Prognostic Factor For Better Survival Research Articles

Survival outcomes and prognostic factors of advanced gastrointestinal stromal tumors: in the era of multiple tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have shown great efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), significantly prolonging the survival of patients. In the era of imatinib, a few studies reported some prognostic factors for patients with advanced GISTs, such as age, sex, performance status, diameter of the largest lesions, KIT exon mutations, and some hematological examination results. However, with the advent of more TKIs, the prognostic factors for patients with advanced GISTs have not been fully understood in the era of multiple TKIs. In this study, we aimed to identify independent prognostic factors associated with the survival of patients diagnosed with advanced GISTs. Data on clinicopathologic characteristics, treatment approaches, and survival were retrospectively collected for patients with primary unresectable or recurrent GISTs treated from January 2010 to July 2023 at the First Affiliated Hospital of Chongqing Medical University, China. Univariable and multivariable Cox proportional hazards regression models were used to identify independent prognostic factors of survival. A total of 194 patients were included in the analysis. The median follow-up duration was 59.9 months (range, 2.7-141.7 months). The median overall survival (mOS) in this cohort was 76.5 months (95% confidence interval, 63.4 to 89.6 months). All patients received TKI therapy during the follow-up period, and 56.2% received two or more types of TKIs. In multivariable Cox analysis, younger age, a single lesion at enrollment, no previous use of TKIs, smaller tumor burden, good Eastern Cooperative Oncology Group performance status (ECOG PS ≤1), and lesions limited to the liver were independent prognostic factors for better survival. We found that a single lesion at enrollment, no previous use of TKIs, a smaller tumor burden, and lesions limited to the liver were associated with better survival. Drug resistance is a severe challenge for advanced GISTs, and several factors mentioned above may be correlated with the development of drug resistance, leading to the poor survival of patients.

Nutritional Status as a Prognostic Factor for Survival in Palliative Care: A Retrospective Observational Analysis of Home Parenteral Nutrition in Cancer Patients with Inoperable Malignant Bowel Obstruction.

Palliative care patients with malignant bowel obstruction are particularly at risk of developing malnutrition, which in turn directly shortens survival time and worsens quality of life (QoL). According to the available data, the survival time in this patient group is often less than three months. To avoid further complications related to malnutrition and poor outcomes in oncological therapy, nutritional therapy such as home parenteral nutrition (HPN) is offered. The aim of this study was to investigate whether nutritional status is a prognostic factor for survival in palliative care patients with malignant inoperable bowel obstruction qualified for home parenteral nutrition and which nutritional assessment tool has the most accurate prognostic value. This retrospective observational analysis included 200 patients with malignant bowel obstruction referred for home parenteral nutrition between January 2018 and August 2023. The analysis included laboratory test results, body mass index (BMI), Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI) and malnutrition as defined by the Global Leadership Initiative on Malnutrition (GLIM). The average survival time of the patients was 75 days. Patients with higher NRI and PNI scores were more likely to survive (NRI: p < 0.001; PNI: p < 0.001). The GLIM criteria, SGA scores and BMI values did not prove to be good prognostic factors for survival (GLIM p = 0.922, SGA p = 0.083, BMI p = 0.092). The results suggest that the use of NRI and PNI may be helpful in prognosing survival in these patients and that prevention of the development of malnutrition through earlier nutritional assessment and intervention should be considered in this patient group.

Prognostic significance of antifibrotic agents in idiopathic pulmonary fibrosis after initiation of long-term oxygen therapy.

Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown. We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT. The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106). In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.

