Pattern of breast cancer presentation during the coronavirus disease pandemic: results from a cohort study in the UK

Background: This study aimed to explore the hypothesis that the stage of breast cancer at initial diagnosis in 2020 is more advanced compared with 2019. Methods: Tumor, node, metastasis and Union for International Cancer Control (UICC) stages of new breast cancer diagnoses at the Bucks Breast Unit from May to October 2019 and 2020 were reviewed. A p < 0.05 was considered significant. Results: Average UICC stage increased from 1a in 2019 to 2a in 2020 (p < 0.01). Excluding cancers detected through screening, UICC stage still increased from 1b in 2019 to 2a in 2020 (p = 0.0184). There was a significant increase in the percentage of node-positive patients (p = 0.0063) and patients with metastatic disease (p = 0.0295) on initial presentation. Conclusion: Overall, patients presented with higher UICC stages and more node-positive and metastatic disease on initial diagnosis in 2020 compared with 2019.

Loss of SATB2 Occurs More Frequently Than CDX2 Loss in Colorectal Carcinoma and Identifies Particularly Aggressive Cancers in High-Risk Subgroups

Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and correlated with clinicopathological and morphological factors, CDX2 expression as well as survival parameters within the overall cohort and in clinicopathological subgroups. Results: SATB2 loss was a strong prognosticator in univariate analyses of the overall cohort (p < 0.001 for all survival comparisons) and in numerous subcohorts including high-risk scenarios (UICC stage III/high tumour budding). SATB2 retained its prognostic relevance in multivariate analyses of these high-risk scenarios (e.g., UICC stage III: DSS: p = 0.007, HR: 1.95), but not in the overall cohort (DSS: p = 0.1, HR: 1.25). SATB2 loss was more frequent than CDX2 loss (22.2% vs. 10.2%, p < 0.001) and of higher prognostic relevance with only moderate overlap between SATB2/CDX2 expression groups. Conclusions: SATB2 loss is able to identify especially aggressive CRCs in high-risk subgroups. While SATB2 is the prognostically superior immunohistochemical parameter compared to CDX2 in univariate analyses, it appears to be the less sensitive marker for colorectal differentiation as it is lost more frequently.

Prevalence of Lung Metastases among 19,321 Metastatic Colorectal Cancer Patients in Eight Countries of Europe and Asia

Background: Colorectal cancer is one of the most common malignancies in the Western world, and is responsible for about 10% of annual cancer-related deaths. Especially for UICC stage IV, the probability of survival is significantly reduced. Little is known about risk factors for specific metastatic patterns of colorectal cancer that may also influence patients’ overall survival. Methods: We used data from the IQVIA oncology dynamics (OD) database to determine the prevalence of pulmonary metastases in 19,321 patients with UICC stage IV colorectal cancer in eight European and Asian countries. Results: In total, 6132 of 19,321 (31.7%) study patients had lung metastases, with a higher prevalence among patients with rectal (37.5%) than colon (30.1%) cancer. When compared to China as the country with the lowest lung metastases prevalence, the odds for lung metastases were highest in UK (OR: 2.02, 95%CI: 1.80–2.28), followed by Italy (OR: 1.86, 95%CI: 1.52–2.27), Spain (OR: 1.85, 95%CI: 1.64–2.09), and Germany (OR: 1.47, 95%CI: 1.26–1.71). Conclusion: The prevalence of pulmonary metastases in UICC stage IV colorectal cancer varies widely among the different analyzed countries. Although the present data are purely descriptive, a possible combination of ethnic, environmental, and health care system-associated differences could be discussed as the underlying cause. Further studies are needed to investigate the reasons for differences in the prevalence of lung metastases.

Different Prevalence of Alarm, Dyspeptic and Reflux Symptoms in Patients with Cardia and Non-cardia Gastric Cancer

Background and Aims: Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC. Methods: Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire. Results: A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001). Conclusions: In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.

