High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group

Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with systemic inflammation and endothelial dysfunction, increasing risk for thromboembolic events (TEE). In 145 adult recipients who developed cGVHD after a matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 32(22%) developed at least 1 TEE event, and 14(10%) developed 2 TEE events. The 5-year cumulative incidence of TEE was 22% (95% CI, 15–29%) with a median time from cGVHD to TEE of 234 days (range, 12–2050). Median time to the development of LE DVT or PE was 107 (range, 12–1925) compared to 450 days (range, 158–1300) for UE DVT. Cumulative incidence of TEE was 9% (95% CI, 0–20%), 17% (95% CI, 9–25%), and 38% (95% CI, 22–55%) in those with mild, moderate, and severe GVHD, respectively. Higher risk for TEE was associated with cGVHD severity (hazard ratio [HR] 4.9, [95% CI, 1.1–22.0]; p = 0.03), non-O-donor to recipient ABO match compared to O-donor to O-recipient match (HR 2.7, [95% CI, 1.0–7.5]; p = 0.053), and personal history of coronary artery disease (HR 2.4, [95% CI, 1.1–5.3]; p = 0.03). TEE was not associated with 2-year non-relapse mortality or 5-year overall survival.Subject terms: Medical research, Cancer     

FKBPL: a marker of good prognosis in breast cancer

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL''s prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14–1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07–1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13–1.58, p < 0.001, and HR = 1.25, 95% CI 1.04–1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05–1.65, p = 0.02 and HR = 1.23 95% CI 0.99–1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.     

Immunohistochemical prediction of lapatinib efficacy in advanced HER2-positive breast cancer patients

Molecular mechanisms of lapatinib resistance in breast cancer are not well understood. The aim of this study was to correlate expression of selected proteins involved in ErbB family signaling pathways with clinical efficacy of lapatinib. Study group included 270 HER2-positive advanced breast cancer patients treated with lapatinib and capecitabine. Immunohistochemical expression of phosphorylated adenosine monophosphate-activated protein (p-AMPK), mitogen-activated protein kinase (p-MAPK), phospho (p)-p70S6K, cyclin E, phosphatase and tensin homolog were analyzed in primary breast cancer samples. The best discriminative value for progression-free survival (PFS) was established for each biomarker and subjected to multivariate analysis. At least one biomarker was determined in 199 patients. Expression of p-p70S6K was independently associated with longer (HR 0.45; 95% CI: 0.25–0.81; p = 0.009), and cyclin E with shorter PFS (HR 1.83; 95% CI: 1.06–3.14; p = 0.029). Expression of p-MAPK (HR 1.61; 95% CI 1.13–2.29; p = 0.009) and cyclin E (HR 2.99; 95% CI: 1.29–6.94; p = 0.011) was correlated with shorter, and expression of estrogen receptor (HR 0.65; 95% CI 0.43–0.98; p = 0.041) with longer overall survival. Expression of p-AMPK negatively impacted response to treatment (HR 3.31; 95% CI 1.48–7.44; p = 0.004) and disease control (HR 3.07; 95% CI 1.25–7.58; p = 0.015). In conclusion: the efficacy of lapatinib seems to be associated with the activity of downstream signaling pathways – AMPK/mTOR and Ras/Raf/MAPK. Further research is warranted to assess the clinical utility of these data and to determine a potential role of combining lapatinib with MAPK pathway inhibitors.     

The Association between Herpes Zoster and Increased Cancer Risk: A Nationwide Population-Based Matched Control Study

Background: Herpes zoster (HZ) is strongly associated with decreased immune function, a factor of cancer development. Previous studies suggested inconsistent results regarding the association between HZ and increased cancer risk. We aimed to analyze the association between HZ and specific cancer risk. Methods: Of 134,454 patients diagnosed with HZ between 2002 and 2015, 81,993 HZ patients were matched 1:1 with non-HZ individuals by age, sex, and Charlson comorbidity index. Both groups were examined at 1, 3, and 5 years for cancer diagnosis. A Cox proportional hazard regression model was used to estimate cancer risk in both groups. The postherpetic neuralgia (PHN) and non-HZ groups were compared for specific cancer risk. Results: The HZ group showed a slightly decreased overall cancer risk compared with the non-HZ group (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90–0.97, p = 0.002). The HRs for specific cancer risk were 0.41 (95% CI, 0.33–0.50, p < 0.001); 0.86 (95% CI, 0.81–0.91, p < 0.001); 0.87 (95% CI, 0.78–0.97, p = 0.014); 0.80 (95% CI 0.73–0.87, p < 0.001); 1.20 (95% CI, 1.07–1.34, p = 0.001); and 1.66 (95% CI, 1.35–2.03, p < 0.001) for cancers of the lips, mouth, and pharynx; digestive system; respiratory system; unknown secondary and unspecified sites; thyroid and endocrine glands; and lymphoid and hematopoietic systems, respectively. The HZ with PHN group showed higher HR for specific cancer risk, such as lymphoid and hematopoietic systems (95% CI, 1.27–2.39, p < 0.001). Conclusion: HZ was associated with increased or decreased incidence of specific cancers. PHN further increased the risk of developing certain cancers in HZ patients.     