New insights into HER2-low breast cancer brain metastasis: A retrospective analysis

BackgroundA considerable number of patients with breast cancer will suffer from brain metastasis in the advanced setting. The HER2 status serves as a significant prognostic factor and the reference of applying treatment for patients with breast cancer brain metastasis (BCBM). MethodsBetween January 2010 and July 2021, patients with BCBM who had available HER2 status were identified. The patients with HER2 1+ in immunohistochemistry (IHC) or IHC 2+ and fluorescence in situ hybridization (FISH) negative were categorized as HER2-low. Comparisons were conducted between the HER2-low and HER2-zero population. The primary endpoint was overall survival (OS) after the diagnosis of BCBM. Survival outcomes were assessed using Kaplan-Meier curves with log-rank test and Cox proportional hazards model. ResultsIn this study, we analyzed 71 patients with the HER2-low breast cancer subtype and 64 patients with the HER2-zero subtype. Despite the limited sample size, our findings revealed a significantly better OS for patients with HER2-low cancer compared to their HER2-zero counterparts (26 m vs 20 m, p = 0.0017). This trend was particularly notable in the HR-negative group (26 m vs 13 m, p = 0.0078), whereas no significant difference was observed among the HR-positive patients. Furthermore, Cox regression analysis revealed that the HER2-low status was an independent prognostic factor for better survival in the HR-negative patients (p = 0.046 in multivariate analysis). ConclusionsPatients diagnosed with HER2-low BCBM exhibited a more favorable prognosis than those with HER2-zero BCBM, particularly within the HR-negative subgroup. The low expression of HER2 is supposed to be linked to the prolonged survival of BCBM patients.

Family history of cancer is a prognostic factor for better survival in operable esophageal squamous cell carcinoma: A propensity score matching analysis.

Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer is a favorable independent prognostic factor in ESCC. Patients with a family history of cancer, especially digestive tract cancer and esophageal cancer, a family history of cancer in the first degree, and more than one relative affected by cancer were associated with favorable survival when compared to those without a family history of cancer. A family history of cancer (FH) is closely associated with the risk and survival of many cancers. However, the effect of FH on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. We performed a large cohort study in the Chinese population to obtain insight into the prognostic value of FH in patients with operable ESCC. A total of 1,322 consecutive patients with thoracic ESCC who had undergone esophagectomy between January 1997 and December 2013 were included. The FH group included patients with any degree of FH, while the non-FH group included patients without any degree of FH. In total, 215 patients with FH and 215 without FH were matched using the propensity score matching analysis method to adjust for differences in baseline variables between the two groups. The impact of FH on disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier method and Cox's proportional hazards models. Before matching, 280 (21.2%) patients were included in the FH group and 1,042 (78.8%) in the non-FH group. FH was associated with early pathological T stage (p = 0.001), lymph node-negative status (p = 0.022), and early pathological stage (p = 0.006). After matching, FH was an independent prognostic factor for DFS and OS in ESCC patients. Patients with FH had 35% lower risk of disease progression (hazard ratio [HR] = 0.65, 95% CI: 0.51-0.84, p = 0.001) and 34% lower risk of death (HR = 0.66, 95% CI: 0.51-0.86, p = 0.002) than those without FH. Patients with a family history of digestive tract cancer (FH-DC), a family history of esophageal cancer (FH-EC), FH in first-degree relatives (FH-FD), and more than one relative affected by cancer were associated with favorable DFS and OS as compared to those without FH. FH is a favorable independent prognostic factor in ESCC. Patients with FH, especially those with FH-DC, FH-EC, FH-FD, and more than one relative affected by cancer, had improved survival.

286 (PB-110) Poster - Tumor-Infiltrating lymphocytes and its relationship with survival in a series of primary breast cancer patients according to the different surrogated molecular subtypes

Introduction: Tumor-Infiltrating Lymphocytes (TILS) is a well-known predictor of response to primary chemotherapy1,2 and a good prognostic factor for survival in breast different subtypes3. In SABCC20214 we presented data on the relationship between TILs cut-off 20% and pCR (15.6% vs 41.4%, p = 0.0001). In the present study we have analyzed the association of the level of TILs cut-off 20% and survival in the different molecular subtypes at 5 and 10 years.

