Favorable Prognostic Factor For Progression-free Survival Research Articles

Regorafenib plus FOLFIRI with irinotecan dose escalated according to UGT1A1 genotyping in patients with metastatic colorectal cancer.

125 Background: This multicenter, phase II, randomized, open-label, 2-arm parallel trial aims to compare the efficacy and safety profiles of regorafenib plus irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping with regorafenib alone in previously treated patients with metastatic colorectal cancer (mCRC). Methods: A total of 153 patients were planned to randomize at a ratio of 2:1 for receiving regorafenib plus FOLFIRI (arm A, 102 patients) or regorafenib alone (arm B, 52 patients), respectively. For both arms, regorafenib were given for 21 consecutive days (Day 1 to 21) of each 28-day cycle at a maintained dose of 120 mg. However, for arm A, patients received regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1 genotypes. FOLFIRI were on the first day of each 28-day cycle only. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and disease control rate (DCR), and adverse events (AEs). Results: Finally, a total of 116 patients were enrolled to be analyzed, including 74 in arm A and 42 in arm B. The significantly better PFS was observed in arm A, 4.8 and 3.0 months, respectively ( p = 0.016). Moreover, in patients with RAS wild type, the significantly better PFS was observed in arm A, 6.3 and 2.1 months, respectively ( p = 0.003). The OS was not significantly different between group A and B, 9.8 and 12.6 months, respectively ( p = 0.970). However, in patients with RAS wild type, the trend of better OS was observed in arm A, 14.3 and 6.9 months, respectively ( p = 0.158). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively ( p = 0.055). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively ( p = 0.055). Combination treatment of regorafenib plus FOLFIRI was independent favorable prognostic factor for PFS ( P = 0.008; hazard ratio [HR], 1.892; 95% CI, 1.182 – 3.027). Regarding severe AEs, there were no significant differences between the two groups (all P>0.05). Conclusions: Combination treatment of regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1genotyping results in a significant better PFS and comparable AEs. Moreover, patients with RAS wild type of CRC would be more beneficial for this combination treatment.

Clinical Characteristics Analysis of Gastrointestinal Peripheral T-Cell Lymphoma:Impact of Non-Emergency Surgery on Overall Survival

Introduction The gastrointestinal tract is the most common extranodal site involved in non-Hodgkin lymphoma (NHL) and most NHL cases are of B-cell origin. Peripheral T-cell lymphoma (PTCLs) involving the gastrointestinal is less commont, comprising only about 4-6% of gastrointestinal lymphomas. This study retrospectively analyzed the clinical characteristics and potential clinical factors influencing survival outcomes in patients diagnosed with PTCLs through gastrointestinal tissue biopsy at our center. Methods Based on the clinical data, patients were reevaluated for clinical staging and risk stratification, including Ann Arbor staging, IPI scoring, and gastrointestinal lymphoma Lugano staging. Patient's follow-up was conducted through outpatient medical records and telephone communication. For the analysis of categorical data, the chi-square test or Fisher's exact test was used. Survival time was estimated using the Kaplan-Meier method. The Cox proportional hazards model was employed to calculate hazard ratios (HR) and their 95% confidence intervals (CI) to analyze prognostic factors. Data analysis was performed using SPSS 23 for Windows software. Results A total of 622 gastrointestinal tissue biopsy samples from October 2014 to September 2022 were retrieved from the medical records system. Among them, 67 cases (10.8%) were diagnosed as PTCLs. Among them, 5 cases had no available clinical data and were excluded. Detailed information regarding patient clinical characteristics can be found in the table. Treatment and Efficacy: Among the 62 patients with available clinical data, 43 received gastrointestinal surgical resection treatment, including 21 cases (33.9%) of elective non-emergency surgery and 22 cases (35.5%) of emergency surgery due to acute abdomen. The median courses of chemotheray was 5 (1~8). 15 patients (31.3%) achieved complete response (CR)/CRu; 10 patients (20.8%) achieved partial response (PR). Among the 59 patients who received chemotherapy and/or surgical treatment, progression-free survival (PFS) was evaluated with a median follow-up time of 48.4 months, and the median PFS was 4.4 months (95% CI: 2.5-6.3) (Figure). Multivariate analysis identified advanced Ann Arbor stage (stage 3/4) (HR=3.53, 95% CI: 1.53-8.17, P=0.003) as independent adverse prognostic factors for PFS. Receiving chemotherapy (HR=0.24, 95% CI: 0.09-0.66, P=0.005) and elective surgery (HR=0.45, 95% CI: 0.22-0.92, P=0.029) were identified as independent favorable prognostic factors for PFS. As of the last follow-up, a total of 49 patients (79.0%) had died and the median overall survival (OS) was 6.4 months (95% CI: 3.8-8.9) (Figure). Multivariate analysis identified Ann Arbor stages 3-4 (HR=3.01, 95% CI: 1.34-6.74, P=0.007) as an independent adverse prognostic factor for OS, and receiving chemotherapy (HR=0.13, 95% CI: 0.05-0.31, P<0.001), elective surgery (HR=0.36, 95% CI: 0.16-0.74, P=0.006) were identified as independent favorable prognostic factors for OS. Conclusion Data from four hematological disease treatment centers located in Zhejiang Province, southeastern China, showed that PTCLs involving the gastrointestinal tract accounted for approximately 10.8% (67/622) of all gastrointestinal lymphoma patients. These patients had a relatively high incidence of gastrointestinal perforation (35.5%). The overall treatment efficacy for patients was poor, with a majority of them succumbing to disease progression. The median PFS and OS were approximately six months. Elective surgery and chemotherapy appeared to improve the patients' outcomes.

