Importance of Local Ablative Therapies for Lung Metastases in Patients With Colorectal Cancer.

OBJECTIVE: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy. SUMMARY BACKGROUND DATA: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC. METHODS: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered. RESULTS: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased. CONCLUSIONS: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period.

Study protocol for prospective multi-institutional phase III trial of standard of care therapy with or without stereotactic ablative radiation therapy for recurrent ovarian cancer (SABR-ROC).

BACKGROUND: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision. METHODS: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews. DISCUSSION: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.

Dose-response relationship in patients with newly diagnosed atypical meningioma treated with adjuvant radiotherapy.

PURPOSE: This study aimed to identify the radiation dose-response relationship in patients with newly diagnosed atypical meningioma (AM) treated with adjuvant radiotherapy (ART) using conventional fractionation. METHODS: In total, 158 patients who underwent surgery and ART between 1998 and 2018 were reviewed. Among these patients, 135 with complete information on radiotherapy (RT) dose/fractionation and pathological reports were analyzed. We entered RT dose as a continuous variable into the Cox regression model using penalized spline to allow for a nonlinear relationship between RT dose and events. Local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated. The corresponding biological equivalent dose in 2 Gy fractions (EQD2) was calculated using an α/ß ratio of 4 Gy. RESULTS: The median follow-up duration was 56.0 months. The median ART dose delivered was 61.2 Gy in 24-34 daily fractions, corresponding to a median EQD2 of 59.16 Gy. In multivariate analysis, larger size and higher mitotic count were associated with significantly reduced LC (P < 0.001 and P = 0.002, respectively), PFS (P < 0.001 and P = 0.006, respectively), and OS (P = 0.006 and P = 0.001, respectively). Meanwhile, a higher RT dose was significantly associated with improved LC, PFS, and OS. Moreover, RT showed a dose-dependent effect on LC, PFS, and OS; local failure, tumor progression, and death were reduced by 12%, 12%, and 16%, respectively, per 1 Gy increase in the dose (EQD2). CONCLUSION: The dose of ART in AM has a dose-response relationship with LC and survival outcomes.

Radiotherapy in recurrent ovarian cancer: updated results of involved-field radiation therapy.

OBJECTIVE: This study aimed to update the possible clinical benefits of radiation therapy in recurrent ovarian cancer. METHODS: The medical records of 495 patients with recurrent ovarian cancer after initially undergoing maximal cytoreductive surgery and adjuvant platinum-based chemotherapy based on the pathologic stage between January 2010 and December 2020 were analyzed: 309 and 186 patients were treated without and with involved-field radiation therapy, respectively. Involved-field radiation therapy is defined as radiation therapy only to the areas of the body involved by tumor. The prescribed doses were ≥45 Gy (equivalent dose in 2 Gy/fraction). Overall survival was compared between patients treated with and without involved-field radiation therapy. The favorable group was defined as patients who satisfied at least four of the following factors: good performance, no ascites, normal CA-125, platinum-sensitive tumor, and nodal recurrence. RESULTS: The median age of the patients was 56 years (range 49-63) and median time to recurrence was 11.1 months (range 6.1-15.5). 217 patients (43.8%) were treated at a single site. Radiation therapy, performance status, CA-125, platinum sensitivity, residual disease, and ascites were all significant prognostic factors. The 3-year overall survival of all patients, patients treated without radiation therapy, and patients treated with radiation therapy was 54.0%, 44.8%, and 69.3%, respectively. Radiation therapy was associated with higher overall survival rates in the unfavorable and favorable patient groups. Patient characteristics showed higher rates of normal CA-125, lymph node metastasis only, lower platinum sensitivity, and higher rates of ascites in the radiation therapy group. After propensity score matching, the radiation therapy group showed superior overall survival to the non-radiation therapy group. Normal CA-125, good performance status, and platinum sensitivity were associated with a good prognosis in patients treated with radiation therapy. CONCLUSION: Our study showed that higher overall survival was observed in patients treated with radiation therapy in recurrent ovarian cancer.

Validation of a nomogram for predicting the risk of lymphedema following contemporary treatment for breast cancer: a large multi-institutional study (KROG 20-05).