Hepatic Arterial Infusion Chemotherapy with Oxaliplatin Plus Raltitrexed as an Alternative Option in Advanced Hepatocellular Carcinoma Patients with Failure of, or Unsuitability for, Transarterial Chemoembolization.

Background and Objectives: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin plus raltitrexed (HAICROX) as an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients who are ineligible for, or failed, the transarterial chemoembolization (TACE) treatment. Materials and Methods: From July 2020 to November 2021, a total of 35 HCC patients were enrolled and received HAIC with oxaliplatin plus raltitrexed. The overall survival (OS) and time to progression (TTP) were primary and secondary endpoints, respectively. The tumor response was assessed by the modified response evaluation criteria in solid tumors (mRECIST), and the adverse events were investigated using the common terminology criteria for adverse events version 5.0 (CTCAE 5.0). Results: The median OS and TTP were 10 months (95% confidence interval (CI): 5.5–14.6) and 3.5 months (95% CI: 2.3–4.7), respectively. By means of multivariate analysis, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was found to be an independent prognostic factor for better survival. No patients experienced toxicity-related death. Thrombocytopenia, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) elevation were the most common toxicities. No grade 3 or higher adverse events related to HAICROX were observed. Conclusion: HAICROX showed valuable efficacy and tolerable toxicity in advanced HCC patients who progressed on TACE or were ineligible for TACE. HAICROX is a promising treatment for advanced-stage HCC patients with TACE failure or ineligibility.

Expression of Irisin/FNDC5 in Breast Cancer.

Irisin is a myokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. FNDC5 and irisin levels have been poorly studied in the tumor tissues of breast cancer (BC). The aim of this study was to determine the levels of irisin expression in BC tissues and compare them to clinicopathological factors and Ki-67 and PGC-1α expression levels. Tissue microarrays (TMAs) with 541 BC tissues and 61 samples of non-malignant breast disease (NMBD; control) were used to perform immunohistochemical reactions. FNDC5 gene expression was measured in 40 BC tissue samples, 40 samples from the cancer margin, and 16 NMBD samples. RT-PCR was performed for the detection of FNDC5 gene expression. Higher irisin expression was found in BC patients compared to normal breast tissue. FNDC5/irisin expression was higher in patients without lymph node metastases. Longer overall survival was observed in patients with higher irisin expression levels. FNDC5/irisin expression was increased in BC tissues and its high level was a good prognostic factor for survival in BC patients.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Sinonasal Mucosal Melanoma.

Tumor-infiltrating lymphocytes (TILs) predict better outcome in several types of cancers. However, the prognostic value of TILs in sinonasal mucosal melanoma (SNMM) is uncertain. Here, we investigated whether TILs can be used as a prognostic indicator for survival in SNMM. Retrospective cohort study. Patient history and histologic specimens from 27 patients with primary SNMM were retrospectively analyzed. TIL grade was determined and associations between TILs and AJCC tumor stage, overall survival, and recurrence-free survival were analyzed. Patients with TILs in the primary tumor classified as brisk or non-brisk survived significantly longer than patients with SNMMs lacking lymphocyte infiltrates. Brisk TILs were associated with the lower T3 stage and increased recurrence-free and 5-year survival. Our results indicate that TIL density is a strong prognostic factor for better survival in SNMM. Prospective studies with larger case numbers are warranted to determine whether TILs should be included in future AJCC staging guidelines. 3 Laryngoscope, 132:1334-1339, 2022.

Antizyme inhibitor 2 (AZIN2) associates with better prognosis of head and neck minor salivary gland adenoid cystic carcinoma.