Stem Cell Utilization in the Era of Novel Therapies for Multiple Myeloma

Introduction: Stem cell collection is recommended for patients with newly diagnosed multiple myeloma (NDMM) deemed eligible for autologous stem cell transplantation (ASCT). Standard practice at most institutions is to collect an adequate number of stem cells for at least 2 ASCTs, but the benefit of maintaining extra stem cells in storage for future use beyond an initial ASCT warrants re-evaluation in the current era of novel therapies and evolving MM clinical practice. To address this, we reviewed the utilization rates and indications for the use of stored stem cells (SSC) at our institution. Methods: We conducted a single-center, retrospective study of 1470 patients with NDMM who collected sufficient stem cells for at least 2 ASCTs and underwent at least one ASCT at Memorial Sloan Kettering Cancer Center between January 2007 and December 2022. From this cohort, we assessed rates of stem cell utilization for second, non-tandem (salvage) ASCT and/or stem cell boost over time and determined progression-free survival (PFS) and overall survival (OS) from the time of salvage ASCT using the Cox proportional hazard model. Results: The median patient age atinitial ASCT was 61 years (range 24-81), with 58% male, 25% International Staging System stage III, and 42% (542/1283) with at least one high-risk cytogenetic alteration. Granulocyte-colony stimulating factor, either with or without plerixafor, was used for stem cell mobilization in 70% (834/1193) of patients, with the remaining patients undergoing chemotherapy-based mobilization, including high-dose cyclophosphamide (15%) or other multiagent chemotherapy regimens (15%). The median total CD34 + cell collection yield was 10.3 × 10 6/kg (interquartile range, IQR, 8-13). During the entire study period, SSC were used for 14.6% (214/1470) of patients, with 11.2% (n=165) for a salvage ASCT and 2.1% (n=31) for a stem cell boost. Seven patients received both a salvage ASCT and a boost. An additional 25 patients had upfront tandem ASCT (none since 2015) and were excluded from this analysis. Notably, from 2019 to 2022, the annual utilization of salvage ASCT increased compared to pre-2019 levels (median=21, range 11-27 vs. pre-2019 median=7, range 4-12), as did stem cell boosts (median=4, range 1-6 vs. pre-2019 median=1, range 0-3), despite a decline in numbers during the COVID-19 pandemic (Figure 1). The median age at SSC use was 61 years (range 29-78). The median number of prior lines of therapy (LOT) before the use of SSC was 4 (IQR: 2-7) for salvage ASCT and 6 (IQR: 1-6.5) for boosts. The median infused stem cell dose (CD34+ cells/kg) was 4.4 × 10 6 (range 3.2-5.7) for salvage ASCT and 3.1 × 10 6 (range 2.2-3.6) for boosts. The median PFS after salvage ASCT was 16 months (95% confidence interval, CI, 12-21), and the median OS was 37 months (95% CI 29 - 53). On multivariable analyses, receipt of fewer lines of therapy was the sole favorable prognostic factor for PFS and OS. Among patients with ≤ 3 prior LOT, the median PFS after salvage ASCT was 32 months (95% CI 22-42), while those with > 3 LOT had a median PFS of 8.0 months (95% CI 5.8-12) (Figure 2). Post-treatment therapy after salvage ASCT or stem cell boost most commonly included various MM triplet regimens, chimeric antigen receptor T-cell therapy, and bispecific T-cell engagers. Conclusion: While overall rates of SSC utilization at our institution remain low, rates have increased in recent years, as both salvage ASCT and stem cell boosts provide effective platforms for treating disease and treatment-related refractory cytopenias as a bridge to next therapy for patients with advanced MM. Ultimately, institutional practices for stem cell collection and storage require optimizing the balance of clinical utility with resource allocation and costs of maintaining SSC.

TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study

IntroductionLung adenocarcinoma with negative TTF-1 expression is believed to be a poor prognostic factor for certain systemic treatments. Nevertheless, the impact of TTF-1 expression on combined chemoimmunotherapy remains unclear. We aimed to investigate the relationship between tumor TTF-1 expression and the efficacy of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma. MethodsThis multicenter prospective observational study included 58 patients with advanced lung adenocarcinoma treated with combined chemoimmunotherapy across 10 institutions in Japan. The expression of TTF-1 in pretreatment tumors was determined using immunohistochemistry. ResultsThe objective response rate of combined chemoimmunotherapy was significantly higher in TTF-1–positive groups than in TTF-1–negative groups (p = 0.02). The median progression-free survival (PFS) and overall survival were significantly longer in TTF-1–positive groups than in TTF-1–negative groups (10.9 versus 5.0 mo; p = 0.01). Multivariate analysis revealed that TTF-1 expression was an independent favorable prognostic factor for PFS. Moreover, TTF-1 expression in patients with lung adenocarcinoma is significantly associated with programmed death-ligand 1 expression (p = 0.003). The TTF-1–positive group with programmed death-ligand 1 tumor proportion score greater than or equal to 50% had a significantly longer PFS than the other groups (p = 0.02). ConclusionsTTF-1 positivity is associated with better clinical outcomes in patients with advanced lung adenocarcinoma treated with combined chemoimmunotherapy.

Ten-year treatment outcomes of consolidation hyperthermic intraperitoneal chemotherapy for ovarian cancer (HIPEC-KOV-03R).

We aimed to evaluate the long-term efficacy of consolidation hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with primary epithelial ovarian cancer. This retrospective cohort study included patients who underwent second-look surgery either with or without HIPEC after having complete or partial response to primary cytoreductive surgery and adjuvant platinum-based chemotherapy between January 1991 and December 2003 at Seoul St. Mary's Hospital. The 10-year progression-free survival (PFS), overall survival (OS), and toxicity within postoperative 28 days were investigated. A total of 87 patients were identified, 44 (50.6%) received second-look surgery with HIPEC whereas 43 (49.4%) received only second-look surgery. The 10-year PFS and OS were significantly longer in the HIPEC group compared with the control group (PFS, 53.6% vs. 34.9%, log-rank p=0.009; OS, 57.0% vs. 34.5%, log-rank p=0.025). Multivariable analysis identified HIPEC as an independent favorable prognostic factor for PFS (adjusted hazard ratio [HR]=0.42; 95% confidence interval [CI]=0.23-0.77; p=0.005) but not for OS (adjusted HR=0.58; 95% CI=0.32-1.07; p=0.079). The more common adverse events in the HIPEC group were thrombocytopenia (90.9% vs. 68.3%, p=0.005), elevated liver enzymes (65.9% vs. 29.3%, p=0.002), and wound complications (18.2% vs. 2.4%, p=0.032). However, these adverse events were reversible and did not delay subsequent consolidation chemotherapy. The consolidation HIPEC demonstrated a significant improvement in 10-year PFS but not OS, with acceptable toxicity in patients with primary epithelial ovarian cancer. Further randomized controlled trials are warranted to confirm these results.

