Significant Prognostic Factors For Overall Survival Research Articles

Role of Adjuvant Radiotherapy in Patients with Cervical Cancer Undergoing Radical Hysterectomy.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine adjuvant RT's impact on survival in accordance with Sedlis criteria. Patients with early-stage cervical cancer undergoing radical hysterectomy between 2005 and 2022 at a single tertiary care institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analysed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. 121 patients were included in this retrospective study, of whom 48 (39.7%) received adjuvant RT due to the presence of unfavourable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p = 0.584) or disease-free survival (DFS) (p = 0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate risk factors.

Long-Term Outcomes in a Phase II Study of Hypofractionated IGRT 60Gy/ 20F in Patients with Isolated Lymph Node Recurrence after Surgery for Esophageal Carcinoma

In oligo metastases in lymph node recurrence after surgery for esophageal cancer, since SBRT (BED>100 Gy10) to mediastinal and abdominal lymph node lesions was not an option due to toxicities in the organs at risk (OAR) such as vessels and gastrointestinal tract, we performed a prospective cohort study of hypofractionated IGRT for isolated lesions. The primary end-points of this study are disease specific survival (DSS) and late treatment toxicities. From 2011 to 2021, 60 Gy/20F/4-4.5wks (78 Gy10) hypofractionated IGRT was performed in a total ITT population of 70 patients after radical surgery (67 cases) and ESD (3 cases), who were diagnosed by CT/PET-CT as having solitary lymph node recurrence (62 cases) or up to 2 adjacent nodes (8 cases). The mean time from surgery to recurrence was 17.9 months (SD 18.1) with a mean age of 67.5 years (SD 9.3), and male to female ratio was 62:8. Pathological results showed that 63 patients (90%) had squamous cell carcinoma. The mean maximum diameter of lesions was 2.5 cm (SD; 1.1 cm). And 51 cases (73%) were treated with CRT concurrently using 5FU plus CDDP (FP), and the rest were treated with RT alone. Lymph node location was lower neck or upper mediastinum in 42 cases, middle and lower mediastinum in 16 cases, and abdomen in 12 cases, respectively. Treatment planning was performed by taking 4DCT fusing PET or MRI images. The Kaplan-Meier method and the Cox proportional hazards regression model were used for overall survival (OS), DSS, and progression free survival (PFS). The mean observation period was 38 months. Primary efficacy was CR in 45 cases (64%), but CR was maintained only in 29 cases (41%). Twenty-two of the 70 patients were relapse-free. OS were 53% and 34% at 2 and 5 years, DSS were 56% and 38% at 2 and 5 years, and PFS were 40% and 39% at 2 and 5 years, respectively. The site of first recurrence was the same or adjacent lymph nodes in 33 cases (47%) and distant metastases in 9 cases (13%). Number of tumors (1 vs. 2), age, and CRT were not significant prognostic factors for OS, DSS, or PFS. In a multivariate analysis, the time from surgery to recurrence ≥12 months was the only significant prognostic factor for PFS (p = 0.018, HR0.50). The same multivariate analysis showed that the only significant prognostic factor for DSS was the location of the recurrent lymph node in the neck and upper mediastinal regions (p = 0.009, HR 0.59). The only late adverse events of Grade 2 or higher were Grade 2 pleural effusion (little and transient) in 6 cases and Grade 2 radiation pneumonitis in 1 case. No acute adverse events were observed other than hematologic toxicity due to FP administration. In locally advanced esophageal cancer, a relatively reliable regional lymph node dissection is often performed, so there is still a chance to aim for cure in cases of solitary recurrence. We found that if the lesion is solitary, localized RT of about 60 Gy/20F/4-4.5 weeks with IGRT can achieve a long-term survival in 40% of patients without any significant adverse events.

Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment (molGPA) for Elderly Glioblastoma (eGBM-molGPA)