The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer; however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We performed immunohistochemical study on minor salivary and mucous gland ACC tissue samples of patients treated at the Helsinki University Hospital (Helsinki, Finland) during 1974-2012. We scored AZIN1 and 2 immunoexpression in 42 and 45 tumor tissue samples, respectively, and correlated them with clinicopathological factors and survival. Enhanced AZIN2 expression was associated with better survival. In addition, both AZINs were seen more commonly in cribriform and tubular than in solid growth patterns. AZIN1 expression did not correlate with the studied clinicopathological factors. It seems that AZIN2 expression is higher in cancer tissue with secretory functions. In ACC tissue, high AZIN2 expression could be related to well-differentiated histological type which still has a functioning vesicle transportation system. Thus, AZIN2 could be a prognostic factor for better survival of ACC patients.

RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival.

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

Consolidation radiotherapy for patients with extended disease small cell lung cancer in a single tertiary institution: impact of dose and perspectives in the era of immunotherapy.

BackgroundConsolidation radiotherapy (cRT) in extended disease small cell lung cancer (ED-SCLC) showed improved 2-year overall survival in patients who responded to chemotherapy (ChT) in CREST trial, however results of two meta - analysis were contradictive. Recently, immunotherapy was introduced to the treatment of ED-SCLC, making the role of cRT even more unclear. The aim of our study was to access if consolidation thoracic irradiation improves survival of ED-SCLC patients treated in a routine clinical practice and to study the impact of cRT dose on survival. We also discuss the future role of cRT in the era of immunotherapy.Patients and methodsWe retrospectively reviewed 704 consecutive medical records of patients with small cell lung cancer treated at the Institute of Oncology Ljubljana from January 2010 to December 2014 with median follow up of 65 months. We analyzed median overall survival (mOS) of patients with ED-SCLC treated with ChT only and those treated with ChT and cRT. We also compared mOS of patients treated with different consolidation doses and performed univariate and multivariate analysis of prognostic factors.ResultsOut of 412 patients with ED-SCLC, ChT with cRT was delivered to 74 patients and ChT only to 113 patients. Patients with cRT had significantly longer mOS compared to patients with ChT only, 11.1 months (CI 10.1–12.0) vs. 7.6 months (CI 6.9–8.5, p < 0.001) and longer 1-year OS (44% vs. 23%, p = 0.0025), while the difference in 2-year OS was not significantly different (10% vs. 5%, p = 0.19). The cRT dose was not uniform. Higher dose with 45 Gy (in 18 fractions) resulted in better mOS compared to lower doses 30–36 Gy (in 10–12 fractions), 17.2 months vs. 10.3 months (p = 0.03) and statistically significant difference was also seen for 1-year OS (68% vs. 30%, p = 0.01) but non significant for 2-year OS (18% vs. 5%, p = 0.11).ConclusionsConsolidation RT improved mOS and 1-year OS in ED-SCLC as compared to ChT alone. Higher dose of cRT resulted in better mOS and 1-year OS compared to lower dose. Consolidation RT, higher number of ChT cycles and prophylactic cranial irradiation (PCI) were independent prognostic factors for better survival in our analysis. For patients who received cRT, only higher doses and PCI had impact on survival regardless of number of ChT cycles received. Role of cRT in the era of immunotherapy is unknown and should be exploited in further trials.

DNASE1L3 as an indicator of favorable survival in hepatocellular carcinoma patients following resection.

Hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis. It is of great importance to identify biomarkers for the prediction of patients’ survival.The mRNA expression level of deoxyribonuclease 1 like 3 (DNASE1L3) and its correlation with survival were accessed in 424 samples from The Cancer Genome Atlas database. Its expression level was confirmed by real-time quantitative polymerase chain reaction and western blotting in 20 pairs of postsurgical specimens. In addition, immunohistochemistry staining of DNASE1L3 was also performed in 113 postoperative samples, using a histochemistry score system. The relationship between patients’ survival and DNASE1L3 expression level was evaluated by the Kaplan-Meier method.DNASE1L3 is downregulated in both mRNA and protein levels in HCC tissues, compared with adjacent normal tissues. 52 of 113 HCC specimens showed positive DNASE1L3 protein expression. Patients with positive DNASE1L3 expression had significantly longer overall survival, compared with patients with negative expression (p = 0.023). However, the DNASE1L3 fails to discriminate progression-free survival (p = 0.134). Multivariate COX analysis revealed that positive DNASE1L3 expression and higher differentiation were significantly associated with better overall survival.This study demonstrated that positive DNASE1L3 expression is an independent prognostic factor for better survival in HCC patients following radical resection.

