Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Epigenetic regulation of cutaneous T-cell lymphoma is mediated by dysregulated lncRNA MALAT1 through modulation of tumor microenvironment.

Cutaneous T-Cell Lymphoma (CTCL) is a rare non-Hodgkin lymphoma marked by migration of T-lymphocytes to the skin. It has many subtypes some of which are aggressive with documented metastasis. We investigated a possible role of lncRNA MALAT1 in CTCL cells because of its documented involvement in cancer metastasis. A screening of MALAT1 in CTCL patients revealed its elevated levels in the patients, compared to healthy individuals. For our investigation, we employed HH and H9 CTCL cells and silenced MALAT1 to understand the MALAT1 mediated functions. Such silencing of MALAT1 resulted in reversal of EMT and inhibition of cancer stem cell phenotype, along with reduced cell growth and proliferation. EMT reversal was established through increased E-cadherin and reduced N-cadherin while inhibition of cancer stem cell phenotype was evident through reduced Sox2 and Nanog. CTCL patients had higher circulating levels of IL-6, IL-8, IL-10, TGFß, PGE2 and MMP7 which are factors released by tumor-associated macrophages in tumor microenvironment. MALAT1 sponged miR-124 as this tumor suppressive miRNA was de-repressed upon MALAT1 silencing. Moreover, downregulation of miR-124 attenuated MALAT1 silencing effects. Our study provides a rationale for further studies focused on an evaluation of MALAT1-miR-124 in CTCL progression.

Improving the prognostic ability of PET/CT SUVmax to identify follicular lymphoma with early treatment failure.

Follicular lymphoma (FL) has a high degree of heterogeneity both clinically and molecularly. Early treatment failure (ETF), progression or relapse within 24 months of frontline immunochemotherapy is associated with a poor prognosis in FL. However, the clinical utility of ETF at diagnosis is limited. The maximum standardized uptake value (SUVmax) is a metabolic parameter for positron emission tomography/computed tomography (PET/CT); nevertheless, the relationship between SUVmax and ETF remains unclear. Thus, identifying early biomarkers that incorporate SUVmax and other clinical correlative variables could be helpful in identifying patients at high risk of ETF. A nomogram consisted of three independent variables, including SUVmax ≥ 12, beta-2 microglobulin > 3 mg/L, and Ki67 > 40%, was established to predict ETF in 127 patients with grade 1, 2, or 3a FL from the First Hospital of Jilin University (training cohort) and was validated using data from the Duke University Medical Center (validation cohort, n=95). The nomogram demonstrated prognostic accuracy in predicting ETF (sensitivity 70.8% and specificity 83.5% in the training cohort; sensitivity 84.2% and specificity 68.4% in the validation cohort). The patients were stratified into three groups: low-, intermediate-, and high-risk. In the training cohort, the corresponding 5-year progression-free survival (PFS) rates were 81.7%, 73.4%, and 34.9%, and the 5-year overall survival (OS) rates were 97.4%, 87.4%, and 62.3%, respectively. In the validation cohort, the 5-year PFS rates were 77.7%, 52.9%, and 34.8%, and the 5-year OS rates were 96.4%, 94.1%, and 73.7%, respectively. This was the first study to use a nomogram with SUVmax to predict ETF in FL to identify a subset of patients who might benefit from individualized targeted therapy.

Chidamide Maintenance Therapy Following Induction Therapy in Patients With Peripheral T-Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation: Case Series From China.

