the SD of measured GPR [m] by shifting the device along the longitudinal direction to measure different sampling points. Mimicked best and worst p's [pbest and pworst ] were generated from pDL . The worst limit was defined such that m and p have no correlation [CC ∼ 0]. The worst limit [σMix , rMix , sMix , and aMix ] was generated using the event-mixing (EM) technique originally introduced in high-energy physics experiments. The range of σ, r, s, and a was defined to be [ σ m , σ Mix ] $[ {{\sigma _m},{\sigma _{{\mathrm{Mix}}}}} ]$ , [ 0 , r m ] $[ {0,{r_m}} ]$ , [ s m , s Mix ] $[ {{s_m},{s_{{\mathrm{Mix}}}}} ]$ , and [ a m , a Mix ] $[ {{a_m},{a_{{\mathrm{Mix}}}}} ]$ . The achievement score (AS) independently based on σ, r, s, and a were calculated for pDL , pbest and pworst . The probability that p fails the gamma analysis (alert frequency; AF) was estimated as a function of σ d ${\sigma _d}$ values within the [ σ m ${\sigma _m}$ , σMix ] range for the 3%/2 mm data with a 95% criterion. RESULTS: SDs of the best limit were well reproduced by σ m = 0.531 100 - m ${\sigma _m} = \;0.531\sqrt {100 - m} $ . The EM technique successfully generated the ( m , p ) $( {m,p} )$ pairs with no correlation. The AS using four metrics showed good agreement. This agreement indicates successful definitions of both best and worst limits, consistent definitions of the AS, and successful generations of mixed events. The AF for the DL-based model with the 3%/2 mm tolerance was 31.5% and 63.0% with CL's 99% and 99.9%, respectively. CONCLUSION: We developed the AS to evaluate the predicting model of the GPR in an unbiased manner by excluding the effects of the precision of the radiotherapy system and the spreading of the GPR. The best and worst limits of the GPR prediction were successfully generated using the measured precision of the GPR and the EM technique, respectively. The AS and σ p ${\sigma _p}$ are expected to enable objective evaluation of the predicting model and setting exact achievement goal of precision for the predicted GPR.

Radiation doses of medical radiation workers performing low-dose-rate brachytherapy with 198Au grains and 192Ir pins for patients with oral cancers.

OBJECTIVES: Low-dose-rate brachytherapy (LDR-BT) with 198Au grains and 192Ir pins is an essential treatment option for oral cancer due to its high rate of local control and low invasiveness. However, the radiation exposure of medical radiation workers is concerning. Thus, we aimed to determine the radiation dose delivered to medical radiation workers during LDR-BT using 198Au grains and 192Ir pins for oral cancer. METHODS: Thirty-two patients with oral cancer underwent 198Au grain interstitial LDR-BT between June 2016 and May 2023, and 23 patients with tongue cancer underwent 192Ir pin interstitial LDR-BT between March 2015 and November 2017 at our hospital. Dosimetry was performed by attaching a dosimeter to the chest pocket of the operator and assistant during 198Au grain or 192Ir pin LDR-BT. Since the operator also loads 198Au grains into the implantation device, the operator's radiation dose includes the dose received during this preparation. RESULTS: Mean radiation doses of the operators with 198Au grain and 192Ir pin LDR-BT were 165.8 and 211.2 µSv, respectively. Statistically significant differences between the radioactive sources of 198Au grain and 192Ir pin LDR-BT were observed (p = 0.0459). The mean radiation doses of the assistants with 198Au grain and 192Ir pin LDR-BT were 92.0 and 162.0 µSv, respectively. Statistically significant differences were observed between the radioactive sources of 198Au grains and 192Ir pin LDR-BT (p = 0.0003). CONCLUSIONS: Regarding radioactive source differences, 192Ir pin LDR-BT resulted in higher doses delivered to medical radiation workers than 198Au grain LDR-BT.

Risk factors for aortoesophageal fistula in cT4b esophageal squamous cell carcinoma after definitive radiation therapy.

