5-year PFS Research Articles

SDPS-05 ASSESSING SURVIVAL OUTCOMES AND COMPLICATION PROFILES FOLLOWING SURGICAL EXCISION OF SKULL BASE CHORDOMA: A COMPREHENSIVE SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Despite their precarious behavioral classification (histopathologically benign (low-grade), behaviorally malignant), great strides have been taken to improve prognostication and treatment paradigms for patients with skull base chordoma. However, due to the rarity of this tumor, prior investigations remain limited to small retrospective series. Accordingly, we performed a systematic review and meta-analysis in order to profile surgical and survival outcomes for skull base chordoma. Fixed and random-effect meta-analyses were performed for categorial variables including number of males, GTR, STR, 5-year OS, 10-year OS, 5-year PFS, and 10-year PFS. Following the systematic search and screen, 47 studies published between 1993-2020 reporting data for 2204 patients remained eligible for analysis. Sex distribution was comparable between males and females, with a slight predominance of male-identifying patients (0.5625 [0.5418;0.3909]). Average age at diagnosis was 42.4 ± 12.5 years, while average age of treatment initiation was 43.0 ± 10.6 years. Overall, there was a substantial degree of heterogeneity across the 47 studies (I^2=56.3% [44.0%; 65.9%]). With respect to operative margins, the rate of GTR was 0.3323 [0.2824; 0.3909], I^2 = 91.9% [90.2%; 93.4%], while the rate of STR was significantly higher at 0.5167 [0.4596; 0.5808], I^2 = 93.1% [91.6%; 94.4%]. Interestingly, 5-year OS rate was 0.7113 [0.6685; 0.7568], I^2 = 91.9% [90.0%; 93.5%]. Furthermore, 10-year OS rate was 0.4957 [0.4230; 0.5809], I^2 = 92.3% [89.2%; 94.4%], which was comparable to both 5-year PFS rate of 0.5054 [0.4394; 0.5813], I^2 = 84.2% [77.6%; 88.8%] and 10-yr PFS rate of 0.4949 [0.4075; 0.6010], I^2 = 14.9% [0.0%; 87.0%]. There were 55 reported deaths for a perioperative mortality rate of 2.5%. The most common complication was CSF leak(5.4%). Overall, these results indicate good 5-year outcomes; however, 10-year prognosis for skull base chordoma remains poor due to its radiotherapeutic resistance and high recurrence rate.

TIPS-05 ADJUVANT TEMOZOLOMIDE CHEMOTHERAPY FOLLOWING RADIOTHERAPY IN NEWLY DIAGNOSED LOW-GRADE GLIOMA PATIENT WITH RESIDUE TUMORS: A MULTICENTER, OPEN LABEL, RANDOMIZED TRIAL

Abstract Low-grade glioma (LGG) with infiltrative nature and frequent growth in eloquent area in brain often makes total resection impossible. Although post-radiation adjuvant temozolomide (TMZ) is the standard of care for high-grade gliomas, and radiotherapy and/or TMZ are recommended for the treatment of residue low-grade gliomas, the efficacy of combined radiotherapy with adjuvant TMZ for residue LGG remains to be defined. We have initiated a randomized clinical trial in 2012 to test whether radiotherapy with subsequent TMZ chemotherapy will improve survival of patients with residue LGG compared to radiotherapy alone. This study was approved by the Ethics Committee of the Sun Yat-sen University Cancer Center, Guangzhou, China (approval No. 5010-2012-03) and was registered with ClinicalTrials.gov (NCT01649830). Inclusion Criteria: Patients age of 18 years to 60 years, with incompletely resected supratentorial WHO grade 2 astrocytoma, oligodendroglioma or oligodendroastrocytoma. Enrolled patients were randomized into: radiation therapy alone (RT) or radiotherapy with subsequent TMZ chemotherapy (RC) group. Start Date: July 2012, Estimated Primary Completion Date:August 2025. Radiation therapy will start within 8 weeks after neurosurgical procedures, with a total dose of 54.0 Gy in 27 - 30 fractions over 6 - 7 weeks. Four weeks after radiotherapy, patients in RC group will receive 6 cycle of TMZ dosed at 200 mg/m2 daily for 5 consecutive days, repeated every 28 days. We have completed enrollment on December 2018 with valid cases of 248 patients. Up to last follow-up date of Feb. 2023, 204 cases were analyzed (see table). There is no significant difference between RT group and RC group on both PFS and OS (5-year PFS 68.9% vs 75.2%, p=0.680; 5-year OS 92.0% vs 86.0%, p=0.400). Longer follow-up and molecular subgroup analysis are currently on the way, which could show benefit in special molecular subgroup.

