Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Metastasis of oral squamous cell carcinoma to the parotid lymph nodes

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.     

Thinned-out skin paddle versus collagen matrix as an optimized peri-implant soft tissue following fibula osteoseptocutaneous free flap: 3-year retrospective study

The objective of this study was to compare the implant longevity following two methods of peri-implant soft tissue optimization following free fibula flap (FFF): thinning of skin paddle (SP) and collagen matrix (CM). All patients who underwent rehabilitation with dental implants after mandibular reconstruction with FFF between June 2009 to May 2014 were retrospectively reviewed. Two methods of peri-implant soft tissue optimization were applied: (1) SP group, (2) CM group. Outcome measurements were: modified plaque index (mPI), modified sulcus bleeding index (mSBI), probing depth (PD), marginal bone loss (MBL), implant success rate and complication rates. A total of 24 patients with 69 implants were included in the study, with 8.7% (n = 6) of implants lost in 3 years. No statistically significant difference was found regarding the outcome measurements in both groups. Failed implants presented with statistically significant higher mPI, mSBI, PD and MBL scores during prosthesis delivery and subsequent follow-ups (P<0.03). In the SP group, one patient experienced SP necrosis which later underwent soft tissue optimization using CM. CM is an alternative peri-implant soft tissue, while thinning of SP is feasible if thickness is well controlled.     

经同侧腹直肌易位造口在腹腔镜造口旁疝修补术中的应用

目的分析经同侧腹直肌易位造口在腹腔镜造口旁疝修补术中的应用价值。 方法选取2016年8月至2017年12月，重庆市开州区中医院收治的60例乙状结肠造口旁疝患者，随机分为对照组和观察组，每组30例。对照组行开放造口旁疝修补术，观察组行腹腔镜经同侧腹直肌易位造口修补术。比较2组患者手术和住院情况、并发症发生率、复发率、远期疼痛发生率及切口疝发生率。 结果观察组患者感染发生率、并发症总发生率及复发率分别为0、16.67%及3.33%，明显低于对照组16.67%、43.33%及23.33%，差异有统计学意义（χ²=5.455、5.079、5.192，P=0.020、0.024、0.023）。观察组患者手术时间、住院费用分别为（131.05±12.11）min、（38 946.06±1 019.75）元均高于对照组（96.91±10.54）min、（18 492.19±572.36）元，差异有统计学意义（t=11.647、95.802，P均<0.001）。观察组患者术中出血量、术后下床活动时间及术后恢复活动时间分别为（33.14±8.06）ml、（1.26±0.51）d、（3.59±1.17）d均低于对照组（69.28±9.18）ml、（2.27±1.02）d、（5.44±2.25）d，差异有统计学意义（t=16.204、4.851、3.996，P均<0.001）。 结论经同侧腹直肌易位造口在腹腔镜造口旁疝修补术中应用效果较好，能够有效改善乙状结肠造口旁疝患者手术情况及住院情况，减少术后并发症的发生和疝复发。     

Interdiction de vente de tabac aux mineurs en France et au Québec. Comparaison du cadre législatif,de son application,et du tabagisme des adolescents

Background

Prohibition of tobacco sales to minors is a provision of the World Health Organization Framework Convention on tobacco control. This measure is effective to reduce youth tobacco use, if the legislation adopted is properly implemented and enforced. Through the examples of France and Quebec, the objective of this study is to compare legislative frameworks prohibiting tobacco sales to minors, their enforcement, and possible impact on underage smoking.