Unfavorable Prognostic Factor For Overall Survival Research Articles

Prognostic Factors and Treatment Strategy in Patients with Hodgkin Lymphoma and HIV Infection Treated with ABVD and CART: A Retrospective Study from Spanish Group Geltamo

Background Hodgkin lymphoma (HL) is one of the most frequent non-AIDS defining neoplasm in people living with HIV (PLWH). Since the widespread use of combined antiretroviral therapy (cART), the incidence of most types of non-Hodgkin lymphoma affecting PLWH have decreased, but the incidence of HL has increased. The International Prognostic Score (IPS) is the most widely used score for HL. However, its implementation in PLWH is still controversial. Current HL treatment guidelines consider early and advanced stage. In function of the presence of unfavorable risk factors in early stages, an interim PET-CT can be used to guide therapeutic strategy. Unfavorable risk factors have been described by international groups (EORT, GHSG, NCI-C, and NCCN), which are: ≥3-4 involved lymph node areas, elevated RDW, age ≥50 years, ≥1 extranodal involvement and presence of B symptoms. There is a lack of evidence of the impact of this strategy in patients with HIV. Methods Retrospective multicentric study of patients with HIV infection diagnosed with HL in 9 hospitals from the GELTAMO group in Spain, from 1995 to 2022. All patients were treated with ABVD and cART +/- radiotherapy. The main clinical and biological variables were collected. Peripheral absolute neutrophil, lymphocyte and monocyte counts were studied, including L/M ratio and CD4 + lymphocyte count. Moreover, serum lactate dehydrogenase (LDH), albumin and RDW were evaluated. Univariable and multivariable analysis were performed using the binary logistic regression model for complete response (CR) rate and Cox proportional-hazards regression model for overall survival (OS) and progression-free survival (PFS). Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. Results Ninety patients were retrospectively analyzed with a median follow up of 5.89 [0,4;24,78] years. The characteristics of the patients are summarized in Table 1. Extranodal involvement, hemoglobin <105 g/L, leucocytosis, high RDW, hypoalbuminemia and high LDH were associated with worse probabilities of complete response (CR) achievement. In the univariate analysis, bone marrow involvement and monocytes count ≥0.6 x10^9/L were associated with shorter overall survival (OS) and progression free survival (PFR) probabilities. A lymphocyte/monocyte (L/M) ratio <1.09 was associated with shorter PFR probabilities. By multivariable analysis, only monocyte count ≥0.6 x10^9/L emerged as an unfavorable prognostic factor for OS and PFS ( Figure 1). Data about treatment strategy and CR achievement is described in Table 1. Most patients (74%) presented advanced stage and the presence of unfavorable prognostic factors (described by international groups) was detected in most of the patients with localized stages ( Table 1). Conclusions High monocyte count is a strong prognostic factor which can be used in PLWH with HL. Most patients with HL and HIV infection present an advanced stage at diagnosis or a localized stage with unfavorable prognosis factors. In patients with localized stage, interim PET-CT guided strategy seems to be feasible.

Key factors associated with response in the treatment of liver metastatic melanoma by cryoablation combined with PD-1 blockade therapy: The Cryo-Fire-001 study.

e21500 Background: Liver metastasis remains a challenge in the treatment of advanced stage melanoma through immunotherapy. Although our previous study showed cryoablation could enhance the efficacy of PD-1 blockade therapy in the treatment of melanoma patients with liver metastasis, the key factors correlated with survival and treatment response remains unknown. Methods: Between 2018 and 2022, 45 melanoma patients receiving combined PD-1 blockade therapy and cryoablation of liver metastasis were retrospectively analyzed. The technical parameters of cryoablation, the sequence of the combined treatment, tumor characteristics, important immune markers and their correlations with treatment response were evaluated. The associations between key factors and overall survival (OS) were determined by Cox regression. Results: Of the 45 patients, the 3-month overall response rate (RECIST 1.1 criteria) is 26.7%. Multivariate analysis showed the number of metastatic organs ( > 2 vs ≤2; HR 3.54; 95% CI 1.32-9.49; P = 0.012), pretreatment LDH level ( > 300 vs ≤300 U/L; HR 4.59; 95% CI 1.78-11.85; P = 0.002) and diameter of ablated lesion ( > 30 vs ≤30 mm; HR 3.27; 95% CI 1.17-9.15; P= 0.024) were independent unfavorable prognostic factors for OS. Further analysis showed patients with larger intrahepatic tumors ablated had larger tumor size (P < 0.001). A scatter plot by the two key variables showed patients with intrahepatic tumor size less than 45 mm and size of ablated lesion less than 30 mm had a marginally higher rate of 3-month response (10/28, 35.7%) compared to those not (2/17, 11.7%; P = 0.076). Large diameter of ablated lesion ( > 30 mm) require more ablation needles and cause greater elevation in the level of IL-6, CD8+T cell to Treg cell ratio and neutrophil to lymphocyte ratio after cryoablation while these changes disappeared when tested one month later. Conclusions: Fine selection based on baseline characteristics of patients and size of intrahepatic lesion for cryoablation are essential to achieve a high response rate during cryoablation-PD-1 combination treatment for liver metastatic melanoma.