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton's tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients. We retrospectively reviewed R/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy. 27 R/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had NOTCH2 mutations (n=8, 100%) and TP53 mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached. With high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Benefits of step-by-step debulking microwave ablation for huge unresectable hepatocellular carcinoma patients after transcatheter arterial chemoembolization refractoriness

Objectives To compare the safety and efficacy of step-by-step debulking Microwave Ablation (MWA) with Transarterial Chemoembolization (TACE) monotherapy for huge (≥10 cm in diameter) unresectable hepatocellular carcinoma (HCC) after TACE refractoriness. Methods This is a multi-center retrospective study carried out on 599 patients with huge unresectable HCC who received TACE as first-line therapy at five hospitals from January 2009 to December 2018. A total of 103 patients with TACE refractoriness were divided into two cohorts: monthly step-by-step debulking MWA (n = 52) or continued TACE (n = 51). Overall survival (OS) and progression-free survival (PFS) after refractory TACE were evaluated. Residual liver and tumor volume were recorded for the MWA group. Results Median follow-up period was 24.3 months and median OS and PFS were significantly longer in the MWA group than in the TACE group (OS 21.0 vs. 11.7 months, PFS 6.1 vs. 3.0 months, both p < 0.001). The one-, two-, and three-year OS rates in the MWA and TACE groups were 73.1%, 46.6%, and 37.2% versus 43.1%, 15.5%, and 2.9%, respectively. Furthermore, the 0.5-, 1-, and 2-year PFS rates in the MWA and TACE groups were 51.9%, 36.5%, and 25.0% versus 27.5%, 11.8%, and 0, respectively. Multivariate analyses confirmed that switching to debulking MWA treatment was an independent favorable prognostic factor for PFS and OS. In the MWA group, the average additions of residual liver volume/total liver volume were 7.7% ± 6.7%, 7.2% ± 10.2%, and 10.1% ± 8.8% after the first, second, and third MWA procedure. Conclusion Step-by-step debulking MWA can significantly improve long-term OS and PFS in patients with huge unresectable HCCs compared with repeated TACE after TACE refractoriness. Key Point The debulking MWA therapy provides significantly longer OS and PFS than continued TACE for patients with huge unresectable HCCs after TACE-refractory, especially with complete tumor ablation. The most common complications were fever (48.1%) and pain (46.2%) in the MWA group. Two major complications (abdominal infection) were recorded in the MWA group, which recovered after symptomatic treatment. During the course of repeated MWAs, liver hyperplasia appeared mainly after the second MWA procedure and the average maximum increased RLV/TLV rate was 16.3%±12.7%.

Pazopanib in metastatic soft tissue sarcoma (STS): Results of a multi-institutional observational study.