PURPOSE: We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort. METHODS: Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots. RESULTS: Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/m2 vs. 23.4 kg/m2) and a greater number of removed nodes (median, 17 vs. 6) and more frequently underwent taxane-based chemotherapy (85.7% vs. 41.9%), total mastectomy (73.1% vs. 52.1%), conventionally fractionated radiotherapy (71.9% vs. 54.2%), and regional nodal irradiation (70.7% vs 22.4%) than those who did not develop lymphedema (all P < 0.001). The C-index of the nomogram was 0.7887, and iAUC was 0.7628, indicating good predictive accuracy. Calibration plots confirmed that the predicted lymphedema risks were well correlated with the actual lymphedema rates. CONCLUSION: This nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

Dose escalation in radiotherapy for incomplete transarterial chemoembolization of hepatocellular carcinoma.

PURPOSE: To investigate the efficacy of radiation dose escalation in patients with hepatocellular carcinoma (HCC) after incomplete transarterial chemoembolization (TACE). METHODS: This study evaluated retrospective data of 323 HCC patients who received radiotherapy after incomplete TACE from 2001-2016. Radiation dose in biologically effective dose (BED) (α/ß = 10) was categorized as <72 Gy (261 patients) and ≥72 Gy (62 patients). Simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) was used significantly more frequently in the high-dose group (64.5% vs. 12.9%; P < 0.001). Local failure-free rate (LFFR), progression-free rate (PFR), and toxicities were compared between the two groups. Additionally, propensity score matching was performed. RESULTS: Median follow-up time for patients who were alive at the time of analysis was 47 months (range 18-189 months). Median overall survival after radiotherapy was 14 months. In multivariate analysis, BED ≥72 Gy was an independent predictor of favorable LFFR (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.14-0.72; P = 0.006) and PFR (HR 0.67; 95% CI 0.45-0.98; P = 0.04). In the propensity score-matched cohort (62 pairs), 1­year LFFR (94% vs. 81%; P = 0.002), and 1­year PFR (49% vs. 42%; P = 0.01) were significantly higher in the high-dose group. Treatment-related toxicities were comparable between the high-dose and low-dose groups (classic radiation-induced liver disease: 5.3% [3/57] vs. 13.8% [29/210], P = 0.08; grade 2-4 gastrointestinal bleeding: 3.2% [2/62] vs. 7.3% [19/261], P = 0.39). CONCLUSION: Radiation dose with BED ≥72 Gy improved LFFR and PFR without increasing toxicity. In radiotherapy for incomplete TACE of HCC, dose escalation using SIB-IMRT should be actively considered to improve oncologic outcome.

Acute severe lymphopenia by radiotherapy is associated with reduced overall survival in hepatocellular carcinoma.

PURPOSE: Radiotherapy (RT) for peripheral organs can affect circulating lymphocytes and cause lymphopenia. We aimed to investigate RT-related lymphopenia in patients with hepatocellular carcinoma (HCC). METHODS: Medical records of 920 patients who received RT for HCC during 2001-2016 were reviewed. Total lymphocyte count (TLC) were obtained and analyzed for clinical outcome. Acute severe lymphopenia (ASL) was defined as TLC <500/µL within the first 3 months of the start of RT. RESULTS: The median TLCs before and 1 month after the start of RT were 1120 and 310/µl, respectively, and the TLCs did not recover to their initial level after 1 year. Overall, 87.4% of patients developed ASL. The median overall survival was 13.6 and 46.7 months for patients with and without ASL, respectively (p < 0.001). ASL was independently associated with poor overall survival with a hazard ratio (HR) of 1.40; 95% confidence interval (CI), 1.02-1.91 (p = 0.035). In the multivariate analysis, larger planning target volume (HR, 1.02; 95% CI, 1.01-1.03; p < 0.001) and lower baseline TLC (HR, 0.86; 95% CI, 0.82-0.91; p < 0.001) were significantly associated with an increased risk of ASL, while hypofractionation (stereotactic body RT: HR, 0.19; 95% CI, 0.07-0.49; p = 0.001) was significantly associated with a reduced risk of ASL. CONCLUSION: Acute severe lymphopenia after RT was associated with poor overall survival in patients with HCC. Stereotactic body RT may reduce the risk of ASL. Further attention to and research on the cause, prevention, and reversal of this phenomenon are needed.

Clinical outcomes of radiotherapy for spinal cord ependymoma with adverse prognostic features: a single-center study.

