Prognostic Factor For 5-year Overall Survival Research Articles

HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Importance of Adequate Surgical Local Control in Fusion-Negative Para-Testicular Rhabdomyosarcoma: Data From the Cooperative Weichteilsarkom Studiengruppe Trials (CWS-96 and CWS-2002P) and the European Soft Tissue Sarcoma Registry (SoTiSaR)

BackgroundThis study aimed to assess the impact that the quality of primary and subsequent surgeries has on the survival of patients with para-testicular rhabdomyosarcoma (PTRMS).MethodsPatients with localized (IRS I–III) and metastatic (IRS IV) PTRMS were enrolled in the two Cooperative Weichteilsarkom Studiengruppe (CWS) trials (CWS-96, CWS-2002P) and the Soft Tissue Sarcoma Registry (SoTiSaR).ResultsAmong 196 patients (median age, 8.4 years), 106 (54.1%) had primary complete resection. Image-defined lymph node (LN) disease was detected in 21 (11.5%) patients in the localized cohort and 12 (92.3%) patients in the metastatic cohort. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 87.3% and 94.0% for the patients with localized PTRMS and 46.2% and 42.2% for the patients with metastatic PTRMS. Protocol violations during the primary surgery (PV-PS) were observed in 70 (42%) of the IRS I–III patients. This resulted in higher rates of R1/R2 resections (n = 53 [76%] vs n = 20 [21%]; p < 0.001) with a need for pretreatment re-excision (PRE) (n = 50 [83%] vs n = 10 [17%]; p < 0.001) compared with the patients undergoing correct primary surgery. Protocol violations during PRE occurred for 13 (20%) patients. Although PV-PS did not influence the 5-year EFS or OS in the localized PTRMS cohort, the unadjusted log-rank test showed that R status after PRE is a prognostic factor for 5-year OS (R1 vs R0 [81.8% vs 97.6%]; p = 0.02).ConclusionsThe quality of surgical local control in PTRMS is unsatisfactory. Emphasis should be placed on evaluating the resection status after PRE in further clinical trials.

Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study

BackgroundThe impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. MethodsPatients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. ResultsAmong 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61–0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66–0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33–39% and 28–37%, respectively. ConclusionsTOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.

Prediction values of tertiary lymphoid structures in the prognosis of patients with left- and right-sided colon cancer: a multicenter propensity score-matched study.

Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood. A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively. For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system. Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.

Influence of radiation treatment technique (IMRT vs. 3D-RT) on acute toxicity and prognostic factors for survival for anal cancer

We compared our institutional experience with intensity-modulated radiotherapy (IMRT) and 3D-conformal radiotherapy (3D-RT) for definitive treatment of primary anal cancer. We performed a single-institution retrospective review of all patients with anal squamous cell carcinoma treated with definitive (chemo) radiotherapy with curative intent from 2004 through 2018. We assessed several prognostic factors in respect to relevant survival endpoints. In addition, acute toxicities were determined and compared between IMRT and 3D-RT patients. This study included 94 patients (58 IMRT, 36 3D-RT). Mean follow up for all patients, for IMRT and 3D-RT patients was 61 months (range 6–176), 46 months (range 6–118), and 85 months (range 6–176), respectively. 5-year overall survival (OS) was 86%, disease-free survival (DFS) was 72%, and colostomy-free survival (CFS) was 75% in the IMRT cohort. In the 3D-RT cohort, OS was 87%, DFS was 71%, and CFS was 81% (all p > 0.05). Male gender and Karnofsky Index (KI) were revealed as independent prognostic factors for 5-year OS (p = 0.017; p = 0.023). UICC stage was an independent prognostic factor for DFS and CFS (p = 0.023; p = 0.042). In addition, the pre-treatment leukocyte count was an independent prognostic factor for CFS (p = 0.042). Acute grade ≥ 3 toxicity was not significantly different between IMRT and 3D-RT patients, but the IMRT cohort had favorable outcomes. This study confirmed IMRT as the primary definitive treatment of anal cancer. With similar survival rates, IMRT had the potential to reduce acute toxicity by sparing organs at risk. Promising prognostic factors such as BMI, KI, and leucocyte and hemoglobin levels should be further investigated.

Preoperative serum CA125 level and age at diagnosis: An effective prognosis prediction tool for patients with early-stage endometrial cancer.