Plasma biomarkers of clinical response during chemotherapy plus combination antiretroviral therapy (cART) in HIV+ patients with advanced Kaposi sarcoma

This study aimed to evaluate plasma concentration of selected cancer-associated inflammatory and immune-modulated cytokines in HIV+ patients with advanced Kaposi sarcoma (KS), and to explore candidate biomarkers capable of predicting clinical outcome in response to chemotherapy (CT) plus combination antiretroviral therapy (cART).Thirty-seven plasma cytokines/chemokines were assessed by Luminex technology in 27 consecutive HIV+ KS patients, followed-up during CT and cART of maintanence (m-cART). Associations between plasma concentration of biomarkers and patient clinical response to m-cART were evaluated by means of Hazard Ratios (HRs) and corresponding 95% Confidence Intervals (CIs).Plasma baseline concentration of Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth factor (HGF) and endoglin were found to be associated with m-cART clinical response (HR:1.56, 95%CI:1.09–2.22, p = 0.01; HR:0.32, 95% CI:0.10–0.99, p = 0.05; HR:0.72, 95% CI:0.54–0.96, p = 0.03, respectively). The multivariate analysis confirmed the associations of baseline plasma G-CSF and HGF concentration with m-cART clinical complete remission response (HR:1.78, 95% CI:1.15–2.74, p = 0.009; HR:0.19, 95% CI:0.04–0.95, p = 0.04).Our exploratory study suggested that plasma G-CSF, HGF and endoglin may be novel predictors of clinical response during m-cART in HIV+ KS patients. Nonetheless, these findings should be further validated in an independent population study.     

Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis

Background: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients’ long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. Methods: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: “glioblastoma multiforme”, “dendritic cell”, “vaccination”, “immunotherapy”, “immune system”, “immune response”, “chemotherapy”, “recurrence”, and “temozolomide”. Among the 157 screened, only 15 articles were eligible for the final analysis. Results: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822–2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882–2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396–2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291–5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. Conclusion: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.     

Thioredoxin reductase: A novel,independent prognostic marker in patients with hepatocellular carcinoma

Here we found that hepatocellular carcinoma (HCC) patients with recurrence outcome and nonsurvivors had significantly increased thioredoxin reductase (TrxR) serum levels on reoperation (P < 0.0001 and P < 0.0001). Multivariate regression analysis adjusted for common risk factors showed that TrxR was an independent predictor of recurrence (hazard ratios [HR] = 4.19; 95% confidence intervals [CI]: 3.21–7.08) and overall survival (HR = 5.56; 95% CI: 3.42–10.21). The area under the receiver operating characteristic curve of TrxR was 0.837 (95% CI, 0.794–0.881) for recurrence outcome and 0.901 (95% CI, 0.869–0.933) for mortality, which was superior to high-sensitivity-C-reactive protein and a-fetoprotein (P < 0.001). The preoperative serum TrxR level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC, which offering reliable information for predicting survival.     

Hypomagnesemia at the time of autologous stem cell transplantation for patients with diffuse large B-cell lymphoma is associated with an increased risk of failure

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63–8.98 years) versus 6.29 years (95% CI: 4.73–8.95 years) with HR 1.63 (95% CI: 1.09–2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91—upper limit not estimable) versus 9.7 years (95% CI: 6.92–12.3 years) with HR 1.90 (95% CI: 1.22–2.96, p = 0.005) for OS months 0–12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.Subject terms: B-cell lymphoma, B-cell lymphoma     

Lymph node ratio is a prognostic factor for non-small cell lung cancer

The lymph node ratio (LNR) is defined as the number of pathologically positive LNs divided by the number of LNs examined. Some studies reported that high LNR was significantly associated with poor survival of non-small cell lung cancer (NSCLC). However, other studies could not confirm this result. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies published up to July 2015. Primary outcome was the relationship between LNR and disease-specific survival (DSS) and overall survival (OS). Twelve studies with 25138 NSCLC patients were included in this meta-analysis. Higher LNR was significantly associated with decreased OS (HR = 1.93; 95% CI 1.64 – 2.28; P < 0.00001) and DSS (HR = 1.82; 95% CI 1.55 – 2.14; P < 0.00001). In the subgroup analysis, N1 stage NSCLC patients with higher LNR also showed decreased OS (HR = 1.60; 95% CI 1.25 – 2.28; P = 0.0002) and DSS (HR = 1.82; 95% CI 1.55 – 2.21; P < 0.0001). This meta-analysis indicated that LNR was an independent predictor of survival in patients with NSCLC.     

