Prognostic Factor For Progression-free Survival Research Articles

Multivariable Analyses of Prognostic Factors for Progression-Free Survival (PFS) and Complete Response (CR) with Lenalidomide, Bortezomib, and Dexamethasone (RVd) Alone Versus Rvd Plus Autologous Stem Cell Transplantation (ASCT) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Determination Phase 3 Trial

Multivariable Analyses of Prognostic Factors for Progression-Free Survival (PFS) and Complete Response (CR) with Lenalidomide, Bortezomib, and Dexamethasone (RVd) Alone Versus Rvd Plus Autologous Stem Cell Transplantation (ASCT) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) in the Determination Phase 3 Trial

Exploring a Better Adjuvant Treatment for Surgically Treated High-Grade Neuroendocrine Carcinoma of the Cervix

Objectives: The objective of this study was to explore a better adjuvant treatment for patients with high-grade (HG) neuroendocrine cervical carcinomas (NECC) who had undergone surgery as a primary treatment. Design: A retrospective cohort study, which involved women diagnosed as HG-NECC, was conducted in the Obstetrics and Gynecology Hospital of Fudan University. All patients had undergone radical surgery and pelvic lymphadenectomy with a laparotomy or a minimally invasive surgery. An analysis was made of the prognosis of HG-NECC. Methods: Overall survival (OS) and progression-free survival (PFS) curves were drawn using the Kaplan-Meier method to be compared via log-rank tests. A Cox proportional hazards model was used to estimate the independent prognostic factors. Results: A number of 110 patients diagnosed as HG-NECC at the pathological stage IA2 to IIIC2 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system were initially treated with a primary surgery between 2008 and 2020. The eligible patients had the median age of 42.5 years (range: 22–76), with the median follow-up period of 39.6 months (range: 1.0–156.6). The 5-year OS of the patients at pathological stage I, II, and III accounted for 84.9%, 85.7%, and 60.9%, respectively. The Kaplan-Meier survival curves revealed no significant differences in OS and PFS between postoperative chemoradiotherapy and chemotherapy alone (OS: p = 0.77; PFS: p = 0.41). Etoposide plus platinum therapy did not improve OS when compared with platinum plus paclitaxel therapy after surgery (p = 0.71). The univariable analysis showed that chemotherapy with cycles ≥4 presented a better prognosis than with cycles <4 (OS: p = 0.01; HR = 6.71; PFS: p = 0.02; HR = 5.18). The multivariate analysis indicated that the cycles of chemotherapy (p = 0.02; HR 0.29) were a prognostic factor for PFS. Limitations: A retrospective design and the absence of partial follow-up data are limitations of the study. Conclusions: In initially surgically treated HG-NECC, postoperative chemotherapy alone showed no inferiority when compared with chemoradiotherapy for HG-NECC, and 4+ cycles of chemotherapy tended to produce a better prognosis than 4-ones.

Peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer patients

Anti-programmed cell death-1 (PD-1) therapy exerts beneficial effects in a limited population of cancer patients. Therefore, more accurate diagnostics to predict the efficacy of anti-PD-1 therapy are desired. The present study investigated whether peripheral T cell cytotoxicity predicts the efficacy of anti-PD-1 therapy for advanced non-small cell lung cancer (NSCLC) patients. Advanced NSCLC patients treated with anti-PD-1 monotherapy (nivolumab or pembrolizumab) were consecutively enrolled in the present study. Peripheral blood samples were subjected to an analysis of peripheral T cell cytotoxicity and flow cytometry prior to the initiation of anti-PD-1 therapy. Peripheral T cell cytotoxicity was assessed using bispecific T-cell engager (BiTE) technology. We found that progression-free survival was significantly longer in patients with high peripheral T cell cytotoxicity (p = 0.0094). In the multivariate analysis, treatment line and peripheral T cell cytotoxicity were independent prognostic factors for progression-free survival. The analysis of T cell profiles revealed that peripheral T cell cytotoxicity correlated with the ratio of the effector memory population in CD4+ or CD8+ T cells. Furthermore, the results of flow cytometry showed that the peripheral CD45RA+CD25+/CD4+ T cell ratio was higher in patients with than in those without severe adverse events (p = 0.0076). These results indicated that the peripheral T cell cytotoxicity predicted the efficacy of anti-PD-1 therapy for advanced NSCLC patients.