PURPOSE: This study evaluated the outcomes of radiotherapy (RT) for spinal ependymoma with adverse features, such as incomplete resection or disseminated disease. METHODS: Twenty-five patients underwent RT for spinal cord ependymoma during 1991-2016. Twenty-four patients had gross disease on the pre-RT spinal magnetic resonance images. Six patients (24%) had disseminated disease. The World Health Organization grades were I (12 patients), II (12 patients), and III (1 patient). The RT fields were the tumor bed plus margin in 19 patients (76%), the entire craniospinal axis in 5 patients (20%), and the entire spinal canal with posterior cranial fossa in 1 patient (4%). The median RT dose was 50.4 Gy (range 44.0-59.4 Gy). RESULTS: The median follow-up was 49 months (range 9-321 months), with 5-year overall and progression-free survival rates of 83.7% and 70.8%, respectively. Relative to patients with grade II/III ependymoma, patients with grade I ependymoma had higher 5-year rates of overall survival (100% vs. 69.4%, P = .088) and progression-free survival (100% vs. 42.3%, P = .02). Disease progression was observed in 4 patients who had grade II ependymoma, including 2 of 6 patients with disseminated disease and 2 of 19 patients with localized disease. Twelve patients (48%) exhibited improved neurological function. One patient who underwent craniospinal irradiation developed late hypopituitarism. No other RT-related late toxicities were observed. CONCLUSIONS: Favorable survival outcomes were achieved using RT for spinal ependymoma with adverse prognostic features. Thus, RT may be an effective treatment option when complete tumor removal cannot be achieved.

Risk stratification for locally advanced hepatocellular carcinoma using pretreatment alpha-foetoprotein and 18 F-fluoro-2-deoxyglucose positron emission tomography.

BACKGROUND & AIMS: We investigated the significance of 18 F-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG PET) parameters and alpha-foetoprotein (AFP) levels in patients with locally advanced hepatocellular carcinoma (LA-HCC). METHODS: We retrospectively analysed data of 228 patients with LA-HCC who underwent pretreatment 18 F-FDG PET between January 2003 and December 2013. All patients were treated using liver-directed therapy involving radiotherapy. The maximum standardized uptake values (SUVs) and tumour-to-extratumoural liver SUV ratios were calculated, and pretreatment AFP values were obtained. RESULTS: Patients were divided into high and low maximum SUV (SUVmax) groups according to a SUV cut-off of 4.825 determined via receiver-operating characteristic analysis. High AFP level (>550 ng/mL) and high SUVmax were significant predictors of overall and progression-free survival. Better treatment responses and longer median progression-free and overall survival were observed in the low SUVmax group, compared to the high SUVmax group. Similar results were obtained for SUV ratio-based (cut-off value: 2.355) and AFP-based analyses (cut-off value: 550 ng/mL). Three risk groups were identified using the double biomarkers of SUVmax and AFP value as strong prognosticators predictive of survival outcomes. This risk stratification was identified as a prognosticator of survival outcomes, even after subgroup analyses. Furthermore, in high risk group, significantly high extrahepatic failure was shown while in low risk group, significantly low intrahepatic failure. CONCLUSIONS: Clinical significance of double biomarkers, SUV and AFP, could be translated into risk stratification for LA-HCC. It could be a valuable tool for survival outcome prediction.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 2. Lung (non-small cell lung cancer).

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

Generating 3D images of VMAT plans for predictive models and activation maps associated with plan deliverability.