To investigate the combined predictive value of the preoperative serum cancer antigen 125 (CA125) level and age at diagnosis among patients with early-stage endometrial cancer (EC) after initial treatment. We retrospectively analyzed data from patients with early-stage EC from 1999 to 2015 in multiple institutions in China. All 447 patients received postoperative adjuvant radiotherapy for FIGO 2009 stage I and II EC with complete data on preoperative serum CA125 levels. All patients were divided into four groups according to the ESMO-ESGO-ESTRO risk classification. The predictive probability of 5-year overall survival (OS) and the sensitivity and specificity of CA125 and age were calculated. The median follow-up time was 59 months (3-201 months). The 5-year OS and disease-free survival rates were 94.4% and 89.1%. Multivariate analysis showed that the preoperative CA125 level and age at diagnosis were independent prognostic factors for 5-year OS. The area under the curve for CA125 combined with age at diagnosis for 5-year OS was .692, and the corresponding sensitivity and specificity were 68.2% and 68.2% (p < .002), which were significantly better than the corresponding values for CA125 or age alone. After all 447 patients were divided into four groups according to CA125 combined with age, the 5-year OS of the elderly and higher CA125 group was only 73.7%. Although preoperative CA125 had limited sensitivity in predicting the prognosis for early-stage EC after initial treatment, it remains a useful serum marker for risk assessment of early-stage EC. Combining CA125 with age may increase its predictive sensitivity.

Albumin/fibrinogen ratio, a predictor of chemotherapy resistance and prognostic factor for advanced gastric cancer patients following radical gastrectomy

BackgroundThe objective of this study was to investigate potential predictors of chemotherapy resistance in patients with advanced gastric cancer (GC) following radical gastrectomy.MethodsEligible stage II/III GC patients with adjuvant chemotherapy after radical gastrectomy were enrolled in this study. A receiver operating characteristic (ROC) curve analysis was performed to assess the predictive and optimal cut-off values of continuous variables for chemotherapy resistance. Potential risk factors for chemotherapy resistance were determined with binary univariate and multivariate analyses. Potential prognostic factors for overall survival (OS) were determined by COX regression analysis. The association between survival and AFR level was examined using the Kaplan–Meier curve analysis.ResultsA total of 160 patients were included in the data analysis, and 41 patients achieved chemotherapeutic resistance with an incidence of 25.6%. Pretreatment albumin/fibrinogen ratio (AFR) (cut-off value: 10.85, AUC: 0.713, P < 0.001) was a predictor for chemotherapeutic resistance by ROC curve analysis. Low AFR (< 10.85) was an independent risk factor of chemotherapeutic resistance as determined by the univariate and multivariate logistic regression analyses (OR: 2.55, 95%CI: 1.21–4.95, P = 0.005). Multivariate COX regression analyses indicated low AFR as a prognostic factor for 5-year OS (HR: 0.36, 95%CI: 0.15–0.73, P = 0.011). Low AFR was associated with poorer 5-year disease-free survival and overall survival.ConclusionsThis study indicated that a low level of pretreatment AFR could serve as an independent predictor of chemotherapy resistance and postoperative prognosis in GC patients following radical gastrectomy.

Role of CD5L and SRD5A2 as Prognostic Biomarkers for Hepatocellular Carcinoma.

PurposeDue to the limitations of currently available biomarkers, new biomarkers are needed to accurately predict the prognosis of patients with hepatocellular carcinoma (HCC) patients.MethodsIn this study, we screened for differentially expressed genes (DEGs) in the tumor and the adjacent tissues using the four gene expression array (GSE14520, GSE45267, GSE121248, GSE62232) of the Gene Express Omnibus (GEO) database.ResultsSubsequently, 47 overlapping DEGs were identified in four GEO datasets, which were mostly located on chromosomes 5q and 6q, distributed in the liver and CD105-positive endothelial cells, and closely related to HCC. Function enrichment revealed 47 DEGs were related to HCC, and involved in steroid /lipid /retinol metabolism, bile secretion and p53 signalling pathway. The Kaplan–Meier plotter analysis (http://www.kmplot.com/) identified 26 and 40 genes associated with the 5-year overall survival (OS) and relapse-free survival (RFS). We found that CD5L and SRD5A2 were independent prognostic factors for 5-year OS (P=0.036) and RFS (P=0.044) in HCC patients from GSE14520, respectively. Clinicopathological features including BCLC stage, cirrhosis, and risk signature for predicted metastasis were used to construct and validate a nomogram for 5-year OS with C-index of 0.732 and 0.717 in the training and validation cohort, respectively. SRD5A2, BCLC stage and gender was independent prognostic factors for RFS which were used to build a nomogram with the C-index of 0.666 and 0.682 in the training and validation cohort, respectively.ConclusionCD5L can facilitate individualized, targeted therapy for HCC patients.

Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Prognostic Factors in De Novo Metastatic Renal Cell Carcinoma: A Report From the Latin American Renal Cancer Group.

PURPOSETo assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries.PATIENTS AND METHODSOf 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method.RESULTSOf 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58).CONCLUSIONOur study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: a preferential benefit for squamous cell carcinoma.

BackgroundThe beneficial effect of postoperative radiotherapy (PORT) on completely resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of the study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC.Patients and methodsBetween October 2010 and September 2016, 288 consecutive patients with completely resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed, which consisted of 194 cases of LADC and 85 cases of LSCC. There were 42 (21.6%) patients treated with PORT in LADC cases and 19 (22.3%) patients treated with PORT in LSCC cases. The 5-year overall survival (OS), loco-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The prognostic factors were determined using Cox’s regression model.ResultsAmong 194 cases of LADC, the 1-, 3-, and 5-year OS in the PORT group were 95.2%, 61.9% and 40.0%, respectively, while in the non-PORT group were 90.1%, 63.3% and 45.0% (p = 0.948). The use of postoperative chemotherapy (POCT) and smoking index ≥ 400 were both prognostic factors of 5-year rates of OS, LRFS and DMFS. On the other hand, among 85 cases of LSCC, the 1-, 3-, and 5-year OS in the PORT group were 94.7%, 63.2% and 63.2%, respectively, whereas in the non-PORT group were 86.4%, 48.5% and 37.1% (p = 0.026). In this group, only the use of PORT was a favorable prognostic factor for 5-year OS, LRFS and DMFS.ConclusionsDue to clinicopathological differences among completely resected pIIIA-N2 NSCLC, PORT may not be suitable to all patients. Our study distinguishes pIIIA-N2 LSCC from LADC by their positive responses to PORT.

Prognostic Nomograms Predicting Survival in Patients With Locally Advanced Cervical Squamous Cell Carcinoma: The First Nomogram Compared With Revised FIGO 2018 Staging System.

ObjectivesTo develop nomograms to assess prognostic factors for 5-year overall survival (OS) and 5-year progression-free survival (PFS) in locally advanced cervical squamous cell carcinoma (LACSC).MethodsOverall, 618 patients with LACSC were included in this retrospective analysis. Nomograms for 5-year OS and PFS were developed based on Cox proportional hazards regression models. Concordance index (C-index) and calibration curves were used to define the predictive and discriminatory capacity of the nomogram. A comparison between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO) staging system was conducted using time-dependent receiver operating characteristic (tROC) and area under the curve (tAUC).ResultsMultivariate analysis identified several prognostic factors for OS including squamous cell carcinoma antigen (SCC-Ag), body mass index (BMI), tumor size, pelvic wall involvement, and para-aortic lymph node metastasis (PALNM). Prognostic factors for PFS included BMI, hemoglobin (HGB), tumor size, pelvic wall involvement, pelvic lymph node metastasis (PLNM) and PALNM. Following bootstrap correction, the C-index of OS and PFS was 0.713 and 0.686, respectively. These nomograms showed superior performance compared with the FIGO 2009 and 2018 staging schema.ConclusionsNomograms were developed to identify prognostic factors for 5-year OS and PFS in patients with LACSC. These nomograms showed good prognostication and are more comprehensive in predicting survival outcomes than existing staging criteria.