Prognostic value of fibroblast activation protein expressing tumor volume calculated from [68Ga]Ga-FAPI PET/CT in patients with esophageal squamous cell carcinoma.

This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann-Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan-Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24months (16-29months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13-15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55-18.79, P = 0.001). This pilot study revealed that [68Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed.

Prognostic value of PERCIST and PET/CT metabolic parameters after neoadjuvant treatment in patients with esophageal cancer

AimTo assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival (CSS) in patients with esophageal cancer treated by chemoradiotherapy. Material and methodsFifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan–Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. ResultsThe average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in CSS curves for PERCIST criteria and variation of MTV and TLG. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither SUVmax nor tumor size were predictors for any of the assessment criteria. ConclusionApplication of PERCIST criteria as well as change in MTV and TLG from PET/CT studies proved to be prognostic factors for CSS in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.

The Prognostic value of Serum Ferritin in Breast cancer patients

Background: Breast cancer is the most common tumor among women worldwide, and elevated pretreatment serum ferritin levels are a poor prognostic factor in patients with many malignancies, but the relationship between serum ferritin levels and disease prognosis in breast cancer patients remains unclear. Aim: To estimate the relationship between pretreatment serum ferritin, overall survival (OS) and progression-free survival (PFS) in breast cancer patients. Patients and Methods: We evaluated pretreatment serum ferritin in 96 newly diagnosed breast cancer patients who have been followed up for 27months. Statistical analysis was performed using MedCalc (version 19.1.6). A p value &lt;0.05 was considered statistically significant. Results: Among patients with serum ferritin levels less than 146ng/ml, the estimated mean PFS survival was 26.561±0.328 months compared to 15.2121.396 months for those with serum ferritin levels 146ng/ml or higher (p=0.001). The estimated mean OS survival for patients with serum ferritin levels &lt; 146ng/ml was 27 months, compared to 23.5331.224 months for patients with serum ferritin levels ≥ 146ng/ml (P=0.002), their 27 months OS survival rates were 68.75% and 27.08%, respectively (p=0.008). Conclusion: Serum ferritin can be useful prognostic factor for PFS and OS in breast cancer patients, and elevated levels of it at 146ng/ml or more are a poor prognostic factor for 27month survival rates.

P11.15.B First multicentric real-life experience with the combination of lomustine and temozolomide in newly diagnosedMGMT promoter methylatedIDH wildtype glioblastoma