BACKGROUND: Intensity modulation with dynamic multi-leaf collimator (MLC) and monitor unit (MU) changes across control points (CPs) characterizes volumetric modulated arc therapy (VMAT). The increased uncertainty in plan deliverability required patient-specific quality assurance (PSQA), which remained inefficient upon Quality Assurance (QA) failure. To prevent waste before QA, plan complexity metrics (PCMs) and machine learning models with the metrics were generated, which were lack of providing CP-specific information upon QA failures. PURPOSE: By generating 3D images from digital imaging and comminications in medicine in radiation therapy (DICOM RT) plan, we proposed a predictive model that can estimate the deliverability of VMAT plans and visualize CP-specific regions associated with plan deliverability. METHODS: The patient cohort consisted of 259 and 190 cases for left- and right-breast VMAT treatments, which were split into 235 and 166 cases for training and 24 cases from each treatment for testing the networks. Three-channel 3D images generated from DICOM RT plans were fed into a DenseNet-based deep learning network. To reflect VMAT plan complexity as an image, the first two channels described MLC and MU variations between two consecutive CPs, while the last channel assigned the beam field size. The network output was defined as binary classified PSQA results, indicating deliverability. The predictive performance was assessed by accuracy, sensitivity, specificity, F1-score, and area under the curve (AUC). The gradient-weighted class activation map (Grad-CAM) highlighted the regions of CPs in VMAT plans associated with deliverability, compared against PCMs by Spearman correlation. RESULTS: The DenseNet-based predictive model yielded AUCs of 92.2% and 93.8%, F1-scores of 97.0% and 93.8% and accuracies of 95.8% and 91.7% for the left- and right-breast VMAT cases. Additionally, the specificity of 87.5% for both cases indicated that the predictive model accurately detected QA failing cases. The activation maps significantly differentiated QA failing-labeled from passing-labeled classes for the non-deliverable cases. The PCM with the highest correlation to the Grad-CAM varied from patient cases, implying that plan deliverability would be considered patient-specific. CONCLUSION: This work demonstrated that the deep learning-based network based on visualization of dynamic VMAT plan information successfully predicted plan deliverability, which also provided control-point specific planning parameter information associated with plan deliverability in a patient-specific manner.

Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Experience of Implementing Deep Learning-Based Automatic Contouring in Breast Radiation Therapy Planning: Insights From Over 2000 Cases.

PURPOSE: This study evaluated the impact and clinical utility of an auto-contouring system for radiation therapy treatments. METHODS AND MATERIALS: The auto-contouring system was implemented in 2019. We evaluated data from 2428 patients who underwent adjuvant breast radiation therapy before and after the system's introduction. We collected the treatment's finalized contours, which were reviewed and revised by a multidisciplinary team. After implementation, the treatment contours underwent a finalization process that involved manual review and adjustment of the initial auto-contours. For the preimplementation group (n = 369), auto-contours were generated retrospectively. We compared the auto-contours and final contours using the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD95). RESULTS: We analyzed 22,215 structures from final and corresponding auto-contours. The final contours were generally larger, encompassing more slices in the superior or inferior directions. Among organs at risk (OAR), the heart, esophagus, spinal cord, and contralateral breast demonstrated significantly increased DSC and decreased HD95 postimplementation (all P < .05), except for the lungs, which presented inaccurate segmentation. Among target volumes, CTVn_L2, L3, L4, and the internal mammary node showed increased DSC and decreased HD95 postimplementation (all P < .05), although the increase was less pronounced than the OAR outcomes. The analysis also covered factors contributing to significant differences, pattern identification, and outlier detection. CONCLUSIONS: In our study, the adoption of an auto-contouring system was associated with an increased reliance on automated settings, underscoring its utility and the potential risk of automation bias. Given these findings, we underscore the importance of considering the integration of stringent risk assessments and quality management strategies as a precautionary measure for the optimal use of such systems.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 1. Brain and head and neck.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

A practical review of watch-and-wait approach in rectal cancer.

Rectal resection surgery after neoadjuvant treatment has been the mainstay treatment of locally advanced rectal cancer. However, functional outcomes and quality of life after radical resection of the rectum remain suboptimal. The excellent oncologic outcomes in patients who achieved pathologic complete response after neoadjuvant treatment questioned the need for radical surgery. The watch-and-wait approach is a noninvasive therapeutic alternative for organ preservation and avoiding operative morbidity. In the watch-and-wait approach, patients with locally advanced rectal cancer who achieve excellent clinical response after neoadjuvant treatment undergo active surveillance rather than rectal cancer surgery. In this practical review, we summarized the main results of studies on the watch-and-wait approach and provided a practical method for implementing the watch-and-wait approach.