Background: Esophageal fistula (EF) is a serious complication in patients with cT4b esophageal squamous cell carcinoma (ESCC) with adjacent organ involvement. Among EFs, aortoesophageal fistula (AEF), forming a fistula with the aorta, could be fatal. This study aimed to identify the risk factors for AEF in patients with cT4b ESCC with obvious or suspected aortic invasion who underwent definitive radiotherapy (DRT). Methods: Forty-four patients with cT4b ESCC with obvious or suspected invasion to the aorta who underwent DRT were included. Blood tests and computed tomography (CT) findings before and after DRT were compared between the patients with and without AEF to identify the potential risk factors for AEF. Results: Nine patients (20.5%) developed AEF after DRT. Comparing between patients with and without AEF, pre-DRT white blood cell counts and post-DRT C-reactive protein (CRP) levels were significantly higher in patients with AEF. Furthermore, pre-DRT CT findings were similar between the two groups. However, post-DRT CT findings demonstrated significantly larger picus angle and lower esophageal wall thickness on the aortic side in patients with AEF. Multivariate analysis identified elevated post-DRT CRP levels [<3.3 versus ≥3.3 mg/dL; odds ratio (OR): 30.7; 95% confidence interval (CI): 2.92-323.2; P=0.004] and esophageal wall thinning on post-DRT CT scans (>6 versus ≤6 mm; OR: 13.2; 95% CI: 1.24-140.1; P=0.033) as risk factors for AEF. Conclusions: We found that post-DRT esophageal wall thinning on the aortic side, as observed on CT scans, and elevated CRP levels were predictive factors for AEF in patients with cT4b ESCC with obvious or suspected invasion to the aorta.

Efficacy of Supportive Care for Radiodermatitis in Patients with Head and Neck Cancer: Supplementary Analysis of an Exploratory Phase II Trial.

Self-care demonstrated efficacy in preventing severe acute radiation dermatitis among patients with head and neck squamous cell carcinoma undergoing chemoradiotherapy (CRT). This prospective trial aimed to confirm the feasibility and safety of transcutaneous electrical sensory stimulation while examining the relationship between changes in self-care behavior through supportive care interventions and the severity of acute radiation dermatitis during CRT. Patients underwent assessments for dermatitis grading (Grades 1 to ≥3) and were interviewed regarding self-care practices. The self-care questionnaires comprised six items, and a point was deducted for each task that the patient could not perform independently. Statistical analysis was performed to determine the association between G3 radiation dermatitis and the lowest self-care behavior scores. Of the 10 patients enrolled, three experienced G3 dermatitis. During CRT, six patients maintained their initial scores and did not develop ≥G3 dermatitis. Meanwhile, three of four patients with decreased scores exhibited ≥G3 dermatitis. The group with ≥G3 dermatitis had significantly lower scores than those with ≤G2 dermatitis, suggesting that the inability of patients to perform self-care routinely may lead to severe acute radiation dermatitis. Further prospective studies are needed to confirm the potential of self-care interventions in preventing severe dermatitis.

Novel simulation for dosimetry impact of diaphragm respiratory motion in four-dimensional volumetric modulated arc therapy for esophageal cancer.

BACKGROUND AND PURPOSE: The diaphragm respiratory motion (RM) could impact the target dose robustness in the lower esophageal cancer (EC). We aimed to develop a framework evaluating the impact of different RM patterns quantitatively in one patient, by creating virtual four-dimensional computed-tomography (v4DCT) images, which could lead to tailored treatment for the breathing pattern. We validated virtual 4D radiotherapy (v4DRT) along with exploring the acceptability of free-breathing volumetric modulated arc therapy (FB-VMAT). METHODS AND MATERIALS: We assessed 10 patients with superficial EC through their real 4DCT (r4DCT) scans. v4DCT images were derived from the end-inhalation computed tomography (CT) image (reference CT) and the v4DRT dose was accumulated dose over all phases. r4DRT diaphragm shifts were applied with magnitudes derived from r4DCT scans; clinical target volume (CTV) dose of v4DRT was compared with that of r4DRT to validate v4DRT. CTV dosage modifications and planning organ at risk volume (PRV) margins of the spinal cord were examined with the diaphragm movement. The percentage dose differences (ΔDx) were determined between the v4DRT and the dose calculated on the reference CT image. RESULTS: The CTV ΔDx between the r4DRT and v4DRT were within 1% in cases with RM ≦ 15 mm. The average ΔD100% and ΔDmean of the CTV ranging from 5 to 15 mm of diaphragm motion was 0.3% to 1.7% and 0.1% to 0.4%, respectively. All CTV index changes were within 3% and ΔD1cc and ΔD2cc of Cord PRV were within 1%. CONCLUSION: We postulate a novel method for evaluating the CTV robustness, comparable to the conventional r4DCT method under the diaphragm RM ≦ 15 mm permitting an impact of within 3% in FB-VMAT for EC on the CTV dose distribution.