The relationship between adjuvant radiotherapy and survival of osteosarcoma: a case-control study

ABSTRACT To investigate whether adjuvant radiotherapy (RT) is associated with survival rate of osteosarcoma patients. A total of 3938 osteosarcoma patients between 1975 and 2016 from Surveillance, Epidemiology, and End Results (SEER) database were enrolled in this study. Survival rate was obtained by Kaplan-Meier method, with log-rank test identifying the difference. Multivariate Cox regression analysis was used to explore independent prognostic factors. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates in surgery plus adjuvant RT group and surgery alone group were 38.2%, 66.3% (OS), and 41.6%, 68% (CSS), respectively. Multivariate analysis showed that adjuvant RT served as the independent unfavorable prognostic factor for OS and CSS. Based on the propensity score matching (PSM) method, the patients who received adjuvant RT had a poorer prognosis. Adjuvant RT showed an association with survival of osteosarcoma. Patients who received adjuvant RT had poorer survival. In the clinical use of adjuvant RT for osteosarcoma, the potential for reduced survival should be considered.

Percutaneous Radiofrequency Ablation Is an Effective Method for Local Control of Liver Metastases From Lung Cancer.

ObjectiveTo investigate the clinical value of percutaneous radiofrequency ablation (RFA) for liver metastasis from lung cancer (LCLM).Materials and MethodsWe retrospectively enrolled 58 patients who underwent RFA for LCLM between January 2014 and December 2019. Primary lung cancer histology included 38 adenocarcinomas, 15 squamous carcinomas, and 5 small cell carcinomas. For 83 metastatic lesions (mean tumor diameter 3.3 ± 1.1 cm, range 0.9–5.0 cm), 65 RFA sessions were performed. Before RFA, 17 and 41 patients presented no and stable extrahepatic metastasis, respectively, whereas 18 and 40 patients had synchronous and metachronous liver metastasis, respectively. Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards model was used for multivariable analysis.ResultsThe technical success rate was 96.3% (80/83 lesions). Local tumor progression was observed in 8 (9.8%, 8/82) lesions of 57 (14.0%, 8/57) patients at 4–12 months after RFA. New liver metastases occurred in 27 (46.6%) patients. The overall survival (OS) rates at 1, 2, 3, and 5 years after RFA were 55.2%, 26.0%, 22.0%, and 14.4%, respectively. The median OS after RFA and after liver metastasis were 14.0 ± 1.6 and 20.0 ± 1.5 months, respectively. Based on the univariable analysis, tumor size (p=0.017), histological type (p=0.015), and timing of liver metastasis (p=0.046) were related to OS. In further multivariable analyses, squamous carcinoma (hazard ratio= 2.269, 95% confidence interval: 1.186-4.339, p=0.013) was an independent unfavorable prognostic factor for OS. Based on the univariable analysis, histological type (p=0.010) was identified as parameters significantly related to local tumor progression (LTP)-free survival. Further multivariable analyses revealed that squamous carcinoma (hazard ratio=2.394, 95% confidence interval: 1.260–4.550, p=0.008) was an independent unfavorable prognostic factor for LTP-free survival.ConclusionRFA is a safe therapeutic option for LCLM with acceptable local tumor control, especially in patients with a tumor size ≤3 cm, adenocarcinoma/small cell carcinoma, and metachronous liver metastases.

Prognostic analysis and establishment of a nomogram in patients with myoepithelial carcinoma of the salivary gland: A population-based study.