Carbon Ion Radiotherapy in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal cancer with limited treatment options and poor prognosis. Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for HCC due to its unique physical and biological properties. CIRT uses carbon ions to target and destroy cancer cells with a high precision and efficacy. The Bragg Peak phenomenon allows precise dose delivery to the tumor while minimizing damage to healthy tissues. In addition, the high relative biological effectiveness of carbon ions can be shown against radioresistant and hypoxic tumor areas. CIRT also offers a shorter treatment schedule than conventional radiotherapy, which increases patient convenience and compliance. The clinical outcomes of CIRT for HCC have shown excellent local control rates with minimal side effects. Considering its physical and biological properties, CIRT may be a viable option for complex clinical scenarios such as patients with poor liver function, large tumors, re-irradiation cases, and tumors close to critical organs. Further research and larger studies are needed to establish definitive indications for CIRT and to compare its efficacy with that of other treatment modalities. Nevertheless, CIRT offers a potential breakthrough in HCC management, providing hope for improved therapeutic outcomes and reduced treatment-related toxicities.

Normal Tissue Complication Probability Modeling of Severe Radiation-Induced Lymphopenia Using Blood Dose for Patients With Hepatocellular Carcinoma.

PURPOSE: This study aimed to develop a normal tissue complication probability (NTCP) model to estimate the risk of severe radiation-induced lymphopenia (SRIL; absolute lymphocyte count [ALC] < 500/µL) by using the blood dose of patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: We retrospectively collected data from 75 patients with HCC who received radiation therapy (RT) between 2015 and 2018. The hematological dose framework calculated blood dose-volume histograms (DVHs) using a predefined blood flow model, organ DVHs, the number of treatment fractions, and beam delivery time. A Lyman-Kutcher-Burman model with a generalized equivalent dose was used to establish the NTCP model, reflecting the whole-blood DVHs. Optimization of the Lyman-Kutcher-Burman parameters was conducted by minimizing a negative log-likelihood function. RESULTS: There were 6, 4, 18, 33, and 14 patients in the groups with radiation-induced lymphopenia grades 0, 1, 2, 3, and 4, respectively. The median pre- and post-RT ALC values were 1410/µL (range, 520-3710/µL) and 470/µL (range, 60-1760/µL), respectively. There was a correlation between mean blood dose and ALC depletion (Pearson r = -0.664; P < .001). The average mean blood doses in each radiation-induced lymphopenia group were 2.90 Gy (95% CI, 1.96-3.85 Gy) for grade 0 to 1, 5.29 Gy (95% CI, 4.12-6.45 Gy) for grade 2, 8.81 Gy (95% CI, 7.55-10.07 Gy) for grade 3, and 11.69 Gy (95% CI, 9.82-17.57 Gy) for grade 4. When applying the developed NTCP model to predict SRIL, the area under the receiver operating characteristic curve and Brier score values were 0.89 and 0.12, respectively. CONCLUSIONS: We developed the first NTCP model based on whole-blood DVHs for estimating SRIL after abdominal RT in patients with HCC. Our results showed a strong correlation between blood dose and ALC depletion, suggesting the potential to predict the risk of SRIL occurrence using blood dose.

Risk factors for lower extremity lymphedema after surgery in cervical and endometrial cancer.

OBJECTIVE: Lower extremity lymphedema (LEL) is a well-known adverse effect related to cervical and endometrial cancer (CEC); however, very few studies have elucidated the clinicopathologic risk factors related to LEL. We investigated the incidence and risk factors in patients who received primary surgery and/or adjuvant radiotherapy (RT) or chemotherapy for CEC. METHODS: We retrospectively reviewed 2,565 patients who underwent primary surgery following CEC diagnosis between January 2007 and December 2020. LEL diagnosis was based on objective and subjective assessments by experts. We identified important predictors of LEL to construct a nomogram predicting individual risks of LEL. For internal validation of the nomogram, the original data were separated using the split-sample method in a 7:3 ratio of training data and test data. RESULTS: Overall, 858 patients (33.5%) received RT, 586 received external beam RT (EBRT), and 630 received intracavitary RT. During follow-up period, LEL developed in 331 patients, with an overall cumulative 5-year incidence of 13.3%. In multivariate analysis, age at primary treatment, use of docetaxel-based chemotherapy, type of hysterectomy, type of surgical pelvic lymph node (LN) assessment, number of dissected pelvic and para-aortic LNs, and EBRT field were the independent predictors of LEL. We subsequently developed the nomogram showing excellent predictive power for LEL. CONCLUSION: LEL is associated with various treatment modalities, and their interactions may increase the possibility of occurrences. De-escalation strategies for treatment modalities should be considered to reduce LEL in patients with CEC.