Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.Key PointsBALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

A prospective phase II clinical trial of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac: Estimated delivered dose and early toxicity results.

Background: Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac. Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. Results: In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis. Clinical trial registration: Chinese Clinical Trial Registry ChiCTR2000033382.

Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma.

Background: Scarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. Methods: We retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. Results: Hepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. Conclusion: We provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.

Optimizing the prognostic capacity of baseline 18F-FDG PET/CT metabolic parameters in extranodal natural killer/T-cell lymphoma by using relative and absolute thresholds.

Objectives: To investigate the prognostic capacity of baseline 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in extranodal natural killer/T-cell lymphoma (ENKTCL), and the influence of relative thresholds (RT) and absolute thresholds (AT) selection on prognostic capacity. Materials and methods: Metabolic tumor volume (MTV)-based parameters were defined using RTs (41 % or 25 % of maximum standardized uptake value [SUVmax]), ATs (SUV 2.5, 3.0, 4.0, or mean liver uptake) in 133 patients. Metabolic parameters were classified into avidity-related parameters (SUVmax, mean SUV [SUVmean], standard deviation of SUV [SUVsd]), volume-related parameters (RT-MTV), and avidity- and volume-related parameters (total lesion glycolysis [TLG] and AT-MTV). The prognostic capacity of the metabolic parameters and the effects of different threshold types (RT vs. AT) were evaluated. Results: All metabolic parameters were moderately associated with prognosis. However, the area under the receiver operating characteristic curve of MTV and TLG was slightly higher than that of avidity-related parameters for predicting 5-year progression-free survival (PFS) (0.614-0.705 vs. 0.563-0.609) and overall survival (OS) (0.670-0.748 vs. 0.562-0.593). Correlations of MTV and avidity-related parameters differed between RTs (r < 0.06, P = 0.324-0.985) and ATs (r 0.56-0.84, P ≤ 0.001). AT-MTV was the optimal predictor for PFS and OS, while RT-TLG was the optimal predictor for PFS, and the combination of RT-MTV with SUVmax was the optimal predictor for OS. Conclusion: The incorporation of volume and avidity significantly improved the prognostic capacity of PET in ENKTCL. Composite parameters that encompassed both avidity and volume were recommended.

Coagulation as an effective method for cyanobacterial bloom control: A review.

Eutrophication, the over-enrichment with nutrients, for example, nitrogen and phosphorus, of ponds, reservoirs and lakes, is an urgent water quality issue. The most notorious symptom of eutrophication is a massive proliferation of cyanobacteria, which cause aquatic organism death, impair ecosystem and harm human health. The method considered to be most effective to counteract eutrophication is to reduce external nutrient inputs. However, merely controlling external nutrient load is insufficient to mitigate eutrophication. Consequently, a rapid diminishing of cyanobacterial blooms is relied on in-lake intervention, which may encompass a great variety of different approaches. Coagulation/flocculation is the most used and important water purification unit. Since cyanobacterial cells generally carry negative charges, coagulants are added to water to neutralize the negative charges on the surface of cyanobacteria, causing them to destabilize and precipitate. Most of cyanobacteria and their metabolites can be removed simultaneously. However, when cyanobacterial density is high, sticky secretions distribute outside cells because of the small size of cyanobacteria. The sticky secretions are easily to form complex colloids with coagulants, making it difficult for cyanobacteria to destabilize and resulting in unsatisfactory treatment effects of coagulation on cyanobacteria. Therefore, various coagulants and coagulation methods were developed. In this paper, the focus is on the coagulation of cyanobacteria as a promising tool to manage eutrophication. Basic principles, applications, pros and cons of chemical, physical and biological coagulation are reviewed. In addition, the application of coagulation in water treatment is discussed. It is the aim of this review article to provide a significant reference for large-scale governance of cyanobacterial blooms. PRACTITIONER POINTS: Flocculation was a promising tool for controlling cyanobacteria blooms. Basic principles of four kinds of flocculation methods were elucidated. Flocculant was important in the flocculation process.

Prediction of 5-year overall survival of diffuse large B-cell lymphoma on the pola-R-CHP regimen based on 2-year event-free survival and progression-free survival.

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS ) or PFS (HRPFS ) and the HR for OS (HROS ) was estimated at the trial-level. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial- level. Two-year EFS (r = 0.918) or 2-year PFS (r = 0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola-R-CHP regimen is expected to improve 5-year OS.

Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case.

PURPOSE: To report the planning benchmark case results of the POTENTIAL trial-a multicenter, randomized, phase 3 trial-to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. METHODS: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. RESULTS: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. CONCLUSION: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

Prior information guided auto-segmentation of clinical target volume of tumor bed in postoperative breast cancer radiotherapy.