Loss of CDX2 in colorectal cancer is associated with histopathologic subtypes and microsatellite instability but is prognostically inferior to hematoxylin–eosin-based morphologic parameters from the WHO classification

Background Immunohistochemical loss of CDX2 has been proposed as a biomarker of dismal survival in colorectal carcinoma (CRC), especially in UICC Stage II/III. However, it remains unclear, how CDX2 expression is related to central hematoxylin–eosin (HE)-based morphologic parameters defined by 2019 WHO classification and how its prognostic relevance is compared to these parameters. Methods We evaluated CDX2 expression in 1003 CRCs and explored its prognostic relevance compared to CRC subtypes, tumour budding and WHO grade in the overall cohort and in specific subgroups. Results CDX2-low/absent CRCs were enriched in specific morphologic subtypes, right-sided and microsatellite-instable (MSI-H) CRCs (P < 0.001) and showed worse survival characteristics in the overall cohort/UICC Stage II/III (e.g. DFS: P = 0.005) and in microsatellite stable and left-sided CRCs, but not in MSI-H or right-sided CRCs. Compared with CDX2, all HE-based markers showed a significantly better prognostic discrimination in all scenarios. In multivariate analyses including all morphologic parameters, CDX2 was not an independent prognostic factor. Conclusion CDX2 loss has some prognostic impact in univariate analyses, but its prognostic relevance is considerably lower compared to central HE-based morphologic parameters defined by the WHO classification and vanishes in multivariate analyses incorporating these factors.

Heat Shock Proteins 27, 70, and 110: Expression and Prognostic Significance in Colorectal Cancer

Heat shock proteins (HSPs) are evolutionarily conserved chaperones occurring in virtually all living organisms playing a key role in the maintenance of cellular homeostasis. They are constitutively expressed to prevent and repair protein damage following various physiological and environmental stressors. HSPs are overexpressed in various types of cancers to provide cytoprotective function, and they have been described to influence prognosis and response to therapy. Moreover, they have been used as a tumor marker in blood serum biochemistry and they represent a potentially promising therapeutic target. To clarify prognostic significance of two canonical HSPs (27 and 70) and less known HSP110 (previously known as HSP105) in colorectal carcinoma (CRC), we retrospectively performed HSP immunohistochemistry on tissue microarrays from formalin-fixed paraffin-embedded tumor tissue from 297 patients with known follow-up. Survival analysis (univariate Kaplan–Meier analysis with the log-rank test and multivariate Cox regression) revealed significantly shorter overall survival (OS, mean 5.54 vs. 7.07, p = 0.033) and borderline insignificantly shorter cancer specific survival (CSS, mean 6.3 vs. 7.87 years, p = 0.066) in patients with HSP70+ tumors. In the case of HSP27+ tumors, there was an insignificantly shorter OS (mean 6.36 vs. 7.13 years, p = 0.2) and CSS (mean 7.17 vs. 7.95 years, p = 0.2). HSP110 showed no significant impact on survival. Using Pearson’s chi-squared test, there was a significant association of HSP27 and HSP70 expression with advanced cancer stage. HSP27+ tumors were more frequently mismatch-repair proficient and vice versa (p = 0.014), and they occurred more often in female patients and vice versa (p = 0.015). There was an enrichment of left sided tumors with HSP110+ compared to the right sided (p = 0.022). In multivariate Cox regression adjusted on the UICC stage, grade and right/left side; both HSPs 27 and 70 were not independent survival predictors (p = 0.616 & p = 0.586). In multivariate analysis, only advanced UICC stage (p = 0) and right sided localization (p = 0.04) were independent predictors of worse CSS. In conclusion, from all three HSPs examined in our study, only HSP70 expression worsened CRC prognosis, although stage-dependent. The contribution of this article may be seen as a large survival analysis of HSPs 27 and 70 and the largest analysis of HSP110 described in CRC.

Adjuvant radiotherapy plus systemic chemotherapy in resected head and neck mucosal melanoma.

