Inferior 5-year Disease-free Survival Research Articles

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

The Prognostic Value of Radiological Extranodal Extension in HPV-Positive Oropharyngeal Carcinoma Treated by (Chemo-)Radiation

<h3>Purpose/Objective(s)</h3> In HPV-positive (HPV+) oropharyngeal carcinoma (OPC), N-status is defined exclusively by size and laterality of lymph node metastasis. In HPV-unrelated head and neck cancers, extranodal extension has already been included in the clinical N-categories of the TNM-staging system. There is emerging evidence that the presence of radiological extranodal extension (rENE) impacts prognosis and survival for HPV+ OPC. The hypothesis of this study is that the presence of rENE in node positive HPV+ OPC is associated with worse outcome, and rENE may be used to improve prognostication. <h3>Materials/Methods</h3> Consecutive patients treated by definitive radiation or chemoradiation (organ-preservation), using IMRT, for node-positive HPV+ OPC between 2009 and 2018 were retrospectively registered. Baseline diagnostic MRI or CT scans (acquired <60 days of start of treatment) were retrospectively scored for the presence of rENE by two experienced head and neck radiologists, according to previously described methods (<i>Huang et al., JCO 2021</i>) and with scoring for level of certainty for the presence of rENE (<i>Panicek et al., AJR 2016</i>). Outcome measures included Overall Survival (OS), Disease Free Survival (DFS), Locoregional Control (LRC) and Distant Control (DC); each were stratified for rENE status. Multivariate analysis for OS was used to investigate the independent prognostic value of rENE. <h3>Results</h3> This cohort consisted of 111 patients with node-positive HPV+ OPC, treated by organ-preservation. Median age was 62.8 years, gender was male in 78% and female in 22% of cases, median number of pack years of smoking was 15 (range 0-113). T-stage (according to TNM-8) was as follows: T1 in 21, T2 in 34, T3 in 21 and T4 in 35 cases. N-stage consisted of: N1 in 66 cases, N2 in 11 cases and N3 in 1 case. TNM-group staging was stage I in 48, stage II in 27 and stage III in 36 cases. rENE was present (rENE+) in 39 cases (35%) and absent (rENE-) in 72 cases (65%). Median follow-up of all patients was 57 months (range 2-156); median follow-up of patients alive at last follow-up was 63 months (range 31-156). Patients with rENE+ had inferior 5-year OS compared to those with rENE-: 57% vs. 76% (Log-rank p-value = 0.018), inferior 5-year DFS (51% vs. 71%, p-value = 0.016), and inferior 5-year DC (81% vs. 91%, p-value = 0.11) but there was no meaningful difference in 5-year LRC (86% vs. 90%, p-value =0.49). In multivariate analyses, the following factors were independently associated with OS: N-stage (N2 vs. N1, HR 2.66, p-value = 0.01), age (HR 1.05, p-value = 0.005), smoking pack years (HR 1.02, p-value = 0.035) and rENE (HR 2.38, p-value = 0.024). <h3>Conclusion</h3> rENE is indeed an important prognostic factor in a contemporary single-institutional cohort of patients with HPV+ OPC, and is independent of N-stage. rENE may potentially be used to further refine the TNM staging system.

Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001.

While outcomes for pediatric T-cell acute lymphoblastic leukemia (T-ALL) are favorable, there are few widely accepted prognostic factors, limiting the ability to risk stratify therapy. Dana-Farber Cancer Institute (DFCI) Protocols 05-001 and 11-001 enrolled pediatric patients with newly diagnosed B- or T-ALL from 2005 to 2011 and from 2012 to 2015, respectively. Protocol therapy was nearly identical for patients with T-ALL (N=123), who were all initially assigned to the high-risk arm. End-induction minimal residual disease (MRD) was assessed by reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS), but was not used to modify postinduction therapy. Early T-cell precursor (ETP) status was determined by flow cytometry. Cases with sufficient diagnostic DNA were retrospectively evaluated by targeted NGS of known genetic drivers of T-ALL, including Notch, PI3K, and Ras pathway genes. The 5-year event-free survival (EFS) and overall survival (OS) for patients with T-ALL was 81% (95% CI, 73-87%) and 90% (95% CI, 83-94%), respectively. ETP phenotype was associated with failure to achieve complete remission, but not with inferior OS. Low end-induction MRD (<10-4 ) was associated with superior disease-free survival (DFS). Pathogenic mutations of the PI3K pathway were mutually exclusive of ETP phenotype and were associated with inferior 5-year DFS and OS. Together, our findings demonstrate that ETP phenotype, end-induction MRD, and PI3K pathway mutation status are prognostically relevant in pediatric T-ALL and should be considered for risk classification in future trials. DFCI Protocols 05-001 and 11-001 are registered at www.clinicaltrials.gov as NCT00165087 and NCT01574274, respectively.

Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer patients with different tumor size: a big database in China

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Gastric cancer in young patients: a separate entity with aggressive features and poor prognosis.

