Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies.
To explore the effect of ...screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability.
Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only.
A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively.
The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.
Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We ...investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor specimens, including surrogate biomarkers of the HCC immune class (based on intratumoral tertiary lymphoid structures, and glutamine synthase, CD3, and CD79 expression); and (ii) the relationship between HIRAE onset and subsequent treatment outcomes. Fifty-eight patients were included—20 (34%) received ICIs alone, and 38 (66%) received ICIs plus targeted agents as first- or further-line treatment. After a median time of 0.9 months (range, 0.4–2.7), nine patients (15.5%) developed grade ≥ 3 hepatitis, which was significantly associated with higher baseline ALT levels (p = 0.037), and an infectious HCC etiology (p = 0.023). ICIs were safely resumed in six out of nine patients. Time to treatment failure (TTF) was not significantly different in patients developing grade ≥ 3 hepatitis vs. lower grades (3.25 vs. 3.91 months, respectively; p = 0.81). Biomarker surrogates for the HCC immune class were not detected in patients developing grade ≥ 3 hepatitis. Grade ≥ 3 hepatitis has a benign course that does not preclude safe ICI reintroduction, without any detrimental effect on TTF.
Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung ...Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting.
To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates.
Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion.
A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%) had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer, with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000 person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per 100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993; 95% confidence interval, 0.688-1.433).
Because of its limited statistical power, the results of the DANTE (Detection And screening of early lung cancer with Novel imaging TEchnology) trial do not allow us to make a definitive statement about the efficacy of LDCT screening. However, they underline the importance of obtaining additional data from randomized trials with intervention-free reference arms before the implementation of population screening.
Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific ...subgroups of patients with soft tissue sarcomas (STS).
Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m(2) every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS).
Median age was 48 (range, 20-75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0-5). Median number of trabectedin cycles was 3 (range, 1-17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2-23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively.
Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma.
Background.
Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced ...radiologic disease progression was investigated.
Methods.
Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression‐free survival (PFS). Time to progression, overall survival, and safety were also evaluated.
Results.
The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1–2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand‐foot‐skin reaction (49%), abdominal pain (37%), and stomatitis (26%).
Conclusions.
Escalated‐dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second‐line treatment still remains an open issue to be explored in appropriate clinical trials.
摘要
背景 经证实,索拉非尼可以提高晚期肝细胞型肝癌(HCC)患者的生存率。本研究旨在探讨,在出现放射学进展的患者中继续以更高剂量使用索拉非尼的可行性。
方法 将每天接受索拉非尼400 mg bid但仍然出现疾病进展的患者随机分为两组,分别接受以下治疗:索拉非尼 600 mg bid (n = 49) 和最佳支持治疗 (n = 52)。本研究的主要终点是无进展生存期(PFS)。本研究也评估了至进展时间、总生存率以及治疗安全性。
结果 本研究并未达到主要终点。索拉非尼组(3.91个月)与最佳支持治疗组(2.69 个月)的 PFS并不存在显著的统计学差异 (p =0.086)。两组的不良事件基本相似,以1∼2级为主。在索拉非尼组中,最常出现的不良事件包括腹泻(80%)、体重减轻 (75%)、疲乏 (67%)、手足皮肤反应(49%)、腹痛 (37%) 以及口腔炎 (26%)。
结论 对于在接受索拉非尼治疗期间出现疾病进展的晚期HCC 患者而言,进行索拉非尼剂量递增治疗并不能提供任何临床益处。二线治疗仍旧是一个尚无定论的问题,需要在合适的临床试验中进一步探讨。
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Background: Sarcopenia is a loss of skeletal muscle mass that has been studied as prognostic factor in several cancers. Retrospective studies have suggested that sarcopenia is ...associated with poorer survival outcomes and with an increase of major chemotherapy toxicities resulting in dose reduction and delay. This study examined the value of sarcopenia in patients with stage III non-small cell lung cancer (NSCLC). Methods: This retrospective analysis includes 68 patients affected by stage III NSCLC treated with induction chemotherapy followed by surgery or radical radiation therapy in our cancer center. Weight and height were obtained from medical records at diagnosis. Skeletal muscle index (SMI) was measured by the analysis of electronically stored computed tomography images obtained before the start of chemotherapy; sarcopenia was defined by international consensus as a SMI≤39 cm2/m2 for women and ≤55 cm2/m2 for men. Kaplan-Meier method and Log-Rank test were used to determine the impact of sarcopenia on overall survival (OS) and progression-free survival (PFS). Exact Fisher test and Chi-squared test were used to establish the association between the presence of sarcopenia and other variables. Results: A total of 68 patients (stage 3A = 39; stage 3B = 29) with performance status 0-1 and median age 67 yrs were analyzed. Forty-five patients (66%) were sarcopenic: 100% of underweight patients (BMI ≤18.5), 83% of patients with normal weight (BMI 18.5-24.9), 56% of overweight patients (BMI 25-29.9) and 30% of obese (BMI≥30). Sarcopenia was not associated with age≥70 yrs (p = 0.67), Charlson Comorbidity Index (p = 1.00), stage (p = 0.53), response rate to chemotherapy (p = 0.78) or toxicities of grade≥3 (p = 0.83). Median OS in sarcopenic patients was 18.2 months compared with 33.2 months in nonsarcopenic patients (p = 0.03); the difference in terms of PFS was not statistically significant (10.7 vs 14.9 months; p = 0.19). Conclusions: Sarcopenia is associated with shorter OS in patients with locally advanced NSCLC but it seems not related with worse response to induction chemotherapy or higher toxicities. These data should be validated in larger prospective clinical studies.