Abstract Background The CeTeG/NOA-09 trial assessed in a randomized phase 3 setting, whether combined treatment of lomustine together with temozolomide was superior to temozolomide treatment alone in newly diagnosed MGMT (O(6)-methylguanine-DNA-methyltransferase) promoter methylated glioblastoma patients. Survival was significantly improved from 31.4 months with temozolomide alone to 48.1 months with the combination of lomustine plus temozolomide. In view of this encouraging data - suggesting this combination could have a significant impact on the survival of newly diagnosed glioblastoma patients - we were curious to assess safety and efficacy of this regimen under real-life conditions. Material and Methods We collected clinical and radiographic data from adult newly diagnosed MGMT promoter methylated IDH (isocitrate dehydrogenase) wildtype glioblastoma patients treated at five neuro-oncology centers in Germany. As a requirement for inclusion, first-line treatment with lomustine plus temozolomide had to be performed for at least six weeks (one course). The available radiographic data was independently reviewed by an experienced board-certified neuro-radiologist. Results In total, 70 patients were included. Median progression-free survival of the full cohort was 14.4 months and median overall survival was 36.0 months. Patients who received TTFields (Tumor Treating Fields) treatment for eight weeks or longer together with the combination of lomustine plus temozolomide (n=22, 31%) had a prolonged progression-free survival compared to those patients who received TTFields treatment less than eight weeks or did not receive treatment with TTFields (n=48, 69%) (21.5 months versus 11.2 months; HR: 2.118, 95% CI: 1.245-3.605; p=0.0105). In a multivariable Cox regression analysis the use of TTFields for eight weeks or longer together with the combination of lomustine plus temozolomide as well as the application of at least five courses of CeTeG therapy emerged as independent prognostic factors for progression-free survival and overall survival. Pseudoprogression occurred in n=16 (33%) of the patients. We observed no treatment related deaths and high-grade hematotoxicity in n=31 (44%) of the patients. Conclusion The results from this multicentric trial that investigated newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma under real-life conditions indicate toxicity and survival estimates comparable to the CeTeG/NOA-09 trial. The use of TTFields for at least eight weeks in combination with this regimen was independently associated with extended progression-free and overall survival.

Impact of gender on response to immune checkpoint inhibitors in patients with non-small cell lung cancer undergoing second- or later-line treatment.

BackgroundSeveral previous clinical trials have reported that male patients with non-small cell lung cancer (NSCLC) respond better to immunotherapy than females. However, the impact of gender on prognosis remains uncertain because no real-world study considering various factors that affect patients’ response to immunotherapy with gender exists. Therefore, we evaluated the effect of gender on immunotherapy response adjusted by multiple factors in actual clinical practice.MethodsThis study was a single-center real-world retrospective cohort study, comprising 387 patients with NSCLC who received pembrolizumab, nivolumab, or atezolizumab alone as second- or later-line treatments. Subsequently, we compared their progression free survival (PFS) and overall survival (OS) scores based on gender, then analyzed prognostic factors accounting for immunotherapy response.ResultsThe mean age of the understudied patients was 64.0 years old, comprising 68.7% males, with non-squamous cell carcinoma accounting for 70.3% of these patients. Male patients also showed higher smoking rates, programmed death-ligand 1 (PD-L1) expression, and expression of wild type epidermal growth factor receptor (EGFR), known as favorable prognostic factors. However, no difference in PFS and OS according to gender was observed [PFS 2.2 (male) vs. 2.1 (female) months, P=0.144; OS 7.6 (male) vs. 8.8 (female) months, P=0.383]. Furthermore, an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, high expression of PD-L1, and EGFR mutations were proposed as prognostic factors in multivariate analysis for PFS. Besides, ECOG performance status ≥2 and squamous cell carcinoma were poor prognostic factors accounting for OS. Yet, gender was not an independent prognostic factor in PFS and OS.ConclusionsGender was not an independent prognostic factor for immunotherapy in real-world data although various factors affected immunotherapy response, such as wild type EGFR and high expression of PD-L1, which frequently occur in males.

Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in HER2-Positive Metastatic Breast Cancer.

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan–Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543–4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024–4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

Efficacy and Safety of Platinum Rechallenge in Patients With Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer: A Multicenter Retrospective Study.