A Retrospective Comparative Analysis of Outcomes and Prognostic Factors in Adult and Pediatric Patients with Osteosarcoma

Osteosarcoma is the most common primary bone malignancy in both children and adults. Despite introduction of intensive multimodal treatment with chemotherapy and surgery, outcomes are still poor, especially for patients with metastatic disease and adults. Hence, there is an ongoing need for better prognostic markers and outcome data to inform management decisions in both the adult and pediatric setting. Here, we retrospectively analyzed 112 patients with bone osteosarcoma treated at two large adult and pediatric tertiary academic centers between 1989 and 2019. Patients were divided into an adult (≥18 years) and pediatric (<18 years) cohort for comparison. Our aim was to evaluate predictors of outcomes in pediatric and adult patients, with a specific focus on the role of methotrexate when added to a combination of doxorubicin-cisplatin; the prognostic value of tumor necrosis after neoadjuvant chemotherapy; and outlining any differences in outcomes between adults and pediatric patients that could inform clinical management. Adult patients treated with methotrexate-doxorubicin-cisplatin and those treated with doxorubicin-cisplatin had similar 5-year PFS (26%, 95%CI: 45.5%–10% vs. 50%, 95%CI: 69.6%–26.2%, p = 0.1) and 5-year OS (63%, 95%CI: 82%–34%, vs. 78%, 95%CI: 90.6%–52.6%, p = 0.5). In the adult cohort, there was no difference between patients with ≥90% necrosis and <90% necrosis in either 5-year PFS (42%, 95%CI: 71.1%–11.3% vs. 38%, 95%CI: 57.7%–18.2%, p = 0.4) or 5-year OS (85%, 95%CI: 97.8%–33.4% vs. 56%, 95%CI: 76.8%–27.6%, p = 0.4). In the pediatric cohort, compared to patients with <90% necrosis, those with ≥90% necrosis had significantly better 5-year PFS (30%, 95%CI: 49.3%–14.1% vs. 55%, 95%CI: 73.9%–38.5%, p = 0.003) and 5-year OS (64%, 95%CI: 80.8%–41.1% vs. 78%, 95%CI: 92%–60.9%, p = 0.04). Adult and pediatric patients had similar 5-year OS (69%, 95%CI: 83.2%–49.8% vs. 73%, 95%CI: 83.2%–59.3%, p = 0.8) and 5-year PFS (37%, 95%CI: 52.4%–22.9% vs. 43%, 95%CI: 56.2%–30.4% p = 0.3) even though the proportion of patients with ≥90% necrosis after neoadjuvant chemotherapy was higher for children compared to adults (60.3% vs. 30%, OR: 3.54, 95%CI: 1.38–8.46, p = 0.006). In conclusion, in adult patients, the addition of methotrexate to doxorubicin and cisplatin did not correlate with a significant survival benefit, questioning the therapeutic value of methotrexate overall. Our study confirms the prognostic utility of percent tumor necrosis after neoadjuvant chemotherapy in pediatric patients but not in adult patients. Lastly, this is one of the few reported studies where patients with osteosarcoma younger and older than 18 years had similar PFS and OS.     

From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors

Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01–1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00–1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6–92.4 vs. 95.6%, 95% CI, 91.2–97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10–9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.     

Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis

Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A−) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A−, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A− adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A−: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A− significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19–2.00, I² = 31%). Using HRs adjusted for potential confounders, ARID1A− was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19–5.45, I² = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22–3.05, I² = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment.     

Antiangiogenic Drug-Induced Proteinuria as a Prognostic Factor in Metastatic Colorectal Cancer

