Acceptable Adverse Effects Research Articles

Cutoff values for the best management strategy for magnetic resonance-guided focused ultrasound ablation for essential tremor.

The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor. Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics. Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not. MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network). ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.

Establishment of prognostic models for adenocarcinoma of oesophagogastric junction patients with neoadjuvant chemoradiotherapy: a real-world study

BackgroundMultimodal therapies based on surgical resection have been recommended for the treatment of adenocarcinoma of the oesophagogastric junction (AEG). We aimed to evaluate prognostic factors in AEG patients receiving neoadjuvant chemoradiotherapy and to build predictive models.MethodsT3 − T4N + M0 AEG patients with resectable Siewert type II/III tumours were enrolled in this study. All patients underwent neoadjuvant chemoradiation, followed by radical surgery or systemic therapy according to clinical response. Survival analysis was performed using the Kaplan–Meier method; multivariate analysis using the Cox proportional hazards method was also conducted. The Harrell concordance index (C-index) was used to test the prognostic value of models involving prognostic factors, and consistency between actual and predicted survival rates was evaluated by calibration curves.ResultsFrom February 2009 to February 2018, 79 patients were treated with neoadjuvant chemoradiotherapy; 60 patients of them underwent radical surgery. The R0 resection rate was 98.3%, and 46.7% of patients achieved a major pathologic response (MPR), namely, a residual tumour issue less than 10%. The 5-year overall survival (OS) rate was 63%, and the 5-year progression-free survival (PFS) rate was 48%. The incidence of grade 3 complications was 21.5%, and no grade 4 complications were reported. According to the results of univariate and multivariate analyses, we included the neutrophil–lymphocyte ratio (NLR), prognostic nutrition index (PNI), eosinophilic granulocyte (EOS) and postoperative pathologic stage in nomogram analysis to establish prediction models for OS and PFS; the C-index of each model was 0.814 and 0.722, respectively. Both the C-index and calibration curves generated to validate consistency between the actual and predicted survival indicated that the models were well calibrated and of good predictive value.ConclusionsAEG patients achieved favourable downstaging and pathologic response after neoadjuvant chemoradiation, with acceptable adverse effects. Inflammation-based and nutrition-related factors and postoperative pathologic stage had a significant influence on OS and PFS, and the predictive value was verified through prognostic models.

PM 6/3 (5) Biological control agents safely used in the EPPO region

Specific scopeThe purpose of this Standard is to provide a list of biological control agents (BCAs1) used in the EPPO region with no adverse effects or with acceptable adverse effects. This list is aimed to facilitate decision making on the import and release of BCAs within EPPO countries.Specific approval and amendmentsFirst approved in September 2001. Revisions 2–4 included amendments to the Appendices. Revision 5 approved in 2021–09. Revisions of the list are not subject to approval by the EPPO Council but are proposed by the joint EPPO/IOBC Panel on Biological Control Agents and approved by the EPPO Working Party for Phytosanitary Regulations.Authors and contributors are given in the Acknowledgements section.

Comparison of NSAIDS Versus NSAIDS Plus Duloxetine in Knee Osteoarthritis Patients

Objective: To compare the efficacy of Duloxetine with NSAIDS versus NSAIDS alone for the treatment of knee pain secondary to osteoarthritis. Study Design: Randomized clinical trial study. Setting and Duration: Department of Rheumatology, PIMS Hospital, Islamabad, from April to August 2021. Methodology: One hundred and twenty eight patients with knee osteoarthritis were included in the study and were divided in two equal groups; one group was subjected to Duloxetine plus NSAIDs and other to just NSAIDs. The response was assessed at end of 3 months. Reduction in pain more than or equal to 50% from the baseline was considered as efficacy. Results: The mean VAS score was 3.56±1.15 in group A (Duloexetine plus NSAIDS) A while in group B (NSAID alone), 4.45±1.22 and significantly (p-value > 0.05). Similarly, the comparison of WOMAC score for pain showed that the mean WOMAC score was significantly (P-value > 0.05) less 5.68±1.56 in group A in contrast to 6.39 ± 1.69 in group B. Comparison of efficacy between two groups showed that the rate of efficacy was significantly (P-value >0.05) higher in group A 48.4% as compared to 31.3% in group B. Conclusion: Addition of Duloxetine to NSAIDs resulted in more reduction of pain in terms of VAS and WOMAC score with acceptable adverse effects. Keywords: Chronic pain, Duloxetine, Knee pain, NSAIDs, Osteoarthritis