This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT) in each risk group. Patients aged ≥65 years who underwent surgical resection followed by radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed IDH-wildtype eGBM between 2006 and 2021 were included in this multicenter cohort study. Patients who were planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT or HFRT, respectively. Based on the prognostic factors significantly identified through multivariate analysis for overall survival (OS), we developed the molecular GPA for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each factor. Then, the survival outcomes by treatment groups were evaluated according to the eGBM-molGPA scores. A total of 334 and 239 patients who underwent CFRT and HFRT were included, respectively, and 86% of patients were treated with TMZ-based chemoradiation. With a median follow-up of 17.4 months for survivors, the median OS was 18.7 months for CFRT plus TMZ group, 15.1 months for HFRT plus TMZ group, and 10.4 months for RT alone group, respectively (all p<0.001). In the multivariate analysis, Karnofsky performance scale, surgical extent, TMZ, and the methylation status of the MGMT promoter were identified as strong prognostic factors for OS, with an estimated HR of greater than 1.5 (all p<0.001). Additionally, subventricular zone involvement, temporalis muscle thickness, RT regimen, and the mutation status of TERT promoter and TP53 gene were found to be significant prognostic factors for OS, with an estimated HR of less than 1.5. The eGBM-molGPA was established based on these prognostic factors (Table 1) and patients were allocated to three risk groups, which included high risk (total score of 3.0-4.5), intermediate risk (1.5-2.5), and low risk (0.0-1.0). Patients treated with CFRT plus TMZ had significantly improved OS compared to those treated with HFRT plus TMZ or RT alone in the low and intermediate risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p = 0.770). CFRT plus TMZ can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among treatment options. Further prospective studies are warranted to establish optimal RT guidelines for eGBM patients.

Platelet count and MCHC as independent prognostic markers for feline mammary carcinomas

Mammary neoplasms are common in felines species and represent a significant disease for its unfavorable prognosis. Changes in the blood count and serum biochemical profile of these patients have potential as non-invasive prognostic markers prior to mastectomy, however, they are poorly described in literature. In this study univariate and multivariate analyses were performed using these factors to determine the effect of each parameter on the one-year survival time after the surgical procedure in these animals. The median overall survival (OS) and the disease-free survival (DFS) were 365 and 242 days, respectively. In univariate analysis, values within the reference range of monocyte, platelet and creatinine counts were identified as significant prognostic factors for OS and only creatinine was significant for DFS (P < 0.05). In the multivariate analysis, platelets and mean corpuscular hemoglobin concentration (MCHC) remained independent prognostic factors for OS. The results presented suggest that monocytes, platelets and creatinine may be important non-invasive pre-surgical prognostic markers, and that platelet count and MCHC are independent prognostic markers for feline mammary carcinomas (FMC). The correlation between such alterations is of important relevance for veterinary oncology, and prospective studies are needed to validate their clinical use and that platelet count and MCHC are independent prognostic markers for FMC. The results found in this study can also be studied in human medicine, regarding blood markers in human breast cancer (HBC).

The Prognostic Value of Sequential 18 F-FDG PET/CT Metabolic Parameters in Outcomes of Upper-Third Esophageal Squamous Cell Carcinoma Patients Treated with Definitive Chemoradiotherapy.

Objective The aim of this study is to determine prognostic values of sequential 18 F-FDG PET/CT metabolic parameters in locally advanced esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy. Materials and Methods Forty locally advanced ESCC patients treated with definitive chemoradiotherapy (dCRT) who received pre-treatment 18 F-FDG PET/CT (PET1) and 3-months post-treatment 18 F-FDG PET/CT (PET2) were enrolled in the prospective study. 18 F-FDG PET parameters of the primary tumor including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated on PET delineated primary tumor. Using Kaplan-Meier curves to estimated overall survival (OS), progression-free survival (PFS), and local-regional control (LRC). Cox regression analysis was performed to find significant prognostic factors for survival. Results With a median follow-up of 13.5 months, the 4-year OS, PFS, and LRC rates were 67.3%, 52.6%, and 53.4% respectively. Patients with MTV 2 > 5.7 had lower OS, PFS, and LRC rates than the lower MTV 2 group (p < 0.05). Univariate Cox regression analysis showed that MTV2 was a significant prognostic factor for OS, PFS, and LRC (p < 0.05). Conclusion MTV parameter of sequential 18 F-FDG PET/CT could be used as a prognostic factor for OS, PFS, and LRC in locally advanced ESCC patients treated with dCRT.

