Significant Favorable Prognostic Factor Research Articles

Prognostic factors after radical local therapy for oligo-recurrence of non-small cell lung cancer.

Oligo-recurrence refers to the presence of a limited number of metachronous recurrences that can be treated with radical local therapy, and most patients have a good prognosis. However, the clinical course after local therapy for oligo-recurrence of non-small cell lung cancer (NSCLC) varies, and the prognostic factors are unclear. The aim of this study was to elucidate the prognostic factors of patients with oligo-recurrence of NSCLC who underwent radical local therapy. Between 2004 and 2015, 901 patients who underwent complete resection for NSCLC were included. We defined oligo-recurrence as two or fewer recurrences and retrospectively examined the factors that affected post-recurrence survival in patients who underwent radical local therapy for oligo-recurrence. Recurrence was confirmed in 267 patients, and among them, 125 experienced oligo-recurrence. Eighty-five patients with oligo-recurrence received local therapy, and their 5-year post-recurrence survival rate was 42.8%. Multivariable analysis of the prognostic factors of these patients revealed that single recurrence (hazard ratio = 2.19, P = 0.005) and systemic therapy (hazard ratio = 1.75, P = 0.043) were significant favorable prognostic factors associated with post-recurrence survival. However, the presence or absence of epidermal growth factor gene mutations, which is generally a prognostic factor for NSCLC recurrence, did not affect the prognosis of these patients. The number of recurrences and receiving systemic therapy are important prognostic factors for patients with oligo-recurrence who undergo radical local therapy, and these patients have a particularly favorable prognosis.

EFFECT OF GENDER ON 28-DAY SURVIVAL RATES AND TRANSFUSION VOLUME IN SEVERE TRAUMA PATIENTS: A MULTICENTER OBSERVATIONAL STUDY.

Background: This study clarified the relationship between sex with survival and transfusion volume in severe trauma cases. Methods: A multicenter, collaborative post hoc analysis of patients with trauma in Japan was conducted. Patients aged ≥18 years with severe trauma indicated by an Injury Severity Score (ISS) of 16 or higher were enrolled. Patients were matched and analyzed by gender based on propensity score with factors determined at the time of injury. Subgroup analysis was performed on patients younger than 50 years and older than 50 years. The significance level was defined as P < 0.05. Results: The 1,189 patients included in this registry were divided into adjusted groups of 226 male and female patients each. In the main analysis, 28-day survival rates in females were significantly higher than those in males ( P = 0.046). In the subgroup analyses, there was no statistically significant prognostic effect of gender. Secondary outcomes, including transfusion volume, showed no significant gender-based variations. Logistic regression analyses consistently demonstrated that female sex was a significant favorable prognostic factor in all ages. This was true for the over-50 group on subgroup analysis, but no significant gender-prognosis relationship was identified in the under-50 age group. High ISSs were associated with poorer outcomes across all age groups. Conclusion: In severe trauma, survival at 28 days was significantly lower in males. However, this trend was not observed in patients aged <50 years. Factors other than sex hormones may be responsible for differences in posttraumatic outcomes by gender.

Does the quality of endoscopic equipment influence the recurrence rate after photodynamic diagnosis-assisted transurethral resection of bladder tumor?

BackgroundPhotodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) for nonmuscle-invasive bladder cancer is superior to conventional white-light TURBT for cancer detection. However, when performing PDD-TURBT, cystoscopy findings vary depending on the quality of the endoscopic equipment. In this study, we compared the effects of different types of endoscopic equipment on postoperative outcomes. MethodsPatients who underwent their first PDD-TURBT at our clinic were selected. Patients on whom PDD-TURBT was performed using endoscopic equipment A were sorted into Group A, and patients on whom PDD-TURBT was performed using equipment S were sorted into Group S. The characteristics, recurrence-free survival (RFS), and recurrence frequency of these patients were retrospectively investigated and compared. The prognostic factors for RFS were also analyzed. ResultsA total of 49 patients were included in Group A and 46 in Group S. In Group S, a higher detection rate (8.2% vs. 30.4 %, p < 0.01) of carcinoma in situ (CIS) was noted. RFS tended to be better in Group S (HR 0.63, p = 0.15). The frequency of recurrence also tended to be lower in Group S (4.92 vs. 3.66 per 10,000 person-days, p = 0.08). Furthermore, CIS (HR 0.30, p = 0.04) and Bacillus Calmette–Guerin therapy (HR: 0.26, p = 0.01) were significant favorable prognostic factors for RFS. ConclusionThe quality of the endoscopic equipment may influence postoperative recurrence after PDD-TURBT. Higher-quality endoscopic instruments have superior CIS detection capabilities, which can lead to improvements in postoperative outcomes with the appropriate selection of postoperative adjuvant therapy.