Ovarian cancer diagnosed with platinum-resistant recurrence has very poor prognosis and single-agent chemotherapy with no cross-resistance to prior chemotherapy is recommended for its treatment. In this study, we retrospectively evaluated the efficacy and safety of platinum rechallenge therapy for once diagnosed with platinum-resistant ovarian cancer who had a platinum-free interval (PFI) of at least 6 months. The study included 49 patients who received platinum rechallenge therapy for ovarian, fallopian tube or primary peritoneal cancer who were once diagnosed with platinum-resistant recurrence between January 2010 and March 2021 and evaluated the efficacy and safety of this treatment. In addition, patient background factors were identified, and independent prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated. A complete response was noted in 7 cases, partial response in 21, stable disease in 9, and progressive disease in 10. The response and disease control rates were 55% and 76%, respectively. The median PFS and OS were 8.5 months and 35.8 months, respectively. The independent prognostic factor was PFI for OS, and there was no independent prognostic factor for PFS. Seven patients discontinued chemotherapy owing to serious adverse events, including one patient with treatment-related death. Platinum rechallenge therapy for patients with platinum-resistant recurrence did not cause previously unreported adverse events, and the adverse events were manageable. In addition, high response and disease control rates were observed, as well as long-term OS. Platinum rechallenge therapy for platinum-resistant ovarian cancer may be a viable treatment option.

Impact of osteopenia and neutropenia in patients with colorectal cancer treated with FOLFOXIRI: a retrospective cohort study.

This study was performed to assess the impact of osteopenia on chemotherapy-induced neutropenia and the prognosis for patients treated with FOLFOXIRI for colorectal cancer. In total, 77 patients who underwent FOLFOXIRI for un-resectable metastatic and advanced colorectal cancer were retrospectively evaluated. Osteopenia was evaluated by the bone mineral density, which was measured using the average pixel density of the trabecular bone in the 11th thoracic vertebra by computed tomography before the introduction of chemotherapy. The relationship between osteopenia and neutropenia was evaluated. Progression-free survival and overall survival of patients with osteopenia and patients with neutropenia were evaluated. Grade ≥ 3 neutropenia was significantly more common in patients with than without osteopenia (p = 0.002). The multivariate analysis showed that osteopenia was a significant independent predictive factor for grade ≥ 3 neutropenia (p = 0.016). There was no significant difference in progression-free survival or overall survival between patients with and without osteopenia. Patients with grade ≥ 3 neutropenia tended to have a higher progression-free survival rate than others (p = 0.059). The overall survival rate was significantly higher in patients with grade ≥ 3 neutropenia than in others (p = 0.011). Osteopenia might be a predictor of chemotherapy-induced neutropenia, and neutropenia might be a prognostic factor for progression-free survival and overall survival in patients with colorectal cancer treated with FOLFOXIRI.

Correlation Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Programmed Death-Ligand 1 Expression as Prognostic Markers in Non-Small Cell Lung Cancer.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) at baseline treatment is an important marker of systemic inflammation, which is correlated with survival benefits in lung, breast, ovarian, bladder, and colorectal cancer. Programmed death-ligand 1 (PD-L1) expression is a biomarker with discording results regarding survival benefits in lung cancer. In our research, we studied the relationship between these two markers in patients with lung cancer.MethodsPatients with stage I, II, III, and IV lung cancer (n = 80) were included in this retrospective study. The NLR baseline was recorded before the initiation of treatment. The NLR cut-off value was 4. PD-L1 expression was determined by immunohistochemical staining. Univariate and multivariate survival analyses were conducted to test their prognostic value.ResultsNLR proved to be a significant prognostic factor for progression-free survival (PFS) (p=0.002, Log Rank) with a mean PFS of 27.7 months for low NLR patients and 12.8 months for high NLR patients. It was also significant for overall survival (OS) (p=0.007, Log Rank) with a mean OS of 52 months for low NLR patients and 41.6 months for high NLR patients. The prognostic impact of PD-L1 expression on PFS and OS was not statistically significant with a mean PFS of 23.1 months for PD-L1-negative patients and 15.8 months for PD-L1-positive patients (p=0.422, Log Rank). Mean OS was 49 months for PD-L1-negative patients while for PD-L1-positive patients, it was 43.3 months (p=0.550 Log Rank). Regarding the correlation between PD-L1 expression and NLR value, PFS mean survival times were 13.1 months for PD-L1(+)/NLR>4, 15.1 months for PD-L1(-)/NLR>4, 16.4 months for PD-L1(+)/NLR<4 and 27.8 months for PD-L1(-)/NLR<4. This correlation between PFS and the combined PD-L1 and NLR prognostic factor was statistically relevant (p=0.04). For OS, the PD-L1/NLR combined prognostic factor was not statistically relevant (p=0.055). A mean PFS time of 27.8 months was reported for PD-L1(-)/NLR<4 group patients while for the other groups, the mean PFS was 14.9 months (p=0.045). In univariate analysis, the elevated NLR was significantly associated with a decreased PFS time (HR=2.31, 95% CI =1.323- 4.051, p=0.03) as well as OS (HR=3.555, 95% CI=1.310- 9.652, p=0.013). In multivariate analysis, NLR remained statistically significant for PFS (HR=2.160, 95% CI=1.148- 4.062, p=0.013) and OS (HR=4.364, 95% CI=1.474- 12.921, p=0.008) after adjusting for the factors of age, gender, tumor stage, lymph node stage, clinical stage, histology, and PD-L1 expression. PD-L1 expression was not a valid prognostic factor for progression or death in either univariate or multivariate analysis. We also stratified the disease control rate (DCR) depending on PD-L1/NLR combined factor expression. In the PD-L1(-)/NLR<4 group, we had the highest number of partial responses (PRs) and only one complete response (CR) compared to the other groups (p=0.006).ConclusionsAs the number of patients is limited in the present analysis, it is hypothesized that these two markers can be useful in dividing patients into two prognostic groups: the good prognostic group reunites PD-L1(+)/NLR<4 and PD-L1(-)/NLR<4 and the poor prognostic group reunites PD-L1(+)/NLR>4 and PD-L1(-)/NLR>4.