e23542 Background: Soft tissue sarcomas (STS) are a heterogenous group of tumors which have limited therapeutic options and poor prognosis in advanced/metastatic settings. Herein, we present the clinical outcomes of metastatic STS patients treated with pazopanib (PAZ) in real-life. Methods: We retrospectively collected data about adult patients treated with PAZ for metastatic STS in Turkey. We described the clinical characteristics and tumor responses, and estimated the progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. The Cox proportional hazards regression model (HR, 95%CI) was used for evaluation of prognostic factors for PFS. Results: 507 patients (median age: 52 [range: 18-87]; 56.8% female) were included in the analysis. Extremities were the most common primary tumor sites (n:202; 39.8%) followed by abdomen (n:116; 22.9%) and pelvic cavity (n:102;20.1%) where 98% of STSs arose in uterus (n:100). The leading histologic subtypes were leiomyosarcoma (n:192; 37.9%), synovial sarcoma (n:58; 11.4%) and undifferentiated pleomorphic sarcoma (n:48; 9.5%). Of the reported tumor grades (n = 350), 61.4% (n:215) were grade 3. The most common metastatic sites were lungs (52.7%) and liver (20.3%). Doxorubicin plus ifosfamide (45.9%) was the preferred front-line regimen and PAZ was the treatment of choice in second (59.8%) and third-line (61.8%) settings. The median follow-up under PAZ treatment was 5.03 (0.10-84.67) months. Objective response and disease control rates were 31.4% and 42.2%, respectively. Overall, 183 (36.1%) patients were alive at last follow up, 123 of which (67.2%) did not show progression. The median PFS and OS for the study group and the most commonly observed types of STS are shown in Table. Favorable prognostic factors for PFS were low-intermediate tumor grade (HR[95% CI] for grade I and 2 vs 3:1.371[1.016-1.849]; p = 0.039) and ECOG (Eastern Cooperative Oncology Group) score (HR[95% CI] for ECOG score &lt; 2 vs ≥2: 2.698[1.923-3.787]; p = 0.0001). Weakness/asthenia (10.8%), impaired liver function tests (4.7%) and diarrhea (3.6%) were the most common adverse events, no grade 4 or 5 events were observed. Conclusions: This large scale real-life study confirms that PAZ, with its positive impact on clinical outcomes and acceptable tolerability and safety profile is a valuable treatment option for metastatic STS.[Table: see text]

The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Comparison of Different Tyrosine Kinase Inhibitors for Treatment of Poor Performance Status Patients with EGFR-Mutated Lung Adenocarcinoma

Simple SummaryEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments in patients with EGFR-mutated lung adenocarcinoma. However, the clinical data regarding EGFR-TKI efficacy in patients with poor performance status (PS ≥ 2) are limited. We reviewed the clinical outcomes and safety of EFGR-TKI use in patients with poor PS and identified the independent and favorable prognostic factors for progression-free survival and overall survival. We found that patients treated with 40 mg afatinib had better survival results, although only a non-significant trend toward superiority was observed in the multivariable analysis. Dose adjustment was an independent prognostic factor for PFS and OS. This study provided evidence of the use of EGFR-TKIs for patients with poor PS.The aim of this retrospective study was to investigate the tolerability and survival outcomes of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment in patients with a performance status ≥ 2. The data for 517 patients treated with EGFR-TKIs between January 2011 and January 2018 at a regional hospital in northern Taiwan were analyzed. Clinical and pathological features were collected, and univariate as well as multivariable analyses were undertaken to identify potential prognostic factors. The overall objective response rate, median progression-free survival (PFS), and median overall survival (OS) were 56.3%, 11.4 months, and 15.3 months, respectively. The mutation status (exon 19 deletion), locally advanced disease, dose adjustment, and the lack of liver and pleural metastasis were independent and favorable prognostic factors for PFS. Age < 60 years, mutation status (exon 19 deletion), dose adjustment, and lack of lung, liver, and no pleural metastasis were independent and favorable prognostic factors for OS. GFR-TKIs demonstrated acceptable efficacy and safety in the current cohort. Dose adjustment was identified as an independent prognostic factor for both PFS and OS, regardless of which EGFR-TKIs were used. The current research provided novel evidence of the clinical prescription of frontline EGFR-TKIs for EGFR-mutated lung adenocarcinoma patients with a PS score ≥2.

Postoperative Adjuvant Chemoradiotherapy Versus Chemotherapy Alone for Stage III Endometrial Cancer: A Multicenter Retrospective Study