To investigate the clinicopathological features and survival outcomes between young and old patients with gastric cancer (GC), and further determine the role of young age in the prognosis of GC. Patients with stage I-III gastric adenocarcinomas undergoing curative surgery were enrolled, divided into young (aged 18-49years, YG), middle-aged (50-59years, MG), and old (≥ 60years, OG) groups. Exclusion criteria were neoadjuvant therapy and history of malignant tumors. Clinicopathological features, overall survival (OS), disease-free survival (DFS), and recurrence patterns were compared among three groups. 1131 patients were finally included, with 270, 314, and 547 cases in the YG, MG, and OG, respectively. Compared to others, YG had higher proportion of female, middle-third gastric cancer, poor differentiation, N3b stage, and adjuvant chemotherapy. YG demonstrated poorer 5-year OS than MG (62.4% vs. 70.8%, P = 0.019), but better than OG (62.4% vs. 58.7%, P = 0.031). YG also suffered inferior 5-year DFS (75.2% vs. 82.8%, P = 0.040) compared with MG, and higher incidence of peritoneal recurrence than MG (15.1% vs. 5.2%, P < 0.001) and OG (15.1% vs. 4.1%, P < 0.001). Multivariate analysis identified young age as the independent prognostic factor for OS [hazard ratio (HR) = 1.347, 95% CI 1.018-1.781, P = 0.037], DFS (HR = 1.601, 95% CI 1.079-2.376, P = 0.019), and peritoneal recurrence (HR = 2.936, 95% CI 1.505-5.726, P = 0.002). Young GC patients demonstrated aggressive features with poor prognosis and enhanced management may be warranted for this subgroup.

High neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predict poor survival in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy.

This study explored the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy (CCRT).Between January 2006 and December 2016, 184 patients with newly-diagnosed rectal cancer receiving neoadjuvant CCRT were enrolled. Risk of overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method and Cox proportional hazard models. Stratified survival analyses were also performed between post-neoadjuvant pathological (yp) stage.The mean follow-up time was 72.73 ± 36.82 months. High- and low-NLR patients differed significantly in both 5-year DFS (P = .026) and OS (P = .016). High- and low-PLR patients differed significantly in 5-year DFS (P = .011) but not OS (P = .185). Multivariate analyses revealed worse 5-year DFS (adjusted HR [aHR] = 2.8; 95% CI: 1.473-5.41; P = .002) and 5-year OS (aHR = 1.871; 95%CI: 1.029-3.4; P = .04) in the high-NLR group after adjusting for covariates. After adjustments, the high-PLR group had inferior 5-year DFS (aHR = 2.274; 95%CI: 1.473-5.419; P = .038) but not 5-year OS (aHR = 1.156; 95%CI: 0.650-2.056; P = .622). Further stratified analysis indicated that yp stage II and III patients with high NLR had worse 5-year DFS (aHR = 2.334; 95% CI: 1.158-4.725; P = .018) and OS (aHR = 2.226; 95% CI: 1.165-4.251; P = .015). Additionally, yp stage II and III patients with high PLR had inferior 5-year DFS (aHR = 2.012; 95% CI: 1.049-3.861; P = .036).Pre-CCRT NLR and PLR are independent prognostic factors for rectal cancer patients and could be used as a potential biomarker to identify high-risk patients for more intense treatment and care.

TNM stage at diagnosis is more predictive of prognosis than pathological complete response in young breast cancer treated with neoadjuvant chemotherapy.

TNM stage at diagnosis is more predictive of prognosis than pathological complete response in young breast cancer treated with neoadjuvant chemotherapy.

PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR-21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS, which may require more aggressive treatment.

Comparative analysis of radiofrequency ablation and resection for resectable colorectal liver metastases

To evaluate the therapeutic efficacy of radiofrequency ablation (RFA) for resectable colorectal liver metastases (CRLM) compared with that of resection. Between June 2004 and June 2009, we retrospectively analyzed 29 patients with resectable CRLMs; 17 patients underwent RFA, and 12 underwent hepatic resection. All of the patients were informed about the treatment modalities and were allowed to choose either of them. RFA including an intraoperative approach was performed by a radiologist; otherwise, hepatic resection was performed by a surgeon. Comparative analysis of the two groups was performed, including comparisons of gender, age, and clinical outcomes, such as primary tumor stage and survival rates. The mean tumor size was significantly larger in the resection group (3.59 cm vs 2.02 cm, P < 0.01), and the 5-year overall survival (OS) rate for all patients was 44.7%. There was no difference in the 5-year OS rates between the RFA and resection groups (37.8% vs 66.7%). Univariate analysis indicated significantly lower 5-year OS rates for patients with a tumor size > 3 cm. The 5-year disease-free survival (DFS) rates were 17.6% and 22.2% in the RFA and resection groups, respectively (P = 0.119). Univariate analysis revealed that in cases of male gender, age > 65 years, T stage < IV, absence of lymphatic metastasis, and tumor size > 3 cm, RFA resulted in significantly inferior 5-year DFS rates compared with surgical resection. Surgical resection revealed superior outcomes in the treatment of resectable CRLMs, particularly in cases with a hepatic tumor size > 3 cm.

Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma

The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC). We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue. The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years. Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.

Immunoglobulin concentrations in untreated lymphoblastic leukemia.

Early studies indicated that low immunoglobulin (Ig) concentrations at diagnosis predict a worse outlook for children with acute lymphoblastic leukemia (ALL). We re-examined this suggestion in the light of immunophenotypic disease subtyping and more modern therapy. The concentrations of Ig, IgA, and IgM at diagnosis of ALL in 199 children were reviewed. One hundred forty-one (71%) had normal values and 58 (29%) had at least one abnormal value. No obvious pattern of abnormality relating to disease immunophenotype emerged. Disease-free survival (DFS) was not significantly different when simply comparing children with normal and abnormal values. Those with a white blood cell count lower than 20 x 10(9)/L (n = 106) included 22 with at least one low Ig whose 5-year DFS was inferior to the "normal" group (56% vs 83%; P < 0.005). The 140 children with CD10 + B precursor ALL included 31 with one or more low Ig concentrations who also showed an inferior 5-year DFS to the remainder (55% vs 77%; P < 0.02). Minor abnormalities in Ig concentrations are seen in approximately one third of children with ALL regardless of immunologic subtype. Low values may relate to poor outcome in patients with the disease at otherwise good risk.