BackgroundCurrently, the clinicopathological characteristics and prognosis of myoepithelial carcinoma of salivary gland (MC‐SG) have not been defined well. The present study aimed to describe the clinicopathological characteristics and prognosis of MC‐SG patients.MethodsThe Surveillance, Epidemiology, and End Results database was searched for all patients diagnosed with MC‐SG between 1991 and 2016. The Kaplan–Meier method and log‐rank tests were used to evaluate the survival. Univariate and multivariate Cox regression analysis were used to identify prognostic biomarkers for overall survival (OS) and disease‐specific survival (DSS). Furthermore, a prognostic nomogram was established, and its predictive accuracy and discriminative ability were determined using the concordance index (C‐index).ResultsIn total, 245 patients diagnosed with MC‐SG were identified. The median OS was 152.0 months, with 3‐, 5‐, and 10‐year survival rates of 79.8%, 69.2%, and 50.3%. The 3‐, 5‐, and 10‐year DSS rates were 82.5%, 77.1%, and 61.9%, respectively. Regarding the treatment regimen, most patients (92.2%) underwent surgery, and 103 patients (42.4%) received postoperative radiotherapy. Surgery could significantly prolong OS and DSS (p < .05), but postoperative radiotherapy did not significantly prolong OS and DSS when compared with individuals receiving surgery alone (p > .05). Multivariate Cox analysis revealed that T category (T4), lymph node metastasis (N2), distant metastasis (M1), and poor differentiation were independent unfavorable prognostic factors for OS and DSS. Older age (>62 years) was also independently associated with OS. In addition, the C‐index for the established OS‐ and DSS‐specific nomogram was 0.80 (95% CI: 0.72–0.88) and 0.82 (95% CI: 0.73–0.90).ConclusionAge, tumor invasion, metastases, and pathological grade were independently associated with prognosis of MC‐SG patients, and the prognostic nomogram of this rare disease was established.

Sequential treatment in advanced non-small cell lung cancer harboring EGFR mutations.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation. Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0-67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5-34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS. This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.

Validation of New International Prognostic Scores, Including Baseline Peripheral Blood Variables, in Patients with Diffuse Large B-Cell Lymphoma and HIV Infection Treated with R-CHOP and Combined Antiretroviral Therapy. Retrospective Study from Spanish Lymphoma Group Geltamo

Validation of New International Prognostic Scores, Including Baseline Peripheral Blood Variables, in Patients with Diffuse Large B-Cell Lymphoma and HIV Infection Treated with R-CHOP and Combined Antiretroviral Therapy. Retrospective Study from Spanish Lymphoma Group Geltamo

Prognostic value of hypertension in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

BackgroundThe prognostic value of hypertension remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). In this study, we aimed to develop hypertension as a prognostic signature for improving the clinical outcome of non-metastatic NPC patients treated with IMRT.MethodsA clinical cohort, comprising 1,057 patients with non-metastatic, histologically proven, NPC who were treated with IMRT were retrospectively reviewed. Associations between hypertension and overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were estimated by Cox regression. A subgroup analysis of the relationship between hypertension grade and NPC prognosis was also conducted.ResultsAmong the 1057 patients, 94 (8.9%) had hypertension. Significant differences were observed between patients with hypertension and patients without hypertension in relation to OS (66.6% vs. 85.4%; P<0.0001), PFS (60.8% vs. 76.3%; P=0.001), LRRFS (85.3% vs. 90.5%; P=0.024), and DMFS (77.4% vs. 85.1%; P=0.048), and patients without hypertension had greater treatment success rates. The Cox analysis showed that hypertension was an independent unfavorable prognostic factor for OS [hazards ratio (HR), 2.056; P=0.001], PFS (HR, 1.716; P=0.005), and DMFS (HR, 1.658; P=0.049). The patients with more severe levels of hypertension had worse OS and LRRFS. Specifically, the 5-year OS and LRRFS for grades 1, 2, and 3 were 70.6%, 64.3%, and 62.4% (P=0.712), and 89.5%, 86.4%, and 76.1% (P=0.376), respectively.ConclusionsHypertension is an independent adverse prognostic factor in NPC patients treated with IMRT. The question of whether the severity of hypertension affects prognosis needs to be further verified by large sample data.

The Clinical and Biological Implications of Aberrant Alternative Splicing in Patients with De Novo, Non-M3 Acute Myeloid Leukemia