Impact of PD-L1 expression on survival in patients with unresectable/recurrent gastric cancer receiving first-line chemotherapy without immune checkpoint inhibitors.

391 Background: Although high PD-L1 expression predicts a favorable response of advanced solid tumors to immune checkpoint inhibitors (ICIs), its impact on survival in patients with unresectable/recurrent gastric cancer (GC) has remained unclear. We investigated the prognostic value of PD-L1 expression for survival in unresectable/recurrent GC patients receiving first-line chemotherapy without ICIs. Methods: JCOG1013, a phase 3 randomized trial, demonstrated the addition of docetaxel to cisplatin and S-1 as first-line chemotherapy was of no benefit to patients with unresectable/recurrent GC (N=741) either for overall survival (OS) or progression-free survival (PFS). Tumor specimens prior to chemotherapy were collected for assessing PD-L1 expression for this ancillary study. PD-L1 expression was determined using immunohistochemistry (Dako, 28-8 pharmDx) and used to derive the PD-L1 combined positive score (CPS) and PD-L1 tumor proportion score (TPS). As with the CheckMate 649 study, the cutoff values for PD-L1 CPS and PD-L1 TPS were set at 5 and 1%, respectively. Multivariable analyses were performed using Cox proportional hazard models to evaluate the prognostic significance of PD-L1 CPS and PD-L1 TPS as predictors of OS and PFS. All p values were 2-sided; values &lt;0.05 were considered statistically significant. Results: We analyzed 427 patients with unresectable/recurrent GC. The prevalence of PD-L1 CPS≥5, and PD-L1 TPS≥1% was 33% and 24%, respectively. There was no significant difference in OS and PFS between the PD-L1 CPS ≥5 group and the PD-L1 CPS &lt;5 group (Table). The PD-L1 TPS ≥1% group had superior OS and PFS compared to the PD-L1 TPS &lt;1% group (Table). In multivariable analyses for OS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (hazard ratio (HR) = 0.64 [95% CI: 0.50–0.83], p&lt;0.001), but PD-L1 CPS≥5 was not (HR = 0.82 [95% CI: 0.65–1.02], p = 0.073). In multivariable analyses for PFS, PD-L1 TPS ≥1% was a significant favorable prognostic factor (HR = 0.67 [95% CI: 0.52–0.84], p&lt;0.001), but PD-L1 CPS≥5 was not (HR = 0.83 [95% CI: 0.67–1.03], p = 0.090). Conclusions: PD-L1 TPS≥1% is significantly correlated with longer OS and PFS in patients with unresectable/recurrent GC receiving first-line chemotherapy without ICIs. PD-L1 TPS should be considered as a stratification factor in randomized clinical trials for unresectable/recurrent GC. Clinical trial information: UMIN000007652 . [Table: see text]

P16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes

p16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006–2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection. We found that 12.7% of the patients exhibited p16 overexpression, which was significantly more common in the nasal cavity and increased from 2015 onward. The HPV was a high-risk type and viral loads ranged from 4.2 to 1.6 × 106 copies/ng DNA with genome integration. Five-year overall survival (OS) and five-year relapse-free survival (RFS) rates were 74.6% and 69.9%, respectively. Our multivariate analysis showed that T category (T1–4a) and hemoglobin levels (≥13.7) were significant favorable prognostic factors for OS, while T category, performance status, and p16 overexpression were significantly associated with RFS. In patients with p16 overexpression, OS was 100% and RFS was 90%. Our findings suggest that p16 overexpression is a reliable surrogate marker for transcriptionally active HPV infection and predicts a favorable prognosis.