5-Year survival in Danish patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitor monotherapy

Background Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. Materials and methods A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan–Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. Results Median time of follow-up (FU) was 48.7 months (IQR 37.2–54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5–45.0) compared to 11.4 months (IQR 4.6–27.1) in ≥2nd line (HR 1.48, 95% CI 1.25–1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22–0.43) compared to 5% (95% CI 0.01–0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. Conclusions Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates.

Organ preservation strategies after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: A multi-center retrospective cohort study.

Neoadjuvant chemoimmunotherapy has shown a good therapeutic effect on non-small cell lung cancer, which also opens up the possibility of applying organ preservation strategies. This study investigated the feasibility of modified surgery after potent neoadjuvant chemoimmunotherapy in central type non-small cell lung cancer. In this multi-center retrospective cohort study, patients with central type non-small cell lung cancer who received 2-4 cycles of neoadjuvant chemoimmunotherapy between January 2019 and June 2022 at XXX Hospital and XXX Hospital were eligible. Patients were divided into modified and non-modified groups according to the extent of surgery, after which, safety and long-term prognosis of surgery were investigated. A total of 84 patients were enrolled. Of 36 (42.9%) patients who underwent modified surgery, 21 patients underwent lobectomy, 12 patients underwent lobectomy with bronchoplasty, 2 patients underwent sleeve lobectomy, and 1 patient underwent bilobectomy. The modification rate for the initially estimated pneumonectomy, sleeve lobectomy, and bilobectomy was 48.6%, 44.8%, and 30%, respectively. Grade II-V postoperative complications were found in 5 (13.9%) patients in the modified group and 17 (35.4%) patients in the non-modified group (relative risk, 0.393; 95% CI, 0.016 to 0.963; P=0.026). No significant difference was observed regarding the surgical approach, operative duration, blood loss, or R0 resection rate. The 2-year local recurrence rate was 3.7% (95% CI, 0.004-0.175) and 5.2% (95% CI, 0.012-0.168) in the modified group and non-modified group, respectively. The one-year PFS rate of modified and non-modified groups was 97.1% (95% CI, 83.7-99.8) and 86.9% (95% CI, 73.4-94.4), respectively, while two-year PFS were 89.8% (95% CI, 74.1-96.9) and 71.8% (95% CI, 56.7-83.4), respectively. Applying organ preservation strategies, i.e., undergoing modified surgery after neoadjuvant chemoimmunotherapy, is feasible for selected central-type NSCLC patients with favorable safety and long-term survival.

Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

Hypofractionated radiotherapy compared with conventionally fractionated radiotherapy to treat initial distant metastases in nasopharyngeal carcinoma: A multicenter, prospective, randomized, phase II trial

Background and PurposeTo investigate the safety and efficacy of hypofractionated plus chemotherapy in patients with initially distant metastatic nasopharyngeal carcinoma (mNPC). Materials and MethodsBetween May 2014 and June 2020, 35 patients initially diagnosed with mNPC were enrolled on prospective trial. The enrolled patients were assigned randomly to receive either hypofractionated plus chemotherapy (HFRT) or conventionally fractionated radiotherapy plus chemotherapy (CFRT). 60 Gy over 25 fractions was administered to the HFRT group (n = 17) and 69.96 Gy over 33 fractions was administered to the CFRT group (n = 18), both groups five times each week.Progression free survival (PFS) comprised the primary endpoint. Overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and acute and late toxicity comprised the secondary endpoints. ResultsTwenty-eight patients (seven were excluded) were enrolled. The 2-year PFS was 33.3% (HFRT group) versus 30.0% (CFRT group) (stratified hazard ratio (HR):1.09; 95% confidence interval (CI): 0.45–2.65, P = 0.843). The 2-year OS was 66.7% (HFRT group) versus with 62.5% (CFRT group) (stratified HR, 0.88; 95% CI; 0.31–2.51, P = 0.806). All patients experienced acute grade 1 or 2, skin toxicity, oral mucositis, difficulty swallowing, xerostomia, but no acute grade 3 or 4 toxicities. All patients had grade 1 late xerostomia. Two patients experienced hearing loss in the HFRT group (one grade 1 and one grade 3), and three patients experienced grade 1 hearing loss in the CFRT group. One patient developed mucosal necrosis in the HFRT group. ConclusionImproving the balance between severe late toxicities and local control by appropriately reducing the total dose but increasing the fractionated dose has marked clinical significance for those patients.