Prognostic value of the ratio of maximum to minimum diameter of primary tumor in metastatic clear cell renal cell carcinoma

BackgroundSeveral models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC).MethodsPatients with mccRCC (n = 213) treated with sunitinib from January 2008 to December 2018 were identified. Cutoff value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan–Meier method.ResultsThe optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD ≥ 1.34 group had shorter PFS (9.6 versus 17.7 months, p < 0.001) and OS (25.5 versus 32.6 months, p < 0.001) than patients in ROD < 1.34 group. After adjustment for other factors, multivariate analysis showed ROD ≥ 1.34 was an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.006). Patients in ROD ≥ 1.34 group presented higher proportions of pT3/4 stage (89.2% versus 10.8%, p = 0.021), WHO/ISUP grade III/IV (72.0% versus 28.0%, p = 0.010), tumor necrosis (71.0% versus 29.0%, p = 0.039), sarcomatoid differentiation (79.1% versus 20.9%, p = 0.007), poor MSKCC risk score (78.4% versus 21.6%, p < 0.001) and poor IMDC risk score (74.4% versus 25.6%, p < 0.001) than ROD < 1.34 group.ConclusionPrimary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high pT stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score.

Does Gross Total Resection Improve Progression-Free and Overall Survival in Pediatric Intracranial Ependymomas? Single-Center Clinical Experience Of 61 Cases

To share our clinical experience of 25 years and identify prognostic factors for progression-free and overall survival in pediatric intracranial ependymomas. In total, 61 children who were treated between 1995 and 2020 in a single institution were included in the study. Medical records of the patients were retrospectively reviewed to obtain and analyze the following data: patient age at first surgery, sex, presenting symptoms, hydrocephalus and any invasive treatment, anatomic site, extent of resection, pathologic grade, time to progression, and time to death. Progression-free and overall survival rates and affecting factors were analyzed by Kaplan-Meier method. Dysphagia, number of surgeries, and spinal seeding were associated with progression free and overall survival in univariate analysis. The extent of resection, World Health Organization grade, and visual problems were also associated with progression whereas sex was associated with overall survival. Cox regression identified the extent of resection and single surgery as an independent prognostic factor for progression-free survival. No independent factor was found for overall survival. This single center experience of 25 years confirms the beneficial effect of gross total resection on disease progression. Although spinal seeding seems to affect survival rates, greater number of cases are needed to reveal its full effect.

