Transvaginal approach combined intracavitary and interstitial brachytherapy assisted by transrectal ultrasound: results from 30 patients with locally advanced cervical cancer.

PURPOSE: This study evaluated the efficacy and safety of transvaginal approach combined intracavitary and interstitial brachytherapy (IC/IS BT) assisted by transrectal ultrasound (TRUS) for treatment of locally advanced cervical cancer (LACC). MATERIALS AND METHODS: A total of 30 patients of LACC treated with external beam radiotherapy and IC/IS BT via transvaginal approach assisted by transrectal ultrasound were observed retrospectively. The 2-year local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan-Meier method. Late adverse events were also evaluated to assess the safety of IC/IS BT. RESULTS: The median follow-up period was 22 months. The 2-year LC, PFS, and OS were 90%, 61%, and 82%, respectively. We observed no critical complications related to the IC/IS BT technique. Late adverse events of grade 3 or more included one case of grade 4 colon perforation. CONCLUSION: Our patient series demonstrated that radiotherapy combined with transvaginal approach, TRUS-assisted IC/IS BT achieves favorable local control and safety for LACC.

Combination of Clinical Factors and Radiomics Can Predict Local Recurrence and Metastasis After Stereotactic Body Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: Radiomics, which links radiological image features with patient prognoses, is expected to be applied for the prediction of the clinical outcomes of radiotherapy. We investigated the clinical and radiomic factors associated with recurrence patterns after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with histologically confirmed NSCLC who underwent SBRT between April 2003 and June 2017 at our institution. A radiomic score was calculated from five radiomics features (histogram and texture features) selected using the LASSO Cox regression model. These features were extracted from the gross tumor volume (GTV) in three-dimensional wavelet decomposition CT images. We used univariate and multivariate analyses to determine the associations between local control (LC) time and metastasis-free survival (MFS), clinical factors (age, sex, performance status, operability, smoking, histology, and tumor diameter), and the radiomic score. RESULTS: With a median follow-up of 37 months, the following 3-year rates were observed: overall survival, 80.9%; progression-free survival, 61.7%; LC, 75.1%, and MFS; 74.5%. In multivariate analysis, histology (squamous cell carcinoma vs. non-squamous cell carcinoma, p=0.0045), tumor diameter (>3 cm vs. ≤3 cm, p=0.039); and radiomic score (>0.043 vs. ≤0.043, p=0.042) were significantly associated with LC, and the radiomic score (>0.304 vs. ≤0.304, p<0.001) was significantly associated with MFS. CONCLUSION: Histology, tumor diameter, and radiomic score could be significant factors for predicting NSCLC recurrence patterns after SBRT.

Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

Investigation of uncertainty in internal target volume definition for lung stereotactic body radiotherapy.

This study evaluated the validity of internal target volumes (ITVs) defined by three- (3DCT) and four-dimensional computed tomography (4DCT), and subsequently compared them with actual movements during treatment. Five patients with upper lobe lung tumors were treated with stereotactic body radiotherapy (SBRT) at 48 Gy in four fractions. Planning 3DCT images were acquired with peak-exhale and peak-inhale breath-holds, and 4DCT images were acquired in the cine mode under free breathing. Cine images were acquired using an electronic portal imaging device during irradiation. Tumor coverage was evaluated based on the manner in which the peak-to-peak breathing amplitude on the planning CT covered the range of tumor motion (± 3 SD) during irradiation in the left-right, anteroposterior, and cranio-caudal (CC) directions. The mean tumor coverage of the 4DCT-based ITV was better than that of the 3DCT-based ITV in the CC direction. The internal margin should be considered when setting the irradiation field for 4DCT. The proposed 4DCT-based ITV can be used as an efficient approach in free-breathing SBRT for upper-lobe tumors of the lung because its coverage is superior to that of 3DCT.

Deep learning model fusion improves lung tumor segmentation accuracy across variable training-to-test dataset ratios.

