Independent Prognostic Influence Research Articles

Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma.

Background: Significant progress has been achieved in the management of multiple myeloma (MM) by implementing high-dose therapy and stem cell transplantation. Moreover, the prognosis of patients has been enhanced due to the introduction of novel immunomodulatory drugs and the emergence of new targeted therapies. However, predicting the survival rates of patients with multiple myeloma is still tricky. According to recent researches, platelets have a significant impact in affecting the biological activity of tumors and are essential parts of the tumor microenvironment. Nonetheless, it is still unclear how platelet-related genes (PRGs) connect to the prognosis of multiple myeloma. Methods: We analyzed the expression of platelet-related genes and their prognostic value in multiple myeloma patients in this study. We also created a nomogram combining clinical metrics. Furthermore, we investigated disparities in the biological characteristics, immunological microenvironment, and reaction to immunotherapy, along with analyzing the drug susceptibility within diverse risk groups. Results: By using the platelet-related risk model, we were able to predict patients' prognosis more accurately. Subjects in the high-risk cohort exhibited inferior survival outcomes, both in the training and validation datasets, as compared to those in the low-risk cohort (p < 0.05). Moreover, there were differences in the immunological microenvironments, biological processes, clinical features, and chemotherapeutic drug sensitivity between the groups at high and low risk. Using multivariable Cox regression analyses, platelet-related risk score was shown to be an independent prognostic influence in MM (p < 0.001, hazard ratio (HR) = 2.001%, 95% confidence interval (CI): 1.467-2.730). Furthermore, the capacity to predict survival was further improved when a combined nomogram was utilized. In training cohort, this outperformed the predictive value of International staging system (ISS) alone from a 5-years area under curve (AUC) = 0.668 (95% CI: 0.611-0.725) to an AUC = 0.721 (95% CI: 0.665-0.778). Conclusion: Our study revealed the potential benefits of PRGs in terms of survival prognosis of MM patients. Furthermore, we verified its potential as a drug target for MM patients. These findings open up novel possibilities for prognostic evaluation and treatment choices for MM.

The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (β=-0.0; p=0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.

Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia.

Nucleophosmin‐1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3‐internal tandem duplication (FLT3‐ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo‐HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1‐mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow‐up for survivors was 23.7 months. FLT3‐ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia‐free survival (LFS) were negatively affected by concomitant FLT3‐ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10−5 and HR 1.71, p < 10−5, respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3‐ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10−5), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3‐ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1‐mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.

Effect of Number of Retrieved Lymph Nodes on Prognosis in FIGO Stage IA1-IIA2 Cervical Cancer Patients Treated With Primary Radical Surgery.

Background:The influence of the number of removed lymph nodes (RLNs) on patients with early-stage cervical cancer (ESCC) is still questionable. The objective of this study was to explore the prognostic value of RLNs on ESCC patients.Methods:A retrospective study was performed including all ESCC patients who underwent radical surgery from January 2016 to December 2018. Cox regression analysis was performed to verify the correlation between the number of RLNs and the prognosis (recurrence-free survival [RFS], disease-specific survival [DSS]) of ESCC. According to the guidelines, all the patients were divided into high-risk and non-high-risk groups. The optimal cut-off values of RLNs were determined by receiver operating characteristic curve analysis and Youden index and further the prognostic value of them was explored.Results:A total 1101 patients were enrolled. The number of RLNs was an independent prognostic influence factor of the prognosis of ESCC (P < .001 for RFS, P < .001 for DSS). The optimal cut-off values of RLNs (40 in the high-risk group and 23 in the non-high-risk group) were significantly associated with the prognosis of ESCC, in the high-risk group (P < .001 for RFS, P = .002 for DSS) and non-high-risk group (P < .001 for RFS, P < .001 for DSS), respectively.Conclusions:More extensive lymph node dissection (RLNs ⩾ 40) could benefit the high-risk ESCC patients. However, in the non-high-risk group, moderate lymph node dissection (RLNs ≈23) could also benefit them and may reduce the incidence of related complications. Those findings may help to determine the scope of lymph node dissection in ESCC patients before operation.

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

Prognostic Impact of NPM1 and FLT3 Mutations at Diagnosis and Presence of Measurable Residual Disease (MRD) after Intensive Chemotherapy (IC) for Patients with Acute Myeloid Leukemia (AML) in Remission: Outcomes from the QUAZAR AML-001 Trial of Oral Azacitidine (Oral-AZA) Maintenance

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

Impact of Direct-Acting Antivirals on the Outcome of HIV/HCV Coinfected Patients with Non-Hodgkin Lymphomas in the Modern Anti-Retroviral Therapy Era: A Retrospective Multicenter Study of 74 Cases

TP53 Combined Phenotype Score Is Associated with the Clinical Outcome of TP53-Mutated Myelodysplastic Syndromes.