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta-analysis.

Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1-year/2-year progression-free survival [PFS], and overall survival [OS]) and safety (vaccine-related grade 3-5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non-small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6-17.0%) and 34.6% (95%CI, 24.1-45.9%). The estimates for 1-year and 2-year PFS were 38.4% (95%CI, 24.8-53.0%) and 20.0% (95%CI, 10.4-31.7%), respectively. The estimates for 1-year and 2-year OS were 75.3% (95%CI, 62.4-86.3%) and 45.5% (95%CI, 34.0-57.2%), respectively. The estimate for vaccine-related grade 3-5 AEs was 1.0% (95%CI, 0.2-2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3-5 AEs.

Improved survival of autologous stem cell transplantation in primary refractory and relapsed Hodgkin lymphoma in the brentuximab vedotin era — real-world data from Hungary

Autologous stem cell transplantation (ASCT) is the standard treatment of primary refractory or relapsed Hodgkin-lymphoma, which can provide a cure rate of about 50%. The aim of our study was to analyze the data of 126 HL patients undergoing AHSCT in Hungary between 01/01/2016 and 31/12/2020. We assessed the progression-free and overall survival, the prognostic role of PET/CT performed before transplantation and effect of brentuximab vedotin (BV) treatment on survival outcomes. The median follow-up time from AHSCT was 39 (1–76) months. The 5-year OS comparing PET- and PET + patients was 90% v. 74% (p = 0.039), and 5-year PFS was 74% v. 40% (p = 0.001). There was no difference in either OS or PFS compared to those who did not receive BV before AHSCT. We compared BV treatments based on their indication (BV only after AHSCT as maintenance therapy, BV before and after AHSCT as maintenance treatment, BV only before AHSCT, no BV treatment). There was statistically significant difference in the 5-year PFS based on the inication of BV therapy. Recovery rates of our R/R HL patient population, who underwent AHSCT, improved significantly. Our positive results can be attributed to the PET/CT directed, response-adapted treatment approach, and the widespread use of BV.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3)

We previously reported the primary results of JCOG0701, a randomized, multicenter, phase III, non-inferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer (GC). In the primary results, although the similar efficacy of 3-year PFS and toxicity of Ax compared with SF was observed, the non-inferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. In JCOG0701, 370 patients were randomly assigned to receive SF of 66-70 Gy (33-35 fractions) (n=184) or Ax of 60-64.8 Gy (25-27 fractions) (n=186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia (CNSI) were analyzed. With median follow-up period of 7.1 years (range: 0.1-12.4), PFS of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (p=0.44). OS of SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (p=0.92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of SF and Ax arms were 11.9% and 7.4% at 8 years (HR: 0.53, 95% CI: 0.28-1.01, p=0.06). CNSI of Grade 2 or higher was observed in 4.1% for SF arms and 1.1% for Ax arm (p=0.098). After a long-term follow-up Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early GC because of its convenience in minimizing treatment time, cost, and labor.

Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center. Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects. We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate-high-grade, 24% low-grade STSs. Among BS, 32% were high-grade. Median TTD and TTT were 120 (0-8255) and 7 days (0-83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow-up was 72.9 months(1.6-145), 5-year and 10-year OS were 78.5% and 62%, respectively. Kaplan-Meyer analysis showed a significantly better 5-year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5-year OS was 69.8% versus 82.2%, respectively (p = 0.047). Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.

Neoadjuvant Versus Adjuvant Systemic Therapy for Early-Stage Non-Small Cell Lung Cancer: The Changing Landscape Due to Immunotherapy.

