Association of overall survival benefit of radiotherapy with progression-free survival after chemotherapy for diffuse large B-cell lymphoma: A systematic review and meta-analysis.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639-0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882-0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60-80%, >40-60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51-0.97) to 0.48 (95% CI, 0.36-0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

Multidisciplinary team quality improves the survival outcomes of locally advanced rectal cancer patients: A post hoc analysis of the STELLAR trial.

PURPOSE: We sought to determine the association between multidisciplinary team (MDT) quality and survival of patients with locally advanced rectal cancer. METHODS: In a post hoc analysis of the randomized phase III STELLAR trial, 464 patients with distal or middle-third, clinical tumor category cT3-4 and/or regional lymph node-positive rectal cancer who completed surgery were evaluated. Disease-free survival (DFS) and Overall survival (OS) were stratified by Multidisciplinary team (MDT) quality, which was also included in the univariable and multivariable analyses of DFS and OS. RESULTS: According to the univariable analyses, a significantly worse DFS was associated with a fewer specialized medical disciplines participating in MDT (<5 vs ≥ 5; P=0.049),a lower frequency of MDT meetings ( 200; P=0.039). In addition, a lower number of specialized medical disciplines participating in MDT (<5 vs ≥ 5; P<0.001), a lower frequency of MDT meetings ( 200; P=0.001) were the variables associated with OS. These 3 factors were considered when assessing MDT quality, which was classified into 2 categories: high quality or general quality. Patients treated in hospitals with high MDT quality had longer 3-year OS (90.5 % vs 78.1 %; P=0.001) and similar 3-year DFS (70.3 % vs 61.3 %; P=0.109) compared to those treated in hospitals of the general MDT quality group. Furthermore, multivariable analyses revealed a significance for DFS (HR, 1.648; 95 % CI, 1.143-2.375; P=0.007) and OS (HR, 2.771; 95 % CI, 1.575-4.877; P<0.001) in MDT quality. CONCLUSIONS: The use of hospitals with optimized multidisciplinary infrastructure had a significant influence on survival of patients with locally advanced rectal cancer.

Post-hoc analysis of clinicopathological factors affecting lateral lymph node metastasis based on STELLAR study for rectal cancer.

PURPOSE: In post-hoc analyses of phaseIII randomized controlled study(STELLAR), to analyzethe prognostic impact oflateral pelvic lymph node (LPLN)metastasis in locally advanced rectal cancer (LARC). METHODS: LPLN metastasis was defined as a short diameter > 7 mm on magnetic resonance imaging (MRI).The studyincluded 591 patients with LARC.All patients received neoadjuvant (chemo)radiotherapy combined withradical resection. RESULTS: Among 591 patients, 99 (16.8 %) were diagnosed with LPLN metastasis, mostly with unilateral metastasis (79.8 %), with internal iliac lymph node metastasis being more common (81.8 %).Significant differences were found among with and without LPLN metastasis in rectal segmentation (P=0.001),N disease (P<0.001), mesenteric LN metastasis or not (P=0.030). The median follow-up timewas 34.0 months, three-year disease-free survival (DFS),overall survival (OS), andmetastasis-free survival (MFS)were significantly lower in LPLN metastaticgroup than those in LPLN non-metastaticgroup (51.4 % vs. 68.2 %, P<0.001; 71.8 % vs. 84.2 %, P=0.006; 60.8 % vs. 80.1 %,P<0.001), respectively; while there were no significant differences in locoregional recurrence(11.4 % vs. 8.5 %, P=0.564). Multivariate analysis found that LPLN metastasis was an independent prognostic factor affecting DFS (P=0.005), OS (P=0.036),MFS (P=0.001).No significantly survival benefit was observed for the short-term radiotherapy based total neoadjuvant therapy compared to long-term concurrent chemoradiotherapy. CONCLUSIONS: LPLN metastasis observed byMRI should be considered in LARC patients, especially in populations with lowrectal cancer, N2 disease, and mesenteric LN metastasis. LPLN metastasis diagnosed by MRI is a significant and independent risk factor and is associated with worse DFS, OS, MFS.