High grade tumor budding is associated with poor survival in pathologic stage I lung adenocarcinoma

AimTumor budding is a significant prognostic parameter that has been related to aggressive behavior in early-stage tumors of various origins. The aim of this study was to evaluate the clinicopathological significance of tumor budding in pathologic stage (pStage) I lung adenocarcinomas. MethodsThis study comprised 107 patients who underwent curative resection for pStage I lung adenocarcinomas at our hospital between December 2010 and January 2016. We examined tumor budding on routine hematoxylin and eosin (H&E) slides from resected specimens. Tumors were categorized into two groups based on the degree of tumor budding: low grade (grade 0–1) and high grade (grade 2–3). We evaluated the relationship between tumor budding and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. ResultsThere is a significant difference (p = 0.002) between the 5-year DFS rates of the high-grade and the low-grade tumor budding group, which were 70 % and 90 %, respectively. High-grade tumor budding positive patients from the same pathological stage (p < 0.001; HR = 2.93 [1.51–5.68]) and clinical stage (p = 0.002) had poorer cumulative survival rates than low grade tumor budding positive patients. High grade tumor budding was positively associated with spread through air spaces (STAS) (p < 0 0.001), lymphovascular invasion (LVI) (p < 0.001), tumor necrosis (p < 0.001), high SUVmax value (SUVmax>3.0) (p < 0.001), and tumor size >20 mm (p = 0.024). High-grade tumor budding was significant prognostic factor of OS (p < 0.006) and DFS (p < 0.001) on univariate Cox regression hazard model analysis. However, it did not show significance in the multivariate analysis (p > 0.05). ConclusionsHigh-grade tumor budding is an independent prognostic factor and associated with adverse clinicopathological features and poor survival rates. We proposed that high-grade tumor budding should be recognized as a new prognostic parameter and will be beneficial in predicting the clinical course in pStage I lung adenocarcinomas.

Prognostic value of soluble programmed cell death ligand-1 (sPD-L1) in lymphoma: a systematic review and meta-analysis.

Previous studies on the prognostic value of soluble programmed cell death ligand 1 (sPD-L1) in lymphoma patients have yielded inconsistent results. Here, we conducted a meta-analysis and systematic review to investigate the prognostic significance of sPD-L1 in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL) and NK/T-cell lymphoma (NK/TCL). A total of 11 studies with 1185 patients were included in the meta-analysis, and the combined results indicated that high sPD-L1 levels were associated with worse overall survival (OS) (HR=2.27, 95%CI: 1.70-3.04) and progression-free survival (PFS) (HR=2.68, 95%CI: 1.92-3.75). Furthermore, subgroup analysis showed that sPD-L1 remained a significant prognostic factor for OS. The meta-analysis indicated that sPD-L1 may be a potential prognostic biomarker for lymphoma, especially in DLBCL and NK/TCL, and high sPD-L1 levels were associated with worse survival prognosis.

Intensity-modulated radiotherapy for the management of primary and recurrent chordomas: a retrospective long-term follow-up study.

Chordomas have a high risk of recurrence. Radiotherapy (RT) is required as adjuvant therapy after resection. Sufficient radiation doses for local control (LC) can be achieved using either particle therapy, if this technology is available and feasible, or intensity-modulated radiotherapy. 57 patients (age, 11.8-81.6 years) with chordomas of the skull base, spine and pelvis who received photon radiotherapy between 1995 and 2017 were enrolled in the study. Patients were treated at the time of initial diagnosis (68.4%) or during recurrence (31.6%). 44 patients received adjuvant radiotherapy and 13 received definitive radiotherapy. The median total dose to the physical target volume was 70 Gy equivalent dose in 2 Gy fractions (EQD2) (range: 54.7-82.5) in 22-36 fractions. LC was 76.4%, 58.4%, 46.7% and 39.9% and overall survival (OS) was 98.3%, 89%, 76.9% and 47.9% after 1, 3, 5 and 10 years, respectively, with a median follow-up period of 6.5 years (range, 0.5-24.3 years). Age, dose and treatment concept (post-operative or definitive) were significant prognostic factors for OS. Primary treatment, macroscopic tumour at RT and size of the irradiated volume were statistically significant prognostic factors for LC. Photon treatment is a safe and effective treatment for chordomas if no particle therapy is available. The best results can be achieved against primary tumours if the application of curative doses is possible due to organs at risk in direct proximity. We recommend high-dose radiotherapy, regardless of the resection status, as part of the initial treatment of chordoma, using the high conformal radiation technique if particle therapy is not feasible.

