Notes

Evaluation of Elafin like a Prognostic Biomarker in Serious Graft-versus-Host Condition.
Urothelial carcinoma (UC) is a common malignancy of the lower and upper urinary tract. Recurrent UC has poor prognosis due to delayed diagnosis and a lack of clinical management guidance, especially for upper urinary tract UC. Patients with germline or somatic BRCA1/2 mutations are a special population in UC. No evidence is available so far on the effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) in this population. Here, we report a 60-year-old female patient diagnosed with left ureter high-grade UC. Recurrent lesions were found 20 months after radical surgery. Computed tomography (CT) examination showed a slightly high-density soft tissue mass (3.2 × 3.1 cm) on the left posterior wall of the abdomen (waist), soft tissue mass adjacent to the left inner wall of the pelvis (3.2 × 4.2 cm), and multiple enlarged lymph nodes to the left of abdominal aorta. A next-generation sequencing (NGS)-based 605-gene panel detected a novel BRCA2 pathogenic germline mutation c.1670T>A (p.L557*), and a series of somatic insertion and deletion (INDEL) mutations of BRCA1, RB1, and JAK2, and single nucleotide variation (SNV) mutations of TP53, KMT2D, MET, ROS1, and IL7R. The above lesions were reduced significantly or disappeared (partial response, PR) after a 3-month Olaparib treatment, and the patient's general condition remained well. In conclusion, this study proved for the first time that PARPi was effective for UC treatment in patients carrying germline BRCA2 pathogenic mutations, providing new treatment options for such patients. In addition, the circulating tumor DNA (ctDNA) test can be used for drug selection and response monitoring in UC treatment.
To study the efficacy and toxicity of irinotecan combined with oxaliplatin and S-1 in patients with metastatic pancreatic adenocarcinoma.

Previously untreated patients with cytologically or histologically confirmed metastatic pancreatic adenocarcinoma underwent a treatment regimen consisting of an intravenous infusion of irinotecan 165 mg/m
and oxaliplatin 85 mg/m
on day 1, and oral S-1 40 mg/m
twice daily on days 1-14, repeating the regimen every 21 days until one of the following occurred disease progression, intolerable toxicity, or patient death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate, toxicity, and quality of life. This ongoing study had been registered on ClinicalTrials.gov, NCT03726021.

A total of 41 patients were enrolled in this study, 18 men and 23 women. The median PFS was 4.33 months [95% confidence interval (CI) 2.83-5.88] and the median OS was 11.00 months (95% CI 9.16-12.84). There were no instances of a complete response; the partial response, stable disease, and disease progression rates were 39.02% (16/41), 29.27% (12/41), and 31.71% (13/41), respectively.The most common adverse side effects were mild to moderate nausea, vomiting, neutropenia, and thrombocytopenia. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 29.27% (12/41) and 12.20% (5/41) of the patients, respectively. No treatment-related death was observed.

Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. Selleck CNQX A larger study population is needed for further evaluation.
Irinotecan combined with oxaliplatin and S-1 is a safe and effective treatment for metastatic pancreatic adenocarcinoma, and any toxicities are mild to moderate and tolerable. A larger study population is needed for further evaluation.
Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT.

Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1-6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1.

A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240
<240 (1.34-2.77),
 < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDH
LDH
) were associated with tumour response [partial response
progressive disease median value across CT1-6 = 168-190
222-398 (absolute); 0.738-0.988
1.039-1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65-0.80)].

Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.
Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.
We explored the effect of teriflunomide on cortical gray matter (CGM) and whole brain (WB) atrophy in patients with clinically isolated syndrome (CIS) from the phase III TOPIC study and assessed the relationship between atrophy and risk of conversion to clinically definite MS (CDMS).

Patients (per McDonald 2005 criteria) were randomized 111 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ⩽108 weeks (core study). In the extension, teriflunomide-treated patients maintained their original dose; placebo-treated patients were re-randomized 11 to teriflunomide 7 mg or 14 mg. Brain volume was assessed during years 1-2.

Teriflunomide 14 mg significantly slowed annualized CGM and WB atrophy
placebo during years 1-2 [percent reduction month 12, 61.4% (CGM;
= 0.0359) and 28.6% (WB;
 = 0.0286); month 24, 40.2% (CGM;
= 0.0416) and 43.0% (WB;
< 0.0001)]. For every 1% decrease in CGM or WB volume during years 1-2, risk of CDMS conversion increased by 14.5% (
=
0.0004) and 47.3% (
< 0.0001) during years 1-2, respectively, and 6.
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