Safety of treatment with ulipristal acetate on the mammary gland: A pilot prospective study

IntroductionHeavy menstrual bleeding is the major complaint in women with symptomatic fibroids. Ulipristal acetate (UPA) is a “selective progesterone receptor modulator” in which mixed agonist and antagonist activity appears to offer a novel approach to medical management of symptomatic uterine fibroids. There are currently no studies that have assessed its effect on the mammary gland in humans. MethodsProspective observational study conducted in a tertiary hospital, in which 14 consecutive patients diagnosed with uterine fibroids by transvaginal ultrasound were included. The patients received two cycles of UPA 5mg/day for 3 months each, with a rest period of two months between both cycles. To assess the safety on the mammary gland, 3 mammary ultrasounds were performed at three different points: prior to the first cycle of UPA, between the two cycles and at the end of the second cycle. ResultsOf the 14 recruited patients, 9 completed the study period. Breast ultrasound reports were normal in all patients. In 4 patients (44.4%), the 3 breast ultrasounds were classified as BI-RADS 2. In 2 patients (22.2%) the 3 breast ultrasounds were classified as BI_RADS1; and in 3 patients (33.3%), the first breast ultrasound was classified as BI-RADS 3 and the last two as BI-RADS 2. ConclusionIn conclusion, our study showed that 2 cycles of treatment with UPA in patients with symptomatic uterine fibroids is safe for normal breast tissue with an acceptable adverse effects profile. Nonetheless, further research is required to confirm our findings.

Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study.

PurposeHigh‐dose methotrexate (HD‐MTX)-based chemotherapy regimen is the first-line treatment of primary central nervous system lymphoma (PCNSL). At present, doses of MTX in the range of 3.5–8 g/m2 are frequently used. However, the optimal dose of methotrexate for PCNSL remains controversial. The purpose of this real-world study was to compare the efficacy and toxicity of HD-MTX in patients with untreated PCNSL.MethodsImmunocompetent adults with newly diagnosed PCNSL between January 2015 and December 2018 were investigated and followed up to June 2019. All patients’ initial treatments were based on HD‐MTX chemotherapy regimens.ResultsA total of 73 patients were reviewed. For patients who received HD-MTX at 8 g/m2 vs.3.5 g/m2, the complete response (CR) rates were 68.29% vs 43.75% (p = 0.03), and the median PFS times were 17.7 months vs 9.05 months (HR=0.455, 95% CI 0.239–0.865, p=0.016). There was no significant difference in OS between the two groups. Serious adverse effects were uncommon and clinically manageable.ConclusionThere is a correlation of treatment response and clinical outcomes between the dosage of MTX in initial induction therapy in newly diagnosed PCNSL. MTX dose of 8 g/m2 provided a higher CR rate and PFS benefits with acceptable adverse effects.

Treatment Outcome of Dasatinib in Combination with Less-Intensive Induction, Homobarringtonie, Cytarabine, G-SCF in Newly Diagnosed Patients with Ph+ALL