IntroductionWe aimed to evaluate the efficacy and toxicity of the combination of 6 cycles of chemotherapy and radiation therapy compared with chemotherapy alone as postoperative adjuvant therapy for patients with stage III endometrial cancer.MethodsThis retrospective cohort study included patients with stage III endometrial cancer who received postoperative chemoradiotherapy or chemotherapy alone at 6 hospitals between January 2009 and December 2019. The progression-free survival (PFS) and overall survival (OS) for each treatment group were analyzed using the Kaplan–Meier method. We also assessed differences in toxicity profiles between the treatment groups.ResultsA total of 133 patients met the inclusion criteria. Of these, 80 patients (60.2%) received adjuvant chemoradiotherapy and 53 (39.8%) received chemotherapy alone. The PFS and OS did not differ significantly between the groups. For patients with stage IIIC endometrioid subtype, the chemoradiotherapy group had significantly longer PFS rate than did the chemotherapy alone group (log-rank test, P = .019), although there was no significant difference in the OS (log-rank test, P = .100). CRT was identified as a favorable prognostic factor for PFS in multivariate analysis (adjusted HR, .37; 95% CI, .16-.87; P = .022). Patients treated with chemoradiotherapy more frequently suffered from grade 4 neutropenia (73.8% vs 52.8%; P = .018) and grade 3 or worse thrombocytopenia (36.3% vs 9.4%; P = .001) compared with the chemotherapy alone group. There were no differences between the 2 treatment groups in the frequency of toxicity-related treatment discontinuation or dose reduction.ConclusionWe confirmed that chemoradiotherapy yields longer progression-free survival than does chemotherapy alone for patients with stage IIIC endometrioid endometrial cancer, with an acceptable toxicity profile.

Real-World Outcome and Prognostic Factors of Pazopanib in Advanced Soft Tissue Sarcoma.

PurposePazopanib has been approved for treating soft tissue sarcomas (STS) after chemotherapy. We aimed to evaluate the prognostic factors, clinical outcomes, and tolerability of pazopanib in patients with STS.Patients and MethodsForty-five patients treated between June 2015 and August 2019 were reviewed. Clinical outcome was measured by assessing the disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors (version 1.1). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse effects were assessed using the Common Terminology Criteria for Adverse Events (version 5.0).ResultsThe median age of patients at diagnosis was 28 (interquartile range (IQR), 23–45) years. Pazopanib was used as the second-line treatment in 46.7% and the subsequent line in 53.3% of patients. The overall DCR was 55.6%, and at 8 and 12 weeks, it was 52.3% and 35.5%, respectively; the median duration of response was 7 (IQR: 2–18) months. Pazopanib-induced hypothyroidism was associated with DCR, with an odds ratio of 7 (95% confidence interval [95% CI: 1.7–27.5], p<0.01). The median PFS and OS were 4.1 (95% CI: 0.85–7.42) and 12.4 months (95% CI: 6.5–18.36), respectively. Hypothyroidism and response to pazopanib, better ECOG PS, histological subtypes desmoid tumor/aggressive fibromatosis (DT/AF), and alveolar soft part sarcoma (ASPS) were favorable prognostic factors for PFS. Hypothyroidism and response to pazopanib were significant favorable factors for OS. There was no statistical difference in the OS between patients using pazopanib as the second-line therapy and those using it as the subsequent-line therapy.ConclusionPazopanib is an effective treatment for STS. However, it showed variability in the clinical outcome in favor of ASPS and an outstanding response in the DT/AF subtype. Pazopanib-induced hypothyroidism is a good prognostic factor for disease control and is associated with prolonged PFS and OS.

Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study

BackgroundAfatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2.MethodsThe data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy.ResultsUntil February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control.ConclusionAfatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.

Comparisons of survival outcomes between bevacizumab and olaparib in BRCA-mutated, platinum-sensitive relapsed ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3052).

ObjectiveTo compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in BRCA-mutated, platinum-sensitive relapsed (PSR) high-grade serous ovarian carcinoma (HGSOC).MethodsFrom 10 institutions, we identified HGSOC patients with germline and/or somatic BRCA1/2 mutations, who experienced platinum-sensitive recurrence between 2013 and 2019, and received second-line platinum-based chemotherapy. Patients were divided into BEV (n=29), OLA (n=83), and non-BEV/non-OLA users (n=36). The OLA and non-BEV/non-OLA users were grouped as the OLA intent group. We conducted 1:2 nearest neighbor-matching between the BEV and OLA intent groups, setting the proportion of OLA users in the OLA intent group from 65% to 100% at 5% intervals, and compared survival outcomes among the matched groups.ResultsOverall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280−0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184−0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users.ConclusionCompared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with BRCA-mutated, PSR HGSOC.