SUVmean on baseline [18F]PSMA-1007 PET and clinical parameters are associated with survival in prostate cancer patients scheduled for [177Lu]Lu-PSMA I&T

BackgroundQuantification of [68 Ga]-labeled PSMA PET predicts response in patients with prostate cancer (PC) who undergo PSMA-targeted radioligand therapy (RLT). Given the increasing use [18F]-labeled radiotracers, we aimed to determine whether the uptake derived from [18F]PSMA-1007 PET can also identify responders and to assess its prognostic value relative to established clinical parameters.MethodsWe retrospectively analyzed 103 patients with metastatic, castration-resistant PC who were treated with [177Lu]Lu-PSMA I&T. We calculated SUVmean, SUVmax, PSMA-avid tumor volume (TV), and total lesion PSMA (defined as PSMA-TV*SUVmean) on pre-therapeutic [18F]PSMA-1007 PET. Laboratory values for hemoglobin, C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alkaline phosphatase (AP) were also collected prior to RLT. We performed univariable Cox regression followed by multivariable and Kaplan–Meier analyses with overall survival (OS) serving as endpoint. Last, we also computed a risk factor (RF) model including all items reaching significance on multivariable analysis to determine whether an increasing number of RFs can improve risk stratification.ResultsA total of 48 patients died and median OS was 16 months. On univariable Cox regression, SUVmean, CRP, LDH, hemoglobin, and the presence of liver metastases were significantly associated with OS. On multivariable Cox regression, the following significant prognostic factors for OS were identified: SUVmean (per unit, HR, 0.91; P = 0.04), the presence of liver metastases (HR, 2.37; P = 0.03), CRP (per mg/dl, HR, 1.13; P = 0.003), and hemoglobin (per g/dl, HR, 0.76; P < 0.01). Kaplan–Meier analysis showed significant separation between patients with a SUVmean below or above a median SUVmean of 9.4 (9 vs 19 months, HR 0.57; P = 0.03). Of note, patients with only one RF (median OS not reached) showed longest survival compared to patients with two (11 months; HR 2.43 95% CI 1.07–5.49, P = 0.02) or more than two RFs (7 months; HR 3.37 95% CI 1.62–7.03, P < 0.001).ConclusionA lower SUVmean derived from [18F]PSMA-1007, higher CRP, lower hemoglobin, and the presence of liver metastases are associated with reduced OS in patients undergoing RLT. An early RF model also demonstrated that an increasing number of those factors is linked to worse outcome, thereby emphasizing the importance of clinical and imaging parameters for adequate risk stratification.

Induction immunochemotherapy conversion rate and survival outcomes versus chemotherapy in initially unresectable esophageal squamous cell carcinoma.

e16077 Background: Currently, no comparative study has been reported to elucidate whether the addition of immunotherapy in the induction setting could improve treatment efficacy and prolong the overall survival of initially-unresectable locally advanced esophageal squamous cell carcinoma (iuESCC). This study aimed to compare surgical conversion rate and short-term overall survival in induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with iuESCC. Methods: In this multicenter retrospective cohort study, patients with the guideline-defined unresectable disease were included at four high-volume institutions. The primary endpoints were conversion surgical rate and overall survival (OS). Pathological complete response (pCR) was defined as the disappearance of tumor cells in the primary lesion site. Multivariate cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting (IPTW) was applied to confirm the survival comparison between iIC and iC cohorts. Results: A total of 309 patients (150 in iIC and 159 in iC cohort) were included. A significantly higher conversion surgical rate was observed in iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P &lt; 0.001). In terms of pathological response, the rates of pCR were 22.0% and 5.1% in the iIC and the iC cohort, respectively (P = 0.001). A significant difference in OS was observed between iIC (not reached) and iC cohorts (median [95% CI]: 36.3 [27.2 – 45.5] months). The stabilized IPTW yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI: 0.102 - 0.454, P &lt; 0.001) and operation (Yes vs. No, HR 0.262, 95% CI: 0.161 - 0.427, P &lt; 0.001) were the significant prognostic factors for OS. Further, subgroup analysis revealed that significantly higher OS was seen in iIC cohort than that in the iC cohort (P = 0.003) in patients who had non-pCR disease. Conclusions: Immunochemotherapy plus conversion surgery in the induction setting had higher pathological response rate and better OS in iuESCC patients. Moreover, this combined modality also contributed to improving OS in patients with residual tumor burden. This study provided evidence for future randomized control trial designs.

Molecular landscape and survival outcomes on early phase clinical trials in sporadic young onset colorectal cancer.