Unprecedented achievement has been made in the treatment of childhood ALL within the past decades. However, how to improve the outcome of Ph+ALL remains a conundrum for the care providers towards the cure of the disease. Using Auto-hematopoietic stem cell transplant (HSCT), after a negative BCR-ABL, or allo-HSCT has become the curative options for Ph+ALL cases although either relapse or life threatening transplant related complications could lead to treatment failure.To determine the safety and efficiency of a dasatinib based mild induction with homobarringtonie, cytarabine, G-SCF (HAG) contained regimen, we enrolled 67 patients with de novo Ph+ALL from 2012-2017 for the trial. The medium follow-up time was 39 months (17 months to 65 months). In brief, the induction consisted of vincristine and prednisone, in addition to daily dasatinib (70mg; bid), followed by six cycles of HAG regimen (homobarringtonie 1mg/m2/days 1-14; G-CSF 5ug/kg on day one; Ara-C 10mg/q12h/days 1-14; every three month/cycle) plus daily dasatinib (70mg; bid). The maintenance included two cycles of HAG (every six months) in addition to daily dasatinib. The intrathecal injection was given 11 times along with the treatment to prevent CNS leukemia. A serial MRD detection of BCR-ABL by qPCR was performed every three months.There were four patients eligible for the study. Among the 63 evaluated patients, 55 (88%) achieved CR in induction. There was no treatment related mortality during the induction. Good prednisone response was indicated among 51 patients (81%) on day eight. The day 30 MRD detection for those in CR indicated 43 (68%) reached ≤5 *10-2 and four (7%) achieved 10-3. The MRD detection at month three and six suggested that 38 (60%) vs 33 (52%) patients were within the level of ≤5 *10-2 and six (10%) vs 10 (16%) achieved 10-3, respectively. Relapse-related death occurred in 11 of 63 patients (16%), and four patients (6%) experienced treatment-related mortality. Grade 3-4 adverse events were observed among 10 cases (30%). The main toxicities were liver dysfunction and coagulation abnormality which can be solved by close monitoring and multi-disciplinary care. Four-year probability of event-free survival (pEFS) was found to be 58%. Those who went with hematopoietic stem cell transplantation (HSCT) after chemotherapy achieved significantly better pEFS than only chemotherapy (65.7% vs 50.5%,p=0.03). Our protocol can be used as an effective and less toxic treatment option to improve the outcome of Ph+ALL with promising survival and acceptable adverse effects shedding new light on treating Ph+ALL. DisclosuresNo relevant conflicts of interest to declare.

Platinum-based chemotherapy combined with endostar in the treatment of advanced NSCLC: A real world study.

e21033 Background: Recombinant human endostatin (endostar), an angiogenesis inhibitor, has been approved for the treatment of NSCLC in combination with chemotherapy in China. This study aims to evaluate real world efficacy and safety of endostar combined with platinum-based chemotherapy in the treatment of advanced NSCLC. Methods: This study retrospectively collected electronic medical record system (EMR) information of NSCLC patients (pts) who received endostar combined with platinum-based chemotherapy regiments from June 2012 to August 2019 in 7 cancer hospitals after obtaining ethical approval. Baseline characteristics, efficacy evaluation and safety data were analyzed. Tumor response was evaluated according to RECIST 1.1. Adverse events (AEs) were graded according to NCI-CTC AE 4.0. The endpoints include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: 512 advanced NSCLC pts who received endostar combined with platinum-based chemotherapy regiments were analyzed. The median age of pts was 59.2 years. Most pts were male, accounting for 75.2%. 63.3% pts was diagnosed at stage IV. 40.0% pts was adenocarcinoma and 35.4% pts was squamous cell carcinoma. 81.4% pts received endostar combined with chemotherapy as first-line. 292 people were included in the efficacy analysis set. The ORR, DCR and median PFS were 34%, 73% and 8.2 (95% CI 6.0-13.7) months, respectively. There were no significant differences of ORR and DCR among common platinum-based chemotherapy. The most common AEs were gastrointestinal reactions (29%), bone marrow suppression (14%), and liver damage (12%). Conclusions: The real-world data confirmed the superiority of endostar plus platinum-based chemotherapy in Chinese advanced NSCLC pts, with acceptable adverse effects. Clinical trial information: ChiCTR2000035129.

Effectiveness and safety of tocilizumab in patients with refractory or severe Takayasu's arteritis: A prospective cohort study in a Chinese population

To assess the effectiveness and safety of tocilizumab (TCZ) in treating severe/refractory Takayasu's arteritis (TAK). A prospective cohort study was started on 1 November 2013 and terminated on 10 June 2020. Thirty-seven patients diagnosed as severe/refractory TAK, treated with TCZ combined with or without immunosuppressors were enrolled. Treatment response (complete remission (CR) and partial remission (PR)), imaging progression and side effects were analyzed at 6-month treatment. Disease flare was analyzed during the remaining follow-up. The CR and RR rates were 70% and 88% at 6 months of TCZ treatment, respectively. Glucocorticoids was tapered from 30.0 (20.0-40.0) to 15.0 (10.0-15.0) mg/day at 6 months. Younger patients (≤26 years) (OR=14.6, 95% CI 1.27-170.4, P<0.05) and those with involvement of bilateral carotid arteries or vertebral arteries (OR=14.6, 95% CI 1.27-169.1, P<0.05) might show a better response to TCZ at 6 months. Combined therapy of immunosuppressors had no significant effects on the effectiveness of TCZ at 6 months. Among the total 23 patients with CR at 6 months, 14 cases discontinued TCZ therapy after 6 months, and disease flare was observed in six ones (43%), with medium flare at 7 (7-9.8) months. One patient (11%) who continued TCZ therapy suffered disease flare at 8 months. Infections were the most commonly observed side effects (38%), with four patients discontinuing TCZ treatment due to severe infections. TCZ treatment achieved a favorable response with acceptable adverse effects for TAK.