Salvage esophagectomy for initially unresectable locally advanced T4 esophageal squamous cell carcinoma.

Definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) is a potentially curative treatment modality, even for patients with unresectable T4 tumors. For patients who fail dCRT, salvage esophagectomy is known to be a high-risk procedure. However, the efficacy and safety of salvage surgery for these patients remain unclear. A total of 35 patients who underwent salvage esophagectomy after dCRT for initially unresectable locally advanced T4 ESCC were assessed, and both outcomes and prognostic factors after surgery were investigated. Among the study population, R0 resection was achieved in 19 patients (54.3%). Postoperatively, 8 patients (22.9%) experienced Clavien-Dindo grade IIIb or higher complications, and 3 patients (8.6%) registered surgery-related mortality. Overall survival rates were 45.7%, 28.6%, and 5.7% at 1, 2, and 5years, respectively. In Cox regression analysis, residual or relapsed tumor limited to T2 or less was an independent prognostic factor for better survival (P = 0.010). On the other hand, postoperative pneumonia and incomplete resection were negative prognostic factors (P < 0.001 and P = 0.019, respectively). Nodal involvement and extent of lymph node dissection did not impact patient survival. Although salvage esophagectomy for initially unresectable T4 ESCC is considered a high-risk surgery with poor prognosis, long-term survival may be achieved in patients with ≤ T2 residual tumors. In addition, R0 resection and postoperative pneumonia prevention are crucial to improve patient survival.

Long-term effects of radiation prior to surgery and chemotherapy on survival of esophageal cancer undergoing surgery.

Esophageal cancer (EC) is one of the most common cancers in the world, with continuously growing diagnoses and morbidity. Because it is still unclear how to choose the best treatment for EC patients, a multimodal treatment is necessary to improve the prospect of the malignancy, including a sequence of surgery, chemotherapy, and radiotherapy, whether alone or combination. Therefore, this paper aims to analyze the effect of the sequence of chemotherapy, radiotherapy, and surgery on the prognosis and survival rate of patients with EC.The Surveillance, Epidemiology, and End Results (SEER) database was used to extract a dataset of patients who were diagnosed with EC from 1973 to 2015, with follow-up data for 6 years after diagnosis. The data were analyzed using correlation analysis, logistic regression Cox regression, and Kaplan–Meier analysis.EC patients who had radiation prior to surgery and chemotherapy had a better prognosis than the cases without chemotherapy. Based on univariate logistic regression, the odds radios of vital status recoded for “radiation prior to surgery combined with chemotherapy” is the lowest one among the 8 groups classified by radiation sequence with surgery and chemotherapy (P < .001). Further, radiation prior to surgery and chemotherapy is an independent prognostic factor for better survival among EC patients.In conclusion, in the treatment of EC, administering radiation prior to surgery and chemotherapy is better than no radiotherapy, perioperative radiotherapy, postoperative radiotherapy, and other combinations without chemotherapy.