BackgroundAberrant alternative splicing (AS) were reported important in the pathogenesis and prognosis of acute myeloid leukemia (AML). Previous studies reported inferior outcomes in AML patients carrying mutations in genes encoding RNA-splicing proteins, which accounted for 18% of AML patients. However, whether aberrant AS is correlated with these mutations or carried clinical and biological significances in AML patients remain unknown. In this study, we aimed to answer these questions by a set of array data from a large cohort.Materials and MethodsA total of 171 newly diagnosed non-M3 AML patients, who received standard induction chemotherapy and had complete clinical and genetic information were enrolled. There were 20 healthy marrow donors for comparison. We extracted RNA from mononuclear cells (MNC) in the bone marrow (BM), followed by hybridization on the microarrays of Affymetrix Human Transcriptome Array 2.0, which contained >6 million distinct probes covering 44710 coding, 22829 non-coding transcripts, and exon-exon junctions. This comprehensive coverage facilitated investigation of the global splicing patterns. The splicing index (SI) of a probe in a gene was derived from the ratio between AML patients and normal controls in terms of the probe intensity divided by the gene expression level, i.e., SI = [(intensity of probe A in gene A) / (gene A expression level)] of AML patient / [(intensity of probe A in gene A) / (gene A expression level)] of normal control. When the value is less than 1, SI is defined as the negative reciprocal. SI had to be less than -2 or more than 2 to be denoted as an aberrant AS event. A gene with at least one aberrant AS event would be called an aberrant AS gene. SI values were log2 transformed and analyzed for the association with overall survival (OS) by the univariable Cox proportional hazards model. Functional annotation for significant aberrant AS events was performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) web tool with default settings. The aberrant AS events were then merged into a Least Absolute Shrinkage and Selection Operator (LASSO) regression, which identified the best subset of aberrant AS events for the prediction of OS. We adopted a leave-one-out cross validation scheme to identify the subset with the best performance. A beta value was assigned to each of the selected aberrant AS events by LASSO. Based on the results, we constructed a scoring system by a weighted sum of the selected features, where the weights were LASSO beta values. The scoring system was applied to predict OS and relapse-free survival (RFS).ResultsAt first, univariable Cox analysis identified 95 OS-associated aberrant AS events (P<0.01; n=171) in 69 coding and 6 non-coding genes. A DAVID analysis was performed to explore the functional relevance of these events. Of note, 41 of the involved coding genes were known involved in RNA splicing pathways (P=0.049). Furthermore, the aberrant AS genes were associated with AMPK signaling pathway (P=0.007), PI3K-Akt signaling pathway (P=0.025), and HIF-1 signaling pathway (P=0.042). We used a LASSO regression model to identify the subset of aberrant AS events that best predicted OS by a leave-one-out cross validation test. As a result, a simple scoring system of 9 aberrant AS events was developed. The system was composed of a weighted sum of aberrant AS events on APP, CD93, CT45A3, CUX2, PIK3R3, RORA, SCRN1, and ZSCAN31, and a non-coding transcript. A high score was predictive of inferior OS (Figure 1A; P<0.001; median survival, 18.0 and 108.1 months) and RFS (Figure 1B; P=0.005; median survival, 10.2 vs. 88.8 months; n=137). Patients with detectable mutations in spliceosome (n=16) did not have a higher aberrant AS score (P=0.589). Age, hemogram, cytogenetics, and FAB classification were not correlated with aberrant AS score, either. However, a higher score was predictive of lower complete remission rate (P=0.01), a higher relapse rate (P=0.006), and higher incidence of FLT-3 -ITD. In addition, multivariate analyses revealed a higher aberrant AS score as an unfavorable prognostic factor for OS and RFS (both P< 0.001) independent of age, WBC counts, cytogenetics, genetic mutations of NPM1 and CEBPA and FLT-3 -ITD (Table 1).We present the clinical significance and prognostic impact of an aberrant AS scoring system in de novo, non-M3 AML patients. Large prospective cohorts are needed to confirm our observations. [Display omitted] DisclosuresTang:Celgene International Sàrl: Research Funding. Yao:Celgene International Sàrl: Research Funding. Li:Celgene International Sàrl: Research Funding. Huang:Celgene International Sàrl: Research Funding. Ko:Celgene International Sàrl: Research Funding. Hsu:Celgene International Sàrl: Research Funding. Lin:Celgene International Sàrl: Research Funding. Wu:Celgene International Sàrl: Research Funding. Tsai:Celgene International Sàrl: Research Funding. Tien:Celgene International Sàrl: Research Funding.

Outcomes and Prognostic Factors of Patients with Metastatic Colorectal Cancer Who Underwent Pulmonary Metastasectomy with Curative Intent: A Brazilian Experience.