Combined Treatment of Rolling Acne Scars in Ethnic Skin Using Extensive Subcision, Trichloracetic Acid Peel, and Fractional Ablative Erbium Laser.

BACKGROUNDSuccessful treatment of acne scars in ethnic skin requires procedures that are safe and effective with a low incidence of hyper or hypopigmentation postoperatively.OBJECTIVEIn this study, the safety and efficacy of a combined treatment protocol including tumescent anesthesia, subcision, trichloracetic acid peel, and fractional erbium laser resurfacing was evaluated.METHODSThis is a retrospective study of 56 patients (22 women and 34 men) with predominantly rolling acne scars and Fitzpatrick skin Types IV–VI who were treated using a combination of tumescent anesthesia, extensive subcision, fractional ablative erbium laser, and a blending 20% trichloracetic acid (TCA) peel.RESULTSThe mean improvement after a single treatment, assessed by 3 independent evaluators (2 dermatologist and 1 dermatology physician assistant), was 2.52 (SD = 1.04) on a scale of 1 to 4.CONCLUSIONThe combination of tumescent anesthesia, extensive subcision, fractional ablative erbium laser resurfacing, and a blending 20% TCA peel (combined procedure) is both safe and effective in the treatment of rolling acne scars in ethnic skin types with acceptable temporary adverse effects.

Phase II study of systemic chemotherapy with S-1 plus oxaliplatin followed by surgery in patients with cT3-T4a and/or node-positive advanced adenocarcinoma of the esophagogastric junction: Primary endpoint results of the ESOX trial.

214 Background: Perioperative chemotherapy has been suggested to be beneficial in patients with advanced gastric cancer. Based on the German FLOT-4 study, the FLOT regimen is considered as the new standard perioperative chemotherapy regimen for resectable gastric cancer in Europe. However, most clinical trials have included few or no cases of esophagogastric junction (EGJ) cancer, because of the difference in surgical procedures. The benefit of neoadjuvant chemotherapy in patients with advanced adenocarcinoma of the EGJ thus remains controversial in Japan. Methods: We conducted a phase II study in 13 Japanese institutions. Eligible patients had histopathologically confirmed adenocarcinoma of the EGJ (Siewert type I or II with invasion of the esophagus ≥30 mm) with clinical T3/4a and/or node-positive on imaging findings, who required thoracic surgery to achieve R0 resection. Patients received three cycles of S-1 (80 mg/m2) twice a day on days 1–14 and oxaliplatin (130 mg/m2) (SOX) on day 1 of a 21-day cycle before surgery. The primary endpoint was R0 resection rate and the secondary endpoints were overall response rate, pathological complete response (pCR) rate, 2-year and 3-year disease-free survival, overall survival, and toxicity. The planned sample size was 50 patients based on an expected R0 resection rate of 85% and the threshold was 70%, with a one-sided alpha of 0.1 and power of 80%. Results: Fifty patients were enrolled in this study between June 2016 and April 2020. Totals of 21/29 and 7/4/22/8/8/1 had Siewert type I/II and clinical stage IIA/IIB/IIIA/IIIB/IIIC/IV disease, respectively. The completion rates for preoperative chemotherapy and surgery were 92% and 88%, respectively. Neoadjuvant therapy resulted in downstaging in 46% of patients (95% confidence interval (CI) 31.8%-60.7%). The pCR rate was 18% (95% CI 8.6%-31.4%) and the R0 resection rate was 82.0% (95% CI 68.6%-91.4%, 80% CI 73.1%-88.9%). Adverse events ≥ grade 3 during chemotherapy included thrombocytopenia (10%), neutropenia (8%), anemia (4%), anorexia (4%), nausea(2%), hypocalcemia(2%), hyponatremia(2%) and diarrhea (2%). Surgical morbidity was acceptable (Clavien-Dindo Grade IIIa surgical complications included anastomotic leakage (6.3%), pleural effusion (4.2%), thromboembolism (2.1%), and anastomotic infection (2.1%)). Conclusions: Neoadjuvant SOX met the primary endpoint of R0 resection rate 82% ( &gt; 70%), with acceptable adverse effects and no impression on surgeries, suggesting that neoadjuvant SOX might be a new treatment strategy for patients with EGJ adenocarcinoma in Japan. Clinical trial information: 000020815.

Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series

BackgroundStereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC.MethodsThis retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method.ResultsFourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3–4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively.ConclusionsSBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.

Rozpoznanie i leczenie nowotworów typu angiomyolipoma (AML)

Angiomyolipoma (AML) is the most commonly occurring tumour from the PEComa family (PEC tumours; perivascular epithelioid cell tumours), a rare group of neoplasms of mesenchymal origin. AML may occur sporadically or in the course of tuberous sclerosis and lymphangioleiomyomatosis. The sporadic type form is the most common subtype of benign kidney tumours and is four times more frequent in women. Kid ney tumours of the angiomyolipoma type are most commonly detected by chance during an abdominal cavity ultrasound scan, during which they are visible as hyperechogenic tumours, and in most cases they are not a diagnostic problem. AML growth is slow, and complications are rare. The main AML complication can be bleeding to the retroperitoneal space or to the pelvicalyceal system. The typical method of AML care is active surveillance (AS). Asymptomatic tumours with a diameter under 4 cm require control by ultrasound examination every 12 months whereas tumours with a diameter of less than 2 cm are considered not to require control ultrasounds. AML with a diameter of over 4 cm require more frequent ultrasound scans — every six months. The size of the tumour, the presence of symptoms (e.g. pain in a tumour projection, haematuria), planned pregnancy, or suspicion of a malignant tumour are critical in therapeutic decisions. Active treatment options include: embolisation, ablation techniques, nephron-sparing surgery (NSS), and radical nephrectomy. In adult patients with tuberous sclerosis, who require treatment but do not require rapid surgical treatment, everolimus is used. In the case of AML, initially doses of 1 × 10 mg per day should be used (an appropriate dose decrease is required in the case of liver insufficiency), and subsequently treatment may be individualised after determining the lowest effective dose with acceptable adverse effects. A rare epithelioid variety of AML (EAML) shows the potential for a malignant course. The basis of EAML treatment is radical resection, ensuring a high percentage of cures. For non-resectable EAML, chemotherapy, mTOR inhibitors, and VEGFR inhibitors (pazopanib, apatinib) are used, but objective responses have been described only in a very small percentage of patients

Chemotherapy for patients with unresectable or metastatic small bowel adenocarcinoma: a systematic review.

There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess the efficacy and safety of chemotherapy for patients with unresectable or metastatic SBA. In accordance with the PRISMA statements, literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The included studies were prospective randomized, nonrandomized, or observational studies. Risk of bias was assessed the ROBINS-I tool. Seven prospective single-arm Phase II studies were included in this review. Six of them were assessed as having a moderate risk of bias and one as having a serious risk of bias. A meta-analysis was not performed, because the studies were single-arm. Systemic chemotherapy based on fluoropyrimidine regimens achieved favorable outcomes with acceptable adverse effects as a first therapy; however, the regimens differed in each study. The object response rate was 18-50%, and the disease control rate was 29-87%. With 5-fluorouracil, adriamycin, and mitomycin-C regimen, one treatment-related death occurred. A second line of therapy including chemotherapy with nab-paclitaxel also showed favorable efficacy. The object response rate was 20%, and the disease control rate was 50%. Systemic chemotherapy based on fluoropyrimidine regimens was mainly used for unresectable or metastatic SBA. While it may achieve favorable outcomes with acceptable adverse effects, further evidence is needed.