This study aimed to investigate the robustness of a deep learning (DL) fusion model for low training-to-test ratio (TTR) datasets in the segmentation of gross tumor volumes (GTVs) in three-dimensional planning computed tomography (CT) images for lung cancer stereotactic body radiotherapy (SBRT). A total of 192 patients with lung cancer (solid tumor, 118; part-solid tumor, 53; ground-glass opacity, 21) who underwent SBRT were included in this study. Regions of interest in the GTVs were cropped based on GTV centroids from planning CT images. Three DL models, 3D U-Net, V-Net, and dense V-Net, were trained to segment the GTV regions. Nine fusion models were constructed with logical AND, logical OR, and voting of the two or three outputs of the three DL models. TTR was defined as the ratio of the number of cases in a training dataset to that in a test dataset. The Dice similarity coefficients (DSCs) and Hausdorff distance (HD) of the 12 models were assessed with TTRs of 1.00 (training data: validation data: test data = 40:20:40), 0.791 (35:20:45), 0.531 (31:10:59), 0.291 (20:10:70), and 0.116 (10:5:85). The voting fusion model achieved the highest DSCs of 0.829 to 0.798 for all TTRs among the 12 models, whereas the other models showed DSCs of 0.818 to 0.804 for a TTR of 1.00 and 0.788 to 0.742 for a TTR of 0.116, and an HD of 5.40 ± 3.00 to 6.07 ± 3.26 mm better than any single DL models. The findings suggest that the proposed voting fusion model is a robust approach for low TTR datasets in segmenting GTVs in planning CT images of lung cancer SBRT.

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study.

We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Skeletal muscle area predicts the outcomes of non-small-cell lung cancer after trimodality therapy.

OBJECTIVES: Sarcopenia correlates with poor prognosis in various malignancies. However, the prognostic significance of sarcopenia remains to be determined in patients with non-small-cell lung cancer who undergo surgery after receiving neoadjuvant chemoradiotherapy (NACRT). METHODS: We retrospectively reviewed the patients with stage II/III non-small-cell lung cancer who underwent surgery following NACRT. The paravertebral skeletal muscle area (SMA) (cm2) at the 12th thoracic vertebra level was measured. We calculated the SMA index (SMAI) as SMA/squared height (cm2/m2). Patients were divided into low and high SMAI groups, and the association of SMAI with clinicopathological factors and prognosis was assessed. RESULTS: The patients' [men, 86 (81.1%)] median age was 63 (21-76) years. There were 106 patients including 2 (1.9%), 10 (9.4%), 74 (69.8%), 19 (17.9%) and 1 (0.9%) patients with stage IIA, IIB, IIIA, IIIB and IIIC, respectively. Of the patients, 39 (36.8%) and 67 (63.2%) were classified in the low and the high SMAI groups, respectively. Kaplan-Meier analysis showed that the low group had a significantly shorter overall survival and disease-free survival than the high group. Multivariable analysis identified low SMAI as an independent poor prognostic factor for overall survival. CONCLUSIONS: Pre-NACRT SMAI correlates with poor prognosis; therefore, assessing sarcopenia based on pre-NACRT SMAI may help determine optimal treatment strategies and suitable nutritional and exercise interventions.

Relapse predictability of topological signature on pretreatment planning CT images of stage I non-small cell lung cancer patients before treatment with stereotactic ablative radiotherapy.

BACKGROUND: This study aimed to explore the predictability of topological signatures linked to the locoregional relapse (LRR) and distant metastasis (DM) on pretreatment planning computed tomography images of stage I non-small cell lung cancer (NSCLC) patients before treatment with stereotactic ablative radiotherapy (SABR). METHODS: We divided 125 primary stage I NSCLC patients (LRR: 34, DM: 22) into training (n = 60) and test datasets (n = 65), and the training dataset was augmented to 260 cases using a synthetic minority oversampling technique. The relapse predictabilities of the conventional wavelet-based features (WF), topology-based features [BF, Betti number (BN) map features; iBF, inverted BN map features], and their combined features (BWF, iBWF) were compared. The patients were stratified into high-risk and low-risk groups using the medians of the radiomics scores in the training dataset. RESULTS: For the LRR in the test, the iBF, iBWF, and WF showed statistically significant differences (p < 0.05), and the highest nLPC was obtained for the iBF. For the DM in the test, the iBWF showed a significant difference and the highest nLPC. CONCLUSION: The iBF indicated the potential of improving the LRR and DM prediction of stage I NSCLC patients prior to undergoing SABR.