Outcome of Hypofractionated Radiotherapy for Localized Gastric Mucosa-associated Lymphoid Tissue Lymphoma.

BACKGROUND/AIM: With the prevalence of COVID-19, the importance of short-course radiotherapy (RT) in many cancers has been discussed. The aim of this study was to evaluate the results of hypofractionated schedule RT for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. PATIENTS AND METHODS: We assessed 45 patients with localized gastric MALT lymphoma who underwent RT between 2005 and 2019. The total RT dose ranged from 24-36 Gy in 10-18 fractions (median of 28 Gy/14 fractions). Patients were divided into three groups according to the dose fractionation: Group A, 30-36 Gy in 15-18 fractions; Group B, 26-28 Gy in 13-14 fractions; and Group C, 24-25 Gy in 10 fractions. RESULTS: All the patients achieved complete remission without local recurrence. The 5-year overall, cause-specific, and progression-free survival rates were 97.5%, 100%, and 97.5%, respectively, with a median follow-up period of 82 months. Among the dose fractionation groups, there were no statistically significant differences in local control or incidence of grade 2 or worse adverse events. CONCLUSION: Results of RT for localized gastric MALT lymphoma showed excellent local control and survival with no serious adverse events, regardless of dose fractionation. In situations where short-term RT is required, a hypofractionated RT schedule of 24-25 Gy in 10 fractions could be an option for RT schedules.

Endoscopic findings suggestive of a high risk of non-radical cure after definitive chemoradiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (DCRT) is a curative treatment option for cT1bN0M0 esophageal squamous cell carcinoma (ESCC); however, local residual disease and recurrence after complete remission may occur. We aimed to identify endoscopic findings associated with the risk of non-radical cure (local remnant or recurrence) after DCRT for cT1bN0M0 ESCC. METHODS: We retrospectively analyzed 40 consecutive patients with cT1bN0M0 ESCC who had undergone DCRT between January 2007 and December 2017. We examined the endoscopic findings in patients with residual or recurrent (RR) disease (RR group) and those without RR disease [non-RR (NRR) group] after DCRT. We also evaluated outcomes after DCRT for each endoscopic finding. RESULTS: There were 10 patients in the RR group and 30 patients in the NRR group. The RR group had a significantly larger tumor size and a higher proportion of lesions with type 0-I. The 5-year relapse-free survival rate was significantly lower in type 0-I and in the presence of B3 vessels. Endoscopic findings in 15 patients with cT1bN0M0 ESCC, type 0-I, who underwent DCRT revealed significantly more reddish lesions in the RR group compared to the NRR group. CONCLUSIONS: cT1bN0M0 ESCC large size, with B3 vessels, and type 0-I has a high risk of non-radical cure after DCRT, especially the reddish type 0-I, which may need to be considered for treatment similar to advanced cancer, including surgery with preoperative DCRT.

Effectiveness of Spacers in Brachytherapy With 198Au Grains for Patients With Buccal Mucosa Cancer.