Objective: To assess the potential benefit of chidamide maintenance therapy after induction treatment in peripheral T-cell lymphoma (PTCL). Materials and Methods: The clinical data of 48 transplantation-ineligible patients with different PTCL subtypes who received continuous chidamide treatment after first-line therapy were collected. Progression-free survival (PFS), overall survival (OS), and safety were analyzed. Results: In total, 68.8% of patients were male (33/48), the median age was 59.5 years (22~80). The pathological subtypes were angioimmunoblastic T-cell lymphoma (AITL, 43.8%), anaplastic large cell lymphoma (ALCL, 16.6%), PTCL-not otherwise specified (NOS, 25%), NK/T-cell lymphoma (NKT, 14.6%). 35.4% (7/48) patients had intermediate or high risk (IPI=3~5). 20 patients (41.7%) received chidamide as a maintenance treatment after achieving a complete response (CR). 57.1% (16/28) exhibited a better response after chidamide (9 cases partial response [PR] to CR, 7 from stable disease [SD] to PR). The CR and overall response rate (ORR) were 60.4% and 93.8%, respectively. In addition, 21/21 AITL, 10/12 PTCL-NOS, and 8/8 ALCL, 6/7 NK/T exhibited CR/PR as the best response during the follow-up period. Meanwhile, the CR and ORR did not differ by age (<60 vs ≥60: 50.0% vs 70.8%, P = 0.091; and 91.7% vs 95.8%, P = 0.551). The median follow-up period was 12.8 months (3.0-66.6), 14 patients developed PD (29.2%), 10 of them died of lymphoma (20.8%). Totally, the 40 cases achieved CR/PR from 1st line regimen got better PFS as well as OS than the rest 8 cases (the 1-year PFS was 80.8% vs 46.9% and the 2-year PFS was 71.9% vs 46.9%, P=0.012. the 1-year OS was 89.9% vs 72.6% and the 2-year OS was 85.9% vs 48.6%, P=0.032). No patients discontinued treatment because of adverse events. The most common toxicities were neutropenia (75.0%), anemia (79.2%), thrombocytopenia (58.3%), and anorexia (45.8%), and fatigue (43.8%). Conclusion: Chidamide maintenance therapy led to improvements of PFS and OS with a manageable safety profile in patients with PTCL. Further randomized studies are required to examine the role of chidamide maintenance therapy in PTCL.

The Short-Term Efficacy and Safety of Brentuximab Vedotin Plus Cyclophosphamide, Epirubicin and Prednisone in Untreated PTCL: A Real-World, Retrospective Study.

INTRODUCTION: Brentuximab vedotin (BV) showed high overall remission rates in refractory/relapsed classical Hodgkin's lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Although the efficacy of BV has been reported in clinical trials, its efficacy as a frontline therapy in real world for patients with CD30 positive subtypes of non-Hodgkin's lymphoma (NHL) such as peripheral T-cell lymphoma with T-follicular helper cell (TFH) phenotype (PTCL, TFH), anaplastic large-cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL) in China has not been well documented. METHODS: Analysis of a real-world, observational, retrospective case series in patients suffering from AITL, sALCL and peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) and other types of PTCL treated with BV in frontline treatment was conducted. The patients were given treatment from May 2020 till June 28, 2021. All patients were pathologically diagnosed to have PTCL before treatment and expressed CD30. Patients received BV (1.8 mg/kg) combined with CEP (cyclophosphamide, epirubicin, prednisone acetate every 3 weeks). The primary endpoint was objective response rates (ORR), and secondary endpoints were duration of response and incidence of adverse events (AEs). Exploratory endpoints such as progression-free survival (PFS) are discussed even though after such a short period. RESULTS: Nineteen patients completed ≥ 1 cycles of BV-CEP treatment (16 cases completed ≥ 4 cycles, 3 cases only completed 1 cycle). Among them, the ORR reached 89.5% [CR 52.7%; partial response (PR) 36.8%]. In the ALCL group, CR reached 100% with the median duration of response of up to 8 months, while in the AITL group, the ORR was 75% and 2 patients had disease progression after treatment with BV + CEP. We also observed that BV-CEP may extend the PFS compared to traditional chemotherapy such as the CHOEP regimen (BV-CEP: not evaluable, CHOEP: 6.5 months), although the median follow-up was only 6.7 months. Adverse events (AEs), including incidence and severity of febrile neutropenia (26% patients in the BV-CEP group and 30% in the CHOEP group), were similar between groups. There was no incidence of AEs leading to treatment withdrawal or death under BV-CEP treatment. CONCLUSION: BV is a promising treatment in patients with ALCL, AITL and PTCL-TFH in frontline treatment settings.