Synergistic combination of a topologically invariant imaging signature and a biomarker for the accurate prediction of symptomatic radiation pneumonitis before stereotactic ablative radiotherapy for lung cancer: A retrospective analysis.

OBJECTIVES: We aimed to explore the synergistic combination of a topologically invariant Betti number (BN)-based signature and a biomarker for the accurate prediction of symptomatic (grade ≥2) radiation-induced pneumonitis (RP+) before stereotactic ablative radiotherapy (SABR) for lung cancer. METHODS: A total of 272 SABR cases with early-stage non-small cell lung cancer were chosen for this study. The occurrence of RP+ was predicted using a support vector machine (SVM) model trained with the combined features of the BN-based signature extracted from planning computed tomography (pCT) images and a pretreatment biomarker, serum Krebs von den Lungen-6 (BN+KL-6 model). In all, 242 (20 RP+ and 222 RP-(grade 1)) and 30 cases (8 RP+ and 22 RP-) were used for training and testing the model, respectively. The BN-based features were extracted from BN maps that characterize topologically invariant heterogeneous traits of potential RP+ lung regions on pCT images by applying histogram- and texture-based feature calculations to the maps. The SVM models were built to predict RP+ patients with a BN signature that was constructed based on the least absolute shrinkage and selection operator logistic regression model. The evaluation of the prediction models was performed based on the area under the receiver operating characteristic curves (AUCs) and accuracy in the test. The performance of the BN+KL-6 model was compared to the performance based on the BN, conventional original pCT, and wavelet decomposition (WD) models. RESULTS: The test AUCs obtained for the BN+KL-6, BN, pCT, and WD models were 0.825, 0.807, 0.642, and 0.545, respectively. The accuracies of the BN+KL-6, BN, pCT, and WD models were found to be 0.724, 0.708, 0.591, and 0.534, respectively. CONCLUSION: This study demonstrated the comprehensive performance of the BN+KL-6 model for the prediction of potential RP+ patients before SABR for lung cancer.

Changes in the Relapse Pattern and Prognosis of Glioblastoma After Approval of First-Line Bevacizumab: A Single-Center Retrospective Study.

BACKGROUND: Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course and relapse pattern in patients with glioblastoma. METHODS: We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n = 51) and post-bevacizumab (n = 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated. RESULTS: Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P = 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P = 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 [0.26-2.62], P = 0.7377). The rate of early focal recurrence was significantly lower (P = 0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P = 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P = 0.0021, univariate analysis; P = 0.0144, multivariate analysis). CONCLUSIONS: Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.

The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.

Clinical significance of CDKN2A homozygous deletion in combination with methylated MGMT status for IDH-wildtype glioblastoma.

OBJECTIVE: Accumulating evidence from recent molecular diagnostic studies has indicated the prognostic significance of various genetic markers for patients with glioblastoma (GBM). To evaluate the impact of such genetic markers on prognosis, we retrospectively analyzed the outcomes of patients with IDH-wildtype GBM in our institution. In addition, to assess the impact of bevacizumab (BEV) treatment, we compared overall survival (OS) between the pre- and post-BEV eras. METHODS: We analyzed the data of 100 adult patients (over 18 years old) with IDH-wildtype GBM from our database between February 2006 and October 2018. Genetic markers, such as MGMT methylation status, EGFR amplification, CDKN2A homozygous deletion, and clinical factors were analyzed by evaluating the patients' OS. RESULTS: CDKN2A homozygous deletion showed no significant impact on OS in patients with methylated MGMT status (p = 0.5268), whereas among patients with unmethylated MGMT status, there was a significant difference in OS between patients with and without CDKN2A homozygous deletion (median OS: 14.7 and 16.9 months, respectively, p = 0.0129). This difference was more evident in the pre-BEV era (median OS: 10.1 and 15.6 months, respectively, p = 0.0351) but has become nonsignificant in the post-BEV era (median OS: 16.0 and 16.9 months, respectively, p = 0.1010) due to OS improvement in patients with CDKN2A homozygous deletion. However, these findings could not be validated in The Cancer Genome Atlas cohort. CONCLUSIONS: MGMT and CDKN2A status subdivided our cohort into three race-specific groups with different prognoses. Our findings indicate that BEV approval in Japan led to OS improvement exclusively for patients with concurrent unmethylated MGMT status and CDKN2A homozygous deletion.