Simple SummaryTP53 is the most frequently mutated genes in cancer, and mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS). In patients with MDS, TP53 mutations are associated with adverse outcomes; however, there is still significant heterogeneity in these disease courses. We performed retrospective review of 107 patients with untreated TP53-mutated MDS, and identified that the functional impact of TP53 mutations, represented by phenotypic annotation of TP53 mutations (PHANTM) combined phenotype score is associated with prognosis. In patients with TP53-mutated MDS, we found that a higher PHANTM combined phenotype score is associated with poorer clinical outcome, and this has independent influence on prognosis accounting for IPSS-R and other risk variables. Our findings suggest that TP53-mutated MDS is heterogeneous and not all TP53 mutations harbor the same impact on prognosis. The PHANTM combined score adds to prognostic precision in MDS beyond previously reported TP53 allelic state.Mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the TP53 allelic state and variant allele frequency of TP53 mutation impact patient outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with TP53-mutated MDS. We assessed each mutation according to the phenotypic annotation of TP53 mutations (PHANTM) and analyzed the associations between predicted TP53 mutant function, represented by the PHANTM combined phenotype score, and overall survival (OS) using the log rank test and Cox regression. Our results indicated that patients with PHANTM combined phenotype score above the median (>1) had significantly shorter OS compared to those with scores below the median (median OS: 10.59 and 16.51 months, respectively, p = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), p = 0.044) and identified to have an independent prognostic influence, accounting for known risk such as IPSS-R and other standard risk variables. Our results suggest that the functional information of TP53 mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with TP53-mutated MDS.

Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence: A Nested Case-Control Study

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IRm) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted P trend=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted P trend=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IRm positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IRm positive tumors but not in those with IGF-IRm negative tumors (P interaction=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER+ tumors. Postoperative changes >10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.

Prognosis after surgery for gastric adenocarcinoma in the Swedish Gastric Cancer Surgery Study (SWEGASS)

Background Most studies examining prognostic factors after gastrectomy come from selected patients and non-Western populations. This nationwide population-based cohort study aims to identify prognostic factors after surgery for gastric adenocarcinoma in an unselected Western cohort. Methods This study included 98% of patients who underwent gastrectomy for gastric adenocarcinoma in Sweden in 2006–2015, with follow-up through 2019. Data were collected from medical records and national registries. Exposures were sex, age, education, comorbidity, tumor sub-localization, tumor stage, calendar period, and pre-operative chemotherapy. Outcomes were 3-year all-cause and disease-specific mortality. Cox regression produced hazard ratios (HRs) with 95% confidence intervals (95% CIs), adjusted for the other study exposures. Results Among all 2154 patients, 3-year all-cause mortality was 53.3%. Factors influencing 3-year all-cause mortality after multivariable adjustment were tumor stage (stage IV vs. stage 0–I: HR 8.72, 95% CI 6.77–11.24), comorbidity (Charlson comorbidity score ≥2 vs. 0: HR 1.63, 95% CI 1.39–1.90), age (>75 vs. <65 years: HR 1.48, 95% CI 1.24–1.78), and calendar period (2006–2010 vs. 2011–2015: HR 0.83, 95% CI 0.73–0.95). No independent prognostic influence was found for sex (women vs. men: HR 1.01, 95% CI 0.85–1.09), pre-operative chemotherapy (yes vs. no: HR 0.92, 95% CI 0.78–1.08), tumor sub-localization (non-cardia vs. cardia: HR 1.01, 95% CI 0.83–1.22), or education (≥13 vs. ≤9 years: HR 0.89, 95% CI 0.74–1.07). The results were similar for 3-year disease-specific mortality. Conclusion Survival after gastrectomy for gastric adenocarcinoma needs further improvement. Tumor stage, comorbidity, age, and calendar period were independently prognostic, while sex, pre-operative chemotherapy, tumor sub-localization, and education were not.