We aimed to identify clinicopathological and molecular features associated with progression-free survival (PFS) and overall survival (OS) after pulmonary metastasectomy for metastatic colorectal cancer in a retrospective cohort in Brazil. We did a retrospective review of thoracic surgeries performed in a single large academic hospital in Brazil from January 1985 to September 2019. Demographics, previously described prognostic factors, and clinicopathological and molecular characteristics were abstracted. Univariate Cox regression was performed for each variable, and, when significant, data were dichotomized to provide clinically meaningful thresholds. Records from 698 patients were reviewed. Fifty-eight patients underwent pulmonary metastasectomy with curative intent. Of those, 53.4% had a single metastatic lesion. The median size of the largest lesion was 1.5 cm. Results of RAS, RAF, and mismatch repair testing and of cytokeratin 20 (CK20) and CDX2 testing were available for 13.8% and 58.6% of the sample, respectively. Median PFS was 14 months, median OS was 58 months, and 5-year survival was 49.8%. Unfavorable prognostic factors for OS included disease-free interval (DFI) <24 months, synchronous presentation, size of the largest lesion ≥2 cm, and loss of CK20 expression. Presenting with more than one lesion was prognostic for PFS but not for OS. In this Brazilian cohort, our findings corroborate existing data supporting DFI, synchronous presentation, and number and size of lesions as prognostic factors. Furthermore, we found that loss of CK20 expression may be associated with more aggressive disease and shorter OS. Additional molecular prognostic factors after pulmonary metastasectomy for colorectal cancer should be further explored. This study consolidates disease-free interval, synchronous presentation, and number and size of lesions as clinically relevant data that may help guide therapy for patients with colorectal cancer and lung metastases who are candidates for curative-intent metastasectomy. Additionally, in this sample, lack of cytokeratin 20 expression in metastases was associated with shorter progression-free survival and overall survival, suggesting that biomarkers also may have a role in guiding therapy in this setting and that additional biomarkers should be further explored.

High Expression of RhoF Predicts Worse Overall Survival: A Potential Therapeutic Target for non-M3 Acute Myeloid Leukemia.

Rho GTPases are involved in multiple human malignancies and diverse biological functions. However, the patterns and prognostic significance of the expression of RhoD subfamily in acute myeloid leukemia (AML) remain unknown. Here, we detected the expressions of RhoD subfamily genes in AML on the basis of several published datasets and analyzed the survival of RhoD subfamily across the TCGA profiles and in a GEO series. We found that the expression of RhoF, but not RhoD, increased in AML patients in TCGA and GEO (all P<0.001); the survival analysis of two independent cohorts demonstrated that higher RhoF expression was significantly associated with poorer overall survival (OS) (P<0.001), whereas RhoD expression had no significant effect on OS in patients with AML (P>0.05); the subgroup analysis showed that high RhoF expression was correlated with poor 1-, 3-, and 5-year OS (P<0.05 for all); upregulated RhoF expression had a more significant prognostic value for OS in the younger patients (age<60), the intensive chemotherapy group, and wild-type groups (IDH1, NRAS, and TP53) (P<0.05 for all). Multivariate analysis indicated high RhoF expression as a strongly independent unfavorable prognostic factor for OS in patients without transplantation (P<0.05). Furthermore, a higher RhoF expression was closely associated with an older age, intermediate-/poor-risk cytogenetics and mutations in IDH1, NRAS, and TP53. RhoF expression was negatively correlated with BM blasts (P=0.020) and WBC (P=0.003). These findings suggest that high RhoF expression is associated with worsening OS in AML patients and is a potential therapeutic target for the treatment of AML.

The expression levels of long non-coding RNA KIAA0125 are associated with distinct clinical and biological features in myelodysplastic syndromes.

Long non-coding RNAs (lncRNAs) have important functions in cancer biology. Among them, lncRNA KIAA0125 is one of the genes proposed to play a critical role in leukaemia stem cell (LSC). In this study, we aimed to investigate the clinical relevance of the expression levels of lncRNA KIAA0125 in myelodysplastic syndromes (MDS), a disease with highly heterogeneous clinical and biological features. Using RNA arrays, we measured the expression of KIAA0125 in 176 primary MDS patients. We found that higher KIAA0125 expression was associated with higher risk MDS, based on the revised International Prognostic Scoring System (IPSS-R), mutations in ASXL1 and NRAS, and predicted poorer overall survival (OS) and leukaemia-free survival (LFS). Multivariate analysis revealed that higher KIAA0125 expression was an independent, unfavourable prognostic factor for OS and LFS, irrespective of IPSS-R and mutation status. Further global gene expression profile analysis suggested a close association of higher KIAA0125 expressions with LSC signatures. The expression of KIAA0125 may be a potential biomarker to guide the treatment choice in MDS patients, especially those with lower risk subtypes, in whom palliative treatment is usually used.