Automated approach for segmenting gross tumor volumes for lung cancer stereotactic body radiation therapy using CT-based dense V-networks.

The aim of this study was to develop an automated segmentation approach for small gross tumor volumes (GTVs) in 3D planning computed tomography (CT) images using dense V-networks (DVNs) that offer more advantages in segmenting smaller structures than conventional V-networks. Regions of interest (ROI) with dimensions of 50 × 50 × 6-72 pixels in the planning CT images were cropped based on the GTV centroids when applying stereotactic body radiotherapy (SBRT) to patients. Segmentation accuracy of GTV contours for 192 lung cancer patients [with the following tumor types: 118 solid, 53 part-solid types and 21 pure ground-glass opacity (pure GGO)], who underwent SBRT, were evaluated based on a 10-fold cross-validation test using Dice's similarity coefficient (DSC) and Hausdorff distance (HD). For each case, 11 segmented GTVs consisting of three single outputs, four logical AND outputs, and four logical OR outputs from combinations of two or three outputs from DVNs were obtained by three runs with different initial weights. The AND output (combination of three outputs) achieved the highest values of average 3D-DSC (0.832 ± 0.074) and HD (4.57 ± 2.44 mm). The average 3D DSCs from the AND output for solid, part-solid and pure GGO types were 0.838 ± 0.074, 0.822 ± 0.078 and 0.819 ± 0.059, respectively. This study suggests that the proposed approach could be useful in segmenting GTVs for planning lung cancer SBRT.

Radiomic prediction of radiation pneumonitis on pretreatment planning computed tomography images prior to lung cancer stereotactic body radiation therapy.

This study developed a radiomics-based predictive model for radiation-induced pneumonitis (RP) after lung cancer stereotactic body radiation therapy (SBRT) on pretreatment planning computed tomography (CT) images. For the RP prediction models, 275 non-small-cell lung cancer patients consisted of 245 training (22 with grade ≥ 2 RP) and 30 test cases (8 with grade ≥ 2 RP) were selected. A total of 486 radiomic features were calculated to quantify the RP texture patterns reflecting radiation-induced tissue reaction within lung volumes irradiated with more than x Gy, which were defined as LVx. Ten subsets consisting of all 22 RP cases and 22 or 23 randomly selected non-RP cases were created from the imbalanced dataset of 245 training patients. For each subset, signatures were constructed, and predictive models were built using the least absolute shrinkage and selection operator logistic regression. An ensemble averaging model was built by averaging the RP probabilities of the 10 models. The best model areas under the receiver operating characteristic curves (AUCs) calculated on the training and test cohort for LV5 were 0.871 and 0.756, respectively. The radiomic features calculated on pretreatment planning CT images could be predictive imaging biomarkers for RP after lung cancer SBRT.

The prognosis and the impact of radiotherapy in clinically regional lymph node-positive prostate cancer: Which patients are candidates for local therapy with radiation?

BACKGROUND: This study aimed to identify the prognostic and predictive factors of local radiotherapy in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: This study includes patients who were newly diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017. We investigated the prognostic value of clinicopathological parameters for progression-free survival (PFS) and overall survival (OS) as well as the differential prognostic impact of radiotherapy by subgroup analysis. RESULTS: Among the 93 men enrolled as patients, 48 (51.6 %) were treated with radiotherapy. The biopsy positive core rate and biopsy Gleason score were associated with PFS, and the number of lymph node metastases was associated with both PFS and OS. Patients who underwent radiotherapy showed better PFS and OS. High-risk features (at least 2 criteria among ≥75% biopsy positive core rate, Gleason score ≥9, and ≥2 positive lymph nodes) were especially associated with improved outcomes after undergoing radiotherapy. CONCLUSION: We identified prognostic factors for clinically regional lymph node-positive prostate cancer and showed the benefits of local radiation therapy. Patients with high-risk features may be especially suitable candidates for radiotherapy.