Efficacy and Safety of Lenalidomide Monotherapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma: Systematic Review and Meta-Analysis.

INTRODUCTION: Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes. RESULTS: We included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months. CONCLUSION: This study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.

In Situ-Formed Novel Elastic Network Binder for a Silicon Anode in Lithium-Ion Batteries.

High energy density lithium-ion batteries with preferable cycling stability are critical for the development of all-electric vehicles. Silicon (Si) has demonstrated a remarkable potential for application as anode materials due to its superior capacity performance and worldwide abundance. However, Si intrinsically undergoes substantial volume fluctuation during repeated lithiation/delithiation processes, which pulverizes the Si particles and undermines the integrity of the electrode structures, thus resulting in frustrating cycling stability. We developed a polymer binder with a highly stretchable and elastic network structure that can accommodate volume variation of Si. This was realized by an in situ cross-linking of polyacrylic acid (PAA) with isocyanate-terminated polyurethane oligomers that consist of polyethylene glycol (PEG) chains and 2-ureido-4-pyrimidinone (UPy) moieties through the reaction between isocyanate and carboxyl during the electrode preparation process. In this binder network, PAA could strongly adhere to the Si particles by forming hydrogen bonding with the surface hydroxyl groups. The PEG chains induce the flexibility of the polymer network, while the UPy moieties endow the polymer network with desirable mechanical strength through the formation of reversible and strong quadruple H-bonding cross-linkers. This binder not only can sufficiently accommodate the volume change of Si but can also provide a strong mechanical support to effectively sustain the integrity for the Si anode, consequently enhancing cycle stability and rate performance.

Circular RNA: A potential diagnostic, prognostic, and therapeutic biomarker for human triple-negative breast cancer.

Triple-negative breast cancer (TNBC), which is the most malignant subtype of breast cancer (BC), accounts for 10%-20% of all BC cases. TNBC, which occurs more frequently in young women, is characterized by high rates of cell proliferation and metastasis and poor prognosis. Chemotherapy is the primary systemic therapeutic strategy for TNBC. However, chemotherapy is largely unsuccessful, and effective targeted therapies for TNBC have not been established. Therefore, it is a matter of great urgency to identify precise molecular targets for the promising prognosis of patients with TNBC. Circular RNAs (circRNAs), which are a type of non-coding RNAs (ncRNAs), are abundantly expressed in the eukaryotic cells and exhibit diverse cellular functions. The roles of circRNAs are to sponge microRNA or RNA-binding proteins, regulate gene expression, and serve as templates for translation. Here, we review the current findings on the potential of circRNAs as a diagnostic, prognostic, and therapeutic biomarker for TNBC. However, further studies are essential to elucidate the functions of circRNAs in TNBC. This review also discusses the current limitations and future directions of TNBC-associated circRNAs, which can facilitate the translation of experimental research into clinical application.

Insights into the mechanisms of Th17 differentiation and the Yin-Yang of Th17 cells in human diseases.

Th17 cells are a lineage of CD4+ T helper cells with Th17-specific transcription factors RORγt and RoRα. Since its discovery in 2005, research on Th17 has been in rapid progress, and increasing cytokines or transcription factors have been uncovered in the activation and differentiation of Th17 cells. Furthermore, growing evidence proves there are two different subsets of Th17 cells, namely non-pathogenic Th17 (non-pTh17) and pathogenic Th17 (pTh17), both of which play important roles in adaptive immunity, especially in host defenses, autoimmune diseases, and cancer. In this review, we summarize and discuss the mechanisms of Th17 cells differentiation, and their roles in immunity and diseases.

The protective role of short-chain fatty acids acting as signal molecules in chemotherapy- or radiation-induced intestinal inflammation.