Modified geriatric nutrition risk index as a prognostic predictor of esophageal cancer.

This study aimed to establish a simple and useful prognostic indicator for elderly esophageal cancer patients. We designed the modified geriatric nutrition risk index (mGNRI) using the inverse of C-reactive protein (CRP) instead of albumin and compared its prognostic value with those of the GNRI and other indices. We included 128 patients aged > 65years who underwent esophagectomy for esophageal cancer. We defined mGNRI as (1.489/CRP in mg/dL) + (41.7 × present/ideal body weight) and divided patients into two groups: the low-mGNRI (mGNRI < 70, n = 50) and high-mGNRI (mGNRI ≥ 70, n = 78) groups. We retrospectively examined the relationship between mGNRI and long-term prognosis. The low-mGNRI group had more advanced cancer by stage, higher rates of recurrence, and earlier recurrence than the high-mGNRI group. Univariate analysis identified the following factors as significantly associated with poor overall survival (OS): a lower American society of anesthesiologist performance status (ASA-PS), male gender, CRP-albumin ratio ≥ 0.1, CRP ≥ 1.0, low-mGNRI, tumor depth ≥ T3, Charlson comorbidity index ≥ 2, tumor size ≥ 40mm, and age > 75years. A low-mGNRI, ASA-PS 3, age > 75years, and tumor depth ≥ T3 were independent unfavorable prognostic factors for OS. A low-mGNRI was an independent poor prognostic factor for relapse-free survival. We performed model selection analysis to identify the most clinically useful indices; mGNRI was the best predictive model. mGNRI in patients with esophageal cancer correlated with early recurrence and was a useful independent prognostic factor.

Real-world clinical outcomes and prognostic factors in Japanese patients with recurrent or metastatic squamous cell carcinoma of head and neck treated with chemotherapy plus cetuximab: a prospective observation study (JROSG12-2).

The aims of this study are to evaluate the efficacy and safety of first-line treatment with chemotherapy plus cetuximab in real-world patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) and to identify prognostic factors for overall survival (OS). This is a prospective observation study involving 20 oncology institutions in Japan. Patients with RM-SCCHN treated with a first-line therapy consisting of cetuximab plus any chemotherapy regimen between December 2013 and February 2017 were enrolled. The primary objective of the study was 1-year OS. Secondary objectives included response rate and adverse events. Of 120 patients recruited, 114 patients were analyzed. Median age was 64years. Cetuximab in combination with platinum plus 5-FU (EXTREME regimen) was chosen in 86 patients (75.4%). The median OS was 12.4months. A point estimate of the 1-year survival rate was 51.1%. Overall response rate was 26.3%. Grade 3 or worse adverse events included neutropenia (22.8%), hypokalemia (9.6%), acneiform rash (7.0%), pneumonitis (1.8%), and infusion-related reaction (0.9%). On multivariate analysis, regional lymph node metastasis, absence of intervention by dermatologists, lack of response to therapy, skin metastasis, and non-EXTREME regimen were identified as independent unfavorable prognostic factors for OS. The combination of cetuximab plus chemotherapy was tolerable and efficacious in patients with RM-SCCHN in a real-world setting. Clinical outcomes and prognostic factors extracted from this study provide a reference of the current clinical practice as well as for the future development of novel therapy in RM-SCCHN.

Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study

AbstractMonitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65–specific cytotoxic T lymphocytes (CMV-CTLs). The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or in the CD8+ T cell subset was significantly associated with longer survival. Multivariate analysis identified the clinical subtype (acute or lymphoma type), a higher sIL-2R level, and a lower percentage of CD2−CD19+ B cells in peripheral blood mononuclear cells as significant independent unfavorable prognostic factors for OS. This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment. In conclusion, the MIMOGA study has demonstrated that mogamulizumab exerts clinically meaningful antitumor activity in ATL. The patient's immunological status before mogamulizumab was significantly associated with treatment outcome. Further time series immunological analyses, in addition to comprehensive genomic analyses, are warranted.

Prognostic value of radiation interruption in different periods for nasopharyngeal carcinoma patients in the intensity-modulated radiation therapy era.