Extent of resection and molecular pathologic subtype are potent prognostic factors of adult WHO grade II glioma

We evaluated prognostic factors of adult low-grade glioma (LGG) according to the new 2016 WHO classification. Records of 153 patients diagnosed with WHO grade II LGG between 2003 and 2015 were retrospectively reviewed. Based on the 2016 WHO classification, 80 patients (52.3%) had diffuse astrocytoma, IDH-mutant; 45 (29.4%) had oligodendroglioma, IDH-mutant and 1p/19q-codeleted (ODG); and 28 (18.3%) had diffuse astrocytoma, IDH-wildtype. Gross total resection (GTR) was performed in 71 patients (46.4%), subtotal resection in 31 (20.3%), partial resection in 43 (28.1%), and biopsy in 8 (5.2%). One hundred two patients (66.7%) received postoperative radiotherapy. The 5- and 10-year progression-free survival (PFS) rates were 72.7% and 51.5%, respectively, and the 5- and 10-year overall survival (OS) rates were 82.5% and 63.5%, respectively. GTR and IDH-mutant and/or 1p/19q codeletion were favorable prognostic factors for PFS and OS. Patients with IDH-wildtype had significantly decreased OS. Among patients with ODG who underwent GTR, no recurrence was observed after radiotherapy. Patients who underwent non-GTR frequently experienced recurrence after radiotherapy (IDH-mutant: 47.6%, IDH-wildtype: 57.9%). In conclusion, molecular classification of LGG was of prognostic relevance, with IDH-wildtype patients having a particularly poor outcome, regardless of the treatment. Favorable results were observed in patients who underwent GTR.

Survival without concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma treated with induction chemotherapy plus intensity-modulated radiotherapy

Although induction chemotherapy (IC) combined with intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy (CC) is the new standard treatment option in locoregionally advanced nasopharyngeal carcinoma (NPC), many patients fail to receive CC. The aim of this study was to investigate long-term survival outcomes and toxicities in these patients who are treated with IC before IMRT without CC.We retrospectively reviewed 332 untreated, newly diagnosed locoregionally advanced NPC patients who received IC before IMRT alone at our institution from May 2008 through April 2014. The IC was administered every 3 weeks for 1 to 4 cycles. Acute and late radiation-related toxicities were graded according to the acute and late radiation morbidity scoring criteria of the radiation therapy oncology group. The accumulated survival was calculated according to the Kaplan–Meier method. The log-rank test was used to compare the difference in survival.With a median follow-up duration of 65 months (range: 8–110 months), the 5-year estimated locoregional relapse-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival rates were 93.4%, 91.7%, 85.8%, and 82.5%, respectively. Older age and advanced T stage were adverse prognostic factors for overall survival, and the absence of comorbidity was a favorable prognostic factor for PFS. However, acceptable acute complications were observed in these patients.IC combined with IMRT alone provides promising long-term survival outcomes with manageable toxicities. Therefore, the omission of CC from the standard treatment did not affect survival outcomes.

Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer

ObjectiveTo evaluate impact of germline BRCA mutational status on prognosis in patients with advanced ovarian cancer.MethodsA total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study. We compared patients’ clinicopathological characteristics and survival outcomes after primary treatment according to germline BRCA mutational status. Treatment-related factors that might affect patients’ survival outcome were also investigated.ResultsGermline BRCA1/2 mutations were observed in 51 women (39.8%). There were no differences in age and serum CA-125 levels at the time of HGSOC diagnosis, use of neoadjuvant chemotherapy (NAC), extent of debulking surgery, and overall survival (OS) between the BRCA mutation and wild-type BRCA groups. In contrast, the BRCA mutation group displayed longer progression-free survival (PFS) (median, 22.9 vs. 16.9 months, P = 0.001). Multivariate analyses identified germline BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted HR, 0.502; 95% CI, 0.318–0.795; P = 0.003). In the wild-type BRCA group, patients who received NAC as the primary treatment had shorter PFS compared to those who received primary debulking surgery (PDS) (median, 14.2 vs. 16.9 months, P = 0.003). However, in the BRCA mutation group, PFS did not differ between the NAC and PDS groups (P = 0.082).ConclusionsIn advanced-stage HGSOC, patients with germline BRCA1/2 mutations have better prognosis with longer PFS than those lacking BRCA mutations. Prognosis after NAC was different according to the BRCA mutational status.

