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141.

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Patients and Methods

We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.

Results

Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.

Conclusions

FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.  相似文献   
142.
Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO2 laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.  相似文献   
143.
Harinakshi Sanikini  David C. Muller  Marisa Sophiea  Sabina Rinaldi  Antonio Agudo  Eric J. Duell  Elisabete Weiderpass  Kim Overvad  Anne Tjønneland  Jytte Halkjær  Marie-Christine Boutron-Ruault  Franck Carbonnel  Iris Cervenka  Heiner Boeing  Rudolf Kaaks  Tilman Kühn  Antonia Trichopoulou  Georgia Martimianaki  Anna Karakatsani  Valeria Pala  Domenico Palli  Amalia Mattiello  Rosario Tumino  Carlotta Sacerdote  Guri Skeie  Charlotta Rylander  María-Dolores Chirlaque López  Maria-Jose Sánchez  Eva Ardanaz  Sara Regnér  Tanja Stocks  Bas Bueno-de-Mesquita  Roel C.H. Vermeulen  Dagfinn Aune  Tammy Y.N. Tong  Nathalie Kliemann  Neil Murphy  Marc Chadeau-Hyam  Marc J. Gunter  Amanda J. Cross 《International journal of cancer. Journal international du cancer》2020,146(4):929-942
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.  相似文献   
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