e18042 Background: The median over survival (OS) of resected head and neck mucosal melanoma (HNMM) is 49.0 months. About 65% of patients experience local recurrence or distant metastasis after surgery. Therefore, adjuvant therapy is critical to improve the poor prognosis. Methods: Data regarding HNMMs with radical surgery (stage III-IVa, AJCC HNMM 8th version) between September 1, 2006 and February 28, 2020 at Peking University Cancer Hospital was collected retrospectively. Postoperative radiotherapy was usually prescribed as GTV 60-70Gy/CTV 60Gy/30f. Patients were divided into four groups by the adjuvant regimens: radiotherapy+chemotherapy (RC), chemotherapy (C), radiotherapy (R) and observation (O). Results: In total, 368 patients were enrolled, including 104 RC,114 C, 53 R, 97 O, respectively. After median follow-up of 63.9 mo (range: 0.9-146.7), the median local relapse-free survival (LRFS) was 10.1 mo (95%CI: 6.7-13.6) in the O group, as compared with 65.9 mo (95%CI: 31.7-100.1, P＜0.001) in the R group, 75.6 mo (95%CI: 50.1-101.0, P＜0.001) in the C group, and 84.6 mo (95%CI: 48.5-120.8, P＜0.001) in the RC group. The median distant metastasis-free survival (DMFS) was 13.7 mo (95%CI: 8.0-19.5) in the O group, 15.3 mo (95%CI: 8.7-21.9, P = 0.898) in the R group, as compared with 25.7 mo (95%CI: 14.6-36.8, P = 0.001) in the C group, 49.3 mo (95%CI: 32.6-66.0, P＜0.001) in the RC group. Estimated OS was 36.4 mo (95%CI: 24.0-48.8) in the O group, as compared with 30.8 mo (95%CI: 23.0-38.6, P = 0.733) in the R group, 40.8 mo (95%CI: 34.8-46.8, P = 0.289) in the C group, 58.2 mp (95%CI: 36.4-79.9, P = 0.002) in the RC group. Primary location, age, gender, UICC staging and adjuvant regimens were included for multivariate Cox analysis. With regard to OS, UICC stage and RC were the prognostic factors. With regard to DMFS, UICC stage, RC and C were the prognostic factors. With regard to LRFS, UICC stage, RC, R, C were the prognostic factors. Conclusions: It is the largest study on the role of adjuvant radiotherapy and chemotherapy on HNMM till now. The results demonstrate that postoperative radiotherapy improves LRFS but has no impact on DMFS, while adjuvant radiotherapy plus chemotherapy prolongs OS. It further validates the clinical practice of UICC stage of HNMM, which might shed lights on the study of the whole mucosal melanoma.

Complex Liver Resections for Intrahepatic Cholangiocarcinoma

The only curative treatment option for intrahepatic cholangiocarcinoma (iCCA) is liver resection. Due to central tumor localization and vascular invasion, complex liver resections play an important role in curative treatment. However, the long-term outcomes after complex liver resection are not known. Methods: A retrospective cohort study was conducted for all patients undergoing liver surgery for iCCA. Complex liver resections included ante situm resections, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and major liver resection with vascular reconstructions. Results: Forty-nine patients (34%) received complex liver resection, 66 patients (46%) received conventional liver resection and 28 patients (20%) were not resectable during exploration. Preoperative characteristics were not different between the groups, except for Union for International Cancer Control (UICC) stages. The postoperative course for complex liver resections was associated with more complications and perioperative mortality. However, long-term survival was not different between complex and conventional resections. Independent risk factors for survival were R0 resections and UICC stage. Four patients underwent ante situm resection without any mortality. Conclusions: Complex liver resections are justified in selected patients and survival is comparable with conventional liver resections. Survival in iCCA is affected by UICC stage or resections margins and not by the complexity of the case.

Prognostic Value of Preoperative Circulating Tumor Cell Counts in Patients with UICC-Stage I-IV Colorectal Cancer

The detection of CTCs in peripheral blood is one of the most promising approaches to identify disseminated disease in colorectal cancer (CRC). This study aims to evaluate the prognostic relevance of preoperative CTCs using the Cellsearch® system (CS)in patients, who underwent resection with curative intent of different stages of colorectal cancer (UICC I-IV). CTC analysis was performed in 68 CRC patients at UICC stages I-IV immediately before surgery. Data were correlated with clinicopathological parameters and patient outcomes. One or more CTCs/7.5 mL were detected in 45.6% (31/68) of patients. CTCs were detected in all stages of the Union of International Cancer Control (UICC), in stage I (1/4, 25%), in stage II (4/12, 33.3%), in stage III (5/19, 26.3%) in stage IV (21/33, 63.6%).The detection of CTCs was associated to the UICC stage (p = 0.035) and to the presence of distant overt metastases (p = 0.014). The presence of ≥ 1 CTCs/ 7.5 ml correlated significantly with shorter progression-free (p = 0.013) and overall survival (p = 0.014). Multivariate analyses showed that preoperative CTCs are an independent prognostic indicator for overall survival (HR, 2.68; 95% CI, 1.05–6.92 7; p = 0.039, ≥ 1 CTC). In conclusion, detection of CTCs is an independent and strong prognostic factor in CRC, which might improve the identification of high-risk patients in future clinical trials.