Cancer treatment and research communications最新文献

Objectives

Endometrial cancer is a collection of heterogeneous histologies and molecular subtypes with different risk profiles. High-risk endometrial cancer surveillance regimens vary amongst providers. The National Comprehensive Cancer Network (NCCN) recommends symptom and exam-based surveillance for all endometrial cancers after remission, regardless of cancer stage and histology. Our objective was to identify the first method of detection of recurrence in high-risk endometrial cancers and examine disease recurrence and treatment patterns.

Methods

A retrospective review of patients diagnosed with high-risk endometrial cancer between November 2013 and February 2020 was conducted at a large academic institution. High-risk endometrial cancers were classified by histology and pathologic stage and were categorized by primary method of detection.

Results

Two hundred and twenty-nine patients were identified with high-risk endometrial cancer, 63 (28 %) of whom had a recurrence. Most recurrences were first detected with routine imaging in 31 patients (49.2 %) and symptom surveillance in 24 patients (38.15 %). Regardless of the detection method, most patients underwent systemic treatment. The average survival after recurrence was 2.0 years in the imaging cohort and 1.6 years in the non-imaging surveillance cohort.

Conclusions

The most common site of recurrence in our cohort of high-risk endometrial cancer was in the lung, and most recurrences were identified with asymptomatic imaging. Though there was no statistically significant difference between the survival of those who underwent imaging surveillance vs. standard of care, there was a trend toward survival that deems further exploration with a larger cohort.

Background & Aims

Accumulating evidence showed that inflammation contributes markedly to cancer progression, with C-reactive protein (CRP) being one of the lengthily studied inflammation marker. For breast cancer (BCa), pre-treatment elevated CRP upon diagnosis was linked with increased mortality. This study aimed to identify factors predictive of elevated CRP in pre-treatment BCa population that can serve as potential therapeutic targets to reduce inflammation.

Methods

This is a cross-sectional study using multiple logistic regression to identify predictors of elevated CRP among pre-treatment, newly diagnosed BCa patients. Studied variables were socio-demographic and medical characteristics, anthropometric measurements [body weight, Body Mass Index, body fat percentage, fat mass/fat free mass ratio, muscle mass, visceral fat], biochemical parameters [albumin, hemoglobin, white blood cell (WBC), neutrophil, lymphocyte], energy-adjusted Dietary Inflammatory Index, handgrip strength (HGS), scored Patient Generated-Subjective Global Assessment, physical activity level and perceived stress scale (PSS).

Results

A total of 105 participants took part in this study. Significant predictors of elevated CRP were body fat percentage (OR 1.222; 95 % CI 1.099–1.358; p < 0.001), PSS (OR 1.120; 95 % CI 1.026–1.223; p = 0.011), low vs normal HGS (OR 41.928; 95 % CI 2.155–815.728; p = 0.014), albumin (OR 0.779; 95 % CI 0.632–0.960; p = 0.019), and WBC (OR 1.418; 95% CI 1.024–1.963; p = 0.036).

Conclusion

Overall, predictors of elevated CRP in pre-treatment, newly diagnosed BCa population were body fat percentage, PSS, HGS category, albumin and WBC.

Objectives

The incidence of cervical cancer increases every year during pregnancy. Cervical cytology in pregnant women has a unique morphology and liquid-based cytology methods are prone to cause false positives. The aim of this study was to investigate the serum cytokeratin 19 fragment antigen 21–1 (CYFRA21–1) and squamous cell carcinoma associated antigen (SCC-Ag) concentrations in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.

Methods

In this prospective study, 165 healthy non-pregnant women, 441 healthy pregnant women and 22 patients with cervical cancer in pregnancy were recruited. The healthy pregnant women group included 143 women in the first trimester (T1), 147 in the second (T2) and 151 in the third (T3).

Results

Both SCC-Ag and CYFRA21–1 levels were significantly different in the healthy pregnant women group compared to the control group. The CYFRA21–1 and SCC-Ag were higher in the T1 and T3 than in the control groups. However, there was no statistically significant difference in serum CYFRA21–1 and SCC-Ag levels in the T2 group compared to the control group. The AUCs of CYFRA21–1, SCC-Ag and CYFRA21–1 combined with SCC-Ag were 0.674, 0.792, and 0.805, respectively. The cut-off values of CYFRA21–1 and SCC-Ag were 6.64 ng/mL and 1.75 ng/mL, respectively.

Conclusions

Serum CYFRA21–1 and SCC-Ag levels were higher in pregnant women during early and late pregnancy compared to non-pregnant individuals, while they were not statistically different from non-pregnant women during mid-trimester. CYFRA21–1 and SCC-Ag have diagnostic value for cervical cancer in pregnancy.

Introduction

We aimed to assess the safety, pharmacokinetic profile, and antitumor activity of adavosertib monotherapy in Japanese patients with advanced solid tumors.

Materials and methods

This was a single-center, open-label, phase I study with two consecutive cohorts (250 mg and 200 mg cohorts). Patients received adavosertib at 250 mg or 200 mg, orally once daily for 5 days on and 2 days off for Weeks 1 and 2 of a 21-day cycle.