BACKGROUND: Accurate delineation of clinical target volume of tumor bed (CTV-TB) is important but it is also challenging due to surgical effects and soft tissue contrast. Recently a few auto-segmentation methods were developed to improve the process. However, those methods had comparatively low segmentation accuracy. In this study the prior information was introduced to aid auto-segmentation of CTV-TB based on a deep-learning model. METHODS: To aid the delineation of CTV-TB, the tumor contour on preoperative CT was transformed onto postoperative CT via deformable image registration. Both original and transformed tumor contours were used for prior information in training an auto-segmentation model. Then, the CTV-TB contour on postoperative CT was predicted by the model. 110 pairs of preoperative and postoperative CT images were used with a 5-fold cross-validation strategy. The predicted contour was compared with the clinically approved contour for accuracy evaluation using dice similarity coefficient (DSC) and Hausdorff distance. RESULTS: The average DSC of the deep-learning model with prior information was improved than the one without prior information (0.808 vs. 0.734, P < 0.05). The average DSC of the deep-learning model with prior information was higher than that of the traditional method (0.808 vs. 0.622, P < 0.05). CONCLUSIONS: The introduction of prior information in deep-learning model can improve segmentation accuracy of CTV-TB. The proposed method provided an effective way to automatically delineate CTV-TB in postoperative breast cancer radiotherapy.

Decreased lymphoma-related deaths and improved long-term relative survival with radiotherapy for early-stage diffuse large B-cell lymphoma in the rituximab era.

BACKGROUND: We aimed to investigate the incidence of lymphoma-related death (LRD) and the long-term net survival benefit of radiotherapy (RT) for early-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era. METHODS: 10,841 adults diagnosed with early-stage DLBCL between 2002-2015 were retrospectively analyzed using data from the Surveillance, Epidemiology, and End Results database. Primary therapy was categorized into combined-modality treatment (CMT, n = 3,631) and chemotherapy alone (n = 7,210). Competing risk analysis was used to evaluate the cumulative incidence of mortality. Inverse probability of treatment weighting (IPTW) was used to balance groups. The net survival benefit of RT was estimated through relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression, while controlling for background mortality. RESULTS: Patients initially treated with CMT had a lower cumulative incidence of LRD compared to those who received chemotherapy alone (HR 0.63, 95%CI: 0.57-0.69; P < 0.001). The 10-year overall survival (OS), RS, and SMR for CMT were 66.1%, 85.0%, and 1.71 respectively, which were significantly better than those for chemotherapy alone (53.0%; 69.8%; 2.62; all P < 0.001). IPTW and multivariable analysis revealed that the addition of RT led to better OS (HR 0.67, 95%CI: 0.62-0.71; P < 0.001) and RS (HR 0.69, 95%CI: 0.65-0.74; P < 0.001). Moreover, compared with chemotherapy alone, the benefit of OS and RS for CMT increased over time within 10 years of diagnosis. CONCLUSION: RT reduced LRD and improved the long-term net survival in early-stage DLBCL in the rituximab era. Further prospective studies are warranted to assess the specific patient population that would benefit the most from consolidative RT in early-stage DLBCL.

Efficient segmentation using domain adaptation for MRI-guided and CBCT-guided online adaptive radiotherapy.

BACKGROUND: Delineation of regions of interest (ROIs) is important for adaptive radiotherapy (ART) but it is also time consuming and labor intensive. AIM: This study aims to develop efficient segmentation methods for magnetic resonance imaging-guided ART (MRIgART) and cone-beam computed tomography-guided ART (CBCTgART). MATERIALS AND METHODS: MRIgART and CBCTgART studies enrolled 242 prostate cancer patients and 530 nasopharyngeal carcinoma patients, respectively. A public dataset of CBCT from 35 pancreatic cancer patients was adopted to test the framework. We designed two domain adaption methods to learn and adapt the features from planning computed tomography (pCT) to MRI or CBCT modalities. The pCT was transformed to synthetic MRI (sMRI) for MRIgART, while CBCT was transformed to synthetic CT (sCT) for CBCTgART. Generalized segmentation models were trained with large popular data in which the inputs were sMRI for MRIgART and pCT for CBCTgART. Finally, the personalized models for each patient were established by fine-tuning the generalized model with the contours on pCT of that patient. The proposed method was compared with deformable image registration (DIR), a regular deep learning (DL) model trained on the same modality (DL-regular), and a generalized model in our framework (DL-generalized). RESULTS: The proposed method achieved better or comparable performance. For MRIgART of the prostate cancer patients, the mean dice similarity coefficient (DSC) of four ROIs was 87.2%, 83.75%, 85.36%, and 92.20% for the DIR, DL-regular, DL-generalized, and proposed method, respectively. For CBCTgART of the nasopharyngeal carcinoma patients, the mean DSC of two target volumes were 90.81% and 91.18%, 75.17% and 58.30%, for the DIR, DL-regular, DL-generalized, and the proposed method, respectively. For CBCTgART of the pancreatic cancer patients, the mean DSC of two ROIs were 61.94% and 61.44%, 63.94% and 81.56%, for the DIR, DL-regular, DL-generalized, and the proposed method, respectively. CONCLUSION: The proposed method utilizing personalized modeling improved the segmentation accuracy of ART.

Breast-conserving surgery versus mastectomy for treatment of breast cancer after neoadjuvant chemotherapy.