Clinical characteristics and analysis of prognostic factors of 222 patients diagnosed with Hodgkin's lymphoma

Objective: To analyze the clinical characteristics and prognostic factors of patients with Hodgkin's lymphoma(HL). Methods: The clinical data of HL patients who were newly treated in Guizhou Cancer Hospital from August 2007 to March 2019 was retrospectively collected, and the efficacy and prognostic factors were analyzed. Results: The clinical data of a total of 222 patients were analyzed in this study. The 5-year progression-free survival (PFS) and overall survival (OS)rate of them were 82.8% and 81.3%, respectively. The 5-year PFS rate and OS rate of early (stage Ⅰ-Ⅱ) HL were 87.3% and 86.1%, respectively, and the 5-year PFS rate and OS rate of progressive (stage Ⅲ-Ⅳ) HL were 77.9% and 76.3%, respectively. Among the 118 patients with early Hodgkin's lymphoma, the complete remission(CR) rate of chemotherapy alone was 55.6%(15/27), and chemotherapy plus radiotherapy was 86.8% (79/91), the difference between which was statistically significant (P<0.05). Compared with chemotherapy plus radiotherapy in early stage patients, 5-year PFS (93.0%) and 5-year OS (92.0%) rate in patients with chemotherapy plus radiotherapy were better than those with chemotherapy alone which were 63.7% and 62.1%, respectively. Multivariate analysis showed that age, LDH, ABVD cycle number and chemoradiotherapy were independent prognostic factors for 5-year OS and PFS rate in HL patients. The adverse reactions were increased level Ⅰ-Ⅱ aminotransferase with an incidence of 47.7% (106/222), decreased level Ⅰ-Ⅱ neutrophils with an absolute value of 54.1% (120/222), and decreased level Ⅲ-Ⅳ neutrophils with an absolute value of 45.9% (102/222). No adverse cardiac and pulmonary reactions or secondary tumors associated with chemotherapy was found in all patients. Conclusions: HL is a type of malignant tumor with good prognosis, and the short-term and long-term efficacy of chemotherapy combined with radiotherapy in early patients is better than that of chemotherapy alone. Age, LDH, ABVD cycle number and chemoradiotherapy are associated with prognosis in patients with Hodgkin's lymphoma. Adverse reactions can be tolerated.

Association between Ki-67 expression and clinicopathological features in prognosis of breast cancer: A retrospective cohort study.

Background:Breast cancer is the most common diagnosed female cancer. Breast cancer is also the leading cause of cancer death in females accounting for 13.7% of female cancer-related mortality globally. Variable known prognostic factors such as histological tumor type, tumor size, nodal status, grade, age, and estrogen receptor (ER) status and the proliferation marker – Ki-67 influence the type of treatment decision. The purpose of this present study is to investigate the association between Ki-67 expression with several clinicopathological variables and patients’ outcome.Materials and Methods:This is a retrospective cohort study from September 2008 to March 2017; 165 newly diagnosed breast cancer patients were enrolled in the study. Ki67 levels were measured using immunohistochemistry and compared with clinicopathological variables. The relation of Ki67 expression with disease-free survival (DFS) and overall survival (OS) was also analyzed.Results:The result of this study revealed that age, tumor size, menopausal status, and human epidermal growth factor receptor 2 (HER2) status had no effect on the patients’ outcome. Patients with ER-positive, progesterone receptor (PR)-positive, and HER2-negative tumors expressed a higher rate of Ki-67 (>10%) than patients with ER-negative, PR-negative, and HER2-positive tumors, respectively. However, we found that Ki-67 levels were not significantly increased statistically with ER, PR, and HER2 statuses. There was a statistically significant correlation between Ki-67 expression and with higher stages of the disease. Multivariate analysis showed that Ki-67 expression could not to be an independent prognostic factor for 5-year OS and DFS. Furthermore, p53 status was only prognostic factor for 5-year OS whereas higher stages of disease and p53 status were prognostic factors for 5-year DFS.Conclusion:Ki67 could not be an independent variable for prediction of breast cancer outcome.

Hematopoietic Cell Transplantation for Children with Acute Megakaryoblastic Leukemia without Down Syndrome