3600 Background: Sporadic young onset colorectal cancer (YOCRC, ages 30-49) is a public health crisis with a persistent rise in incidence globally. While a proportion of patients (pts) develop YOCRC due to hereditary predisposition, the majority develop sporadic microsatellite stable (MSS) colorectal cancer with limited options beyond standard of care in advanced settings. We report the early phase clinical trial experience at a large academic cancer center to elucidate clues regarding molecular landscape and impact of clinical trials in refractory MSS YOCRC. Methods: Patient and clinical characteristics were summarized using descriptive statistics. Kaplan-Meier method was used to estimate the probabilities of overall survival (OS) and progression free survival (PFS). Log-rank tests were used to assess the differences in OS and PFS between subgroups. Cox proportional hazards regression models were fit to assess the association between OS or PFS and patient characteristics. Statistical analyses were performed using SAS and Splus. Results: 240 MSS YOCRC pts were analyzed. Median age 42.8 (20.5-49), &gt; 80% were white and only 10% black. 21% received at least 3 lines of therapy. The top five mutations were TP53, KRAS, APC, PI3CKA and BRAFV600E. Median OS was 39.2 months (95% CI: 34.8 – 42.5 months). CTNNB1 mutation was associated with a lower risk of death (HR = 0.28, 95% CI: 0.09 – 0.87, p-value = 0.03) while BRAFV600E mutation was associated with an increased risk (HR = 3.28, 95% CI: 2.00 – 5.38, p-value &lt; 0.001). Multivariable Cox model for OS revealed both CTNNB1 and BRAFV600E mutations are significant prognostic factors for OS, unlike KRAS. There was no difference in OS or PFS among pts who entered a mutation specific clinical trial vs. those enrolled on an unmatched clinical trial (p = 0.35, p = 0.68, respectively, log-rank test). Median PFS was 1.9 months (95% CI: 1.8 – 2.1 months). CTNNB1 mutation was associated with a lower risk of progression/death (HR = 0.29, 95% CI: 0.09 – 0.92, p-value = 0.04) while NRAS mutation was associated with an increased risk (HR = 2.13, 95% CI:1.19– 3.80, p-value = 0.01). Among 145 pts who have data on response, 9 had partial response, 41 had stable disease and 95 had progressive disease. BRAFV600E mutation is associated with a higher probability of response (OR = 6.89, 95% CI: 1.64 – 28.94, p-value = 0.01) and pts enrolled on matched clinical trials had a higher probability of response (OR = 6.23; 95% CI: 1.24 – 31.09, p-value = 0.03). However, increased response did not translate to improved OS. No survival differences were appreciated based on a pts race or BMI. Conclusions: CTNNB1, BRAFV600E &amp; NRAS mutations may have prognostic implications in YOCRC. Pts enrolled on mutation specific clinical trials did not achieve improved outcomes compared to unselected trials, highlighting aggressive biology, current lack of therapeutic targets and need for novel drug development in sporadic YOCRC.

Prognostic factors of overall survival (OS) in non-small cell lung cancer (NSCLC) patients after failure on immune checkpoint inhibitors (IO) treated with anticancer vaccine OSE2101 or chemotherapy (CT) in phase 3 ATALANTE-1 randomized trial.

e21037 Background: OSE2101 (Tedopi) is an anticancer vaccine that has shown an improvement in overall survival (OS) compared with Chemotherapy (CT) (HR 0.59; p = 0.017) in HLA-A2+ NSCLC patients with IO secondary resistance (ESMO 2021 #47LBA). The objective of this analysis was to identify the prognostic factors of OS in each treatment group. Methods: 118 NSCLC EGFR and ALK negative patients who progressed after sequential CT-IO and who received at least 12 weeks IO (defining IO secondary resistance), were randomized (2:1) in OSE2101 or SoC (docetaxel or pemetrexed). Stepwise multivariate analysis of OS was performed after the selection of factors with p &gt; 0.10. Classical baseline factors (disease stage, histology, patient general status) and treatment effect, including best response (Complete Response CR, Partial Response PR, Stable Disease SD versus Progressive Disease PD), severe adverse events and ECOG PS deterioration, were studied and correlated to OS. Results: The statistically significant prognostic factors of OS in multivariate analysis are described in table below. When PS ≤1 was maintained, median OS with OSE2101 was 14.0 [11.1; 16.8] months and 6.3 [2.9; 8.2] when PS deteriorated &gt; 1 (HR 0.23 [0.13; 0.41]); with CT, median OS was respectively 7.5 [4.4; 10.3] and 7.2 [2.3; 15.7] months (HR 0.92 [0.44; 1.96]). When best response to study treatment was CR/PR/SD, median OS with OSE2101 was 12.6 [8.8;16.8] months and 8.0 [5.5; 11.1] when best response was DP (HR 0.61 [0.36; 1.04]); with CT, median OS was respectively 9.8 [7.4; 13.8] and 5.0 [1.0; 7.2] months (HR 0.34 [0.14; 0.84]. Conclusions: Prognostic factors of OS differ between cancer vaccine OSE2101 and standard CT. Maintenance of good ECOG PS was the most important for OSE2101, while best response (CR/PR/SD) to treatment correlated with longer OS with CT and was not prognostic for OSE2101. This analysis supports the mechanism of action of the cancer vaccine in improving OS by controlling tumor growth regardless of best response. Clinical trial information: NCT02654587 . [Table: see text]

The Prognostic and Diagnostic Value of [18F]FDG PET/CT in Untreated Laryngeal Carcinoma.