The efficacy and safety of immunosuppressive therapies in the treatment of IgA nephropathy: A network meta-analysis

Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerulonephritis that can result in end-stage renal disease (ESRD). Whether immunosuppressants are superior or equivalent to supportive care is still controversial. A network meta-analysis was conducted to compare the efficacy and safety of immunosuppressive treatment for IgAN. Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and EMBASE were searched on December 30, 2018. We used a random-effects model with a Bayesian approach to appraise both renal outcomes and serious adverse effects. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to present the relative effects. The ranking probabilities were calculated by the surface under the cumulative ranking curve (SUCRA). In total, 24 RCTs comprising 6 interventions were analyzed. Steroids significantly delayed the progression of renal deterioration with acceptable serious adverse effects, compared with supportive care (RR = 0.28, 95% CI = 0.13–0.51, SUCRA = 48.7%). AZA combined with steroids might be an alternative immunosuppressive therapy. Tacrolimus might decrease the proteinuria level (RR = 3.1, 95% CI = 1.2–9.4, SUCRA = 66.5%) but cannot improve renal function, and the side effects of tacrolimus should not be neglected. MMF and CYC showed no superiority in the treatment of IgAN. In summary, steroids might be recommended as the first-line immunosuppressive therapy for IgAN.

Particle radiation therapy in the management of malignant glioma: Early experience at the Shanghai Proton and Heavy Ion Center.

BackgroundThe objective of this study was to evaluate the outcomes of patients with high‐grade glioma who received treatment with particle radiotherapy.MethodsBetween June 2015 and October 2018, 50 consecutive and nonselected patients with glioblastoma multiforme (n = 34) or anaplastic glioma (n = 16) were treated at the Shanghai Proton and Heavy Ion Center. Twenty‐four patients received proton radiotherapy (at a dose of 60 gray‐equivalents in 30 daily fractions), and 26 patients received proton radiotherapy plus a carbon‐ion radiotherapy (CIRT) boost in various dose‐escalating schemes. All patients received temozolomide because of their age or their O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation status. Progression‐free survival (PFS) and overall survival (OS) rates, as well as treatment‐induced toxicities, were analyzed.ResultsAt a median follow‐up of 14.3 months (range, 4.8‐39.6 months), the 12‐month and 18‐month OS rates were 87.8% (95% CI, 77.6%‐98.0%) and 72.8% (95% CI, 56.7%‐88.9%), respectively, and the 12‐month and 18‐month PFS rates were 74.2% (95% CI, 60.9%‐87.5%) and 59.8% (95% CI, 43.1%‐76.5%), respectively. Univariate analyses revealed that age (>50 vs ≤50 years), World Health Organization grade (3 vs 4), and Karnofsky performance status (>80 vs ≤80) were significant prognosticators for OS, and IDH mutation and World Health Organization grade were significant for predicting PFS. Furthermore, MGMT promoter methylation, performance status, and age showed a trend toward predicting PFS. No significant predictive factors for PFS or OS were identified in multivariate analyses. Twenty‐nine patients experienced grade 1 treatment‐related acute adverse effects, and 11 developed grade 1 (n = 6) or grade 2 (n = 5) late adverse effect of radiation‐induced brain necrosis. No grade 3, 4, or 5 toxicities were observed.ConclusionsParticle radiotherapy produced 18‐month OS and PFS rates of 72.8% and 59.8%, respectively, with acceptable adverse effects in patients with high‐grade glioma. Particle radiotherapy at a dose ≥60 gray‐equivalents appears to be safe and potentially effective.

Early results of the randomized, multicenter, controlled evaluation of S-1 and oxaliplatin as neoadjuvant chemotherapy for Chinese advanced gastric cancer patients (RESONANCE Trial).