Clinical implications of neoadjuvant chemotherapy in advanced endometrial cancer: a multi-center retrospective cohort study

BackgroundThe mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer.MethodsFrom the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC–IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients’ clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed.ResultsOverall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032).ConclusionsNAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS.

Assessing the Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Stage I Non-Small-Cell Lung Cancer with Complete Resection

Purpose To explore the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in stage I non-small-cell lung cancer (NSCLC) undergoing surgery. Patients and Methods. Between 2014 and 2016, a total of 190 patients with postoperative pathology of stage I NSCLC who underwent radical surgery at Nanjing Chest Hospital were studied. Clinical data were analyzed and classified into low-risk, moderate-risk, and high-risk groups based on independent risk factors to assess the prognosis. Results NLR was associated with histological type and gender, and patients with an elevated NLR have poor overall survival (OS). Lymphovascular invasion, red blood cell distribution width-standard deviation (RDW-SD), and carcinoembryonic antigen (CEA) were independent prognostic factors for progression-free survival (PFS) in postoperative patients with stage I NSCLC, while NLR, RDW-SD, and CEA were independent risk factors for OS. Both PFS and OS were shorter in the low-risk group than in the medium-risk and high-risk groups. Conclusions NLR, RDW-SD, CEA, and lymphovascular invasion are independent risk factors for postoperative prognosis in patients with stage I NSCLC, and the combination has a predictive value.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies

Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs.≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstratedto be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Abstract 5169: Sentinel lymph node gene expression signature predicts survival outcome in cutaneous melanoma

Abstract Background: Sentinel lymph node status is an important prognostic factor for melanoma progression. We sought to develop a sentinel lymph node gene expression signature score predictive of disease progression in patients with cutaneous melanoma. Methods: Cases were retrieved from University of Pittsburgh protocol “Sentinel Node and Non-Sentinel Lymph Nodes (SLN and non-SLN) Procurement from Melanoma Subjects for Molecular Profiling.” Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with progression-free survival (PFS) were selected and a penalized regression function was used to select genes with a non-zero coefficient. A risk score was calculated from a 12 gene signature. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and PFS. Results: In total, 45 patients were included [female=18 (40%), median age (range)= 56 (16-81) years]. The median Breslow thickness (IQR) was 4.1 (3.3-6.0) mm, ulceration was present in 29 (67%) cases, and 25 (56%) lesions had nodular histology. Among patients, 23 (51%) had a positive SLN via H&amp;E. Twenty-one (46.7%) patients developed disease recurrence/progression with a median follow-up of 8.3 years. The median time to progression was 9.6 years. Among the top 25 genes, 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, ZNF223, PDE6G, CXCL3, CHRFAM7A, HLA-DRB-decreased risk, DCTN1, ASPSCR1, HEXIM1-increased risk). A 12-gene signature score was significantly associated with PFS (p&amp;lt;0.0001) and produced a bootstrap cross-validated C index of 0.888. Stratifying by SLN status the gene signature risk score remained highly significant (p&amp;lt;0.0001). In univariate analysis, Breslow thickness (HR=1.41), presence of ulceration (HR=3.61), SLN positivity (HR=2.50), and acral-lentiginous histology compared to nodular (HR=4.07) were each significantly associated with PFS (all p&amp;lt;0.05). After simultaneously adjusting for all of these factors plus the gene signature, the 12-gene score remained a significant predictor for PFS (p&amp;lt;0.0001). Conclusion: A SLN 12-gene signature risk score is associated with melanoma progression regardless of SLN status and can be used as a prognostic factor for PFS of patients. External validation of the gene signature is warranted. Citation Format: Lilit Karapetyan, William Gooding, Xi Yang, Andrew Knight, Aofei Li, Cindy Sander, Monica Panelli, Walter J. Storkus, Ahmad A. Tarhini, John M. Kirkwood. Sentinel lymph node gene expression signature predicts survival outcome in cutaneous melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5169.

