Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

The value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma staged with PET/CT.

BACKGROUND: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)-based staging in this patient population. PATIENTS AND METHODS: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients. RESULTS: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early-stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression-free survival (PFS) compared with the corresponding durations in patients without BM involvement (2-year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy. CONCLUSION: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early-stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced-stage nasal-type ENKTCL.

The role of radiotherapy in patients with refractory Hodgkin's lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors.

Background: Approximately 10%-30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9-46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2-23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Synchronization of Coupled Neural Networks With Constant Time-Delay Using Sampled-Data Information.

In this article, a synchronization control method is studied for coupled neural networks (CNNs) with constant time delay using sampled-data information. A distributed control protocol relying on the sampled-data information of neighboring nodes is proposed. Lyapunov functional is constructed to analyze the synchronization of CNNs with constant time delay. Using Park's integral inequality and improved free-weight matrix integral inequality, sufficient conditions are provided for CNNs to achieve synchronization with less conservatism. In addition, the maximum sampling interval is determined by transforming the sufficient conditions into an optimization problem, and an aperiodic sampling control technique is implemented to reduce the communication energy load. Finally, numerical simulations are provided to demonstrate that the proposed method is capable of achieving synchronization.

Deep Reinforcement Learning on Autonomous Driving Policy With Auxiliary Critic Network.

Deep reinforcement learning (DRL) is a machine learning method based on rewards, which can be extended to solve some complex and realistic decision-making problems. Autonomous driving needs to deal with a variety of complex and changeable traffic scenarios, so the application of DRL in autonomous driving presents a broad application prospect. In this article, an end-to-end autonomous driving policy learning method based on DRL is proposed. On the basis of proximal policy optimization (PPO), we combine a curiosity-driven method called recurrent neural network (RNN) to generate an intrinsic reward signal to encounter the agent to explore its environment, which improves the efficiency of exploration. We introduce an auxiliary critic network on the original actor-critic framework and choose the lower estimate which is predicted by the dual critic network when the network update to avoid the overestimation bias. We test our method on the lane- keeping task and overtaking task in the open racing car simulator (TORCS) driving simulator and compare with other DRL methods, experimental results show that our proposed method can improve the training efficiency and control performance in driving tasks.

Pirfenidone for the prevention of radiation-induced lung injury in patients with locally advanced oesophageal squamous cell carcinoma: a protocol for a randomised controlled trial.

INTRODUCTION: Radiation-induced lung injury (RILI) is one of the most clinically-challenging toxicities and dose-limiting factors during and/or after thoracic radiation therapy for oesophageal squamous cell carcinoma (ESCC). With limited effective protective drugs against RILI, the main strategy to reduce the injury is strict adherence to dose-volume restrictions of normal lungs. RILI can manifest as acute radiation pneumonitis with cellular injury, cytokine release and cytokine recruitment to inflammatory infiltrate, and subsequent chronic radiation pulmonary fibrosis. Pirfenidone inhibits the production of inflammatory cytokines, scavenges-free radicals and reduces hydroxyproline and collagen formation. Hence, pirfenidone might be a promising drug for RILI prevention. This study aims to evaluate the efficacy and safety of pirfenidone in preventing RILI in patients with locally advanced ESCC receiving chemoradiotherapy. METHODS AND ANALYSIS: This study is designed as a randomised, placebo-controlled, double-blinded, single-centre phase 2 trial and will explore whether the addition of pirfenidone during concurrent chemoradiation therapy (CCRT) could prevent RILI in patients with locally advanced ESCC unsuitable for surgery. Eligible participants will be randomised at 1:1 to pirfenidone and placebo groups. The primary endpoint is the incidence of grade >2 RILI. Secondary endpoints include the incidence of any grade other than grade >2 RILI, time to RILI occurrence, changes in pulmonary function after CCRT, completion rate of CCRT, disease-free survival and overall survival. The follow-up period will be 1 year. In case the results meet the primary endpoint of this trial, a phase 3 multicentre trial with a larger sample size will be required to substantiate the evidence of the benefit of pirfenidone in RILI prevention. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Fujian Union Hospital (No. 2021YF001-02). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2100043032.

IgD multiple myeloma with central nervous system involvement: A case report and literature review.

Central nervous system (CNS) involvement is a rare manifestation of multiple myeloma (MM) and the optimal management strategies have yet to be determined. The aim of the present study was to describe the case of a 47-year-old male patient with immunoglobulin D-λ MM who presented with multiple extramedullary infiltrations at diagnosis. This patient achieved stringent complete response after 9 cycles of treatment with bortezomib, lenalidomide and dexamethasone, and then received lenalidomide as maintenance therapy. CNS involvement and extramedullary relapse developed 3 months after the last chemotherapy cycle. Despite receiving a second-line treatment protocol, the patient succumbed to the disease within 1 month after recurrence. The characteristics and treatment options for CNS MM are discussed in this case report.

Modified method to improve the diagnostic efficiency of 18F-FDG PET/CT in regional lymph node metastasis of esophageal squamous cell carcinoma.

BACKGROUND: Regional lymph node (LN) metastasis is a significant factor influencing the treatment choice of esophageal squamous cell carcinoma (ESCC). The performance PET/CT as an imaging evaluation method for regional LNs in ESCC, is unsatisfactory due to the lack of logical criterion. We explored how a modified criterion improved the diagnostic value of 18F-FDG PET/CT in regional LN metastasis. METHODS: The data from 111 patients with ESCC were analyzed retrospectively. All patients underwent preoperative PET/CT examination, resection of the cancer, and regional LN dissection. The PET/CT images were interpreted by two experienced diagnosticians. LNs were allocated to five subregions. Each LN was diagnosed by two diagnostic criteria of PET/CT (traditional criterion and the modified criterion) one by one across the same field, and the accuracy of PET/CT was determined using the histopathologic results as the reference standard. RESULTS: A total of 4,847 LNs were dissected, of which 147 were confirmed as metastases by postoperative pathology. A total of 656 LNs were screened by 18F-FDG PET/CT imaging. The determination of all 656 LNs by PET/CT was compared with the pathological results. The diagnostic accuracy of the modified and traditional criteria for the five subregions (paraesophageal, neck, upper mediastinal, middle-lower mediastinal and ventral subregions) was: 74.60% vs. 61.90%, 86.44% vs. 81.36%, 90.26% vs. 70.78%, 96.19% vs. 75.09%, and 87.91% vs. 85.71%, respectively. CONCLUSIONS: The modified diagnostic criterion had better diagnostic efficiency because it combined PET and CT imaging data.

[Diagnostic value of ¹8F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography in colorectal cancer liver metastasis].

OBJECTIVE: To explore the preoperative diagnostic value of ¹8F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (¹8F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis. METHODS: Clinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent ¹8F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and ¹8F-FDG PET-ceCT were calculated. RESULTS: A total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign, of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT, ceCT and ¹8F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%, 100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Kappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Kappa value -0.005, 0.305, 0.848). The area under curve(AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651(95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for ¹8F-FDG PET-ceCT respectively. The AUC of ¹8F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05). CONCLUSION: (18)F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.