Can Optical Surface Imaging Replace Non-coplanar Cone-beam Computed Tomography for Non-coplanar Set-up Verification in Single-isocentre Non-coplanar Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Single and Multiple Brain Metastases?

AIMS: To conduct a direct comparison regarding the non-coplanar positioning accuracy between the optical surface imaging system Catalyst HDTM and non-coplanar cone-beam computed tomography (NC-CBCT) in intracranial single-isocentre non-coplanar stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). MATERIALS AND METHODS: Twenty patients with between one and five brain metastases who underwent single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) SRS or HSRT were enrolled in this study. For each non-zero couch angle, both Catalyst HDTM and NC-CBCT were used for set-up verification prior to beam delivery. The set-up error reported by Catalyst HDTM was compared with the set-up error derived from NC-CBCT, which was defined as the gold standard. Additionally, the dose delivery accuracy of each non-coplanar field after using Catalyst HDTM and NC-CBCT for set-up correction was measured with SRS MapCHECKTM. RESULTS: The median set-up error differences (absolute values) between the two positioning methods were 0.30 mm, 0.40 mm, 0.50 mm, 0.15°, 0.10° and 0.10° in the vertical, longitudinal, lateral, yaw, pitch and roll directions, respectively. The largest absolute set-up error differences regarding translation and rotation were 1.5 mm and 1.1°, which occurred in the longitudinal and yaw directions, respectively. Only 35.71% of the pairs of measurements were within the tolerance of 0.5 mm and 0.5° simultaneously. In addition, the non-coplanar field with NC-CBCT correction yielded a higher gamma passing rate than that with Catalyst HDTM correction (P < 0.05), especially for evaluation criteria of 1%/1 mm with a median increase of 12.8%. CONCLUSIONS: Catalyst HDTM may not replace NC-CBCT for non-coplanar set-up corrections in single-isocentre NC-VMAT SRS and HSRT for single and multiple brain metastases. The potential role of Catalyst HDTM in intracranial SRS/HSRT needs to be further studied in the future.

[Epidemiological trend of early-onset gastric cancer and late-onset gastric cancer in China from 2000 to 2019].

Objective: In order to understand the changing trends of gastric cancer incidence and mortality in early-onset and late-onset in China from 2000 to 2019. Methods: The Global Burden of Disease research data was collected, and Excel and R 4.2.1 softwares were used to examine the incidence rate, mortality rate, and disability-adjusted life years (DALY) of Chinese people from 2000 to 2019, with a focus on gender, age, and year. Results: In 2019, the crude incidence rates were 7.06/100 000 (95%UI: 6.63/100 000-7.59/100 000) and 114.52/100 000 (95%UI: 108.79/100 000-121.63/100 000) for early- and late-onset gastric cancer, respectively. The crude mortality rate for early-onset gastric cancer was 3.29/100 000 (95%UI: 3.11/100 000- 3.50/100 000), while the crude mortality rate for late-onset gastric cancer was 81.88/100 000 (95%UI: 78.15/100 000-86.04/100 000). Additionally, the crude DALY rates for these two types of gastric cancer were 156.48/100 000 (95%UI: 148.82/100 000-165.84/100 000) and 1 750.13/100 000 (95%UI: 1 661.21/100 000-1 852.99/100 000). The standardized incidence of early-onset gastric cancer decreased from 5.49/100 000 in 2000 to 4.76/100 000 in 2019, and that of late-onset gastric cancer decreased from 143.45/100 000 in 2000 to 123.02/100 000 in 2019.The standardized mortality rate of early-onset gastric cancer decreased from 4.16/100 000 in 2000 to 2.18/100 000 in 2019, and that of late-onset gastric cancer decreased from 140.82/100 000 in 2000 to 91.49/100 000 in 2019. The standardized DALY rate for early-onset gastric cancer in 2019 was 105.87/100 000 (95%UI: 87.98/100 000 -125.60/100 000), lower than 198.84/100 000 (95%UI: 179.47/100 000- 219.83/100 000) in 2000. The standardized DALY rate for late onset gastric cancer in 2019 was 1 821.11/100 000 (95%UI: 1 509.42/100 000-2 158.53/100 000), lower than 2 932.52/100 000 (95%UI: 2 665.92/100 000-3 252.60/100 000) in 2000. Conclusions: The standardized mortality rate of early-onset gastric cancer in China showed a decreasing trend from 2000 to 2019. The standardized mortality rate of late onset gastric cancer showed a trend of first increasing and then decreasing. Notably, the incidence, mortality, and DALY of late-onset gastric cancer were significantly higher than those of early-onset gastric cancer during this period. Additionally, male incidence, mortality, and crude DALY rates were higher than female.