BACKGROUND/AIM: The aim of this study was to investigate the use of spacers and their efficacy in brachytherapy with 198Au grains for buccal mucosa cancer. PATIENTS AND METHODS: Sixteen patients with squamous cell carcinoma of the buccal mucosa who were treated with 198Au grain brachytherapy were included. The distance between 198Au grains, distance between 198Au grains and the maxilla or mandible, and the maximum dose/cc to the jawbone (D1cc) with and without a spacer was investigated in three out of 16 patients. RESULTS: The median distance between 198Au grains without and with a spacer was 7.4 and 10.7 mm, respectively; this was significantly different. The median distance between 198Au grains and the maxilla without and with a spacer was 10.3 and 18.5 mm, respectively; again this was significantly different. The median distance between 198Au grains and the mandible without and with a spacer was 8.6 and 17.3 mm, respectively; the difference was significant. The D1cc to the maxilla without and with a spacer were 14.9, 68.7, and 51.8 Gy and 7.5, 21.2, and 40.7 Gy in cases 1, 2, and 3, respectively. The D1cc to the mandible without and with a spacer were 27.5, 68.7, and 85.8 Gy and 11.3, 53.6, and 64.9 Gy in cases 1, 2, and 3, respectively. No osteoradionecrosis of the jaw bones was observed in any case. CONCLUSION: The spacer enabled maintenance of the distance between 198Au grains, and between 198Au grains and the jawbone. In buccal mucosa cancer, using a spacer in brachytherapy with 198Au grains appears to reduce jawbone complications.

Xenopus laevis Oocyte Array Fluidic Device Integrated with Microelectrodes for A Compact Two-Electrode Voltage Clamping System.

We report on a compact two-electrode voltage clamping system composed of microfabricated electrodes and a fluidic device for Xenopus laevis oocytes. The device was fabricated by assembling Si-based electrode chips and acrylic frames to form fluidic channels. After the installation of Xenopus oocytes into the fluidic channels, the device can be separated in order to measure changes in oocyte plasma membrane potential in each channel using an external amplifier. Using fluid simulations and experiments, we investigated the success rates of Xenopus oocyte arrays and electrode insertion with respect to the flow rate. We successfully located each oocyte in the array and detected oocyte responses to chemical stimuli using our device.

Pain Response Rates After Conventional Radiation Therapy for Bone Metastases Assessed Using International Consensus Pain Response Endpoints: A Systematic Review and Meta-Analysis of Initial Radiation Therapy and Reirradiation.

Previous meta-analysis of conventional radiation therapy for painful bone metastases showed overall response (OR) rates of 72% to 75% (evaluable patients), 61% to 62% (intent-to-treat patients) for initial radiation therapy, and 68% for reirradiation (evaluable patients). However, the definition of pain response differed among the studies included. Hence, we conducted a systematic review and meta-analysis to determine the pain response rates assessed by the International Consensus Pain Response Endpoints (ICPRE) for both initial radiation therapy and reirradiation. The PubMed and Scopus databases were searched for articles published between 2002 and 2021. The inclusion criteria were (1) prospective studies or studies based on prospectively collected data and (2) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were the OR rates (sum of the complete and partial response rates) for both initial radiation therapy and reirradiation. Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for the analysis of initial radiation therapy and reirradiation, respectively. The OR rates of initial radiation therapy in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2-65.4) and 45.4% (95% CI, 38.7-52.4), respectively. The OR rates of reirradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7-96.9) and 62.2% (95% CI, 5.3-98.0), respectively. Subgroup analyses of initial radiation therapy including the comparison of randomized and nonrandomized studies showed no significant differences in any comparison, indicating similar response rates across different study designs. For initial radiation therapy, we determined the ICPRE-assessed response rates, which were lower than previously reported. The OR and complete response rates should be benchmarks for future randomized and nonrandomized studies. For reirradiation, the wide CIs demonstrate that the response rates based on ICPRE require further investigation.

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

BACKGROUND: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil. RESULTS: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment. CONCLUSION: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events.

Influence of different air CT numbers for IVDT on the dose distribution in TomoTherapy MVCT.