We aimed to investigate the prognostic value of radiation interruptions at different times on the overall survival (OS) and disease‐free survival (DFS) of patients with nasopharyngeal carcinoma receiving intensity‐modulated radiation therapy. Totally, 4510 patients were identified from a well‐established big‐data intelligence platform. Optimal interruption thresholds were identified using Recursive partitioning analyses. Actuarial rates were plotted using the Kaplan–Meier method and were compared using the log‐rank test. Patients with preceding interruptions ≥1 d (5‐year OS, 89.6% vs. 85.7%, p < 0.001; 5‐year DFS, 81.4% vs. 76.4%, p < 0.001), or latter interruptions ≥4 d (88.4% vs. 82.3%, p < 0.001; 79.2% vs. 75.1%, p = 0.006) showed significant detrimental effects on OS and DFS than patients without those interruptions. However, no significant lower survival was identified in latter interruptions ≥1 d (5‐year OS: 89.0% vs. 86.7%, p = 0.053; 5‐year DFS, 80.2% vs. 77.8%, p = 0.080). Latter interruptions ≥4 d was an independent unfavorable prognostic factor for OS (HR, 1.404; 95% CI, 1.143–1.723, p = 0.001) and DFS (HR, 1.351; 95% CI, 1.105–1.652, p = 0.003) in multivariate analysis. Radiation interruptions longer than 3 days that occurred in the latter period of treatment with IMRT were independent factors in poorer survival. Efforts are needed to minimize radiation interruptions and improve the timely provision of treatment.

960P A real-world clinical outcomes and prognostic factors in Japanese patients with recurrent or metastatic squamous cell carcinoma of head and neck treated with chemotherapy plus cetuximab: A prospective observation study (JROSG12-2)

Cetuximab (Cmab), an anti-EGFR monoclonal antibody, was approved for the treatment of recurrent or metastatic squamous cell carcinoma of head and neck (RM-SCCHN). Cmab has been combined not just with platinum-based chemotherapy, but also with other chemotherapy regimens. The aims of this study are to evaluate the clinical outcomes and safety of first-line treatment with chemotherapy plus Cmab in the real-world patients with RM-SCCHN and to identify prognostic factors for overall survival (OS). This is a prospective observation study involving 20 oncology institutions in Japan. All consecutive patients with RM-SCCHN treated with a first-line therapy consisting of any chemotherapy regimens plus Cmab between December 2013 and February 2017 were included. The primary objective of the study was 1-year OS. Secondary objectives included response rate and adverse events. This work is supported by Merck Biopharma. Of 120 patients recruited, 114 patients were analyzed. Patients characteristics were as follows: median age, 64 years; PS0/1/2, 48.2%/49.1%/2.6%; primary tumor sites, hypopharynx/oral cavity/oropharynx/larynx, 34.2%/27.2%/25.4%/13.2%; combined chemotherapy, FP/FU+CBDCA/PTX/S-1, 52.6%/22.8%/14.9%/5.3%. Of 78 patients who achieved disease control, 31 patients continued Cmab monotherapy as maintenance. The median OS was 1.0 year (95% confidence interval [CI] 0.8-1.2). A point estimate of 1-year survival rate was 51.1%. On multivariate analysis, independent unfavorable prognostic factors for OS were performance status ≥1, primary tumor site (oral cavity), nodal staging (≥2), presence of distant metastasis, no salvage chemotherapy, and lack of objective response. Overall response rate was 26.3% (95%CI 18.5 - 35.4). Grade 3 and 4 adverse events included neutropenia (22.8%), hypokalemia (9.6%), rash acneiform (7.0%), pneumonitis (1.8%), and infusion related reaction (0.9%). Combination of chemotherapy and Cmab showed promising signs of efficacy and tolerability in patients with RM-SCCHN in the real-world. Several prognostic factors were identified for OS.

Long term follow-up of a large series of stage-II/III atypical proliferative serous ovarian tumors

BackgroundThe aim of this study was to assess prognostic factors and implications on further management in a large series of stage-II or III Atypical Proliferative Serous Tumors (APST) with a long-term follow-up. Patients and methodsPatients with APSTs and peritoneal implants treated in, or referred to, our institution were retrospectively reviewed. Prognostic factors on invasive recurrence, disease-free (DFS) and overall survival (OS) were analyzed. ResultsBetween 1971 and 2017, 212 patients were identified and followed (33 having invasive implants). After a median follow-up of 115 months, 70 recurrences were observed, 28 of them under the form of invasive disease. DFS at 5 years and 10 years was 73% and 62% respectively. The use of a conservative treatment (HR = 5.5[3.33–9.08], p < .0001), the presence of ≥3 peritoneal sites with implants (HR = 1.65[1.01–2.72], p = .045) were unfavorable prognostic factors for DFS. The presence of ≥3 peritoneal sites with implants (HR = 3.02[0.96–9.53], p = .049) and the presence of stromal microinvasion (HR = 3.19[1.12–9.1], p = .022) were unfavorable prognostic factors for OS. Non-conservative surgery (HR = 7[2.35–20.87], p = .0002), invasive implants (HR = 5.37[1.29–22.26], p = .013), and ≥ 3 peritoneal sites with implants (HR = 3.56 [1.11–11.39], p = .024) were identified as predictors of recurrence in the form of an invasive disease. Invasive implants were not associated with DFS (HR = 1.39[0.77–2.51], p = .27), nor OS (HR = 1.76[0.57–5.47], p = .32). ConclusionAfter a long-term follow-up, type of peritoneal implants is no longer a prognostic factor for OS. Implants ≥3 peritoneal sites seem to impact significantly OS and then require a specific follow-up in this subgroup of patients.