Abstract 12602: Poor Quality of Life in Patients With and Without Frailty: Co-prevalence and Prognostic Implications in Patients Undergoing Percutaneous Coronary Interventions and Cardiac Catheterization

Introduction: Relationship of QOL and frailty are poorly defined. Hypothesis: To study the prevalence and prognosis of poor QOL in frail patients. Methods: Predismissal standardized tests for frailty and QOL in 2 cohorts were administered. In cohort 1, 629 patients ≥ 65 years underwent percutaneous coronary intervention (PCI) from 2005-2008, frailty (Fried) and QOL [SF-36 and SAQ] were ascertained. Cohort 2 [921 patients, 535 PCI, ≥55 years] underwent cardiac catheterization from 2014-18, frailty (Rockwood) and QOL (Likert) were determined. Results: In cohort 1, 19%; and 20% in cohort 2 were frail. Lower median SAQ (58.9 vs. 82.2); physical (29.5 vs. 43.9) and mental (49.2 vs. 57.4) scores of SF-36 in cohort 1 higher rates of fair/poor health (56% vs 18%) in cohort 2 (all comparisons, p&lt;0.001) was seen in frail patients. As compared to without, frail patients were 5 times more likely (59% vs. 11%, p&lt;0.001) in cohort 1 and 7 times more likely (56% vs. 8%) in cohort 2 to have poor QOL. Adjusted three year all-cause death and death/myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [HR (95% CI) death, 4.20 (2.63, 6.68) and death or MI HR 2.72 (1.91, 3.87), p&lt;0.001) and with poor QOL [HR death 2.47 (1.59, 3.84) and death or MI 1.61 (1.16, 2.24) p&lt;0.001). There was no significant interaction between frailty and QOL (p=0.64) indicating their independent prognostic influence. Conclusions: Poor QOL is commonly seen with frailty. Both frailty and poor QOL had significant and independent association with long-term survival.

Multifactorial influence on duration of exclusive breastfeeding; a Danish cohort study.

The multifactorial aspects of breastfeeding require measures at many levels to identify mothers in need of breastfeeding support from healthcare professionals. Our objective was to examine the relative importance of sociodemographic, pre/perinatal-, infant-, psychosocial-, and interaction-related factors affecting duration of exclusive breastfeeding. We used self-reported data from a community-based trial including 1265 women (response rate 49%) giving birth from January 2017 to February 2018. Data on outcome, duration of exclusive breastfeeding, were collected three and nine months postpartum; data on the study variables concerning known risk factors for breastfeeding cessation were collected two weeks postpartum. Crude and multiple Cox proportional hazards models were used for statistical analyses with additional analyses for time varying effects. Factors with an independent prognostic influence on duration of exclusive breastfeeding in fully adjusted models included early skin-to-skin contact (HR = 1.18 CI:1.04–1.33), intention to breastfeed (HR = 0.77 CI: 0.73–0.80), positive outcome evaluation, meaning the value mothers attributed to breastfeeding (HR = 1.33 CI: 1.08–1.63), higher level of self-efficacy (HR = 1.46 CI: 1.24–1.72), and maternal sense of security in relation to breastfeeding (HR = 1.31 CI: 1.14–1.50). Higher maternal BMI, lower self-efficacy, shorter breastfeeding duration of previous child, and hospitalization during birth were time dependent by affecting the exclusive breastfeeding duration primarily in the first months following birth. The results suggest that target groups in special need of early breastfeeding support are defined by being hospitalized, obese, having low self-efficacy or short previous breastfeeding experience. The extensive influence of psychosocial factors emphasizes the importance of including both practical facilitating guidance and positive verbal encouragement to ensure effective breastfeeding support.

Poor quality of life in patients with and without frailty: co-prevalence and prognostic implications in patients undergoing percutaneous coronary interventions and cardiac catheterization.

We hypothesize that poor quality of life (QOL) is highly prevalent in frail older adults and is associated with worse prognosis. Predismissal standardized tests for frailty and QOL were prospectively administered to patients included in two cohorts. In Cohort 1, 629 patients ≥65 years who underwent percutaneous coronary intervention (PCI) from 2005 to 2008, frailty (Fried criteria), and QOL [SF-36 and Seattle Angina Questionnaires (SAQ)] were ascertained. Cohort 2 included 921 patients ≥55 years who underwent cardiac catheterization (535 had PCI) from 2014 to 2018 and frailty was determined by Rockwood criteria and QOL by single-item, self-reported health questionnaire. In Cohort 1, 19% were frail and 20% patients in Cohort 2 were frail with a frailty index >0.30. The median SAQ for physical limitation (58.9 vs. 82.2, P < 0.001), physical (29.5 vs. 43.9, P < 0.001), and mental (49.2 vs. 57.4, P < 0.001) component scores of SF-36 in Cohort 1 were lower and self-rating of fair/poor health (56% vs 18%, P < 0.001) in Cohort 2 was significantly higher in frail patients. As compared to patients without frailty, frail patients were five times more likely (59% vs. 11%, P < 0.001) in Cohort 1 and seven times more likely (56% vs. 8%) in Cohort 2 to be classified with poor QOL. Age- and gender-adjusted 3-year all-cause death and death or myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [hazard ratio (95% confidence interval) death, 4.20 (2.63-6.68, P < 0.001) and death or MI hazard ratio (HR) 2.72 (1.91-3.87, P < 0.001)] and with poor QOL [HR death 2.47 (1.59-3.84, P < 0.001)] and death or MI 1.61 (1.16-2.24, P < 0.001). There was no significant interaction between frailty and QOL (P = 0.64) and only modest attenuation was observed when considered together indicating their independent prognostic influence. In elderly patients undergoing cardiac catheterization or PCI, poor QOL is seen more frequently in frail patients. Both frailty and poor QOL had significant and independent association with long-term survival.