PF593 THE IMPACT OF RESPONSE KINETICS FOLLOWING INITIAL THERAPY FOR MULTIPLE MYELOMA IN THE ERA OF NOVEL AGENTS

Background:Rapid remission has long been recognized as an important predictor for long‐time survival in acute leukemia (AL). However, the effects of response kinetics on survival seems to be different from those in AL. A rapid reduction of tumor burden probably indicates a chemotherapy‐sensitive population. But on the other hand, a high proliferative activity of plasma cell may be responsible for the rapid response. The effects of response kinetics on outcome for MM remain largely unexplored.Aims:In the era of novel drugs, the proportion of patients attaining complete remission (CR) has been significant increased. However, a deep response has not always translated into an improved survival. In both transplant‐eligible and ineligible patients, we identified different response kinetic patterns after induction therapy which are associated with distinct patient outcomes.Methods:The relationship between response kinetics and outcome were prospectively assessed in 626 patients with newly diagnosed MM that were included in a prospective, non‐randomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drugs‐based or proteasome inhibitors‐based therapy. The response depth, time to best response (TBR) and duration of best response (DBR) were collected. Modified progression‐free survival (mPFS) and overall survival (mOS) from time of first detectable best response were calculated.Results:Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as TBR ≤ 3 months) showed significantly worse survival compared with late responders. There was no significant difference in survival between patients with a rapid CR and those with a late partial remission (PR) (mPFS 33.4 vs. 36.2 months, P = 0.382; mOS 62.6 vs. 64.2 months, P = 0.169). TBR remained an independent predictor of outcome in multivariate analysis (HR = 1.9 and HR = 2.8 for mPFS and mOS).Moreover, four distinct response kinetic patterns were identified: 1) late response and late relapse (“U‐valley” pattern) (n = 157, 25%); 2) early response and late relapse (n = 101, 16%); 3) late response and early relapse (n = 130, 21%); 4) early response and early relapse (“Roller coaster” pattern) (n = 172, 25%), and best response less than PR (n = 66, 11%). Response kinetics based stratification resulted in remarkable differences in outcome. Patients with gradual and sustained remission identified as “U‐valley” pattern experienced superior outcomes, followed by patients with “early response and late relapse” and “late response and early relapse”, while poorest outcomes were observed in rapid and transient responders (“Roller coaster” pattern) (median OS 126, 81, 44 and 30 months, respectively). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant‐eligible patients and those attaining different extents of response depth.Summary/Conclusion:Our data indicate that a slow and gradual response is a good prognostic factor for survival, arguing against premature change to more intensive regimens, especially for elderly or unfit patients. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.image

Nomogram for Individualized Prediction and Prognostic Factors for Survival in Patients with Primary Spinal Chordoma: A Population-Based Longitudinal Cohort Study

Chordoma is a type of rare bone tumor and is a relatively slow-growing, low-grade malignancy that is locally invasive and aggressive. The nomogram is widely used in the field of cancer because it can provide a clear picture for clinicians to predict the survival rate, which can lead more accurate decisions in clinical treatment. Overall, 875 patients with a primary spinal chordoma were identified and collected from the Surveillance, Epidemiology, and End Results registry databases (1973-2015). The nomogram was established based on 425 patients with complete data. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and calibration curve. The statistical nomogram was built on 10 independent prognostic factors: age, sex, race, disease stage, surgery, year of diagnosis, marital status, primary site, radiation, and tumor size, with C-indices of 0.76. The calibration curve to determine the probability of survival showed good agreement between the predictions by the nomogram and actual observation. Tumor diameter >10 cm (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.77-4.90, P < 0.001), regional invasive (HR 1.71, 95% CI1.16-2.53, P < 0.01), and distant metastasis (HR 3.44, 95% CI 1.98-5.96, P< 0.001) were independent risk factors for poor survival. Undergoing subtotal resection or gross total resection (HR 0.37, 95% CI 0.25-0.56, P < 0.001; HR 0.26, 95% CI 0.17-0.41, respectively) and a primary site located in the sacrum/pelvis (HR 0.51, 95% CI 0.34-0.78, P < 0.01) were prognostic factors for better survival. The nomogram provided more accurate prognostic predictions for patients with spinal chordoma. Moreover, our study suggests that tumor diameter >5 cm, distant metastasis, and not performing resection are major risk factors that can dramatically decrease the survival time of patients with spinal chordoma.

Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia in Era of Tyrosine Kinase Inhibitors -a Single Centre Experience from India

Background Transplant remains most curative option for patients with TKI resistant disease or in advanced phase of CML. We retrospectively analyzed transplant outcome of CML patients in era of TKI from our centre. Methods All patients who underwent allogeneic stem cell transplant for CML between Aug 2010 to Sept 2016 were included. Conditioning regimens included Flu-Mel (67.5%), Bu-Cy (10%), Flu- 7.2 Gy TBI (15%), or Flu-treo-2GyTBI (7.5%). For matched sibling (MSD) or unrelated donor (MUD) transplants, GVHD prophylaxes were cyclosporine (CsA) with methotrexate in 26(65%) or mycophenolate(MMF) in 8 (20%) patients respectively . Post transplant cyclophosphamide (PtCy) with CSA / tacrolimus with MMF was used in 6 (15%) patients who underwent haploidentical transplant (HIT) .Disease Risk Index (DRI), HCT-CI and EBMT scores at transplant were calculated for all . Overall survival (OS) was calculated from date of transplant to date of death or last follow up while relapse-free survival (RFS) was calculated till date of molecular relapse (>0.1% BCR-ABL),death or LFU if in MMR. Prognostic factors evaluated were duration from diagnosis to transplant ( 2 years), EBMT score (≤3 vs>3), acute and chronic GVHD, type of transplant and DRI index. Results Median age was 30 years (12-55) of which 30 (75%) were male. TKI failure was the commonest reason for transplant (95%) .T315I mutation was seen in 17.5% of patients . Twenty-six (65%) were in CP, 8 in AP and 6 in BC at diagnosis. The median EBMT and HCT-CI score were 3 and 2 respectively. Twelve (30%) patients had high DRI. MSD transplant was performed in 33 (82.5%), 6 (15%) underwent HIT and 1 MUD transplant. All except 1 patient received PBSC graft. Grade III/IV mucositis and diarrhea were seen in 19 (47.5%) and 4 (10%) patients respectively. Median time to neutrophil and platelet engraftment were 16 and 13.5 days respectively. Incidence of grade III/IV acute GVHD and chronic GVHD was 50% and 60% respectively. At 1 year post transplant >4.5 log reduction (DMR) was attained in 25 (62.5%) while 5 (12.5%) patients were in MMR. Five patients received DLI (3 patients for clinical relapse,2 for slippage of chimerism). Median follow up was 36 months. Non relapse mortality was seen in 8 (20%) patients. (GVHD-7, Myocarditis1). OS and RFS at 5 years were 70 % and 57 % respectively. In multivariate analysis for RFS, EBMT score≤ 3 and time from diagnosis to transplant > 2 years were independent prognostic factors for better RFS. For OS, presence of chronic and absence of acute GVHD were independent prognostic factors for better survival. Conclusion The long term survival in TKI resistant and advanced CML with transplant is promising. Along with other factors, transplant after 2 years from diagnosis was an independent prognostic factor for better survival contrary to transplant within 1 year of diagnosis in the pre TKI era .This may be due to better disease control with advent of TKIs.

Association of neck dissection with survival for early stage N0 tongue cancer: A SEER population-based study.

The management of the node negative neck in patients with tongue cancer remains a complex and controversial issue, especially in those with early stage tumors. Patients with negative cervical lymph nodes generally have a good prognosis. However, in patients without neck dissection, neck recurrences may occur after excision of the primary tumor due to occult cervical metastases. It often results in poor salvage therapy options and short survival. We used Surveillance, Epidemiology, and End Results data from 2004 to 2013 to investigate the association of neck dissection with survival among early stage tongue cancer patients with negative lymph node metastasis. A total of 4274 eligible patients were subdivided into 2 groups according to their neck management strategies: neck dissection and observation. Univariate and multivariate Cox proportional hazards regression models were used to determine the independent factors of survival. The Kaplan-Meier method was employed for survival analysis. In the overall cohort, patients who underwent neck dissection had better survival than those who were managed with observation in both tongue cancer specific survival and overall survival. After adjusting for confounding variables, neck dissection strategy remains an independent prognostic factor for better survival. When stratifying the patients according to age, gender, race, marital status, histologic grade, stage and radiotherapy, patients in the neck dissection group had significantly better survival than those in the observation group. Neck dissection may improve survival for early stage tongue cancer patients with negative lymph node metastasis. These results may assist clinicians in selecting the most appropriate neck management strategy for individual patients.