This study aims to evaluate the effect of different air computed tomography (CT) numbers of the image value density table (IVDT) on the retrospective dose calculation of head-and-neck (HN) radiotherapy using TomoTherapy megavoltage CT (MVCT) images. The CT numbers of the inside and outside air and each tissue-equivalent plug of the "Cheese" phantom were obtained from TomoTherapy MVCT. Two IVDTs with different air CT numbers were created and applied to MVCT images of the HN anthropomorphic phantom and recalculated by Planned Adaptive to verify dose distribution. We defined the recalculation dose with MVCT images using both inside and outside air of the IVDT as IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ , respectively. Treatment planning doses calculated on kVCT images were compared with those calculated on MVCT images using two different IVDT tables, namely, IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ . The difference between average MVCT numbers ±1 standard deviation on inside and outside air of the calibration phantom was 65 ± 36 HU. This difference in MVCT number of air exceeded the recommendation lung tolerance for dose calculation error of 2%. The dose differences between the planning target volume (PTV): D98% , D50% , D2% and the organ at risk (OAR): Dmax , Dmean recalculated by IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ using MVCT images were a maximum of 0.7% and 1.2%, respectively. Recalculated doses to the PTV and OAR with MVCT showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was 0.5%-0.7% closer to the kVCT treatment planning dose than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ . This study showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was more accurate than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ in recalculating the dose HN cases of MVCT using TomoTherapy.

A phase II study of concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C for squamous cell carcinoma of the anal canal (the JROSG 10-2 trial).

This study assessed the efficacy of chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC). Patients with T1-4N0-3M0 SCCAC received chemoradiotherapy with 5-fluorouracil (5-FU, 800 mg/m2/day, 96-h infusion) and mitomycin-C (MMC, 10 mg/m2 bolus). Patients treated with 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) were administered 36.0 Gy in 20 fractions or 49.5 Gy in 33 fractions for elective nodal irradiation and 59.4 Gy in 33 fractions for primary tumor and metastatic nodal irradiation. The sample size was considered sufficient to estimate 95% confidence intervals (CIs) for the true 2-year disease-free survival (DFS) within a width of +15% when the expected true 2-year DFS was 70%. The primary endpoint was 2-year DFS. The secondary endpoints were 2-year overall survival (OS), locoregional control (LC), colostomy-free survival (CFS) and adverse events. Thirty-one patients were enrolled between January 2014 and July 2019. The median follow-up was 33.3 months (range, 16.2-65.8 months). Among the 31 patients, 13%, 32%, 16% and 39% had stage I, II, IIIA and IIIB disease, respectively. Thirty patients were treated with IMRT. Complete response (CR) was achieved in 27 patients. The 2-year DFS, OS, LC and CFS rates were 77.4% (95% CI, 58.4-88.5%), 93.5% (95% CI, 76.6-98.3%), 83.9% (95% CI, 65.5-92.9%) and 80.6% (95% CI, 61.9-90.8%), respectively. One patient experienced grade 3 late adverse events; however, no grade ≥ 4 late adverse events occurred. Good DFS with a low rate of late adverse events was observed. Chemoradiotherapy with 5-FU and MMC was effective for SCCAC.

Robust optimization of VMAT for prostate cancer accounting for geometric uncertainty.

The aim of this study was to propose optimal robust planning by comparing the robustness with setup error with the robustness of a conventional planning target volume (PTV)-based plan and to compare the robust plan to the PTV-based plan for the target and organ at risk (OAR). Data from 13 patients with intermediate-to-high-risk localized prostate cancer who did not have T3b disease were analyzed. The dose distribution under multiple setup error scenarios was assessed using a conventional PTV-based plan. The clinical target volume (CTV) and OAR dose in moving coordinates were used for the dose constraint with the robust plan. The hybrid robust plan added the dose constraint of the PTV-rectum to the static coordinate system. When the isocenter was shifted by 10 mm in the superior-inferior direction and 8 mm in the right-left and anterior directions, the doses to the CTV, bladder, and rectum of the PTV-based plan, robust plan, and hybrid robust plan were compared. For the CTV D99% in the PTV-based plan and hybrid robust plan, over 95% of the prescribed dose was secured in all directions, except in the inferior direction. There was no significant difference between the PTV-based plan and the hybrid robust plan for rectum V70Gy , V60Gy , and V40Gy . This study proposed an optimization method for patients with prostate cancer. When the setup error occurred within the PTV margin, the dose robustness of the CTV for the hybrid robust plan was higher than that of the PTV-based plan, while maintaining the equivalent OAR dose.