Radiotherapy with Targeted Therapy or Immune Checkpoint Inhibitors for Hepatocellular Carcinoma with Hepatic Vein and/or Inferior Vena Cava Tumor Thrombi.

Purpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies. Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded. Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up. Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.

Optical Surface-guided Radiation Therapy for Upper and Lower Limb Sarcomas: An Analysis of Setup Errors and Clinical Target Volume-To-Planning Target Volume Margins.

Purpose: To assess the clinical benefits of surface-guided radiation therapy (SGRT) in terms of setup error, positioning time, and clinical target volume-to-planning target volume (CTV-PTV) margin in extremity soft tissue sarcoma (STS). Methods and Materials: Fifty consecutive patients treated with radiation therapy were selected retrospectively. Treatment setup was performed with either laser-based imaging only (control group), or with laser-based and daily optical surface-based imaging (SGRT group). Pretreatment cone beam computed tomography images were acquired daily for the first 3 to 5 fractions and weekly thereafter, with the frequency adjusted as necessary. Translational and rotational errors were collected. CTV-PTV margin was calculated using the formula, 2.5Σ + 0.7σ. Results: Each group consisted of 10 and 15 upper and lower limb STSs, respectively. For patients with upper limb sarcomas, the translation errors were 1.64 ± 1.34 mm, 1.10 ± 1.50 mm, and 1.24 ± 1.45 mm in the SGRT group, and 1.48 ± 3.16 mm, 2.84 ± 2.85 mm, and 3.14 ± 3.29 mm in control group in the left-right, supero-inferior, and antero-posterior directions, respectively. Correspondingly, for patients with lower limb sarcomas, the translation errors were 1.21 ± 1.65 mm, 1.39 ± 1.71 mm, and 1.48 ± 2.10 mm in the SGRT group, and 1.81 ± 2.60 mm, 2.93 ± 3.28 mm, and 3.53 ± 3.75 mm in control group, respectively. The calculated CTV-PTV margins of the SGRT group and control group were 5.0, 3.8, 4.1 versus 5.9, 9.1, 10.1 mm for upper limb sarcomas; and 4.2, 4.7, 5.2 mm versus 6.3, 9.6, and 11.4 mm for lower limb sarcomas in the left-right, supero-inferior, and antero-posterior directions, respectively. Conclusions: Daily optical surface guidance can effectively improve the setup accuracy of extremity STS patients, and safely reduce the required CTV-PTV margins.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Cloning, characterization, and evolutionary patterns of KCNQ4 genes in anurans.

Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high-frequency hearing to minimize the low-frequency noise. However, the molecular mechanisms underlying the high-frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high-frequency hearing-related gene (KCNQ4) from 11 representative anuran species and compared them with orthologous sequences from other four anurans. The sequence characteristics and evolutionary analyses suggested the highly conservation of the KCNQ4 gene in anurans, which supported their functional importance. Branch-specific analysis showed that KCNQ4 genes were under different evolutionary forces in anurans and most anuran lineages showed a generally strong purifying selection. Intriguingly, one significantly positively selected site was identified in the anuran KCNQ4 gene based on FEL model. Positive selection was also found along the common ancestor of Ranidae and Rhacophoridae as well as the ancestral O. tianmuii based on the branch-site analysis, and the positively selected sites identified were involved in or near the N-terminal ion transport and the potassium ion channel functional domain of the KCNQ4 genes. The present study revealed valuable information regarding the KCNQ4 genes in anurans and provided some new insights for the underpinnings of the high-frequency hearing in frogs.

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.

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.

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.

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.

BALT 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.

Gut microbiota reflect adaptation of cave-dwelling tadpoles to resource scarcity.