Clinical Feasibility of Using Single-isocentre Non-coplanar Volumetric Modulated Arc Therapy Combined with Non-coplanar Cone Beam Computed Tomography in Hypofractionated Stereotactic Radiotherapy for Five or Fewer Multiple Intracranial Metastases.

AIMS: To evaluate the clinical feasibility of single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) with non-coplanar cone beam computed tomography (NC-CBCT) in hypofractionated stereotactic radiotherapy (HSRT) for five or fewer multiple brain metastases. MATERIALS AND METHODS: Ten patients with multiple brain metastases who underwent single-isocentre NC-VMAT HSRT with limited couch rotations (within ±45°) and NC-CBCT with a limited scanning range (150-200°) were included in the current analysis. Conventional single-isocentre coplanar VMAT (C-VMAT) plans were generated and compared with NC-VMAT plans. The intracranial response and toxicities of single-isocentre NC-VMAT HSRT were also evaluated. RESULTS: Compared with C-VMAT, NC-VMAT generated better target conformity (P < 0.05), a lower gradient index (P < 0.05) and better normal brain tissue sparing, especially for volume ≥12 Gy, with a median reduction of 12.65 cm3. For 45° couch rotation, NC-CBCT produced sufficient image quality to differentiate bony anatomy, even with a 150° scanning range, which could be successfully used for patient set-up correction. After NC-CBCT, 57.1% of the measured non-coplanar set-up errors exceeded the threshold value. The median gamma passing rate of NC-VMAT was higher than that of C-VMAT plans (P < 0.05). The non-coplanar beam of NC-VMAT with NC-CBCT corrections exhibited superior gamma passing rate to that without NC-CBCT corrections. The intracranial objective response rate and disease control rate for all patients were 80% (8/10) and 100% (10/10), respectively, and the most common toxicities were headache (20%) and dizziness (20%). CONCLUSION: NC-VMAT with limited couch rotation (within ±45°) combined with NC-CBCT with a limited scanning range (150-200°) markedly improves the plan quality and set-up accuracy in single-isocentre multiple-target HSRT.

Effects of corn particle size on growth performance, gastrointestinal development, carcass indices and intestinal microbiota of broilers.

This experiment was conducted to investigate the effects of different corn particle sizes on growth performance, gastrointestinal development, carcass processing yields and intestinal microbiota of caged broilers. One-day-old Ross 308 broilers were randomly divided into 8 treatments with 10 replicates per treatment and 30 birds per replicate pen. The experiment lasted 37 d. Feed and water were provided ad libitum. The results showed as follows: birds fed diets with the FG corn between d 1 and 13 and CG corn between d14 to 37 had increased body weight, daily gain, and feed intake (P < 0.05). Birds fed diets with CG corn between d 24 to 37 had a heavier relative weight of gizzard at d 38 (P < 0.05). Birds fed diets with FG corn from d 1 to 13 and the CG corn from d 14 to 37 had a higher carcass yield and a relative thigh weight at d 38 (P < 0.05). The intestinal microbiota was significantly affected by different corn particle sizes. The relative abundance of Lactobacillaceae was significantly decreased, whereas that of Peptostreptococcaceae was increased (P < 0.05) in birds fed with the CG corn between d1 to 37. The relative abundance of Acinetobacter was significantly increased in birds fed the FG corn between d1 to 37 (P < 0.05). In conclusion, the use of FG corn in the starter phase and CG corn in the grower and finisher phases was beneficial to growth performance, gastrointestinal development and intestinal microbial structure of broilers reared in cages.

Prevalence and risk factors of anaemia in hospitalised HIV-infected patients in southeast China: a retrospective study.

The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients' information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts <50 cells/µl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916-21.215, P = 0.003), CD4 counts 50-199 cells/µl (OR: 6.303, 95% CI = 1.874-21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349-5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147-15.299, P < 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.

[Waldenström's macroglobulinemia]. / Macroglobulinémie de Waldenström.