This study aims to determine the diagnostic accuracy of staging PET/CT and neck MRI in patients with laryngeal carcinoma and to assess the value of PET/CT in predicting progression-free survival (PFS) and overall survival (OS). Sixty-eight patients who had both modalities performed before treatment between 2014 and 2021 were included in this study. The sensitivity and specificity of PET/CT and MRI were evaluated. PET/CT had 93.8% sensitivity, 58.3% specificity, and 75% accuracy for nodal metastasis, whereas MRI had 68.8%, 61.1%, and 64.7% accuracy, respectively. At a median follow-up of 51 months, 23 patients had developed disease progression and 17 patients had died. Univariate-survival analysis revealed all utilized PET parameters as significant prognostic factors for OS and PFS (p-value < 0.03 each). In multivariate analysis, metabolic-tumor volume (MTV) and total lesion glycolysis (TLG) predicted better PFS (p-value < 0.05 each). In conclusion, PET/CT improves the accuracy of nodal staging in laryngeal carcinoma over neck MRI and adds to the prognostication of survival outcomes through the use of several PET metrics.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Clinical Significance of Combining Preoperative and Postoperative Albumin-Bilirubin Score in Colorectal Cancer.

Albumin-bilirubin (ALBI) score is a well-known prognostic factor for various diseases, including colorectal cancer (CRC). However, little is known about the significance of postoperative ALBI score changes in patients with CRC. A total of 723 patients who underwent surgery were enrolled. Preoperative ALBI (ALBI-pre) and postoperative ALBI (ALBI-post) scores were divided into low and high score groups. ALBI-trend was defined as a combination of four groups comprising the low and high ALBI-pre and ALBI-post score groups. Kaplan-Meier survival curves were used to compare the overall survival (OS) between the different ALBI groups. The Cox proportional hazards model was used to examine the independent relevant factors of OS. Stratification performance was compared between the different ALBI groupings using Harrell's concordance index (C-index). ALBI-pre, ALBI-post, and ALBI-trend score groups were significant prognostic factors of OS in the univariable analysis. However, multivariable analysis showed that ALBI-trend was an independent prognostic factor while ALBI-pre and ALBI-post were not. The C-index of ALBI-trend (0.622; 95% confidence interval [CI], 0.587 to 0.655) was higher than that of ALBI-pre (0.589; 95% CI, 0.557 to 0.621; bootstrap mean difference, 0.033; 95% CI, 0.013 to 0.057) and ALBI-post (0.575; 95% CI, 0.545 to 0.605; bootstrap mean difference, 0.047; 95% CI, 0.024 to 0.074). Combining ALBI-pre and ALBI-post scores is an independent prognostic factor of OS and shows superior predictive power compared to ALBI-pre or ALBI-post alone in patients with CRC.

Efficacy and safety of combined immunotherapy and stereotactic radiosurgery in NSCLCBM patients and a novel prognostic nomogram: A real-world study.

To explore the effectiveness of combined immunotherapy (IT) and stereotactic radiosurgery (SRS) and address the gap between evidence-based clinical practice and academic knowledge of optimal timing of IT relative to SRS. In addition, to meet the unmet need for an up-to-date prognostic assessment model in the era of IT. The data of 86 non-small cell lung cancer brain metastasis (NSCLCBM) patients treated with SRS to 268 brain metastases (BMs) were retrospectively extracted from our hospital database. The Kaplan-Meier analysis was employed for overall survival (OS) and a log-rank test for comparison between groups. Cox proportional hazards regression models were used to identify the significant prognostic factors. The prognostic nomogram was established utilizing the rms package of R software. IT was found to be associated with improved OS (from BM diagnosis: HR 0.363, 95% CI 0.199 - 0.661, P < 0.001; from SRS: HR 0.472, 95% CI 0.260 - 0.857, P = 0.014). Individuals who received IT in combination with SRS had better OS than those who didn't (from the day of BM diagnosis: 16.8 vs. 8.4 months, P = 0.006; from the day of SRS: 12 vs. 7 months, P = 0.037). Peri-SRS timing of IT administration was a significant prognostic factor for OS (from BM diagnosis: HR 0.132, 95% CI 0.034 - 0.517, P = 0.004; from SRS: HR 0.14, 95% CI 0.044 - 0.450, P = 0.001). Initiating IT after SRS led to superior OS than concurrent or before (from BM diagnosis: 26.5 vs. 14.1 vs. 7.1 months; from SRS: 21.4 vs. 9.9 vs. 4.1 months, respectively). Additionally, we build a nomogram incorporating IT, cumulative intracranial tumor volume (CITV), and recursive partitioning analysis (RPA), demonstrating a remarkable prognosis prediction performance for SRS-treated NSCLCBM patients. Peri-SRS IT is a promising approach in treating NSCLCBM, as improved OS was observed without significantly increasing adverse events. Receipt of IT post-SRS was associated with superior OS than those who received IT concurrently or before. Incorporating IT and CITV into the RPA index could augment its prognosis assessment value for SRS-treated NSCLCBM patients, predominantly in the wild-type.