Gut microbiota are significant to the host's nutrition and provide a flexible way for the host to adapt to extreme environments. However, whether gut microbiota help the host to colonize caves, a resource-limited environment, remains unknown. The nonobligate cave frog Oreolalax rhodostigmatus completes its metamorphosis within caves for 3-5 years before foraging outside. Their tadpoles are occasionally removed from the caves by floods and utilize outside resources, providing a contrast to the cave-dwelling population. For both cave and outside tadpoles, the development-related reduction in their growth rate and gut length during prometamorphosis coincided with a shift in their gut microbiota, which was characterized by decreased Lactobacillus and Cellulosilyticum and Proteocatella in the cave and outside individuals, respectively. The proportion of these three genera was significantly higher in the gut microbiota of cave-dwelling individuals compared with those outside. The cave-dwellers' gut microbiota harbored more abundant fibrolytic, glycolytic, and fermentative enzymes and yielded more short-chain fatty acids, potentially benefitting the host's nutrition. Experimentally depriving the animals of food resulted in gut atrophy for the individuals collected outside the cave, but not for those from inside the cave. Imitating food scarcity reproduced some major microbial features (e.g. abundant Proteocatella and fermentative genes) of the field-collected cave individuals, indicating an association between the cave-associated gut microbiota and resource scarcity. Overall, the gut microbiota may reflect the adaptation of O. rhodostigmatus tadpoles to resource-limited environments. This extends our understanding of the role of gut microbiota in the adaptation of animals to extreme environments.

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.

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.

Pretreatment information-aided automatic segmentation for online magnetic resonance imaging-guided prostate radiotherapy.

BACKGROUND: It is necessary to contour regions of interest (ROIs) for online magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). These updated contours are used for online replanning to obtain maximum dosimetric benefits. Contouring can be accomplished using deformable image registration (DIR) and deep learning (DL)-based autosegmentation methods. However, these methods may require considerable manual editing and thus prolong treatment time. PURPOSE: The present study aimed to improve autosegmentation performance by integrating patients' pretreatment information in a DL-based segmentation algorithm. It is expected to improve the efficiency of current MRIgART process. METHODS: Forty patients with prostate cancer were enrolled retrospectively. The online adaptive MR images, patient-specific planning computed tomography (CT), and contours in CT were used for segmentation. The deformable registration of planning CT and MR images was performed first to obtain a deformable CT and corresponding contours. A novel DL network, which can integrate such patient-specific information (deformable CT and corresponding contours) into the segmentation task of MR images was designed. We performed a four-fold cross-validation for the DL models. The proposed method was compared with DIR and DL methods on segmentation of prostate cancer. The ROIs included the clinical target volume (CTV), bladder, rectum, left femur head, and right femur head. Dosimetric parameters of automatically generated ROIs were evaluated using a clinical treatment planning system. RESULTS: The proposed method enhanced the segmentation accuracy of conventional procedures. Its mean value of the dice similarity coefficient (93.5%) over the five ROIs was higher than both DIR (87.5%) and DL (87.2%). The number of patients (n = 40) that required major editing using DIR, DL, and our method were 12, 18, and 7 (CTV); 17, 4, and 1 (bladder); 8, 11, and 5 (rectum); 2, 4, and 1 (left femur head); and 3, 7, and 1 (right femur head), respectively. The Spearman rank correlation coefficient of dosimetry parameters between the proposed method and ground truth was 0.972 ± 0.040, higher than that of DIR (0.897 ± 0.098) and DL (0.871 ± 0.134). CONCLUSION: This study proposed a novel method that integrates patient-specific pretreatment information into DL-based segmentation algorithm. It outperformed baseline methods, thereby improving the efficiency and segmentation accuracy in adaptive radiotherapy.

Effects of interventions on the screening behavior in female first-degree relatives of breast cancer patients: A systematic review.

BACKGROUND: Women are more likely to develop breast cancer if their first-degree relatives (FDRs) have the disease, but they are often unaware of their individual risk and conduct screening behaviors. OBJECTIVE: This study aimed to evaluate the effectiveness of interventions in increasing breast self-examination, clinical breast examination, and mammography rates in FDRs of breast cancer patients. METHODS: We selected randomized clinical trials and quasi-experimental studies in eight databases. Interventions in each study were categorized as "promising", or "non-promising" according to whether they led to a positive change in screening behaviors. Interventions were also coded using the Behavioral Change Techniques (BCTs) Taxonomy and a promise ratio calculated for each. BCTs with a promise ratio ≥2 was classified as "promising". RESULTS: Thirteen studies with 21 different BCTs were included. The most frequent BCTs were "Prompts/cues", "Credible source", and "Instructions on how to perform the behavior". Seven BCTs had a promise ratio of ≥2 and the four most promising were "Information about health consequences" (promise ratio = 6), "Problem solving" (promise ratio = 4), "Demonstration of the behavior" (promise ratio = 4), and "Adding objects to the environment" (promise ratio = 4). CONCLUSIONS: This review indicated an overall weak use of theory, and an insufficient description of several interventions to support the assessment of how specific BCTs were activated.