JS05.5.A INTRAOPERATIVE MRI-GUIDED RESECTION IS NOT SUPERIOR TO 5-ALA-GUIDANCE IN NEWLY DIAGNOSED GLIOBLASTOMA: A PROSPECTIVE CONTROLLED MULTICENTER CLINICAL TRIAL

Abstract BACKGROUND Prospective data suggested a superiority of intraoperative MRI (iMRI) over 5-aminolevulinic acid (5-ALA) for achieving complete resections of contrast enhancement in glioblastoma surgery. We investigated this hypothesis in a prospective clinical trial and correlated residual disease volumes with clinical outcome in newly diagnosed glioblastoma. MATERIAL AND METHODS This is a prospective controlled multicenter parallel-group trial with two center-specific treatment arms (5-ALA and iMRI) and blinded evaluation. The primary endpoint was complete resection of contrast enhancement on early postoperative MRI. We assessed resectability and extent of resection by an independent blinded centralized review of pre- and post-operative MRI with 1mm slices. Secondary endpoints included progression-free (PFS) and overall survival (OS), patient-reported quality of life and clinical parameters. RESULTS We recruited 314 patients with newly diagnosed glioblastomas at eleven German centers. 127 patients in the 5-ALA and 150 in the iMRI arm were analyzed in the as treated analysis. Complete resections, defined as a residual tumor ≤0.175 cm³, were achieved in 90 patients (78%) in the 5-ALA and 115 (81%) in the iMRI arm (p=0.79). Incision-suture times (p&amp;lt;0.001) were significantly longer in the iMRI arm (316 vs. 215 [5-ALA] minutes). Median PFS and OS were comparable in both arms. The lack of any residual contrast enhancing tumor (0cm³) was a significant favorable prognostic factor for PFS (p&amp;lt;0.001) and OS (p=0.048), especially in MGMT unmethylated tumors (p=0.006). CONCLUSION We could not confirm superiority of iMRI over 5-ALA for achieving complete resections. Neurosurgical interventions in newly diagnosed glioblastoma shall aim for safe complete resections with 0 cm³ contrast-enhancing residual disease, as any other residual tumor volume is a negative predictor for PFS and OS.

Clinical Impact of Radical Resection of Synchronous and Metachronous Peritoneal Metastases from Colorectal Cancer.

According to some case series, patients with colorectal cancer (CRC) who underwent radical resection of synchronous peritoneal metastases (PM) with the primary tumor had better survival than patients who underwent non-surgical treatment. However, little evidence exists regarding the significance of radical resection for metachronous PM. This study aimed to evaluate the clinical significance of surgical intervention for isolated PM from CRC, with a particular focus on time to PM. A total of 74 consecutive patients with isolated PM from CRC, including 40 and 34 patients with synchronous and metachronous PM, respectively, treated between 2007 and 2018 were retrospectively analyzed. The primary outcome measure was overall survival (OS) from diagnosis, and the OS was compared between radical resection and palliative chemotherapy. Five-year OS was 39.7% for all patients. Patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy (62.8% vs. 11.0%; p<0.0001). According to time to PM, patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy for both synchronous PM (47.6% vs. 0%; p=0.019) and metachronous PM (77.2% vs. 15.2%; p<0.0001). Multivariable analysis stratified by time to PM revealed that surgical intervention is a significant favorable prognostic factor only in patients with metachronous PM (hazard ratio 0.117, 95% confidence interval 0.020-0.678; p=0.017). Patients with radical resection of PM had good survival compared with those with chemotherapy alone, especially for metachronous PM. Surgical intervention should be considered for isolated metachronous PM when radical resection is feasible.

Safety and efficacy of self-expandable metallic stent combined with 125I brachytherapy for the treatment of malignant obstructive jaundice

BackgroundSeveral previous studies demonstrated that the combination of self-expandable metallic stents (SEMS) and 125I seed implantation might prolong stent patency and obtain survival benefits for malignant obstructive jaundice (MOJ) patients. However, these studies rarely mentioned a comparison between CT-guided intratumoral 125I seed implantation and intraluminal 125I seed strand insertion combined with stenting for the management of MOJ. This study aimed to further evaluate the safety and efficacy of SEMS combined with 125I brachytherapy in the management of unresectable MOJ.MethodsFifty-nine patients with unresectable MOJ were retrospectively included from March 2018 to June 2021. The main therapeutic outcomes were evaluated in terms of stent patency, and overall survival. Cumulative stent patency and overall survival rates were calculated by Kaplan–Meier survival analysis. Both clinical and treatment factors associated with survival were analyzed.ResultsTechnical success was achieved in all patients. The clinical success rate was 94% (32/34) in the seeds group and 92% (23/25) in the control group, no significant difference was found (p =1.000). The median duration of stent patency was significantly longer in the 125I brachytherapy group compared with the control group (289 days vs. 88 days, respectively, p =0.001). The 125I brachytherapy group demonstrated a significantly better median overall survival rate than the control group (221 days vs. 78 days, respectively, p =0.001). In multivariate analysis, stents with 125I brachytherapy (p =0.004) was a significant favorable prognostic factor that affected patient survival. No significant difference was observed between CT-guided 125I seed implantation and 125I seed strand insertion in stent patency (p =0.268), and overall survival (p =0.483).ConclusionSEMS combined with 125I brachytherapy is safe and effective for treating MOJ. 125I brachytherapy may help to maintain stent patency and prolong overall survival. There was no significant difference between CT-guided 125I seed implantation with SEMS and 125I seed strand insertion with SEMS in stent patency and overall survival.

Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER PRODIGE 23): Health-related quality of life longitudinal analysis

BackgroundResults from the phase 3 PRODIGE 23 study showed that neoadjuvant chemotherapy (NAC) with mFOLFIRINOX and preoperative chemoradiotherapy improved disease-free survival compared with preoperative chemoradiotherapy in patients with locally advanced rectal cancer. We aimed to assess the health-related quality of life (HRQOL) outcomes from this study. Patients and methodsA total of 461 patients (231 versus 230 patients) from 35 French hospitals were randomly assigned to either NAC with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, fluorouracil 2400 mg/m2 over 46 h intravenously every 2 weeks for 6 cycles) followed by preoperative chemoradiotherapy or chemoradiotherapy only. HRQOL was assessed at baseline, during treatments and at 2-year follow-up using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. ResultsCompared to baseline, HRQOL scores during NAC were better for tumour symptoms but worse for global health status, functional domains, fatigue, nausea/vomiting and appetite loss. During follow-up, improved emotional functioning was observed, but deterioration of body image, increased urinary incontinence, and lower male sexual function were observed. Linear mixed model exhibited a treatment-by-time interaction effect for nausea/vomiting and insomnia symptoms showing a greater deterioration in the standard-of-care group. Only treatment arm and baseline physical functioning were independent significant favourable prognostic factors. ConclusionNAC improved tumour-related symptoms and transitorily reduced most functional scores. Adding NAC before chemoradiotherapy and increased physical functioning at baseline were independent significant prognostic factors for longer disease-free survival.

CT-guided 125I brachytherapy for hepatocellular carcinoma in high-risk locations after transarterial chemoembolization combined with microwave ablation: a propensity score-matched study.

This study aimed to evaluate the safety and efficacy of 125I brachytherapy combined with transarterial chemoembolization (TACE) and microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC) in high-risk locations. After 1:2 propensity score matching (PSM), this retrospectively study analyzed 49 patients who underwent TACE +MWA+125I brachytherapy (group A) and 98 patients who only received TACE +MWA (group B). The evaluated outcomes were progression-free survival (PFS), overall survival (OS), and treatment complications. Cox proportional hazards regression analysis survival was used to compare the two groups. The patients in group A showed a longer PFS than group B (7.9 vs. 3.3 months, P = 0.007). No significant differences were observed in median OS between the two groups (P = 0.928). The objective response rate (ORR), disease control rate of tumors in high-risk locations, and the ORR of intrahepatic tumors were 67.3%, 93.9%, and 51.0%, respectively, in group A, and 38.8%, 79.6% and 29.6%, respectively, in group B (P < 0.001, P = 0.025 and P = 0.011, respectively). TACE-MWA-125I (HR = 0.479, P < 0.001) was a significant favorable prognostic factor that affected PFS. The present of portal vein tumor thrombosis was an independent prognostic factor for PFS (HR = 1.625, P = 0.040). The Barcelona clinic liver cancer (BCLC) stage (BCLC C vs. B) was an independent factor affecting OS (HR = 1.941, P = 0.038). The incidence of complications was similar between the two groups, except that the incidence of abdominal pain was reduced in the group A (P = 0.007). TACE-MWA-125I resulted in longer PFS and better tumor control than did TACE-MWA in patients with unresectable hepatocellular carcinoma in high-risk locations.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX.

The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma.

Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Tumor-infiltrating immune cell status predicts successful response to immune checkpoint inhibitors in renal cell carcinoma

Immune checkpoint inhibitors (ICI) have dramatically changed the treatment of metastatic renal cell carcinoma (mRCC). Although many studies have reported biomarkers as predicting the efficacy of ICI in mRCC, they remain controversial and have challenges to apply in real-world practice. We evaluated prognostic significance of multiple molecules associated with tumor immunity in patients treated with ICI. The molecules were detected in tumor tissues by immunohistochemical staining. We identified CD8-positive T cells and CD68-positive macrophages infiltrating into the tumor tissue as significant favorable prognostic factors for ICI treatment. Conversely, high expression of CD4-positive T cells was associated with poor response to ICI. Furthermore, we demonstrated that scoring for the expression status of these three molecules provides a remarkably accurate biomarker in patients with mRCC. Even the classical approach of immunohistochemistry could predict the outcome of ICI treatment by assessing the combined status of tumor-infiltrating immune cells.

BIOM-27. PROGNOSTIC SIGNIFICANCE OF EXTENT OF RESECTION IN GLIOMA ACCORDING TO THE 2021 WHO CLASSIFICATION

Abstract BACKGROUND In the updated 2021 WHO classification, diffuse gliomas were strictly reclassified by molecular statuses. In glioblastoma (GBM), the prognostic significance of the resection has been shown, but the excision rate to be achieved in the new classification has not been defined. Moreover, the correlation between the extent of resection (EOR) and the prognosis is still controversial for other gliomas. METHODS IDH 1/2 mutations and TERT promoter mutations were analyzed by Sanger sequencing, 1p/19q co-deletion by microsatellite or MLPA, and EGFR amplification and CDKN2A deletions by MLPA. The correlation between the resection rate and prognosis of each tumor type in the 2021/2016 WHO classification was analyzed retrospectively. RESULTS According to the 2021 classification, 293 patients with GBM, IDH-wild type, 68 with astrocytoma, IDH-mutant (2/3/4 22/26/20), and 58 with oligodendroglioma, IDH-mutant and 1p/19q co-deleted were identified. Based on the 2016 classification, they were diagnosed as 314 GBM, 106 astrocytoma (Gd II/III 37/69), and 59 oligodendroglioma. For GBM, IDH-wild type (2021 classification), a prolonged OS benefit was observed with &amp;gt;25% removal (p=0.042), whereas, more than 20% of tumor removal for patients with GBM (2016 classification) resulted in OS prolongation. EOR was a significant favorable prognostic factor for grade II/III astrocytoma by the 2016 classification, but not for astrocytoma, IDH-mutant (grade 2/3) in the 2021 classification. When analyzed only in patients with astrocytoma, IDH-mutant by the 2021 classification, EOR was not significantly prognostic, suggesting that poorer prognosis of patients with unresectable IDH-wild type astrocytomas (2016 classification) might have a negative impact on the outcome. CONCLUSION There was a strong correlation between EOR and prognosis in patients with GBM, and &amp;gt;25% removal was considered significant according to the 2021 classification. For astrocytoma in the 2021 classification, EOR did not show a prognostic significance, but further validation including grading effect is warranted.

DNA methylation of the immediate upstream region of BRCA1 major transcription start sites is an independent favorable prognostic factor in patients with high-grade serous ovarian cancer

ObjectiveTo establish a quantitative method to evaluate the DNA methylation level of an immediate upstream region of major BRCA1 transcriptional start sites (TSSs), and to investigate whether methylation of the region is a prognostic factor in high-grade serous ovarian cancer patients after neoadjuvant chemotherapy. MethodsNinety-two FFPE samples of advanced high-grade serous ovarian cancers after neoadjuvant chemotherapy between 2011 and 2018 were used for mutation and methylation analysis. DNA methylation levels were assessed by pyrosequencing and DNA methylation microarray. An association between methylation level (or a mutation) and progression-free survival was assessed by Kaplan-Meier analysis. ResultMajor BRCA1 transcripts and CpG sites immediately upstream of their TSSs were identified, and a pyrosequencing method was developed. BRCA1 methylation, BRCA1/2 mutations, and a RAD51C mutation were detected in 17/79 (21.5%), 17/92 (18.5%), and 1/92 (1.1%) high-grade serious ovarian cancer samples. In univariate analysis, BRCA1 methylation and no residual tumor were associated with progression-free survival (BRCA1 methylation: P = 0.025, no residual tumor: P = 0.0026). Multivariate analysis showed that both BRCA1 methylation (P = 0.038, HR = 0.47, 95% CI: 0.21–0.96) and no residual tumor (P = 0.012, HR = 0.49, 95% CI: 0.28–0.85) were significant favorable prognostic factors. ConclusionA quantitative method to estimate the methylation level of the immediate upstream region of major BRCA1 TSSs was established. Methylation of the region of was an independent favorable prognostic factor in high-grade serous ovarian cancer patients.