Background: To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). Methods: The data of 730 patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. A total of 104 (14.2%) patients received BCS and 626 (85.8%) received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were analyzed using the Kaplan-Meier method. The impact of BCS versus mastectomy on outcomes was assessed by multivariate Cox models. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the two groups. Results: The median follow-up of BCS and mastectomy groups were 86.5 and 87.4 months, respectively. There were significant differences in distribution of most baseline characteristics between two groups. Compared with those who underwent mastectomy, the patients with BCS had similar 5-year LRR, DM, and DFS rates, but had significantly higher 5-year BCSS (98.9% vs. 90.4%, P = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates. Multivariate analysis also showed that BCS significantly improved BCSS (HR = 0.27, 95% CI: 0.08-0.85, P = 0.025) and OS (HR = 0.25, 95% CI: 0.08-0.79, P = 0.018). After IPTW adjustment, the LRR, DM, DFS, BCSS and OS between two groups had no significant differences. Conclusions: The recurrence and survival outcomes are comparable with BCS and mastectomy. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

Voluntary Deep Inspiration Breath-Hold (VDIBH) Whole-Breast Irradiation Assisted by Optical Surface Monitoring System (OSMS) in Patients With Left-Sided Breast Cancer: A Prospective Phase II Study.

Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P < .001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P < .001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system-assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy.

OBJECTIVE: The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). METHODS: The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. RESULTS: We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. CONCLUSIONS: Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Metastasis risk stratification and response prediction through dynamic viable circulating tumor cell counts for rectal cancer in a neoadjuvant setting.

PURPOSE: Distant metastasis (DM) and neoadjuvant treatment response prediction remain critical challenges in the management of locally advanced rectal cancer (LARC). The aim of this study was to investigate the clinical relevance of viable circulating tumor cells (CTCs) for DM or response in patients with LARC in a neoadjuvant setting. METHODS: The detection of viable CTCs at different stages of treatment was planned for consecutive patients from a prospective trial. The Kaplan-Meier method, Cox proportional hazards model, and logistic regression model were utilized to analyze factors associated with DM or pathological complete response (pCR) and clinical complete response (cCR). RESULTS: Between December 2016 and July 2018, peripheral blood samples from 83 patients were collected before any treatment (median follow-up time, 49.3 months). CTCs were present in 76 of 83 patients (91.6%) at baseline, and more than three CTCs detected in the blood sample was considered high risk. Only the CTC risk group was significantly associated with 3-year metastasis-free survival (MFS) (high risk vs. low risk, 57.1% (95% CI, 41.6-72.6) vs. 78.3% (95% CI, 65.8-90.8), p = 0.018, log-rank test). When all the important variables were entered into the Cox model, the CTC risk group remained the only significant independent factor for DM (hazard ratio (HR), 2.74; 95% CI, 1.17-6.45, p = 0.021). The pCR and continuous cCR rates were higher in patients with a decreased number of CTCs of more than one after radiotherapy (HR, 4.00; 95% CI, 1.09-14.71, P = 0.037). CONCLUSIONS: The dynamic detection of viable CTCs may strengthen pretreatment risk assessment and postradiotherapy decision making for LARC. This observation requires further validation in a prospective study.

Dose-Volume Predictors for Radiation Esophagitis in Patients With Breast Cancer Undergoing Hypofractionated Regional Nodal Radiation Therapy.

PURPOSE: Our objective was to assess the incidence and dose-volume predictors of radiation esophagitis (RE) in patients with breast cancer undergoing hypofractionated regional nodal irradiation. METHODS AND MATERIALS: Eligible patients who received intensity modulated radiation therapy (RT) at the chest wall, the supraclavicular/infraclavicular fossa, level II axilla, and/or the internal mammary chain after mastectomy were included. The prescribed dose was 43.5 Gy in 15 fractions. RE was evaluated weekly during RT and at 1 and 2 weeks, followed by 3 and 6 months after RT, and was graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. The esophagus was contoured from the lower border level of the cricoid cartilage to the lower margin of the aortic arch. Esophageal total volume, mean dose, maximum dose, and the relative volumes (RV) and absolute volumes (AV) receiving at least 5 to 45 Gy by 5-Gy increments (RV5-RV45 and AV5-AV45) were evaluated. Univariable and multivariable logistic regression analyses were performed to determine risk factors for RE, and receiver operating characteristic curves were obtained to identify the thresholds of esophageal dosimetric parameters. RESULTS: In total, 298 patients were included between May 8, 2020, and January 5, 2022 (minimum post-RT follow-up: 6 months). Grade 2 and 3 RE incidence was 40.9% (122/298) and 0.3% (1/298), respectively. No grade 4 or 5 RE was observed. Esophageal RV20-RV40 and AV35-AV40 were significantly associated with the risk of grade ≥2 RE after adjusting for tumor laterality and internal mammary nodal irradiation. RV25 and AV35 were optimum dose-volume predictors for grade ≥2 RE at thresholds 20% for RV25 (35.9% vs 60.9%; P = .04) and 0.27 mL for AV35 (31.0% vs 54.6%; P = .04). CONCLUSIONS: RE is common in patients with breast cancer undergoing hypofractionated regional nodal irradiation. Maintaining the upper esophageal V25 at <20% and V35 at <0.27 mL may decrease the risk of RE.