Similar-cases-based planning approaches with beam angle optimizations using water equivalent path length for lung stereotactic body radiation therapy.

This study aimed to propose automated treatment planning approaches based on similar cases with beam angle optimizations using water equivalent path length (WEPL) to avoid lung and rib doses for lung stereotactic body radiation therapy (SBRT). Similar cases to an objective case were defined as cases, which were close to the objective case with respect to the Euclidean distances based on geometrical features. Initial similar-case-based (ISC) plans were generated by applying lung SBRT plans of similar cases to objective cases. Similar cases were selected using the Euclidean distances based on lung shape and geometrical features from a radiation treatment planning database with 174 cases. Beam angles of the ISC plans were optimized using a greedy algorithm based on a cost function to include absorbed doses in the lung and ribs in the WEPL. The 12 dose evaluation indices for the planning target volume, lung, spinal cord, and ribs were evaluated in the original plans, ISC plans, and optimized similar-case-based (OSC) plans with and without WEPL for 20 test cases to investigate its dosimetric impact. These findings revealed that V10 and the mean dose for the lung and V20, V30, and V40 for the ribs in the OSC plan with WEPL improved more significantly than those in the original and ISC plans. This study indicates a potential of similar cases, whose beam angle configurations were optimized with WEPL to avoid lung and rib doses in lung SBRT plans.

First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide.

INTRODUCTION: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. METHODS: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ-BEV], and the correlations of prognostic factors with survival were evaluated. RESULTS: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ-BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ-BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ-BEV, 12.2 vs. 16.7 months; P = 0.04). CONCLUSIONS: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.

Survival and ocular preservation in a long-term cohort of Japanese patients with retinoblastoma.

BACKGROUND: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM). METHODS: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016). RESULTS: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030). CONCLUSIONS: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM.

Observer uncertainties of soft tissue-based patient positioning in IGRT.

PURPOSE: There remain uncertainties due to inter- and intraobserver variability in soft-tissue-based patient positioning even with the use of image-guided radiation therapy (IGRT). This study aimed to reveal observer uncertainties of soft-tissue-based patient positioning on cone-beam computed tomography (CBCT) images for prostate cancer IGRT. METHODS: Twenty-six patients (7-8 fractions/patient, total number of 204 fractions) who underwent IGRT for prostate cancer were selected. Six radiation therapists retrospectively measured prostate cancer location errors (PCLEs) of soft-tissue-based patient positioning between planning CT (pCT) and pretreatment CBCT (pre-CBCT) images after automatic bone-based registration. Observer uncertainties were evaluated based on residual errors, which denoted the differences between soft-tissue and reference positioning errors. Reference positioning errors were obtained as PCLEs of contour-based patient positioning between pCT and pre-CBCT images. Intraobserver variations were obtained from the difference between the first and second soft-tissue-based patient positioning repeated by the same observer for each fraction. Systematic and random errors of inter- and intraobserver variations were calculated in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions. Finally, clinical target volume (CTV)-to-planning target volume (PTV) margins were obtained from systematic and random errors of inter- and intraobserver variations in AP, SI, and LR directions. RESULTS: Interobserver variations in AP, SI, and LR directions were 0.9, 0.9, and 0.5 mm, respectively, for the systematic error, and 1.8, 2.2, and 1.1 mm, respectively, for random error. Intraobserver variations were <0.2 mm in all directions. CTV-to-PTV margins in AP, SI, and LR directions were 3.5, 3.8, and 2.1 mm, respectively. CONCLUSION: Intraobserver variability was sufficiently small and would be negligible. However, uncertainties due to interobserver variability for soft-tissue-based patient positioning using CBCT images should be considered in CTV-to-PTV margins.