A compelling set of links between chemotherapy- or radiation-induced intestinal inflammation and microbial dysbiosis has emerged. It is the proportional imbalance between pathogenic and beneficial bacteria that aggravates intestinal mucositis. Bacteria that ferment fibers and produce short-chain fatty acids (SCFAs), (such as acetate, propionate, and butyrate) are typically reduced in the mucosa and feces of patients undergoing cancer therapy. In contrast, increasing lipopolysaccharide-producing bacteria result in proinflammatory events by interacting with Toll-like receptors. A collective acceptance is that bacterial metabolites are critical in recovering intestinal homeostasis. We herein review evidence supporting the positive roles carried out by SCFAs. SCFAs, acting as signaling molecules, directly activate G-coupled-receptors and inhibit histone deacetylases. Thus, SCFAs are able to strengthen the gut barrier and regulate immunomodulatory functions. Furthermore, it is possible to reverse intestinal microbial dysbiosis and subsequently suppress the secretion of proinflammatory cytokines by directly applying SCFA-producing bacteria. In addition, anticancer effects of SCFAs have proved in the colorectal cancer. In this review, we discuss microbial dysbiosis and its impact on chemotherapy- or radiation-induced intestinal mucositis. Moreover, we summarize the mechanisms of SCFA production and its effects on intestinal mucositis. This review suggests the therapeutic potential of SCFAs for the management of chemotherapy- or radiation-induced intestinal inflammation.

A Micelle Electrolyte Enabled by Fluorinated Ether Additives for Polysulfide Suppression and Li Metal Stabilization in Li-S Battery.

The Li-S battery is a promising next-generation technology due to its high theoretical energy density (2600 Wh kg-1) and low active material cost. However, poor cycling stability and coulombic efficiency caused by polysulfide dissolution have proven to be major obstacles for a practical Li-S battery implementation. In this work, we develop a novel strategy to suppress polysulfide dissolution using hydrofluoroethers (HFEs) with bi-functional, amphiphlic surfactant-like design: a polar lithiophilic "head" attached to a fluorinated lithiophobic "tail." A unique solvation mechanism is proposed for these solvents whereby dissociated lithium ions are readily coordinated with lithiophilic "head" to induce self-assembly into micelle-like complex structures. Complex formation is verified experimentally by changing the additive structure and concentration using small angle X-ray scattering (SAXS). These HFE-based electrolytes are found to prevent polysulfide dissolution and to have excellent chemical compatibility with lithium metal: Li||Cu stripping/plating tests reveal high coulombic efficiency (>99.5%), modest polarization, and smooth surface morphology of the uniformly deposited lithium. Li-S cells are demonstrated with 1395 mAh g-1 initial capacity and 71.9% retention over 100 cycles at >99.5% efficiency-evidence that the micelle structure of the amphiphilic additives in HFEs can prohibit polysulfide dissolution while enabling facile Li+ transport and anode passivation.

Imaging-guided brachytherapy for locally advanced cervical cancer: the main process and common techniques.

Brachytherapy (BT) delivers integrated boost doses to the central tumor while sparing the surrounding organs at risk (OARs) efficiently. It's a mandatory treatment component for locally advanced cervical cancer (LACC) because it results in excellent overall survival and local control compared with other dose boosting modalities. Currently, BT is undergoing a transition from 2-dimensional (2D) to 3-dimensional (3D) treatment planning. Imaging-guided BT (IGBT) employing computed tomography (CT) or magnetic resonance imaging (MRI) can provide exact individual delineation of target and OARs meanwhile prescribe the dose to the target volume instead of "point A" for X-ray-based BT. There are three main techniques for BT: intracavitary (IC), interstitial (IS), and intracavitary/interstitial (IC/IS) combination. The applicator choice depends on the specific tumor extension. The real-time transabdominal ultrasound (US)-guided applicator placement technique is strongly recommended to ensure ideal applicator positioning. MRI is the ideal standard imaging for BT owing to its superior soft tissue visualization than CT. However, CT-based BT is more often performed because of the availability. In developing countries, US-based BT can be adopted. For treatment planning, the applicator reconstruction is easier on CT than on MRI, because the applicator image is more clearly visible. Individual treatment planning should be performed for every single applicator insertion to ensure dose accuracy. In this review article, we explain the main clinical process and common techniques, including the applicator choice and placement, imaging techniques, target delineation, and treatment planning; asthose will help to improve the efficiency of 3D BT.