A personalized nomogram for predicting 3-year overall survival of patients with uterine carcinosarcoma in a tertiary care hospital in Southern Thailand.

To develop a nomogram for predicting 3-year overall survival (OS) and outcomes of surgically staged patients with uterine carcinosarcomas (UCS). This retrospective study analyzed the clinicopathological characteristics, treatment data, and oncological outcomes of 69 patients diagnosed with UCS between January 2002 and September 2018. Significant prognostic factors for OS were identified and integrated to develop a nomogram. Concordance probability (CP) was used as a precision measure. The model was internally validated using bootstrapping samples to correct overfitting. The median follow-up time was 19.4 months (range, 0.77-106.13 months). The 3-year OS was 41.8% (95% confidence interval [CI], 29.9-58.3%). The International Federation of Gynecology and Obstetrics (FIGO) stage and adjuvant chemotherapy were independent factors for OS. The CP of the nomogram integrating with body mass index (BMI), FIGO stage, and adjuvant chemotherapy was 0.72 (95% CI, 0.70-0.75). In addition, the calibration curves for the probability of 3-year OS demonstrated good agreement between the nomogram-predicted and observed data. The established nomogram using BMI, FIGO stage, and adjuvant chemotherapy accurately predicted the 3-year OS of patients with UCS. The nomogram was useful for patient counselling and deciding on follow-up strategies.

Prognosis prediction for glioblastoma multiforme patients using machine learning approaches: Development of the clinically applicable model

Background and purposeWe aimed to develop a clinically applicable prognosis prediction model predicting overall survival (OS) and progression-free survival (PFS) for glioblastoma multiforme (GBM) patients. Materials and methodsAll 467 patients treated with concurrent chemoradiotherapy at Yonsei Cancer Center from 2016 to 2020 were included in this study. We developed a conventional linear regression, Cox proportional hazards (COX), and non-linear machine learning algorithms, random survival forest (RSF) and survival support vector machine (SVM) based on 16 clinical variables. After backward feature selection and hyperparameter tuning using grid search, we repeated 100 times of cross-validations to combat overfitting and enhance the model performance. Harrell's concordance index (C-index) and integrated brier score (IBS) were employed as quantitative performance metrics. ResultsIn both predictions, RSF performed much better than COX and SVM. (For OS prediction: RSF C-index = 0.72 90%CI [0.71–0.72] and IBS = 0.12 90%CI [0.10–0.13]; For PFS prediction: RSF C-index = 0.70 90%CI [0.70–0.71] and IBS = 0.12 90%CI [0.10–0.14]). Permutation feature importance confirmed that MGMT promoter methylation, extent of resection, age, cone down planning target volume, and subventricular zone involvement are significant prognostic factors for OS. The importance of the extent of resection and MGMT promoter methylation was much higher than other selected input factors in PFS. Our final models accurately stratified two risk groups with root mean square errors less than 0.07. The sensitivity analysis revealed that our final models are highly applicable to newly diagnosed GBM patients. ConclusionOur final models can provide a reliable outcome prediction for individual GBM. The final OS and PFS predicting models we developed accurately stratify high-risk groups up to 5-years, and the sensitivity analysis confirmed that both final models are clinically applicable.