Abstract Acute megakaryoblastic leukemia (AMKL) accounts for 10% of childhood acute myeloid leukemia. Although AMKL patients with Down syndrome (DS-AMKL) have an excellent survival rate, patients with non-DS-AMKL experience poor outcomes. Despite therapeutic advances, including use of intensified treatment protocols, there is no consensus on the optimal treatment strategy for non-DS-AMKL. Some study groups recommend hematopoietic cell transplantation (HCT) for patients with non-DS-AMKL in the first complete remission (CR1); however, it is unclear whether HCT in CR1 improves outcomes of these patients. To assess outcomes and risk factors of HCT for patients with non-DS-AMKL, we retrospectively analyzed 203 patients with non-DS-AMKL (male, 95; female, 108) who underwent first HCT between 1986 and 2015 using data from the Japan Society for Hematopoietic Cell Transplantation. The median age at the time of HCT was 2 years (range, 0-16). Out of 203 patients, 12 had translocation t(1;22)(p13;q13), 18 had monosomy 7, 21 had complex karyotype, and 109 had other chromosomal abnormalities. Bone marrow transplantation (BMT) was performed for 114, cord blood transplantation (CBT) for 74, and peripheral blood stem cell transplantation (PBSCT) for 15 patients. Seventy-eight patients underwent HCT from related (HLA-matched, 43; HLA-mismatched, 35), 108 from unrelated (HLA-matched, 56; HLA-mismatched, 52), and 17 from autologous donors. Ninety-two patients underwent HCT in CR1, 21 in the second CR (CR2), and 90 in non-CR. Myeloablative conditioning (MAC) regimen was defined as the use of total body irradiation (TBI) ≥8 Gy, administration of busulfan &gt;8 mg/kg or melphalan &gt;140 mg/m2. All other regimens were included in reduced intensity conditioning (RIC) regimen. MAC regimen was used for 192 and RIC regimen for 11 patients. Median duration of follow-up after HCT was 713 days (range, 3-10008). Out of 203 patients, 183 (90%) exhibited engraftment. Sixteen out of 20 patients who did not exhibit engraftment underwent HCT in non-CR. In the entire cohort, 5-year overall survival (OS) and event free survival (EFS) rates were 43% and 38%, respectively. Seventy-two patients died of disease relapse and 42 died of transplantation-related complications. Five-year OS/EFS rates were not significantly different between BMT (48%/43%), CBT (35%/31%), and PBSCT (31%/27%) (p = 0.221/p = 0.087). In allogeneic HCT, 5-year OS/EFS rates were significantly lower in patients who underwent HCT from HLA-mismatched donors (27%/22%) than those from HLA-matched donors (52%/47%) (p &lt; 0.001/p &lt; 0.001). Five-year cumulative incidence (CI) of relapse after HLA-mismatched HCT (64%) was significantly higher than that after HLA-matched HCT (45%) (p = 0.006). Five-year OS/EFS rates were not significantly different between patients with translocation t(1;22)(p13;q13) (50%/42%), those with monosomy 7 (65%/59%), and those with complex karyotype (61%/52%) (p = 0.094/p = 0.111). Five-year OS/EFS rates of patients who underwent HCT in CR1 (72%/64%) were significantly higher than those of patients who underwent in CR2 (23%/13%) and non-CR (16%/16%) (p &lt; 0.001/p &lt; 0.001). Five-year CI of relapse was significantly lower in CR1 (28%) than in CR2 (73%) and non-CR (73%) (p &lt; 0.001). Five-year non-relapse mortality was significantly higher in non-CR (27%) than in CR1 (15%) and CR2 (14%) (p = 0.022). Among the 92 patients who underwent HCT in CR1, 3-year CI of relapse in patients who received RIC (67%) was significantly higher than that in patients who received MAC regimen (25%) (p = 0.021). Five-year OS/EFS rates associated with HCT from HLA-mismatched (70%/63%) and HLA-matched donors (77%/59%) were not significantly different (p = 0.609/p = 0.761). In the multivariate analysis for 5-year OS, HCT in CR2 and non-CR was found to be a significant risk factor (hazard ratio, 5.16; 95% CI, 3.36-7.92; p &lt; 0.001). In conclusion, multivariate analysis confirmed that HCT in CR1 was a good prognostic factor for 5-year OS. Risk stratification in patients with non-DS-AMKL should be established to determine the indication for HCT in CR1. Disclosures No relevant conflicts of interest to declare.

Association between the diagnosis-to-treatment interval and overall survival in Taiwanese patients with oral cavity squamous cell carcinoma