Survival Benefit with Standard-Dose Decitabine Versus Standard-Dose Azacitidine in Patients with Lower-Risk Myelodysplastic Syndromes

Introduction: Hypomethylating agents (HMAs) are used for the treatment of patients with myelodysplastic syndromes (MDS). Two HMAs, decitabine and azacitidine, are currently available for such treatment. Numerous studies have analyzed the clinical efficacy of HMAs in patients with MDS; however, reports directly comparing decitabine and azacitidine in patients with lower-risk (low and intermediate-1) MDS are limited. The clinical efficacy of standard-dose HMA treatment in lower-risk MDS remains controversial.Patients and methods: The Korea University MDS registry is a longitudinal cohort that contains data on 452 patients consecutively diagnosed with MDS from October 2006 to December 2017 in Korea University Medical Center (Korea University Anam, Guro, and Ansan Hospital). In the Korea University MDS registry, 357 patients were classified as having lower-risk MDS. Among them, 115 patients were treated with HMA (decitabine or azacitidine); 111 patients were eligible for the study. We compared treatment responses, survival outcomes, and adverse events between standard-dose decitabine (20 mg/m2 daily for 5 days every 4 weeks) and azacitidine (75 mg/m2 daily for 7 days every 4 weeks) in lower-risk MDS patients. Treatment responses were assessed according to the modified 2006 International Working Group response criteria. Patients who were evaluated received at least one cycle of HMA therapy. The overall response rate (ORR) included complete remission (CR), partial remission, marrow CR, and hematologic improvement. Progression-free survival (PFS) was measured from the time of treatment initiation until disease progression or death from MDS.Results: The CR rates were 16.4% (10/61) in the decitabine group and 6.0% (3/50) in the azacitidine group with borderline significance (P = .090). The ORRs were 67.2% (41/61) and 44.0% (22/50) for decitabine and azacitidine, respectively (P = .014). The erythroid responses for decitabine and azacitidine were 68.3% (41/60) and 44.2% (19/43), respectively (P = .014). In the multivariable analysis, treatment with decitabine (hazard ratio [HR] 2.553; 95% confidence interval [CI] 1.116-5.840; P = .026), hemoglobin (Hb) concentration of <8 g/dL (HR 3.073; 95% CI 1.340-7.048; P = .008), and ≥5% BM blasts (HR 3.739; 95% CI 1.102-12.683; P = .034) were significantly associated with higher ORRs. The median progression-free survival was significantly better in patients treated with decitabine than in those treated with azacitidine (33 vs. 19 months; P = .019). There were no significant differences in the event-free survival and in the overall survival between the two HMAs. In the multivariable analysis, treatment with decitabine (HR 0.496; 95% CI 0.257-0.957; P = .037) and achievement of CR (HR 0.122; 95% CI 0.015-0.993; P = .049) were significant prognostic factors for better survival, whereas ANC below 0.8 × 109/L (HR 1.905; 95% CI 1.032-3.515; P = .039) was a significant prognostic factor for poor prognosis. The poor cytogenetic risk group, as classified by International Prognostic Scoring System (HR 2.136; 95% CI 0.992-4.556; P = .052), also affected the survival unfavorably with borderline significance. There were no significant differences in grade 3 or higher hematologic adverse events between the two HMAs.Conclusions: The standard-dose decitabine therapy showed significantly better ORR, erythroid response, and longer PFS than did standard-dose azacitidine in patients with lower-risk MDS. The frequencies of hematologic adverse events did not differ between the patients who received decitabine and those who received azacitidine. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.