Treatment with bevacizumab is known to cause adverse events such as proteinuria and hypertension, amongst others. However, while bevacizumab-induced hypertension has been linked to increased overall survival (OS), data on proteinuria are controversial. We performed a retrospective analysis to observe the influence of adverse events developed during treatment with bevacizumab and chemotherapy on the OS in patients with metastatic colorectal cancer (mCRC). Kaplan–Meier and log-rank analyses were used to assess differences in OS, and hazard ratios (HR) were estimated using Cox models. Out of the 3497 mCRC patients admitted to our center between 2014 and 2019, 150 met the criteria for inclusion in our analysis. Out of these, 50.7% experienced proteinuria and had reached a longer OS (40 versus 25 months, p = 0.015) and progression-free survival (15 versus 12 months, p = 0.039). The following groups were identified as having a lower risk of death: patients with proteinuria (HR 0.589; 95% CI 0.402–0.863; p = 0.007), one metastatic site (HR 0.533; 95% CI 0.363–0.783; p = 0.001), and non-metastatic stage at diagnosis (HR 0.459; 95% CI 0.293–0.720; p = 0.001). Patients with anemia and diabetes had an increased risk of death. Proteinuria emerges as a useful prognostic factor in mCRC patients undergoing bevacizumab-based systemic therapy, and it could be easily integrated into the decision-making process, thus allowing physicians to further individualize systemic treatments.     

A Nationwide Study on the Incidence of Breast Cancer in Korean Women with Osteoporosis Receiving Raloxifene Treatment

PurposeRaloxifene is a selective estrogen receptor modulator (SERM), and raloxifene treatment for osteoporosis is reimbursable under the Korean National Health Insurance. Evidence suggests that SERMs use reduces the risk of breast cancer in Asian population. Herein, we retrospectively investigated the protective effect of raloxifene on breast cancer rates in Korean population.MethodsUsing the Health Insurance Review and Assessment Service database, we selected women with osteoporosis aged 50 years and above. Patients treated for at least 2 years with raloxifene were assigned to the user group, whereas the remaining patients were assigned to the non-user group. The effect on breast cancer risk was assessed using the Cox proportional-hazards model with a time-dependent covariate to adjust for immortal time bias.ResultsA total of 322,870 women who were registered between 2010 and 2011 were included. The user group comprised 0.7% (n = 2,307) of the total population. The mean age was 65.7 ± 8.0 years and 67.2 ± 8.6 years in the user and non-user groups, respectively (p < 0.001). There was no difference in the previous use of estrogen replacement between the 2 groups (p = 0.087). The incidence of breast cancer per 1,000 person-years was 0.49 (n = 8) and 0.68 (n = 1,714) in the user and non-user groups, respectively (hazard ratio [HR], 0.63, 95% confidence interval [CI], 0.32–1.27). HR decreased with increase in the treatment duration, but this change was not statistically significant (HR, 1.00, 95% CI, 0.32–3.11 in 2–3 years; HR, 0.63, 95% CI, 0.20–1.94 in 3–4 years; and HR, 0.41, 95% CI, 0.10–1.65 in 4–5 years).ConclusionLong-term treatment with raloxifene in women with osteoporosis was not significantly associated with a reduction in breast cancer rates. However, further investigation is required for a conclusive proof.     

Palbociclib Plus Fulvestrant in Korean Patients from PALOMA-3 With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer

In the PALOMA-3 trial, the median progression-free survival (PFS) was longer among patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) treated with palbociclib plus fulvestrant than those treated with placebo plus fulvestrant. This subgroup analysis examined the efficacy and safety of palbociclib among Korean patients enrolled in PALOMA-3 (n = 43 [palbociclib group, n = 24; placebo group, n = 19]). In both groups, > 40% of patients were pre/perimenopausal at enrollment. The median PFS was significantly prolonged with palbociclib vs. placebo (12.3 [95% confidence interval (CI), 9.1–not estimable] vs. 5.4 months [95% CI, 1.9–9.2]; hazard ratio, 0.40 [95% CI, 0.19–0.83]; one-sided p = 0.005), and the confirmed objective response was 21.1% and 11.8%, respectively (odds ratio, 2.0 [95% CI, 0.24–24.8]). Neutropenia was the most common adverse event associated with palbociclib. Overall, palbociclib plus fulvestrant was effective and generally safe among Korean patients with HR+/HER2− ABC, regardless of menopausal status.     

Prognostic Significance of Tumor Growth Rate (TGR) in Patients with Huge Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization

The prognostic value of the tumor growth rate (TGR) in huge hepatocellular carcinoma (HHCC) patients treated with transcatheter arterial chemoembolization (TACE) as an initial treatment remains unclear. This two-center retrospective study was conducted in 97 patients suffering from HHCC. Demographic characteristics, oncology characteristics, and some serological markers were collected for analysis. The TGR was significantly linear and associated with the risk of death when applied to restricted cubic splines. The optimal cut-off value of TGR was −8.6%/month, and patients were divided into two groups according to TGR. Kaplan–Meier analysis showed that the high-TGR group had a poorer prognosis. TGR (hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.23–3.43; p = 0.006), presence of portal vein tumor thrombus (PVTT) (HR, 1.93; 95% CI, 1.13–3.27; p = 0.016), and subsequent combination therapy (HR, 0.59; 95% CI, 0.35–0.99; p = 0.047) were independent predictors of OS in the multivariate analysis. The model with TGR was superior to the model without TGR in the DCA analysis. Patients who underwent subsequent combination therapy showed a longer survival in the high-TGR group. This study demonstrated that higher TGR was associated with a worse prognosis in patients with HHCC. These findings will distinguish patients who demand more personalized combination therapy and rigorous surveillance.     