Determination of internal target volume with Cine-MRI sequence for prostate MRI-Guided radiotherapy.

BACKGROUND: In prostate radiotherapy, the intrafractional target motion negatively affects treatment accuracy. Generating internal target volume (ITV) using four-dimensional (4D) images may resolve the issue of intrafractional target motion induced by bladder filling and bowel movement. However, no 4D imaging techniques suitable for the prostate are currently available in clinical practice. PURPOSE: This study aimed to determine the ITV based on cine magnetic resonance imaging (MRI) sequence for intrafractional target motion management in prostate MRI-guided radiotherapy. MATERIALS AND METHODS: A reference ITV was generated in simulation process. Then, the reference ITV was adapted with cine MRI sequence before online planning in each fraction. Finally, the reference ITV was updated with the cine MRI sequence acquired during beam delivery after each fraction. Cine MRI sequences and positioning three-dimensional (3D) MRI from 35 patients were retrospectively collected. Clinical target volume (CTV) coverage was computed according to the two-dimensional contour of CTV and ITV on cine MRI images. Relative target size was calculated as the ratio of the volume of ITV and CTV. Isotropic planning target volume (PTV; 5 mm margin) and anisotropic PTV (3 mm margin in the posterior direction and 5 mm margin in other directions) were generated for comparison. RESULTS: The CTV coverage rate of the proposed ITV had a mean value of 98.61% ± 0.51%, whereas the CTV coverage rates of the isotropic and anisotropic PTVs were 97.43% ± 0.41% and 96.58% ± 0.73%, respectively. The proposed ITV had a relative target size of 1.79 ± 0.17, whereas the anisotropic and isotropic PTVs had relative target sizes of 1.92 ± 0.12 and 2.21 ± 0.19, respectively. For both the CTV coverage rate and target relative size, significant differences were observed between the proposed ITV and the other two PTVs (p < 0.05). CONCLUSION: The ITV achieved higher CTV coverage with smaller size than conventional isotropic and anisotropic PTVs, indicating that it can effectively deal with the intrafractional movement of the prostate.

Multidrug-Resistant Escherichia coli Isolate of Chinese Bovine Origin Carrying the blaCTX-M-55 Gene Located in IS26-Mediated Composite Translocatable Units.

Elevated detection rates of the blaCTX-M-55 gene in animals have been reported as a result of antibiotic misuse in clinics. To investigate the horizontal transfer mechanism of blaCTX-M-55 and its associated mobile genetic elements (MGEs), we isolated 318 nonrepetitive strains of Escherichia coli (E. coli) from bovine samples in Xinjiang and Gansu provinces, China. All E. coli strains were screened for the CTX-M-55 gene using PCR. The complete genomic data were sequenced using the PacBio triplet sequencing platform and corrected using the Illumina data platform. The genetic environment of the plasmids carrying the resistance blaCTX-M-55 gene was mapped using the software Easyfig2.2.3 for comparison. The results showed that all blaCTX-M-55-positive strains were resistant to multiple antibiotics. Five strains of Escherichia coli carry the blaCTX-M-55 gene, which is adjacent to other resistance genes and is located on the IncHI2-type plasmid. Four of the five blaCTX-M-55-harbor strains carried translocatable units (TUs). All the donor bacteria carrying the blaCTX-M-55 genes could transfer horizontally to the recipient (E. coli J53 Azr). This study demonstrates that the transmission of blaCTX-M-55 is localized on IS26-flanked composite transposons. The cotransmission and prevalence of blaCTX-M-55 with other MDR resistance genes on epidemic plasmids require enhanced monitoring and control.