Effect of Biliary Tract Invasion with Obstructive Jaundice on the Prognosis of Patients With Unresectable Hepatocellular Carcinoma

Biliary tract invasion (BTI) is associated with poor outcomes in patients with hepatocellular carcinoma (HCC). However, the presence of a BTI is a neglected variable for staging in the current guidelines. This study aimed to explore the effects of BTI with obstructive jaundice on the prognosis of patients with unresectable HCC. We retrospectively included 205 patients initially diagnosed with unresectable HCC who presented with obstructive jaundice due to BTI between January 2010 and June 2021. BTI was classified into four types according to the location of the biliary obstruction. Both clinical and treatment factors that affect median overall survival (mOS) were analyzed. The mOS of patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C, and D was 9.2 months, 3.4 months, and 1.8 months, respectively (p<.001). The mOS of BTI type I patients was superior to that of BTI type II patients (7.1 months vs. 3.2 months, p=.002). Patients who underwent successful biliary drainage had a longer mOS than those who underwent unsuccessful biliary drainage (10.4 months vs. 2.9 months, p<.001). In the multivariate analysis, BTI type I (p=.009), successful biliary drainage (p=.005), and HCC treatment (p<.001) were significant favorable prognostic factors that affected patient survival. HCC patients with BTI type II may have a poorer prognosis than those with BTI type I. Effective biliary drainage and anti-cancer treatment may provide survival benefits to these patients. A more detailed staging system for HCC based on the state of BTI is needed.

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer

Early results at 3 years from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial showed survival benefits with adjuvant treatment with modified FOLFIRINOX vs gemcitabine in patients with resected pancreatic ductal adenocarcinoma; mature data are now available. To report 5-year outcomes and explore prognostic factors for overall survival. This open-label, phase 3 randomized clinical trial was conducted at 77 hospitals in France and Canada and included patients aged 18 to 79 years with histologically confirmed pancreatic ductal adenocarcinoma who had undergone complete macroscopic (R0/R1) resection within 3 to 12 weeks before randomization. Patients were included from April 16, 2012, through October 3, 2016. The cutoff date for this analysis was June 28, 2021. A total of 493 patients were randomized (1:1) to receive treatment with modified FOLFIRINOX (oxaliplatin, 85 mg/m2 of body surface area; irinotecan, 150-180 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 2400 mg/m2, every 2 weeks) or gemcitabine (1000 mg/m2, days 1, 8, and 15, every 4 weeks) as adjuvant therapy for 24 weeks. Primary end point was disease-free survival. Secondary end points included overall survival, metastasis-free survival, and cancer-specific survival. Prognostic factors for overall survival were determined. Of the 493 patients, 216 (43.8%) were women, and the mean (SD) age was 62.0 (8.9) years. At a median of 69.7 months' follow-up, 367 disease-free survival events were observed. In patients receiving chemotherapy with modified FOLFIRINOX vs gemcitabine, median disease-free survival was 21.4 months (95% CI, 17.5-26.7) vs 12.8 months (95% CI, 11.6-15.2) (hazard ratio [HR], 0.66; 95% CI, 0.54-0.82; P < .001) and 5-year disease-free survival was 26.1% vs 19.0%; median overall survival was 53.5 months (95% CI, 43.5-58.4) vs 35.5 months (95% CI, 30.1-40.3) (HR, 0.68; 95% CI, 0.54-0.85; P = .001), and 5-year overall survival was 43.2% vs 31.4%; median metastasis-free survival was 29.4 months (95% CI, 21.4-40.1) vs 17.7 months (95% CI, 14.0-21.2) (HR, 0.64; 95% CI, 0.52-0.80; P < .001); and median cancer-specific survival was 54.7 months (95% CI, 45.8-68.4) vs 36.3 months (95% CI, 30.5-43.9) (HR, 0.65; 95% CI, 0.51-0.82; P < .001). Multivariable analysis identified modified FOLFIRINOX, age, tumor grade, tumor staging, and larger-volume center as significant favorable prognostic factors for overall survival. Shorter relapse delay was an adverse prognostic factor. The final 5-year results from the PRODIGE 24/Canadian Cancer Trials Group PA6 randomized clinical trial indicate that adjuvant treatment with modified FOLFIRINOX yields significantly longer survival than gemcitabine in patients with resected pancreatic ductal adenocarcinoma. EudraCT: 2011-002026-52; ClinicalTrials.gov Identifier: NCT01526135.

Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neuroendocrine carcinoma.

BackgroundWe investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large‐cell neuroendocrine cancer.MethodsThis was a retrospective multicenter study including consecutive patients undergoing resection of node negative large‐cell neuroendocrine carcinoma. Five‐year survival and disease‐free survival rate were evaluated by the Kaplan–Meier method and the log‐rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron‐specific enolase).ResultsOur study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease‐free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease‐free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple‐positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease‐free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple‐positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes.ConclusionsLobectomy seems to be the management of choice in patients with large‐cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm.

Surgical strategy for malignant pleural mesothelioma: the superiority of pleurectomy/decortication.

Both extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are used for the surgical treatment of malignant pleural mesothelioma (MPM). This study aimed to compare the operative and clinical outcomes and survival between EPP and P/D. We performed a retrospective analysis of the surgical and clinical data of 40 patients who underwent either EPP (n = 18) or P/D (n = 22) for MPM at our institution between January 2000 and December 2018. In comparison to EPP, P/D was associated with a higher intraoperative bleeding volume (1175 vs 1805ml, p = 0.0020) and greater duration of postoperative thoracic drainage (3 vs 16days, p < 0.0001). Adjuvant chemotherapy was more common after P/D (81.8%) than after EPP (33.3%; p = 0.0024). For epithelioid-type MPM, overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients who underwent P/D in comparison to those who underwent EPP (p = 0.040 and p = 0.015, respectively), with no difference for the biphasic and sarcomatoid types of MPM. A Cox proportional hazards regression model identified P/D as a significant favorable prognostic factor for OS [hazard ratio (HR), 0.391; 95% confidence interval (CI), 0.175-0.871; p = 0.022] and RFS (HR, 0.418; 95% CI, 0.190-0.920; p = 0.030). Based on our findings, P/D may be superior to EPP for improving the prognosis of patients with resectable epithelioid-type MPM.

Treatment strategies for thymic carcinoma in a real-life setting. Insights from the RYTHMIC network

BackgroundThymic carcinomas are aggressive and difficult to treat a subset of thymic epithelial tumours that represent a heterogeneous group of rare intrathoracic malignancies. The treatment strategy of thymic carcinomas is based on whether surgical resection may be achieved, which represents the most significant favourable prognostic factor on survival. For this study, we took advantage of the unique prospective Réseau tumeurs THYMiques et Cancer (RYTHMIC) database to describe baseline characteristics, analyse treatment strategies in light of existing guidelines and provide landmark patient outcomes data with regards to response and survival of patients in a real-life clinical practice setting. MethodsInclusion criteria for this analysis were the following: (1) histologically-confirmed thymic carcinomas – excluding neuroendocrine tumours-after pathological review by the RYTHMIC pathology panel, (2) discussion of the case at the RYTHMIC multidisciplinary tumour board, (3) at least one active treatment modality. ResultsA total of 213 patients were analysed. Overall, 60 (28%) patients were considered as surgical candidates upfront, 91 (43%) patients received primary chemotherapy, and 62 (29%) patients received exclusive chemotherapy. Median overall survival (OS) was 49.2 months (IC95%: 34.8–63.6); OS was significantly longer in patients with a lower stage at diagnosis (p < 0.001), who were operated on upfront, as opposed to patients who received primary or exclusive chemotherapy (p < 0.001). Surgery, conducted upfront or after primary chemotherapy, was significantly associated with more prolonged OS (p < 0.001); complete resection and postoperative radiotherapy were also predictors of better outcome (p = 0.018 and p = 0.051, respectively). ConclusionsOur cohort is the first to analyse in-depth outcomes and treatment strategies in a prospective cohort of consecutive patients with thymic carcinoma. While we confirm the major prognostic impact of surgery, our data highlight the need for optimised multidisciplinary management and innovative therapies as the survival of patients remains limited.