Non-small cell lung cancer (NSCLC) remains a major cause of morbidity and mortality worldwide. One-third of NSCLC patients present with surgically resectable, non-metastatic disease; however, many of these patients will recur despite curative surgery and adjuvant therapy. The recent publication of randomized trials incorporating immune check-point inhibitors (ICI) to the standard neo-adjuvant and adjuvant treatment regimens has reported improved survival with manageable toxicity profiles. The IMpower 010 studied the use of adjuvant atezolizumab after standard surgery and adjuvant chemotherapy. They demonstrated an improvement in 3-year disease-free survival (DFS) prompting a change in treatment guidelines. The Checkmate 816 and NADIM II studies evaluated the addition of pembrolizumab and nivolumab, respectively, to standard neo-adjuvant chemotherapy. The results from both trials showed an improvement in 2-year event-free survival (EFS) and 2-year PFS (PFS), respectively. In this review, we summarize the prior data regarding adjuvant and neo-adjuvant chemotherapy in NSCLC and elaborate on results from the newer trials incorporating ICIs. We briefly discuss the pros and cons of each treatment approach along with areas that need further clarity to inform clinical practice and future directions for research in this disease.

A clinicopathological analysis of supratentorial ependymoma, ZFTA fusion-positive: utility of immunohistochemical detection of CDKN2A alterations and characteristics of the immune microenvironment

EPN-ZFTA is a rare brain tumor where prognostic factors remain unclear and no effective immunotherapy or chemotherapy is currently available. Therefore, this study investigated its clinicopathological features, evaluated the utility of MTAP and p16 IHC as surrogate markers of CDKN2A alterations, and characterized the immune microenvironment of EPN-ZFTA. Thirty surgically removed brain tumors, including 10 EPN-ZFTA, were subjected to IHC. MLPA was performed for CDKN2A HD in 20 ependymal tumors, including EPN-ZFTA. The 5-years OS and PFS of EPN-ZFTA were 90% and 60%, respectively. CDKN2A HD was detected in two cases of EPN-ZFTA; these cases were immunohistochemically negative for both MTAP and p16 and recurred earlier after surgery. As for the immune microenvironment of EPN-ZFTA, B7-H3, but not PD-L1, was positive in all cases of EPN-ZFTA; Iba-1-positive or CD204-positive macrophages were large, while infiltrating lymphocytes were small, in number in EPN-ZFTA. Collectively, these results indicate the potential of MTAP and p16 IHC as useful surrogate markers of CDKN2A HD in EPN-ZFTA, and tumor-associated macrophages, including the M2 type, may contribute to its immune microenvironment. Furthermore, the expression of B7-H3 in EPN-ZFTA may indicate the usefulness of B7-H3 as a target of immune checkpoint chemotherapy for EPN-ZFTA via B7-H3 pathway.

Efficacy and safety of EGFR inhibitor gefitinib in recurrent or metastatic cervical cancer: a preliminary report

There has been growing interest in the use of epidermal growth factor receptor inhibitors in various cancers. The study was conducted to evaluate the efficacy and safety of gefitinib as a monotherapy in patients with recurrent or metastatic cervical cancer. Patients with cervical carcinoma who experienced locoregional recurrence or distant metastases either at presentation or after definitive combined chemoradiotherapy or postoperative radiotherapy were enrolled. Gefitinib was administered orally at a dose of 250 mg/d to eligible patients. Treatment with Gefitinib was continued until disease progression, intolerable adverse effects were developed, or consent was withdrawn. Clinical and radiological investigations were used to verify the disease response. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The study enrolled 32 patients who met the eligibility criteria. Thirty patients were available for the analysis. The majority of the patients included in the analysis had FIGO stage IIIB disease at their initial presentation. The median follow-up time was 6 months (3–15 months). Two patients (7%) had a complete clinical response, 7 patients (23%) had a partial response, 5 patients (17%) showed a stable disease and 16 patients had progressive disease (53%). The disease control rate was 47%. The median PFS was noted to be 4.5 months and the 1-year PFS was 20%. None of the individuals experienced toxicity of grade 3 or higher. All toxicities were managed conservatively. The study suggests that gefitinib may be a promising therapeutic option for patients with advanced cervical cancer who have limited treatment alternatives.