280 Background: Perioperative chemotherapy brings potential benefits to growing patients with gastric cancer based on several clinical trials including MAGIC, ACTS-GC, CLASSIC and INT-0116. However, the effect of neoadjuvant therapy before D2 gastrectomy remains pending. According to phase II clinical trials, SOX regimen as neoadjuvant chemotherapy is associated with increased rate of D2 lymph nodes dissection and R0 resection. We hypothesize that SOX regimen can improve survival of patients with gastric cancer. Methods: Through CT, EUS and laparoscopic exploration, patients with gastric cancer on the stage IIA-IIIC were included in the study and divided into 2 groups randomly. Patients in neoadjuvant group received 2-4 cycles of SOX before surgery and 4-6 cycles after surgery, while patients in no neoadjuvant group received 8 cycles after surgery. The primary endpoint was 3-y DFS and the secondary endpoint were 5-y OS, ORR, D2/R0 resection rate and side effect. Results: A total of 772 patients were enrolled in the study between September 2012 and July 2019. After neoadjuvant therapy, the downstaging was found in neoadjuvant group (261/386, 67.6%). The pathological efficiency rate and pCR rate of neoadjuvant group were 67.8% and 23.6% respectively. The R0 resection rate in neoadjuvant group was significantly higher than that in adjuvant group(73.1% vs 58.1%, p &lt; 0.05). There was no difference in terms of surgical time, blood loss, postoperative complications and hospital stay. Conclusions: SOX makes increased rate of R0 resection, acceptable adverse effect and no impression on surgeries, which suggest that perioperative chemotherapy using SOX can prolong median survival time, DFS and OS. Clinical trial information: NCT01583361.

Estrogen Receptor Expression in Glial Tumors of Iranian Patients: A Single Center Experience.

Background & Objective:Gliomas are the most common type of primary intracranial tumors in adults. The expression of estrogen receptors varies in different grades of glial tumors, and some studies have suggested that this expression might have a prognostic value. It seems that estrogen receptor expression negatively correlates with the histological grade of gliomas. In the present study, we aimed to determine the expression of estrogen receptor in different glial tumors in Iranian patients and to find a possible correlation between its expression and the grade of glial tumorsMethods:The brain tumors pathology reports from 2014 to 2017 in the Pathology Department of Shohaday-e Tajrish Hospital in Tehran, Iran were evaluated and 104 different gliomas: 79 cases of astrocytoma and 25 cases of oligodendroglioma were selected. All the samples were re-evaluated by a neuropathologist in order to accurately determine the tumor grade. The immunohistochemistry was carried out to detect the expression of estrogen receptor alpha and beta on brain tumors.Results:None of the samples expressed estrogen receptor alpha. In the case of estrogen receptor beta (ERβ), all samples showed various degrees of positivity: 9% weak, 40% moderate, and 51% strong expressions. The level of ERβ expression was found to be conversely correlated with tumor grade.Conclusion:Our study demonstrated that ERβ is expressed in the majority (if not all) of the glial tumors and its expression was conversely related to the tumor grade. Because of well-tolerability and acceptable adverse effects, ER agonists might be considered as therapeutic agents for the patients with glial tumors.

Modulation of capecitabine administration to improve continuity of adjuvant chemotherapy for patients with colorectal cancer: A phase II study.

Adjuvant chemotherapy with capecitabine is frequently not completed due to adverse events, including hand-foot syndrome. A higher completion rate of capecitabine by reduction of the side effects may improve disease-free survival and quality of life of affected patients. In the present study, colorectal cancer (CRC) patients were treated with capecitabine (2,500 mg/m2/day), which was taken for five days, followed by an interval of two days (5-days-on/2-days-off schedule). One course lasted three weeks, and eight courses (24 weeks) were administered. The median number of treatment courses was significantly higher in patients in the 5-days-on/2-days-off regimen group compared with that of patients in the retrospectively included conventional regimen group (P=0.0438). The frequency of completion of the scheduled treatment by patients in the 5-days-on/2-days-off regimen group was significantly higher (P=0.0389). The present phase II study suggests that toxicities associated with the 5-days-on/2-days-off regimen are lower compared with those of the conventional regimen, and that the occurrence of adverse events was higher, but less high-grade toxicities were reported. The time to treatment failure was also favorable in the new regimen and it demonstrated good feasibility. In conclusion, the present study demonstrated good feasibility with retained quality of life and acceptable adverse effects (mostly low-grade), and the 5-days-on/2-days-off regimen should be further evaluated in future randomized controlled trials. The present study was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (no. UMIN000012813).