Acquired pure red cell aplasia in a patient with ankylosing spondylitis- a case report and literature review.

RATIONALE: Acquired pure red cell aplasia (PRCA) can be a secondary response to some autoimmune disorders. However, there is no data about the possibility of acquired PRCA being a secondary complication to ankylosing spondylitis (AS). PATIENT CONCERNS: A 42-year-old male who had a history of AS for 14 years. He got serious anemia 17 months ago. Bone marrow smear indicated PRCA. DIAGNOSE: He was diagnosed with acquired PRCA secondary to AS. INTERVENTION: The combination treatment of immunosuppressants with hematopoiesis stimuli was successful. OUTCOMES: The patient recovered from PRCA, and showed improvement in his AS. LESSONS: Acquired PRCA can be secondary to AS. Cyclosporine is effective in controlling AS arthritis syndrome and in addition to immunosuppressants, promotion of erythroid hematopoiesis is equally important.

Reactive Precipitation of Anhydrous Alkali Sulfide Nanocrystals with Concomitant Abatement of Hydrogen Sulfide and Cogeneration of Hydrogen.

Anhydrous alkali sulfide (M2 S, M=Li or Na) nanocrystals (NCs) are important materials central to the development of next generation cathodes and solid-state electrolytes for advanced batteries, but not commercially available at present. This work reports an innovative method to directly synthesize M2 S NCs through alcohol-mediated reactions between alkali metals and hydrogen sulfide (H2 S). In the first step, the alkali metal is complexed with alcohol in solution, forming metal alkoxide (ROM) and releasing hydrogen (H2 ). Next, H2 S is bubbled through the ROM solution, where both chemicals are completely consumed to produce phase-pure M2 S NC precipitates and regenerate alcohol that can be recycled. The M2 S NCs morphology may be tuned through the choice of the alcohol and solvent. Both synthetic steps are thermodynamically favorable (ΔGmo <-100 kJ mol-1 ), proceeding rapidly to completion at ambient temperature with almost 100 % atom efficiency. The net result, H2 S+2 m→M2 S+H2 , makes good use of a hazardous chemical (H2 S) and delivers two value-added products that naturally phase separate for easy recovery. This scalable approach provides an energy-efficient and environmentally benign solution to the production of nanostructured materials required in emerging battery technologies.

Computed Tomography-Guided Interstitial Brachytherapy for Locally Advanced Cervical Cancer: Introduction of the Technique and a Comparison of Dosimetry With Conventional Intracavitary Brachytherapy.

OBJECTIVE: We present a new technique of 3-dimensional computed tomography-guided interstitial (IS) brachytherapy (BT) for locally advanced cervical cancer, offering a more advantageous clinical treatment approach. MATERIALS/METHODS: Interstitial BT was performed using an applicator combining uterine tandem and metal needles; needles were inserted freehand under real-time 3-dimensional computed tomography guidance. Twenty-eight patients with bulky tumors and/or parametrial extension (tumor size > 5 cm) after external beam radiotherapy received IS BT. Dosimetric outcomes of the IS BT including the total dose (external beam radiotherapy and high dose-rate BT) D90 for the high-risk clinical target volume (HR-CTV) and D2cc for the organs at risk (OARs) were investigated and compared with a former patient group consisting of 30 individuals who received the conventional intracavitary (IC) BT. RESULTS: The mean D90 values for HR-CTV in the IC BT and IS BT groups were 76.9 ± 5.7 and 88.1 ± 3.3 Gy, respectively. Moreover, 85.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IS BT group, and only 6.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IC BT group. The D2cc for the bladder, rectum, and sigmoid were 84.7 ± 6.8, 69.2 ± 4.2, and 67.8 ± 4.5 Gy in the IC BT group and 81.8 ± 6.5, 66.8 ± 4.0, and 64.8 ± 4.1 Gy in the IS BT group. The mean number of needles was 6.9 ± 1.4, with a mean depth of 2.9 ± 0.9 mm for each IS BT. Interstitial BT was associated with only minor complications. CONCLUSIONS: The IS BT technique resulted in better dose-volume histogram parameters for large volume tumors (>5 cm) compared with the conventional IC BT and acceptable risk of acute complications in locally advanced cervical cancer and is clinically feasible.

