We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would ...differ from primary mucosal melanomas at different anatomical sites.
Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites.
The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%,P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%,P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively.
The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.
No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to ...compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM.
From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety.
After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 95% confidence interval (CI) 8.31-19.02 months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms hazard ratio (HR) 1.00; 95% CI 0.65-1.54. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients’ actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%).
Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.
•This is the first study to compare toripalimab versus HDI as adjuvant therapy for resected MM.•In PD-L1-positive patients, the median RFS was ∼6 months longer in the toripalimab arm than in the HDI arm.•The incidence of TEAEs with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm.•Both interventions have potential for MM; toripalimab might be the better treatment option.
Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the ...efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC.
Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib 50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle). The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety.
A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028. The median PFS was 18.0 months in the toripalimab–axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab–axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab–axitinib group and 58.6% of patients in the sunitinib group.
In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile
ClinicalTrials.gov NCT04394975
•Toripalimab plus axitinib provided significantly better PFS than sunitinib as a first-line treatment for advanced RCC.•A significantly higher ORR was found in patients who received toripalimab plus axitinib than those who received sunitinib.•The combination of toripalimab plus axitinib was generally well tolerated.•No new safety signals were identified in the combination outside the known safety profile of toripalimab or axitinib.
To compare diagnostic value of two-dimensional (2D) ultrasonography and elastosonography for suspected axillary lymph node metastasis of breast cancer.
Elastosonography and 2D ultrasonography were ...performed on 78 axillary lymph nodes of 78 patients with suspected breast cancer. Scores of shape, long- to short-axis ratio, cortical thickness, and lymph node hilum were summed as the score of each lymph node at 2D ultrasonography, while a four-point scale was adopted for elasticity scoring. The combined score of each lymph node was obtained by summing the score at 2D ultrasonography and that at elasticity scoring. The strain ratio was calculated by comparison of the average strain of the lymph node with that of the subcutaneous tissue. Diagnostic efficacies of 2D ultrasonography, elasticity scoring, and the combined method were compared.
There were 78 axillary lymph nodes, including 34 non-metastatic and 44 metastatic nodes. The elasticity scores of non-metastatic and metastatic axillary lymph nodes were 1.44±0.82 and 3.11±0.75, respectively (p<0.05). The difference in area under the operating characteristic curve (AUC) was statistically significant between 2D ultrasonography and the combined method (p<0.05). The sensitivity, specificity, and accuracy of 2D ultrasonography and elasticity scoring were 77.3% versus 86.4%, 76.5% versus 85.3%, and 76.9% versus 85.9%, respectively (all p>0.05), and those of the combined method were 93.2%, 73.5%, and 84.6%, respectively. There was a significant difference in sensitivity between 2D ultrasonography and the combined method (p<0.05).
Combined application of 2D ultrasonography with elastosonography can improve the diagnostic capability for metastatic axillary lymph node characterisation in breast cancer.
•We compared diagnostic value for suspected metastatic axillary lymph node in breast cancer with 2D ultrasonography and elastosonography.•Scores in shape, long- to short-axis ratio, cortical thickness and hilum of lymph node were summed up as the score of each lymph node in 2D ultrasonography, while the 4-point scale was adopted for elasticity scoring.•There was a significant difference in sensitivity between 2D ultrasonography and the combined method in differentiating metastatic from non-metatstatic nodes (P<0.05).•Combined application of 2D ultrasonography with elastosonography can improve the diagnostic value for metastatic axillary lymph node in breast cancer.
Elevated levels of circulating triglycerides and increased arterial stiffness are associated with cardiovascular disease. Numerous studies have reported an association between levels of circulating ...triglycerides and arterial stiffness. We used Mendelian randomization to test whether this association is causal. We investigated the association between circulating triglyceride levels, the apolipoprotein A-V (ApoA5) -1131T>C single nucleotide polymorphism and brachial-ankle pulse wave velocity (baPWV) by examining data from 4421 subjects aged 18-74 years who were recruited from the Chinese population. baPWV was significantly associated with the levels of circulating triglycerides after adjusting for age, sex, body mass index (BMI), systolic blood pressure, heart rate, waist-to-hip ratio, antihypertensive treatment and diabetes mellitus status. The -1131C allele was associated with a 5% (95% confidence interval 3-8%) increase in circulating triglycerides (adjusted for age, sex, BMI, waist-to-hip ratio, diabetes mellitus and antihypertensive treatment). Instrumental variable analysis showed that genetically elevated levels of circulating triglycerides were not associated with increased baPWV. These results do not support the hypothesis that levels of circulating triglycerides have a causal role in the development of arterial stiffness.
To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma.
Clinical data of 50 patients with advanced renal cell carcinoma who ...received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed.
Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95%
5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated trans
To investigate the efficacy and the influence factors of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma (mRCC).
Clinical data of mRCC patients with sunitinib ...administered as the first line treatment from August 2008 to December 2015 were retrospectively reviewed. The efficacy and the influence factors of sunitinib treatment was analyzed using the Kaplan-Meier method and Cox proportional hazards models.
In all 166 patients who received sunitinib as first-line treatment, objective response rate was 31.9%, disease control rate was 84.3%. The median progression free survival (PFS) and overall survival (OS) were 11.0 months (95%
9.0-14.0) and 28.0 months (95%
19.0-33.0), respectively. Multivariate analysis showed that pathological types (clear cell carcinoma vs non clear cell carcinoma,
: 1.889 vs 2.353), time from diagnosis to treatment(<1 year vs ≥1 year,
: 0.293 vs 0.322) and the number of metastatic sites (1 vs ≥1,
: 2.360 vs 4.351) were the independent prognostic factors fo
Persistent and impaired inflammation impedes tissue healing and is a characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. In this ...study, we show that in human wound-edge keratinocytes, the expressions of microRNA (miR)-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, are upregulated during wound repair. However, their levels are lower in chronic ulcers than in acute wounds at the proliferative phase. Conditional knockout of miR-17∼92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17∼92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines and cytokines by keratinocytes. Thus, miR-19a/b and miR-20a being crucial regulators of wound inflammation, the lack thereof may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes.
The association between telomere length (TL) in peripheral blood cells and cancer risk remains inconclusive. We carried out a meta-analysis on prospective studies. The study-specific RR estimates ...were first transformed to a common comparable scale and then were pooled by a random-effects model. The dataset was composed of 13,894 cases and 71,672 controls from 28 studies in 25 articles. In the comparison of the longest versus shortest third of TL, we observed a marginally positive association between longer TL and higher risk of total cancers OR = 1.086; 95% confidence interval (CI), 0.952-1.238. Subgroup analyses showed that the association was stronger in lung cancer (
= 3; OR = 1.690; 95% CI, 1.253-2.280), in men (
= 6; OR = 1.302; 95% CI, 1.120-1.514) and in studies with more precise methods for DNA extraction (phenol-chloroform, salting-out or magnetic bead,
= 6, OR = 1.618; 95% CI, 1.320-1.985) and TL measurement (multiplex Q-PCR,
= 8; OR = 1.439; 95% CI, 1.118-1.852). Our meta-analysis suggested longer TL in peripheral blood cells is a likely risk factor for lung cancer or cancers in men. Accurate DNA extraction and TL measurement methods make it more liable to find significant associations between TL and cancer risk and thus should be taken into consideration in future epidemiologic studies.
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