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratio = 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratio = 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer

This study evaluated the efficacy and safety of cisplatin and nedaplatin in three-week doublet agent concurrent chemoradiotherapy (CCRT) for patients with locally advanced cervical cancer (LACC). We retrospectively enrolled patients with stage IIB-IIIC2 cervical cancer who received doublet agent CCRT from January 2015 to December 2020. Clinical outcomes were analyzed using the Kaplan–Meier method and a Cox proportional hazards model. Propensity score (PS) matching analysis was used to compare cisplatin plus docetaxel group and nedaplatin plus docetaxel group. A total of 295 patients were included. The 5-year overall survival rate (OS) and progression free survival rate (PFS) were 82.5% and 80.4%, respectively. After PS matching, there were 83 patients each in the nedaplatin group and cisplatin group. There were no significant differences in objective response rates (97.6% and 98.8%, p = 0.212), 5-year OS rate (96.5 vs 69.8, p = 0.066), PFS rate (90.8 vs 72.4, p = 0.166), and toxicity between the two groups. Doublet agent concurrent chemoradiotherapy is feasible, safe, and shows high efficacy in LACC patients. Here, cisplatin group has a trend of better prognosis, suggesting that cisplatin is preferred and nedaplatin can be considered for replacement when cisplatin is intolerant.

Neoadjuvant nivolumab, paclitaxel, and carboplatin followed by response-stratified chemoradiation in locoregionally advanced HPV negative head and neck squamous cell carcinoma (HNSCC): The DEPEND trial.

6007 Background: The role of neoadjuvant immunotherapy in curative-intent head and neck squamous cell carcinoma (HNSCC) remains poorly defined. Survival for locoregionally advanced (LA) HPV negative (-) HNSCC remains poor with two-year survival of ~50%, and substantial treatment-related toxicity with standard chemoradiation (CRT). Given the activity of anti-PD1 in recurrent/metastatic HNSCC, we studied neoadjuvant nivolumab with chemotherapy and the feasibility of subsequent response-stratified CRT in HPV(-) LA HNSCC. Methods: The DEPEND trial (NCT03944915) is a phase II trial of nivolumab, paclitaxel, and carboplatin followed by response-stratified CRT for previously untreated stage IVA-B (AJCC-8th edition) HPV(-) HNSCC. The ultimate goal is to evaluate radiation volume and/or dose reduction to decrease long-term toxicities. Eligible patients received three 21-day cycles of nivolumab 360mg day 1, paclitaxel 100mg/m2 on days 1/8/15, and carboplatin AUC5 day 1. Patients with ≥50% reduction by RECIST 1.1 received response-adapted CRT to 66Gy with elimination of elective nodal volumes; &lt; 50% reduction received standard-dose CRT to 70-75Gy. Post-CRT nivolumab 480mg every 4 weeks for 9 months was administered. The primary endpoint was deep response rate (DRR) defined as the proportion of patients with ≥50% reduction. Tumor PD-L1 immunohistochemistry was reported as combined positive score (CPS). Results: Thirty-six eligible patients started treatment between September 2019 and June 2022. Median age 59 (range 27-77), 22% female, 80% 20PYH smoking, 39% oral cavity, 19% oropharynx, 25% larynx/hypopharynx, 78% T3/4 and 78% N2/3. PD-L1 CPS ≥1 in 58%. The DRR with nivolumab/chemotherapy was 54% (95% CI 0.37-0.72), which met our statistical endpoint. The ORR was 89%. CRT stratification was as follows: Response-adapted CRT (n = 19) and standard-dose CRT (n = 16). At a median follow-up of 14 months, 2-year PFS and OS were 64% (95%CI 0.41-0.80) and 76% (95%CI 0.53-0.89), respectively. By CRT stratification, 2-year PFS was 79% and 46% in response-adapted and standard-dose CRT, and 2-year OS was 86% and 67% in response-adapted and standard-dose CRT, respectively. One patient died from disease progression during neoadjuvant therapy. 2-year distant control in response-adapted and standard-dose CRT arms was 100% and 63%, and 2-year locoregional control was 85% and 92%, respectively. PD-L1 CPS ≥1 and &lt; 1 demonstrated DRR of 75% and 27%, respectively ( p= 0.01). Conclusions: Nivolumab-based neoadjuvant chemoimmunotherapy led to deep responses, and response-adapted CRT was associated with favorable survival and locoregional control. PD-L1 expression was predictive of deep response to nivolumab-based neoadjuvant therapy. Late toxicity analysis between treatment arms is planned. Clinical trial information: NCT03944915 .

Tislelizumab plus chemotherapy in patients with advanced brain metastases of non-squamous non-small cell lung cancer: A multicenter, prospective, open-label phase 2 study.

