A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

中国抗癌协会神经内分泌肿瘤诊治指南（2022年版）

神经内分泌肿瘤（neuroendocrine neoplasm,NEN）是一类起源于肽能神经元和神经内分泌细胞,具有神经内分泌分化并表达神经内分泌标志物的少见肿瘤,可发生于全身各处,以肺及胃肠胰NEN（gastroenteropancreatic neuroendocrine neoplasm, GEP-NEN）最常见。国内外研究数据均提示,NEN的发病率在不断上升。美国流行病学调查结果显示,与其他类型肿瘤相比,NEN的发病率上升趋势更为显著。中国抗癌协会神经内分泌肿瘤专委会在现有循证医学证据基础上,结合已有国内外指南和共识,制订了首版中国抗癌协会神经内分泌肿瘤诊治指南,为临床工作者提供参考。     

Étude de faisabilité : l’utilisation de l’imagerie médicale en éducation thérapeutique en radiothérapie

PurposeAssess the feasibility of a randomized controlled trial (RCT) exploring the use of medical imaging as a therapeutic education (TPE) intervention in external radiation therapy.Materials and methodsExperimental feasibility trial of “RCT” type carried out in a single-center, between November 2019 and March 2020, following adult patients treated by thoracic radiotherapy. In addition to the information usually given, the experimental group benefited from an intervention consisting in the visualization of their own medical images using the open-source software “Stone of Orthanc”.ResultsForty-nine patients were recruited with a refusal rate of 8.16% (4/49). 20 patients were withdrawn from the study for health reasons (COVID), 10 for medical reasons. All the remaining 15 participants completed the process. Although not significant, the experimental group showed a median gain in the perception of knowledge compared to the control group (+ 1.9 (1.6 – 2.2)) vs (+ 1.4 (1.4 – 1.8)), as well as a decrease in scores related to anxiety (? 3.0 (?4.5 - (?2.0)) vs ? 1.0 (?5.0 - 0.0)) and emotional distress ((? 5.0 (? 7.5 - (? 3.5)) vs (? 2.0 (? 5.0 - (? 1.0)) A significant reduction (p = 0.043) is observed for the depression score ((? 2.0 (?3.0 - (?1.5)) vs (0.0 (0.0 – 0.0)).ConclusionThis study demonstrates the feasibility of the project, with promising preliminary results. Some adaptations in order to conduct a larger-scale RCT are highlighted.     

Morphological imaging and CT histogram analysis to differentiate pancreatic neuroendocrine tumor grade 3 from neuroendocrine carcinoma

PurposeTo compare morphological imaging features and CT texture histogram parameters between grade 3 pancreatic neuroendocrine tumors (G3-NET) and neuroendocrine carcinomas (NEC).Materials and methodsPatients with pathologically proven G3-NET and NEC, according to the 2017 World Health Organization classification who had CT and MRI examinations between 2006-2017 were retrospectively included. CT and MRI examinations were reviewed by two radiologists in consensus and analyzed with respect to tumor size, enhancement patterns, hemorrhagic content, liver metastases and lymphadenopathies. Texture histogram analysis of tumors was performed on arterial and portal phase CT images. images. Morphological imaging features and CT texture histogram parameters of G3-NETs and NECs were compared.ResultsThirty-seven patients (21 men, 16 women; mean age, 56 ± 13 [SD] years [range: 28-82 years]) with 37 tumors (mean diameter, 60 ± 46 [SD] mm) were included (CT available for all, MRI for 16/37, 43%). Twenty-three patients (23/37; 62%) had NEC and 14 patients (14/37; 38%) had G3-NET. NECs were larger than G3-NETs (mean, 70 ± 51 [SD] mm [range: 18 - 196 mm] vs. 42 ± 24 [SD] mm [range: 8 - 94 mm], respectively; P = 0.039), with more tumor necrosis (75% vs. 33%, respectively; P = 0.030) and lower attenuation on precontrast (30 ± 4 [SD] HU [range: 25-39 HU] vs. 37 ± 6 [SD] [range: 25-45 HU], respectively; P = 0.002) and on portal venous phase CT images (75 ± 18 [SD] HU [range: 43 - 108 HU] vs. 92 ± 19 [SD] HU [range: 46 - 117 HU], respectively; P = 0.014). Hemorrhagic content on MRI was only observed in NEC (P = 0.007). The mean ADC value was lower in NEC ([1.1 ± 0.1 (SD)] × 10⁻³ mm²/s [range: (0.91 - 1.3) × 10⁻³ mm²/s] vs. [1.4 ± 0.2 (SD)] × 10⁻³ mm²/s [range: (1.1 - 1.6) × 10⁻³ mm²/s]; P = 0.005). CT histogram analysis showed that NEC were more heterogeneous on portal venous phase images (Entropy-0: 4.7 ± 0.2 [SD] [range: 4.2-5.1] vs. 4.5 ± 0.4 [SD] [range: 3.7-4.9]; P = 0.023).ConclusionPancreatic NECs are larger, more frequently hypoattenuating and more heterogeneous with hemorrhagic content than G3-NET on CT and MRI.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.     

头颈部恶性肿瘤嗜神经侵袭临床诊治现状

嗜神经侵袭是肿瘤通过神经扩散与转移的一种独特的生物学行为,与复发、转移、预后密切相关。随着研究的不断深入,人们普遍认识到嗜神经侵袭的临床意义。但由于头颈部肿瘤发病率相对较低,不同解剖部位、不同病理类型嗜神经发生率各不相同,故缺乏高级别的循证医学证据。目前嗜神经侵袭的病理学机制尚未完全阐明,也无针对神经侵犯的特异性治疗手段,因此头颈部肿瘤嗜神经侵袭的治疗对于临床医师是一个巨大的挑战。本文就头颈部恶性肿瘤中嗜神经侵袭的临床诊治现状做一综述。     

Islanded facial artery osteomyomucosal/osseous flap in head and neck reconstruction

A local pedicled vascularized bone flap can prevent the morbidity and cost of free bone flap surgery in small segmental bone defects or long cartilaginous defects of the head and neck. Such flaps can also be useful in patients who are high risk for surgery. The periosteal vascularity of the mandible can be used to design islanded facial artery-based bone flaps, which can be utilized to that extent. Two patients with a small segmental mandibulectomy defect and one patient with a long cricotracheal resection defect underwent reconstruction using three different designs of islanded facial artery osteomyomucosal/osseous flap (iFOMM). The patients had a minimum follow-up period of 18 months. All flaps were successful, with satisfactory healing and without any functional deficit or disease at last follow-up.