Characterization of IFNγ-producing natural killer cells induced by cytomegalovirus reactivation after haploidentical hematopoietic stem cell transplantation.

During human cytomegalovirus (CMV) infection after umbilical cord blood or HLA-matched hematopoietic stem cell transplantation (HSCT), a population of NKG2C-expressing natural killer (NK) cells expand and persist. The expanded NK cells express high levels of inhibitory killer immunoglobulin-like receptors (KIR) specific for self-HLA and potently produce IFNγ. However, it remains unknown whether similar events would occur after haploidentical HSCT (haplo-HSCT). Here, we demonstrated that IFNγ-producing NK cells were expanded in haplo-HSCT patients with CMV reactivation. We then identified these expanded cells as a subset of CD56dim NK cells that expressed higher levels of both NKG2C and KIR, but lower level of NKG2A. Functionally, the subset of NK cells expressing NKG2C and self-KIR in patients with CMV reactivation accounted for IFNγ production in response to K562 cells. However, these phenomena were not observed in patients without CMV reactivation. We therefore characterized a subset of NK cells with the CD56dim, NKG2C+, and self-KIR+ phenotype that expanded and were responsible for IFNγ production during CMV infection after haplo-HSCT. Together, these findings support a notion that CMV reactivation induces expansion of more mature NK cells with memory-like features, which contributes to long-term control of both CMV infection and leukemia relapse after haplo-HSCT.

Salvage interstitial brachytherapy based on computed tomography for recurrent cervical cancer after radical hysterectomy and adjuvant radiation therapy: case presentations and introduction of the technique.

PURPOSE: Locally recurring cervical cancer after surgery and adjuvant radiotherapy remains a major therapeutic challenge. This paper presents a new therapeutic technique for such patients: interstitial brachytherapy (BT) guided by real-time three-dimensional (3D) computed tomography (CT). MATERIAL AND METHODS: Sixteen patients with recurrent cervical cancer after radical surgery and adjuvant external-beam radiotherapy (EBRT) were included in this study. These patients underwent high-dose-rate (HDR) interstitial BT with free-hand placement of metal needles guided by real-time 3D-CT. Six Gy in 6 fractions were prescribed for the high-risk clinical target volume (HR-CTV). D90 and D100 for HR-CTV of BT, and the cumulative D2cc for the bladder, rectum, and sigmoid, including previous EBRT and present BT were analyzed. Treatment-related complications and 3-month tumor-response rates were investigated. RESULTS: The mean D90 value for HR-CTV was 52.5 ± 3.3 Gy. The cumulative D2cc for the bladder, rectum, and sigmoid were 85.6 ± 5.8, 71.6 ± 6.4, and 69.6 ± 5.9 Gy, respectively. The mean number of needles was 6.1 ± 1.5, with an average depth of 3.5 ± 0.9 cm for each application. Interstitial BT was associated with minor complications and passable tumor-response rate. CONCLUSIONS: Interstitial BT guided by real-time 3D-CT for recurrent cervical cancer results in good dose-volume histogram (DVH) parameters. The current technique may be clinically feasible. However, long-term clinical outcomes should be further investigated.