Immune Checkpoint Inhibitors for Advanced Melanoma: Experience at a Single Institution in Taiwan.

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the current approach to cancer treatment. Although the use of ICIs has become the standard of care for advanced melanoma, reports of ICI use among Asian populations with melanoma are limited. Therefore, we conducted this retrospective study to assess the efficacy and safety of ICI use in Taiwanese patients.Patients: Patients with histologically confirmed melanoma treated with ICIs at Linkou Chang Gung Memorial Hospital from January 2014 to July 2019 were retrospectively reviewed. Univariant and multivariant analyses were performed to identify possible prognostic factors.Results: Among 80 patients, 45 were treatment-naïve (56.3%), and 35 received prior systemic drugs other than ICIs. Regarding treatment regimens, patients were treated with ipilimumab (n = 9), nivolumab (n = 33), pembrolizumab (n = 16), or combination drugs (n = 22). Nine patients achieved either a complete (n = 2) or partial (n = 7) response and 13 patients were stable, with a resulting response rate of 11.3% and disease control rate of 27.5%. As of the last follow-up in January 2020, patients treated with combination drugs had longer median progression-free survival (PFS) of 5.6 (95% confidence interval [CI]: 1.6–9.6) months than nivolumab (2.9 months, 95% CI: 1.9–3.9 months), pembrolizumab (3.2 months, 95% CI: 2.6–3.8 months), and ipilimumab (2.6 months, 95% CI: 2.4–2.8 months; p = 0.011). No significant differences in overall survival (OS) among the four regimens (p = 0.891) were noted. In the multivariate analysis, combination treatment, disease control, and performance ≤ 1 were independent prognostic factors for PFS. Liver metastases and no disease control were independent unfavorable prognostic factors for OS. The most common factor was skin toxicity (45%), followed by endocrine toxicity (18.8%). Patients undergoing combination treatment experienced more frequent and serious adverse events than patients undergoing monotherapy.Conclusion: ICIs demonstrated efficacy and safety in Taiwanese patients with melanoma. Combination treatment showed the greatest efficacy, but this was also accompanied by greater toxicity among the four regimens. In addition, we identified important prognostic factors, such as liver metastases, performance status, and tumor response, for both PFS and OS. These findings could provide physicians with more information to justify clinical outcomes observed in Asian patients with advanced melanoma.

Clinicopathological Analysis of 17 Surgically Resected Pulmonary Pleomorphic Carcinoma Cases.

Objectives: To determine the outcomes and prognostic factors associated with pulmonary resection of pulmonary pleomorphic carcinoma (PPC).Methods: During 2008–2017, 17 patients underwent pulmonary resection for primary PPC at the Saitama Cancer Center, Japan. We investigated clinicopathological characteristics and outcomes of these cases. Overall survival (OS) and disease-free survival (DFS) rates were determined using Kaplan–Meier method and compared using log-rank test. Univariate analysis was performed to identify prognostic factors.Results: The 5-year OS and DFS rates were 27.2% and 51.0%, respectively. The median follow-up period was 30.8±24.9 (3.6–92.8) months after pulmonary resections. Patients with disease-free interval (DFI) <1 year of resection had poorer prognosis than those without (p = 0.001). Patients with N2 status and adenocarcinoma components had significantly poorer disease-free prognosis than their counterparts (p = 0.021 and p = 0.019, respectively). Univariate analysis revealed that DFI <1 year was an unfavorable prognostic factor for OS (p = 0.005); N2 pathological status and presence of adenocarcinoma components were unfavorable prognostic factors for DFS (p = 0.038 and p = 0.036, respectively).Conclusion: PPC patients with an adenocarcinoma component and N2 pathological status may have an earlier relapse and poorer prognosis than their counterparts. Further assessment of cases may help clarify the predictors of PPC.