9080 Background: Patients (pts) with brain metastases (BM) were usually unrepresented in clinical trials assessing the efficacy of PD-(L) 1 inhibitors. Here, we investigated the efficacy and safety of tislelizumab (TIS) plus chemotherapy in NSCLC pts with asymptomatic untreated BM or with stable BM after local radiotherapy. Methods: This multicenter, prospective, open-label phase 2 study enrolled systemic treatment-naïve pts with stage IV non-squamous (nsq) NSCLC without EGFR or ALK mutations who had BM. Pts received TIS combined with pemetrexed and carboplatin for 4 cycles, followed by maintenance TIS and pemetrexed. RECIST v1.1 and RANO-BM were applied for assessment for systematic and brain disease, respectively. The primary endpoint was the investigator-assessed 1-year PFS rate per RECIST v1.1. Results: 36 pts were enrolled with 77.8% having stage IVB disease, 25.0% liver metastases and 41.7% bone metastases. 29 (80.6%) pts were with untreated, asymptomatic brain metastases, and the other 7 (19.4%) received radiotherapy for BM previously. As of 30 Nov 2022, the median follow-up was 12.3 months. 1-year systematic PFS rate was 36.8% (95% CI, 18.0-55.7), with median PFS of 7.5 months (95% CI, 5.1-NE). Systematic ORR was 50.0% (95% CI, 31.9-68.1%). Median OS was not reached, with 1-year OS rate of 70.5% (95% CI, 51.7-83.1). For intracranial efficacy assessment per RANO-BM, 1-year intracranial PFS (iPFS) rate was 56.6 % (95% CI, 31.7-75.5), with 45.5% (95% CI, 19.4, 68.5) and 100% in pts with untreated and pretreated BM, respectively. Intracranial ORR was 56.7% (95% CI, 37.4-74.5%), with 53.8% (95% CI, 33.4-73.4%) in pts with untreated BM and 75% (95% CI, 19.4-99.4%) in pretreated BM. No grade 5 toxicities were observed. Grade 3-4 TRAEs occurred in 33.3% (12/36) of pts. 13.9% of pts experienced irAEs; grade 3-4 irAEs occurred in 2 (5.6%) pts. Conclusions: TIS plus chemotherapy yielded promising systematic and intracranial PFS, and was generally well tolerated in nsq-NSCLC pts with untreated or pretreated BM. Clinical trial information: NCT04507217 . [Table: see text]