Abstract 642: Spatial analysis of tumor infiltrating lymphocytes in histological images using deep learning predicts progression-free survival in colorectal cancer

Abstract Histological distribution and density of tumor infiltrating lymphocytes (TILs) are known to be informative to cancer patients’ outcome. However, due to the heterogeneity and huge size of digitized pathology slides, it has been a challenging problem to quantify TILs-related features in whole slide images (WSI). This study aimed to explore the impact of spatial distribution of TILs quantified by deep learning (DL) approaches based on digitalized WSI stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The cancer and TILs regions are first separately identified by deep learning models in the WSI. The TILs densities at tumor invasive margins are then quantified by image analysis algorithms and used for prognosis of progression-free survival (PFS) in CRC patients. The prognostic impact of spatial distributions of TILs in CRC patients was explored in the Yonsei cohort (n=180) and validated in the TCGA cohort (n=268). Two experienced pathologists manually measured TILs at the most invasive margin as 0-3 by the Klintrup-Mäkinen (KM) grading method and compared to DL approaches. On multivariate analysis, TILs densities within 200µm of the invasive margin (f_im200) was remained as the most significant prognostic factor for PFS (HR 0.004 [95% CI, 0.0001-0.1502], p=.002) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031, [95% CI 0.001-0.645], p=.024). Inter-observer agreement of manual KM grading was insignificant in both cohorts. The survival analysis by pathologists’ manual KM grading showed statistically significant different PFS from the TCGA cohort, but not the Yonsei cohort. In summary, automated quantification of TILs at the invasive margin showed a prognostic utility to predict PFS, and could provide reproducible TILs density measurement in CRC patients. Citation Format: Hongming Xu, Yoon Jin Cha, Jean Clemenceau, Jinhwan Choi, Sung Hak Lee, Jeonghyun Kang, Tae Hyun Hwang. Spatial analysis of tumor infiltrating lymphocytes in histological images using deep learning predicts progression-free survival in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 642.

Efficacy and Safety of Programmed Death-Ligand 1 Inhibitor Plus Platinum-Etoposide Chemotherapy in Patients With Extensive-Stage SCLC: A Prospective Observational Study

IntroductionTo date, the efficacy and safety of programmed death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy for patients with extensive-stage SCLC (ES-SCLC), with real-world evidence, stratified on the basis of age and performance status (PS), have not been fully investigated. The aim of this study was to evaluate the efficacy and safety of PD-L1 inhibitor plus platinum-etoposide chemotherapy in patients with ES-SCLC. MethodsThis multicenter prospective study evaluated patients with ES-SCLC who received PD-L1 inhibitor plus platinum-etoposide chemotherapy between September 2019 and October 2021. ResultsA total of 45 patients with ES-SCLC received the aforementioned treatment, including 18 elderly (≥75 y old) patients and six patients with a PS of 2. Multivariate analysis indicated that a PS of 2 was a significant independent prognostic factor for progression-free survival and overall survival (p = 0.008 and p = 0.001, respectively). Of patients with PS of 2 at the initial phase, those that achieved PS improvement during treatment had significantly longer progression-free survival and overall survival than those who did not (p = 0.02 and p = 0.02, respectively). The incidence of adverse events accompanied with treatment discontinuation was significantly higher in the elderly patients than in the non-elderly patients (p = 0.03). ConclusionsThis real-world prospective study found that PD-L1 inhibitor plus platinum-etoposide chemotherapy had limited efficacy in patients with ES-SCLC with a PS of 2, except for cases with improvement of PS during treatment. Owing to the emergence of adverse events and treatment discontinuation, this treatment should be administered with caution in elderly patients with ES-SCLC.