TLR5 and TLR7 are differentially expressed in human papillomavirus-positive and negative base of tongue squamous cell carcinoma, and TLR7 may have an independent prognostic influence

Background: Human papillomavirus-positive (HPV+) base of tongue squamous cell carcinoma (BOTSCC) has a better outcome than corresponding HPV− cancer. TLR5 and TLR7 expression was previously shown to differ depending on HPV − status and correlate with outcome in oropharyngeal squamous cell carcinoma.Aims/objectives: For validation, TLR5 and TLR7 were analyzed in a BOTSCC-cohort for correlation with HPV, survival, CD4+ and CD8+ tumor-infiltrating lymphocyte (TIL) counts, the latter being a well-documented prognostic marker.Materials and methods: BOTSCC biopsies, (49HPV+/28HPV−) were analyzed by immunohistochemistry for TLR5 and TLR7, and correlated with the above parameters.Results: TLR5 expression was more frequently absent/weak than medium/strong in HPV+ compared to HPV− BOTSCC (p < .001). The opposite was observed for TLR7 (p < .007). TLR5 and TLR7 expression did not correlate to survival in either the HPV− or HPV+ cases, or to CD4+ TILs. TLR5, (but not TLR7) expression was correlated to CD8+ TIL counts (p = .023).Conclusion and significance: Absent/weak TLR5 and medium/strong TLR7 expression was validated as more frequent in HPV+ compared with HPV− BOTSCC. A correlation between CD8+ TIL counts, and TLR5 expression was disclosed, but not with TLR7. Therefore, it could be useful to investigate TLR7 further as a potential independent prognostic marker.

High expression of long non-coding RNA LOC730101 correlates with distant metastasis and exhibits a poor prognosis in patients with osteosarcoma.

Expression of long non-coding RNA LOC730101 (LOC730101) has been closely linked to the carcinogenesis of osteosarcoma and has been shown to function as a tumor promoter. However, the clinical significance of LOC730101 remains unknown. Our present study aimed to investigate the feasibility of LOC730101 as a novel prognostic biomarker for osteosarcoma. Quantitative Real-time RT-PCR (qRT-PCR) was performed to examine LOC730101 expression in osteosarcoma tissues and adjacent non-cancerous tissues. The correlation between LOC730101 expression and clinicopathological features and the overall survival rate was determined. Cox regression analyses were performed to explore whether LOC730101 was an independent predictor of survival for osteosarcoma patients. We found that LOC730101 was significantly upregulated in human osteosarcoma tissues compared with corresponding adjacent normal tissues (p < 0.01). Elevated LOC730101 expression was correlated with advanced clinical stage (p = 0.001) and distant metastasis (p = 0.005). Furthermore, survival assay revealed that osteosarcoma patients in the high LOC730101 expression group had significantly shorter 5-year overall survival time than those in the low LOC730101 expression group (p = 0.0002). In addition, multivariate analysis showed that LOC730101 maintained an independent prognostic influence on overall survival (p = 0.006). Our present study, for the first time, revealed that LOC730101 may serve as a poor prognostic indicator in patients with osteosarcoma.

Метастазы рака молочной железы в парастернальные лимфоузлы: нужна ли морфологическая верификация?