Abstract P2-11-28: Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients

Abstract Background: Triple-negative breast cancer (TNBC) is the most fatal breast cancer subtype, which often shows aggressive progression, a high potential to metastasize, and resistance to chemotherapy. Comprehensive genomic profiling using next-generation sequencing (NGS) has been expected to identify gene alterations that are targetable by drugs. However, the significance of these genomic alterations in the cancer biology of TNBC patients has not yet been fully understood due to the lack of accurate clinical outcome data to compare with the genomic data. The aim of this study was to clarify the clinical impact of genomic profiling data, including copy number alterations (CNAs), in TNBC by comparing comprehensive genomic data with clinical outcomes. Methods: A total of 47 patients diagnosed with stage I-III TNBC (from the cohort reported in JCO Precis Oncol. 2018;2:PO.17.00211) were enrolled in this study. The genomic profiling of 435 known cancer genes by NGS with clinical outcomes were analyzed. Overall survival (OS) was evaluated for its association to gene alterations and distinctively CNAs. The cut-off values of CNA for OS were determined from the receiver operating characteristic curve using the Youden index for area under the curve (AUC). Kaplan-Meier plots and log-rank tests of OS were applied for each group. Univariate and multivariate analyses for OS were performed using a Cox proportional-hazards model to obtain the hazard ratio (HR) and 95% confidence intervals. Results: Utilizing NGS-based genomic profiling, at least one alteration was found in 82 of the 435 cancer-associated genes, and a total of 162 alterations were found in the 47 patients. Among the 82 genes with alterations, the presence or absence of TP53 and PTEN alterations was significantly associated with OS of TNBC patients; patients with TP53 alterations (n = 31) showed significantly shorter OS than those without TP53 alterations (n = 16, p = 0.023), and patients with PTEN alterations (n = 9) showed significantly shorter OS than those without PTEN alterations (n = 38, p = 0.023). The cut-off value of CNA for OS was set at 25 (AUC, 0.788; sensitivity, 0.727; specificity, 0.900). Interestingly, CNA-high patients (n = 20) showed significantly shorter OS than CNA-low patients (n = 27, p = 0.014). Univariate analysis revealed that TP53 alterations and CNAs were significant prognostic factors for OS (HR, 8.81; p = 0.008; and HR, 8.00; p = 0.014, respectively). Finally, multivariate analysis using background clinical data revealed that CNA was an independent prognostic factor for OS in TNBC patients (HR, 7.15; p = 0.044). Conclusion: Our data suggest that CNA is an independent prognostic marker in TNBC, and that can be estimated from comprehensive genomic profiling data by NGS. Further investigation is needed to clarify the mechanisms of how CNAs are associated with this lethal disease. Citation Format: Masayuki Nagahashi, Chie Toshikawa, YiWei Ling, Tetsu Hayashida, Yuko Kitagawa, Manabu Futamura, Takashi Kuwayama, Seigo Nakamura, Hideko Yamauchi, Teruo Yamauchi, Koji Kaneko, Chizuko Kanbayashi, Nobuaki Sato, Junko Tsuchida, Kazuki Moro, Masato Nakajima, Yoshifumi Shimada, Hiroshi Ichikawa, Stephen Lyle, Yasuo Miyoshi, Kazuaki Takabe, Shujiro Okuda, Toshifumi Wakai. Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-28.

The Systemic Inflammation Score is Associated with the Survival of Patients with Prostate Cancer.

The systemic inflammation score (SIS) based on the albumin (Alb) level and lymphocyte-to-monocyte ratio (LMR), has been associated with survival in some cancers. However, its prognostic role in prostate cancer (PCa) remains unclear. The associations between the SIS and the clinicopathological features of PCa were evaluated. The correlations between the SIS and overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier analysis and the Log rank test. Univariate and multivariate Cox analyses were conducted to determine the prognostic factors for PCa. Hazard ratios and 95% confidence intervals were calculated. A total of 253 patients with PCa were included in this study. The Kaplan-Meier analysis and Log rank test suggested that patients with a higher Alb level, higher LMR, or a lower SIS had better 5-year OS and PFS compared with patients with a lower Alb level or lower LMR or higher SIS. Univariate and multivariate Cox analyses showed that drinking, prostate-specific antigen level >100 ng/mL, and neutrophil-to-lymphocyte ratio >2.09 were significant prognostic factors for OS and PFS in patients with PCa. Nomograms for 5-year OS and PFS were established with concordance index values of 0.888 and 0.824, respectively. The calibration curve was consistent between the actual observations and the prediction nomogram for OS and PFS probability at 5 years. A high SIS is associated with unfavorable survival in patients with PCa. The SIS serves as a novel independent prognostic factor for OS in patients with PCa.