Results

Dose-limiting toxicities (Grade 3 febrile neutropenia) occurred in 2/6 patients in the 250 mg cohort. None of the three patients in the 200 mg cohort developed dose-limiting toxicities. The most frequent treatment-emergent adverse event was nausea (250 mg: 83.3 %; 200 mg: 100.0 %). Median time to peak drug concentration was 4.03 and 2.08 h after the first dose and 2.82 and 1.90 h after multiple dosing in the 250 and 200 mg cohorts, respectively; respective mean terminal elimination half-lives were 7.36 and 7.30 h (first dose) and 10.55 and 8.88 h (multiple dosing). Systemic exposure increased in a slightly more than dose-proportional manner. No RECIST v1.1 response was observed. Disease control rate was 0 % and 33.3 % in the 250 and 200 mg cohorts, respectively. One patient (33.3 %) in the 200 mg cohort showed a best overall response of stable disease at ≥ 8 weeks; the rest showed progressive disease.

Conclusions

Adavosertib 200 mg once daily was well tolerated in this patient population and no safety concerns were raised. Exposure increased in a slightly more than dose-proportional manner and limited antitumor activity was shown.

Trial registration

ClinicalTrials.gov, NCT04462952

Purpose

This study aims to evaluate the association between surgical margin status and local recurrence of DCIS.

Methods

A retrospective analysis of a prospectively maintained 20-year DCIS database was performed. >=2 mm margin was defined as clear margin. Local relapse rate between the patients with clear versus close margins were analyzed with Kaplan-Meier analyses.

Results

654 patients were analyzed. Median age was 46.5 (Range 18 – 80). 205 (31.3%) were high grade, 194 (29.7%) were intermediate grade, 143 (21.9%) were low grade. 112 (18.3%) were unknown. 202 (30.9%) were estrogen receptor positive, 49 (7.4%) were negative, 403 (61.6%) patients were unknown.

403 (61.6%) patients received mastectomy while 251 (38.4%) patients received BCS and radiotherapy. 549 (83.9%) patients had clear surgical margin, 50 (7.7%) patients had involved (positive) resection margin, 55 (8.4%) had close margin (<2 mm margin). All patients with involved margin received re-excision of margin, while 21 patients (out of 55 who had close resection margins) received re-excision of margin. Negative surgical margins were achieved after the re-excision. 34 patients with close resection margin decided not to receive re-excision but to undergo adjuvant radiotherapy.

After median follow-up of 128 months, the 10-year ipsilateral breast tumor relapse (IBTR) was 4.5% (N = 28), Of which 27 (96.4%) patients had clear margin after the initial surgical treatment of DCIS. 1 (3.6%) patient had close surgical margin. Difference in IBTR between the two groups was not statistically significant (p = 0.692).

Conclusion

Close surgical margin for DCIS is not associated with increased risk of IBTR.

The management of periocular basal cell carcinoma (BCC) is challenging due to its proximity to the eyeball. Vismodegib, a Hedgehog pathway inhibitor, has emerged as a therapeutic option for locally advanced and metastatic BCC. To critically appraise the relevant evidence, we conducted a systematic review of observational and experimental studies assessing the efficacy and safety of vismodegib for periocular BCC. Thirty-seven trials, including 435 patients, were eligible. No randomized trials were retrieved. Complete and overall clinical response rates were 20–88 % and 68–100 %, respectively. Disease progression was observed at a maximum rate of 14 %. Recurrence rates varied between 0 % and 31 %. The most common side effects were muscle cramps, dysgeusia, weight loss and alopecia. Treatment with vismodegib improved health-related quality of life. In conclusion, vismodegib represents an important novel treatment for advanced periocular BCC, with good response rates and acceptable tolerability profile. Nevertheless, its full potential needs clarification through randomized controlled trials.

Background

NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs).

Methods

This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW).

Results

NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11).

Conclusion

Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

Cervical cancer (CC) remains one of the most common and deadly malignancies among women worldwide, with exceptionally high morbidity and mortality rates. The aberrant activation of the hedgehog pathway is intimately associated with tumor development and progression. Nevertheless, the potential therapeutic targets within the hedgehog pathway in CC have yet to be clearly identified. In this study, we conducted an in-depth investigation of hedgehog pathway-related genes in CC, integrating single-cell sequencing data and spatial transcriptomics. Utilizing a comprehensive scoring algorithm, we identified that myofibroblasts within CC tissue exhibit a highly enriched hedgehog pathway. Our analysis of the myofibroblast development process revealed that MYH9 plays a crucial role. Further exploration using spatial transcriptome data allowed us to delve into the role of MYH9 in myofibroblasts. We discovered that MYH9-negative and MYH9-positive myofibroblasts display distinct profiles. Validation using extensive transcriptome data demonstrated that a high infiltration of MYH9-positive myofibroblasts is a risk factor for CC patients, significantly impacting prognosis and immunotherapeutic efficacy. Our study provides unique insights into the relationship between CC and the hedgehog pathway, offering new directions for cancer treatment strategies.

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Results

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