Imatinib in Children with Chronic Myeloid Leukemia in Chronic Phase: Long-Term Results of the French National Phase IV Trial

Because of the rarity of Chronic Myeloid Leukemia (CML) in children and adolescents, only few studies reported on efficacity and tolerance of imatinib in the pediatric population and scant data are available regarding long-term follow-up. The aim of our analysis was to assess, the long-term efficacity and safety of imatinib in children with CML in early chronic phase included in the French multicentric prospective Glivec Phase IV trial (Millot et al, J Clin Oncol 2011). Methods: Children aged 0 to 18 years with newly diagnosis CML in chronic phase were eligible to received daily imatinib 260 mg/m² according the trial. Long-term analysis included overall survival (OS), progression-free survival (PFS), response to treatment and adverse events. Results: Between March 2004 and December 2008, 44 patients (median age 13.4 years; range 0.8 - 16.7 years) were included in the trial. As of April 2019, with a median follow-up of 10.6 years (range 1.8 - 13.4 years), 2 patients (pts) progressed to blastic crisis and only one death was recorded. The median age was 21.8 years (range 9.3 - 28.8 years) at the last follow-up. The median duration of imatinib therapy was 10.5 years (range 0.2 - 12.5 years) for the entire cohort. To date, 13 pts (29.5%) are still treated with imatinib. Thirty-one pts (70.5%) had discontinued first line treatment with imatinib after a median time of treatment of 2.4 years (range 0.2 - 10.6 years) for the following reasons: 10 pts did not achieve major molecular response (MMR), 1 pt developed blast crisis, 2 pts had unsatisfactory level of molecular response (MR) according to the clinician, 10 pts lost their response (loss of complete hematological response n=1, complete cytogenetic response [CCR] n=6 and MMR n=3), 4 pts attempted treatment free remission (TFR), 3 pts were intolerant to imatinib and 1 pt stopped because of pregnancy. Among these 31 pts who discontinued imatinib, 2 pts are still in TFR, and 29 pts switched to a second line therapy: second generation tyrosine kinase inhibitors (2TKI) (n=25), allogeneic hematopoietic stem cell transplantation (HSCT) (n=3), polychemotherapy (n=1). Sixteen of these 31 pts (51.6%) required subsequent lines of therapy including a second pt who transformed to blastic crisis under a second line therapy with dasatinib. Overall 11 pts (25%) underwent HSCT. Overall, regarding the best response, during the study follow-up 11 pts (25%) achieved MMR after a median time of 2.3 years (range 0.8-5.1), 7 pts (13.6%) achieved MR4 after a median time of 5.1 years (range 2.5-7.8), 25 pts (56.8%) achieved MR4.5 after a median time of 2.92 years (range 1.1-10.4) and 1 pt (2.3%) achieved CCR only. At last follow-up, 43 out the 44 pts were alive : 3 pts (7%) were in CCR, 12 pts (27.9%) in MMR, 6 pts (13.9%) in MR4 and 22 pts (51.2%) in MR4.5. Among the 13 pts still treated with imatinib, 1 pt (7.7%) was in CCR, 6 pts (14%) in MMR, 3 pts (23.1%) were in MR4 and 3 pts (23.1%) in MR4.5. Among the 11 transplanted patients, all pts except one are alive, in at least MR4.5. The death was related to post transplant infection. On an intention to treat basis, the 10-year OS of 44 patients treated was 97.7% (CI 95% 93.3-100). The 10-year PFS was 95.5% (CI 95% 89.3-100). We collected also the long-term safety of imatinib in the 25 pts who have received this therapy for more than 4 years. Newly occurring or worsening grade 3 or 4 hematologic or biochemical adverse events were infrequent after 4 years of imatinib. There is a decrease in the frequency of hematologic and extra hematologic sides effects reported during the first year and those reported after the fourth year of treatment with imatinib: musculoskeletal events 80 vs 24% (p&lt;0,0001), abdominal pain 44% vs 16% (p=0,03), nausea 48% vs 16% (p=0,02), diarrhea 24% vs 0% (p=0,01) and neutropenia 84% vs 28% (p&lt;0,0001), respectively. Conversely, the incidence of lymphopenia appeared with duration of imatinib treatment (p=0,04). Conclusion: With more than 10 years of follow-up, we showed that imatinib remains effective in one third of children included in the Glivec phase IV study with acceptable adverse effects and a low impact over time. Despite the notable proportion of switches, the OS and the PFS remain satisfactory in this pediatric cohort. Disclosures No relevant conflicts of interest to declare.