Relation Between Tumor Size and Lymph Node Metastasis According to Subtypes of Breast Cancer

PurposeTumor size and lymph node metastasis are important factors that contribute to the progression of breast cancer. We aimed to analyze the relationship between tumor size and lymph node metastasis molecular subtype and examine the effects of nodal metastasis on overall survival (OS).MethodsWe retrospectively reviewed the data of 16,552 patients who underwent breast surgery in Samsung Medical Center between 2000 and 2015. Information on tumor size (largest diameter of the invasive component), number of positive lymph nodes, and molecular subtype were obtained. We constructed a linear regression model to evaluate the relationship between tumor size and lymph node metastasis. To determine the effect of nodal metastasis on OS, we performed a Cox proportional regression analysis with Np/T (number of metastatic lymph nodes [n]/tumor size [cm]).ResultsThis study included 12,007 patients with a median follow-up of 62 months. The linear regression coefficients were 1.043 for luminal A, 1.024 for luminal B, 0.656 for HER2, and 0.435 for triple-negative breast cancer (TNBC) subtypes. No significant difference was observed in the coefficients between the luminal A and B subtypes (p = 0.797), while all other coefficients showed significant difference. After adjusting for other risk factors, the hazard ratio (HR) of Np/T for each subtype was significant for OS: luminal A (HR, 1.134; 95% confidence interval [CI], 1.097–1.171; p < 0.001), luminal B (HR, 1.049; 95% CI, 1.013–1.086; p = 0.007), HER2 (HR, 1.069; 95% CI, 1.014–1.126; p = 0.013), and TNBC (HR, 1.038; 95% CI, 1.01–1.067; p = 0.008).ConclusionThe incidence of lymph node metastasis differed according to molecular subtype. Luminal types have higher incidence of nodal metastasis than HER2 and TNBC. The HR of Np/T was highest in luminal A subtypes and lowest in TNBC subtypes.     

Relationship between aspirin use after diagnosis of colorectal cancer and patient survival: a meta-analysis of observational studies

Background:

Epidemiological evidence suggests that use of aspirin after the diagnosis of colorectal cancer can lengthen survival. However, the supporting data vary between studies, and this hypothesis remains controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between use of aspirin after diagnosis of colorectal cancer and patient survival.

Methods:

We searched the Medline and Embase databases up to April 2014 to identify studies related to aspirin use after diagnosis and all-cause mortality or colorectal cancer-specific mortality. Summary effect estimates with 95% confidence intervals (CIs) were derived using a fixed or random effects model, depending on the heterogeneity between the included studies.

Results:

Seven epidemiologic studies that consisted of six cohort studies and one nested case–control study were included in this meta-analysis. The hazard ratio (HR) of the association between aspirin use after colorectal cancer diagnosis and overall mortality, which was reported in five studies, was 0.74 (95% CI, 0.62–0.89) using a random model (heterogeneity test P=0.003, I²=75.3%), and for colorectal cancer-specific mortality (four studies), it was 0.75 (95% CI, 0.51–1.10) using a random model (heterogeneity test P=0.001, I²=84.1%). In addition, we analysed postdiagnosis aspirin use according to whether aspirin was also used before diagnosis. The HR for the overall mortality of patients who did not use aspirin before diagnosis, which was reported in four studies, was 0.84 (95% CI, 0.70–1.00), and for colorectal cancer-specific mortality (three studies), it was 0.79 (95% CI, 0.61–1.02). For those who did use aspirin before diagnosis, the HR for overall mortality (four studies) was 0.88 (95% CI, 0.83–0.93), and for colorectal cancer-specific mortality (three studies), it was 0.80 (95% CI, 0.59–1.09). Subgroup analysis showed that use of aspirin after diagnosis was associated with longer overall survival among patients with the variant PIK3CA gene but not for those with wild-type PIK3CA.

Conclusions:

Based on current evidence, the use of aspirin after diagnosis does not reduce colorectal cancer-specific mortality, but it does reduce all-cause mortality for colorectal cancer patients.     

Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study

Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81–1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52–1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.Subject terms: Epidemiology, Risk factors, Myeloma, Infectious diseases