Waldenström's macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells, along with the presence of an IgM monoclonal gammopathy in the blood. WM remains incurable with a median of 8-year of overall survival for patients with symptomatic WM. Treatment is postponed for asymptomatic patients and progressive anemia is the most common indication for initiation of treatment. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either alone or in combination. Studies involving new combination chemotherapy are ongoing and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival is short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, new therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to better target therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors as bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001. Many other agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This article provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM.

Fluorescence in situ hybridization characterization of ider(20q) in myelodysplastic syndrome.

Isochromosome of the long arm of chromosome 20 with loss of interstitial material [ider(20q)] is a variant of deletion of chromosome 20q and a rare abnormality in myelodysplastic syndrome (MDS). We studied seven cases with an ider(20q) in MDS. Fluorescence in situ hybridization (FISH) studies showed all proximal breakpoints to be consistently located in 20q11.21 band whereas distal breakpoints were variable. Amplification of HCK, TNFRSF6B and DIDO1 genes included in retained regions associated with loss of tumour suppressor genes in deleted regions could explain cell tumour progression and possibly the less favourable prognosis of ider(20q) compared with del(20q).

Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH).

A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.

NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.

Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21).

Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P=0.065). After induction therapy, absolute transcript levels (below 10(-3), compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P=0.02 and P=0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P=10(-5)). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.

Disruption and aberrant expression of HMGA2 as a consequence of diverse chromosomal translocations in myeloid malignancies.

Chromosomal translocations that target HMGA2 at chromosome band 12q14 are seen in a variety of malignancies, notably lipoma, pleomorphic salivary adenoma and uterine leiomyoma. Although some HMGA2 fusion genes have been reported, several lines of evidence suggest that the critical pathogenic event is the expression of truncated HMGA2 isoforms. We report here the involvement of HMGA2 in six patients with myeloid neoplasia, dysplastic features and translocations or an inversion involving chromosome bands 12q13-15 and either 7p12, 8q22, 11q23, 12p11, 14q31 or 20q11. Breaks within or very close to HMGA2 were found in all six cases by molecular cytogenetic analysis, leading to overexpression of this gene as assessed by RT-PCR. Truncated transcripts consisting of HMGA2 exons 1-2 or exons 1-3 spliced to intron-derived sequences were identified in two patients, but were not seen in controls. These findings suggest that abnormalities of HMGA2 play an important and previously unsuspected role in myelodysplasia.

Hypereosinophilia with abnormal T cells, trisomy 7 and elevated TARC serum level.

The idiopathic hypereosinophilic syndrome (HES) is a rare heterogeneous disorder, characterized by persistent blood eosinophilia with possible organ involvement. We describe here the case of a 20-year-old atopic male presenting chronic hypereosinophilia and eczema since childhood. Biological findings included hypereosinophilia (9.5 x 10(9)/L), hyperlymphocytosis (10.9 x 10(9)/L), polyclonal hypergammaglobulinemia and elevated IgE serum level. Flow cytometric analysis of blood lymphoid cells showed a population of CD2+CD3-CD4+TCRab-TCRgd- lymphocytes. These cells displayed a Th0/Th2 cytokine profile, and a clonal TCR rearrangement pattern. A high serum TARC level was observed. Karyotype studies on blood stimulated culture or lymph nodes revealed a cellular hyperdiploïd clone 47, XY, +7. To our knowledge, this chromosomal aberration has never been reported in such case.

[Cutaneous symptoms revealing a monoblastic leukemia]. / Manifestations cutanées révélatrices d'une leucémie monoblastique.

UNLABELLED: Leukemia cutis (LC) are not rare in acute myeloid leukaemia (AML) in children but exceptionally reveal it. Most authors think that they have poor prognosis. CASE REPORT: We report the case of an infant with isolated cutaneous involvement at the time of diagnosis of leukaemia. Bone marrow aspiration showed AML M5. The child was treated by LAME 91 protocol, arm "infant under one year of age". Complete remission, both in bone marrow and skin, was obtained after induction course. Then the patient received consolidation course and megatherapy followed by autologous bone marrow transplantation. Skin relapse occurred early. The complete remission no. 2 was not obtained by second line treatment: new LC appeared when PMN count increased more than 10(9)/l. Then, the child was treated with oral VP16 but disease progressed with more and more LC, followed by bone marrow relapse. Child's death occurred about one year after diagnosis.