BackgroundTo investigate the association between the diagnosis-to-treatment interval (DTI) and overall survival (OS) in patients with oral cavity squamous cell carcinoma (OSCC). MethodsA total of 18,677 patients with first primary OSCC identified in the Taiwanese Cancer Registry Database between 2004 and 2010 were examined. The effect of DTI on 5-year OS rates was investigated with multivariate Cox regression analysis. After the identification of the optimal cutoff for DTI based on the 5-year OS rates, DTI was classified in the following 20-day groups: ≤20 days (57% of the study patients), 21–45 days (34%), 46–90 days (6%) and ≥91 days (3%). In additional exploratory analyses, DTI was reclassified in the following 30-day interval groups: ≤30 days (81% of the study patients), 31–60 days (14%), 61–90 days (2%) and ≥91 days (3%). ResultsMultivariate analyses identified DTI (≤20 days versus other subgroups), sex (female versus male), age (<65 versus ≥65 years), clinical stage (p-stage I versus p-stage II, III, IV) and treatment modality (initial surgery versus initial non-surgery) as independent prognostic factors for 5-year OS. Compared with a DTI ≤20 days, the DTI categories ≥91 days (hazard ratio [HR]: 1.28, P < 0.001), 46–90 days (HR: 1.25, P < 0.001) and 21–45 days (HR: 1.07, P = 0.007) were independently associated with a higher risk of 5-year mortality. Similar results were obtained for DTI ≤30 days groups. ConclusionsDTI is independently associated with 5-year OS in OSCC patients. A DTI longer than 30 days or even 20 days may potentially decrease survival.

The impact of positive nodal chain ratio on individualized multimodality therapy in non-small-cell lung cancer.

This study aimed to analyze the prognostic significance of the positive nodal chain ratio (NCR) in non-small-cell lung cancer (NSCLC). A total of 208 pIIIa-N2 NSCLC patients who underwent complete surgical resections with a systematic nodal dissection were enrolled. The median values of NCR and the positive lymph node ratio (LNR) were used to grouping patients. The differences of overall survival (OS) and disease-free survival (DFS) between the different groups were compared. The median values of NCR and LNR were 0.31 and 0.45, respectively. The patients were separated into group A (NCR ≤0.45 and LNR ≤0.31; 91 cases), group B (NCR ≤0.45 and LNR >0.31 or NCR >0.45 and LNR ≤0.31; 51 cases), and group C (NCR >0.45 and LNR >0.31; 66 cases) according to their combined LCR and LNR values. Groups A, B, and C exhibited significantly different prognoses (5-year OS: 43.7, 25.2, and 12.3 %, respectively, p < 0.0001; 5-year DFS: 30.4, 23.3, and 8.6 %, respectively, p < 0.0001). Multivariate analyses revealed that this novel grouping method based on the combination of NCR and LNR was an independent prognostic factor for 5-year OS and 5-year DFS in pIIIa-N2 NSCLC. In group C, patients who received no postoperative treatment, adjuvant chemotherapy alone, or chemoradiotherapy exhibited different 5-year OS rates (0.0, 11.6, and 37.5 %, respectively, p = 0.003) and 5-year DFS rates (0.0, 7.5, and 25.0 %, respectively, p = 0.009). Therefore, postoperative chemoradiotherapy may significantly improve the prognosis of patients displaying NCR >0.45 and LNR >0.31. NCR combined with LNR may be more effective to guide individualized multimodality therapy including postoperative chemoradiotherapy for pIIIa-N2 NSCLC.

Lymph node ratio as an independent prognostic indicator in stage III colorectal cancer: especially for fewer than 12 lymph nodes examined.

Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer (CRC), marked heterogeneity exists within stage III patients. Lymph node ratio (LNR) may offer more precise prognostication in stage III CRC. The aim of this study is to investigate the prognostic impact of LNR on survival in stage III CRC patients. We retrospectively reviewed the data of 288 consecutive patients who underwent radical resection for stage III CRC between January 2000 and December 2008 in the Gastrointestinal Surgery Department, Peking University People's Hospital. The patients were divided into three groups according to LNR quartiles: LNR < 0.167 (n=72), 0.167 ≤ LNR < 0.562 (n = 140), and LNR ≥ 0.562 (n=76). The association between overall survival (OS) and disease-free survival (DFS) and 11 variables including age, gender, tumor location, size, grade, histology, tumor (T) stage, number of metastatic LNs, and LNR was analyzed by multivariate analysis. Survival curves were plotted by the Kaplan-Meier method. Both LNR and the number of metastatic LNs were significant prognostic factors for 5-year DFS and OS in stage III CRC patients. LNR was an independent prognostic factor for 5-year OS. LNR remained an independent prognostic factor in patients with fewer than 12 lymph nodes examined. LNR was a potent independent prognostic predictor for OS and DFS in stage III CRC patients, especially for patients with fewer than 12 lymph nodes examined.