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: BTK inhibitors (BTKi) monotherapy has introduced the concept of continuous treatment in CLL/SLL until disease progression, leading to several concerns like lack of deep remission, increasing risk of toxic effects and substantial cost. Therefore, time-limited treatment strategies as first line treatment of CLL/SLL were comprehensively explored and BTKi combined with chemoimmunotherapy was one of these options which could induce durable responses in young fit patients. Methods: CLL/SLL patients who were treated with iFCR as initial therapy in the First Affiliated Hospital of Nanjing Medical University were included without any genomic restrictions. Ibrutinib (420 mg daily) was given continuously for 2 years and intravenously rituximab (375 mg/m2 in day 0 of cycle 1; 500 mg/m2 in day 0 of cycle 2–6), fludarabine (25 mg/m2, days 1–3) and cyclophosphamide (250 mg/m2, days 1–3) were administered every 28-day cycle, up to maximal 6 cycles. Patients who achieved complete remission or complete remission with incomplete recovery (CR/CRi) and bone marrow (BM) undetectable MRD (uMRD) 2 years after iFCR initiation were feasible to discontinue ibrutinib maintenance. Results: 34 previously untreated, young fit CLL/SLL patients who received iFCR regimen between January 2019 and March 2021 were included in our cohort. The median age was 55 years (IQR: 48–56). IGHV was unmutated in 21 of 34 (61.8%) patients; complex karyotype was present in 11 of 34 (32.4%) patients; TP53 mutation or del(17p) was detected in 6 of 34 (17.6%) patients. CR/CRi rate and BM uMRD rate was 35.3% (12/34) and 41.2% (14/34) after 3 cycles of iFCR and increased to 55.9% (19/34) 2 months after 6 cycles in both patients who received 3 or 4 and 6 cycles of iFCR. The best CR/CRi and BM uMRD rate were both 73.5% (25/34). With the median follow-up of 33 months (range 7–42 months), the 3-year PFS and OS rate was 80.0% and 95.5% respectively. CR/CRi rate and BM uMRD rate was comparable between patients with IGHV mutated and unmutated status without TP53 aberration, while all patients with TP53 aberration failed to achieve sustainable CR/CRi or BM uMRD. Patients who achieved MRD 10-6 negative post 3 cycles of iFCR sustained remission and discontinued ibrutinib maintenance. The most common hematological adverse events were neutropenia (25/34, 73.5%) and thrombocytopenia (24/34, 70.6%), grade 3–4 neutropenia and thrombocytopenia occurred in 67.6% (23/34) and 35.3% (12/34) patients respectively. The most common non-hematological adverse events were nausea (21/34, 61.8%), fatigue (16/34, 47.1%) and vomiting (15/34, 44.1%). Conclusion: The iFCR regimen could achieve high response rate and uMRD rate as initial treatment for young fit CLL/SLL patient without TP53 aberrations with acceptable tolerability. MRD-guided iFCR courses adjustment in patients who achieved early phase remission could achieved sustainable response and reduced toxicity. Encore Abstract - previously submitted to regional or national meetings (up to <1’000 attendees) The research was funded by: This study was supported by National Natural Science Foundation of China (Grant No. 82170166, No. 82100207, No. 82170186, No. 81970146, No. 81900167), Translational Research Grant of National Clinical Research Center for Hematology (2020ZKZB01), Six Talent Peaks Project in Jiangsu Province 2019 (Grant No. WSN-001) and Youth Talent support Project in Jiangsu Province Hospital (Grant No. YNRCQN035). Keywords: Chronic Lymphocytic Leukemia (CLL), Combination Therapies No conflicts of interests pertinent to the abstract.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Mature T and NK-cell lymphomas represent a heterogeneous group of rare lymphoid disorders arising from mature T cells of post-thymic origin. The T-cell Project 2.0 (TCP2) was launched in 2018 with the aim of better understanding this group of rare disorders, capturing a real-life snapshot of the evolving landscape of T-cell lymphoma biology, treatment strategies, and outcome. Here we report preliminary data on histotype distribution, disease characteristics, front line treatment, and short-term outcome of patients registered between 2018 and 2021. Methods: The TCP2 (ClinicalTrials.gov Identifier: NCT03964480) is a prospective, longitudinal, international, observational study of patients with Peripheral T-cell lymphoma (PTCL). For this analysis we considered cases based on the diagnosis made locally according to the WHO2016 classification. The study was approved by each participating center and required patients to sign informed consent. Results: Between October 2018 and December 2021, 741 eligible cases with newly diagnosed PTCLs were registered by 94 Institutions across 17 Countries. Overall, PTCL-NOS, AITL, ALCL ALK-, ALCL ALK+, ENKTCL, and ATLL resulted the most frequent 6 subtypes, accounting for 91% of cases, while the remaining 9% were represented by few cases of 13 different subtypes. Of note, only 16 cases (2.1%) were classified according to entities not considered in the previous WHO 2008 classification. The median age at diagnosis was 57 years (18–93), 56.5% of patients were male, the presence of systemic symptoms was reported in 30% of cases, 7.4% had ECOG-PS 3–4, 71% advanced disease and 36.6% bone marrow involvement. Overall, 88% were treated with combination chemotherapy and 28% of patients with advanced stage disease in complete or partial remission after chemotherapy were consolidated with high dose therapy and stem cell transplantation. After a median follow-up of 21 months, the 2-year PFS and OS of the whole series were 38% and 52%, respectively. At the same time point, the PFS and OS (in brackets) were: PTCL-NOS (24% and 43%); AITL (40% and 50%); ENKTL (44% and 53%); ALCL ALK- (52% and 67%); ALCL ALK+ (71% and 85%) and ATLL (14% and 27%). Comparing the distribution of cases enrolled in the present study with those in the previous TCP1 (2008–2018), we found a 6% and 3% decrease in the frequency of PTCL-NOS and EATL, respectively, whilst the frequency of other histotypes remained almost unchanged. Of note, no statistically significant differences emerged in terms of PFS and OS for the comparable histotypes of TCP1 and TCP2. Conclusions: Based on the analysis of this large series of cases of PTCL prospectively registered in the TCP2, it seems “Nothing new under the sun”: no improvement in terms of outcome and a very limited effect of the WHO2016 in classification of cases in the real world. The research was funded by: Angela Serra Association for Cancer Research Keywords: Aggressive T-cell non-Hodgkin lymphoma, Pathology and Classification of Lymphomas No conflicts of interests pertinent to the abstract.