First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China.

ObjectiveTo evaluate the efficacy and safety profile of first-line bevacizumab (Bev)-containing pemetrexed-platinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer (NS-NSCLC).MethodsA total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(−) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching (PSM) was conducted and 105 pairs of Bev(−) and Bev(+) cases were identified.ResultsThe median duration of follow-up was 15.8 months. The median progression-free survival (PFS) was prolonged significantly in the Bev(+) group than in the Bev(−) group in overall (9.8vs. 7.8 months, P=0.006) and PSM pairs (9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed (12.3vs. 4.8 vs. 8.6 months; P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy. ConclusionsFirst-line induction and maintenance therapy with Bev (7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

Benefit of Two Additional Cycles of Bortezomib/Thalidomide/Dexamethasone (VTD) Induction Therapy Compared to Four Cycles of VTD for Newly Diagnosed Multiple Myeloma

IntroductionFour cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapy for patients aged less than 65 years with newly diagnosed multiple myeloma (NDMM). Complete remission (CR) status before ASCT is an important prognostic factor for progression-free survival (PFS). We analyzed whether two additional cycles of VTD improved the pre- and post-transplant responses as well as PFS compared to the four cycles of VTD induction therapy.MethodsA total of 222 patients with NDMM between September 2014 and August 2016 from eleven hospitals in South Korea were included in the current study. The patients received at least four or more cycles of VTD induction therapy before administration of high-dose therapy (HDT, melphalan 200mg/m2) followed by ASCT. VTD regimen was consisted of bortezomib subcutaneous infusion (1.3 mg/m2 on days 1, 4, 8, and 11), thalidomide (100 mg daily), and dexamethasone (40 mg on days 1-4, 8-11), which was administered every 4 weeks.ResultsThe median age was 57 years (range 30−64 years), and 120 patients (61.9%) were male. Revised international scoring system (R-ISS) classified 59 (30.4%), 86 (44.3%), and 49 patients (25.3%) as stage I, II, and III, respectively. VTD induction was administered 4 cycles in 194 patients (VTD4, 67.5%) and more than 4 cycles in 63 (VTD6, 32.5%) before HDT. Patient characteristics at diagnosis did not differ between VTD4 and VTD6. CR rate before HDT was significantly higher in VTD6 than VTD4 (31.7% vs 13.0%, P = 0.003). However, CR rate after HDT/ASCT was similar between VTD4 and VTD6 (69.0% vs 65.5%, P = 0.726). There was no difference in the incidence of peripheral neuropathy (PN) (≥ grade 2 or that required dose reduction) between two groups. The median follow-up duration was 18.0 months (range 7.0-43.8 months). The 2-year PFS did not differ between the two groups (51.7 ±5.7% in VTD4 and 62.1±8.6% in VTD6, P = 0.240). Multivariate analysis revealed that the achievement of CR was a favorable prognostic factor for PFS (HR 0.27 [0.08−0.90], P = 0.034). Deletion 17p (HR 2.87 [1.01−7.92], P = 0.048) and t(4;14) (HR 3.38 [1.76−6.48], P < 0.001) in FISH were adverse prognostic factors for PFS. Patients with stage I/II by R-ISS receiving additional two cycles of VTD showed prolonged PFS (median PFS not reached vs. 27.6 months, P = 0.034). In the multivariate analysis, VTD6 was a favorable prognostic factor for PFS for patients with stage I/II by R-ISS, (HR 0.11 [0.02−0.52], P = 0.005).ConclusionCR rates increased with additional cycles of VTD induction therapy for NDMM. However, the PFS benefit was observed only in patients with R-ISS stage I/II. For patients with high-risk MM, intensive induction therapy that overcome poor prognostic factors should be administered to improve long-term outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.