Background. Metastatic involvement of the internal mammary chain lymph nodes (IMN) is associated with poor prognosis for breast cancer (BC) patients. However, parasternal radiation therapy is still a subject for debate. Methods. Results of 1144 consecutively treated patients with primary BC, who underwent one-stage videothoracoscopic (VATS) parasternal lymphadenectomy from 1998 to 2009, were retrospectively studied. Results. Surgical complications associated with thoracoscopic procedure did not exceed 2%. IMN metastases were detected in 211 (18.4%) patients, 6.0% of these cases did not have axillary invasion. In a wide analysis, the frequency of metastasis was statistically more influenced by: tumor localization (different from external quadrants), primary tumor size (T), level of involved axillary lymph nodes (N) and lymphovascular invasion. Patients with IMN metastases showed significantly poorer long-term outcomes: 5-year overall - OS and disease-free survival - DFS (OS 79.0±3.1% vs 91.4±1.0%, p<0.001; DFS 69.0±3.4% vs 86.0±1.2%, p<0.001, respectively) both in the whole group and in the subgroups with and without axillary lymph node metastases. IMN metastases along with tumor size and axillary nodes showed a negative independent prognostic influence on the DFS and OS (hazard ratio 2.24 [1.45-3.46]; 2.50 [1.41-4.43], respectively). Conclusions. IMN status is an important criterion which may influence on the prognosis and adjuvant treatment strategy in BC. Our study is in favor of conducting randomized clinical studies supporting the impact of radiotherapy treatment for involved IMN.

Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis

Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1-93) versus 2 (1-32) median (range), P = 0.023; bone, 3 (1-43) versus 2 (1-27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17-3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37-3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.

Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma

BackgroundMicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC.MethodsmiR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay.ResultsThe expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival.ConclusionThis study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC.

Lymph node ratio predicts local recurrence for periampullary tumours

To better define the prognostic role of nodal disease, evaluation of metastatic lymph node ratio (MLR) has been performed, and this method has recently gained prominence in various gastrointestinal cancers. The present study attempts to identify prognostic factors and evaluate the independent prognostic influence of MLR in patients who have undergone curative pancreaticoduodenectomy. In our institution within the study period, 111 patients received curative pancreaticoduodenectomy for periampullary cancers. Clinicopathologic data were collected and MLR was calculated for each of the patients. Patients were then divided into four groups based on MLR value: MLR 1 = 0; MLR 2 = 0.01-0.2; MLR 3 0.21-0.4; and MLR 4 >0.4. Increasing MLR correlates with high recurrence rate and lower overall survival (OS) with significance (P < 0.001, P < 0.001). The recurrent group showed significantly lower OS than the non-recurrent group (P < 0.001). In the multivariate analysis for recurrence, MLR was identified as the only independent prognostic factor (P < 0.001). The simple and easily obtainable MLR is well qualified as a prognostic factor in patients who undergo curatively radical resection for periampullary cancer. Furthermore, MLR can overcome the limitations of evaluation of lymph nodes status, allowing it to be used as a potential prognostic factor.

Combined cytoplasmic and membranous EGFR and p53 overexpression is a poor prognostic marker in early stage oral squamous cell carcinoma

Our aim was to evaluate the expression of several molecules that regulate growth, the cell cycle and signalling pathways including EGFR, p53, p16 and p27 in oral squamous cell carcinomas (OSCC). We examined their utility as prognostic markers by relating to clinicopathological characteristics and the clinical outcome. Using tissue microarray technology, we analysed 67 primary OSCC and examined immunohistochemical expression of EGFR, p53, p16 and p27. Multivariate analysis was conducted to examine their role in survival. Many of the markers were highly expressed in these cancers. Membranous EGFR expression in 95.2%, both membrane and cytoplasm expression in 35%, p53 expression in 61.6%, p27 expression in 89.5% and p16 expression in 27.9% of cases. In the multivariate analysis, independent prognostic influence of a lower overall survival was determined only for advanced tumour stage (P < 0.001), p53 overexpression (P = 0.004), EGFR cytoplasm and membrane co-expression location (P = 0.002) and p16 reduced expression (P = 0.002). When considering a subgroup of early stage tumours, p53 overexpression (P = 0.028) and combined membranous and cytoplasm EGFR co-expression (P = 0.039) were indicators of a lower overall survival. For disease-free survival, in addition to these three factors, the histological grade (P = 0.011) showed independent prognostic values. The independent value of EGFR subcellular location (cytoplasm and membrane) and p53 overexpression in overall survival even in early stages of OSCC suggests that these markers may serve as reliable biological markers to identify high-risk subgroups and to guide therapy.

The degree of neutropenia has a prognostic impact in low risk myelodysplastic syndrome

The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count<0.5×109/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28months) and patients with a neutrophil count higher than 0.5×109/L (66months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41–3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97–6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.