Favorable Survival Outcomes Research Articles

Clinical Characteristics and Predictive Outcomes of Recurrent Nasopharyngeal Carcinoma-A Lingering Pitfall of the Long Latency.

Simple SummaryUnlike other head and neck cancers, nasopharyngeal carcinoma (NPC) with long-latent recurrence (>five years) is not rare. This study aims to investigate the clinical characteristics and outcomes of long-latent recurrent NPC. We found that 8.1% recurrence occurred after five years. About two thirds of these patients’ primary cancer belonged to the early stages, and almost half of the recurrence was a local recurrence. The five-year overall survival and disease-specific survival rate of long-latent recurrence was 19.7% and 24.5%, respectively. Most long-latent local recurrence was found in unresectable rT3 or rT4 cases, while one-third could not be detected by endoscopy due to recurrence in the skull base. A higher percentage of patients who died after long-latent recurrence were symptomatic with a follow-up interval more than six months, reflecting that delayed detection of recurrence may have a great impact on survival outcome. A long-term follow-up is necessary for early detection of NPC recurrence even after five years of disease-free interval.Purpose: To investigate the clinical characteristics, risk factors, and clinical outcomes of long-latent recurrence (>five years) of nasopharyngeal carcinoma (NPC). Methods: This retrospective study enrolled newly diagnosed NPC patients from the Chang Gung Research Database between January 2007 and December 2019. We analyzed the patients’ characteristics and survival outcomes after recurrence. Results: A total of 2599 NPC patients were enrolled. The overall recurrence rate was 20.5%, while 8.1% of patients had long-latent recurrence (>five years). These patients had a higher percentage of initial AJCC (The American Joint Committee on Cancer) stage I/II (60.5%, p = 0.001) and local recurrence (46.5%, p < 0.001). Unresectable rT3 and rT4 were found in 60% of patients when recurrence and 30% of local recurrence occurred in the skull base, which could not be detected by the regular endoscopy. The five-year overall survival rate of long-latent recurrence was 19.7%. Alive patients tended to be asymptomatic but have regular follow-ups with the interval less than six months. Multivariate analysis showed age and initial advanced AJCC stages were independent risk factors of death after recurrence. In contrast, patients with recurrence between two and five years, salvage surgeries, and regional recurrence had favorable survival outcomes. Conclusion: Long-latent NPC recurrence is not rare, and the survival outcome is poor. Regular follow-up for early detection of NPC recurrence is necessary even after five years of disease-free period.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA 3001) (546)

Objectives: Optimum selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer is often dependent on multiple confounding factors. This study aimed to evaluate the treatment outcomes of recurrent ovarian cancer and investigate the factors identifying patients who most likely benefit from the SCS. Methods: We retrospectively reviewed medical records of recurrent ovarian cancer patients from five referral hospitals in Korea from 2010 to 2020. Recurrent characteristics, following treatment methods and potential factors for survivals were evaluated between the chemotherapy and surgery groups. Results: A total of 670 patients with recurrent ovarian cancer were identified. The patient’s median age was 55 years (24-83), and 88.1% of patients had initial stage III/IV disease. Of all patients, 215 (32.1%) received SCS for the disease recurrence. The median survival was 85 months (95% CI: 65.0-105.0) in the chemotherapy group, whereas the median survival time was not reached in the SCS group. Patients who received the SCS were more likely to be young and had no residual disease at primary surgery, platinum-sensitive recurrence, limited regional recurrence (LRR, ≤3 lesions or regional carcinomatosis) with a low rate of ascites (p<0.001, 0.001, 0.001, 0.001, 0.006, respectively). In multivariate cox analysis, residual disease at primary surgery, PFI, recurrent sites, ascites, and SCS were significant prognostic factors for survival. Meanwhile, predicting factor for complete resection after SCS was only recurrent sites (LRR, p<0.001). Conclusions: SCS resulted in significantly favorable survival outcomes in well-selected patients. Platinum-sensitive recurrence with limited regional diseases (< 3 regions or limited carcinomatosis without ascites) can be considered as optimum criteria for SCS in recurrent ovarian cancer. Objectives: Optimum selection criteria for secondary cytoreductive surgery (SCS) in recurrent ovarian cancer is often dependent on multiple confounding factors. This study aimed to evaluate the treatment outcomes of recurrent ovarian cancer and investigate the factors identifying patients who most likely benefit from the SCS. Methods: We retrospectively reviewed medical records of recurrent ovarian cancer patients from five referral hospitals in Korea from 2010 to 2020. Recurrent characteristics, following treatment methods and potential factors for survivals were evaluated between the chemotherapy and surgery groups. Results: A total of 670 patients with recurrent ovarian cancer were identified. The patient’s median age was 55 years (24-83), and 88.1% of patients had initial stage III/IV disease. Of all patients, 215 (32.1%) received SCS for the disease recurrence. The median survival was 85 months (95% CI: 65.0-105.0) in the chemotherapy group, whereas the median survival time was not reached in the SCS group. Patients who received the SCS were more likely to be young and had no residual disease at primary surgery, platinum-sensitive recurrence, limited regional recurrence (LRR, ≤3 lesions or regional carcinomatosis) with a low rate of ascites (p<0.001, 0.001, 0.001, 0.001, 0.006, respectively). In multivariate cox analysis, residual disease at primary surgery, PFI, recurrent sites, ascites, and SCS were significant prognostic factors for survival. Meanwhile, predicting factor for complete resection after SCS was only recurrent sites (LRR, p<0.001). Conclusions: SCS resulted in significantly favorable survival outcomes in well-selected patients. Platinum-sensitive recurrence with limited regional diseases (< 3 regions or limited carcinomatosis without ascites) can be considered as optimum criteria for SCS in recurrent ovarian cancer.

Discontinuation of pembrolizumab for advanced urothelial carcinoma without disease progression: Nationwide cohort study.

Pembrolizumab, an anti-programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum-refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9months. The 2-year relapse-free survival (RFS), treatment-free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re-administered to 12 patients. Pembrolizumab re-challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score-matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p=0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Outcomes of allogeneic hematopoietic cell transplantation in adults with fusions associated with Ph-like ALL

AbstractAllogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for acute lymphoblastic leukemia (ALL), yet large amounts of data describing alloHCT outcomes in Philadelphia (Ph)-like ALL are lacking. We retrospectively analyzed archived DNA samples from consecutive adults with B-cell Ph-negative ALL who underwent alloHCT in complete remission (CR) (n = 127) at our center between 2006 and 2020. Identification of fusions associated with Ph-like ALL was performed using cumulative results from RNA-seq, conventional cytogenetics, fluorescence in situ hybridization, and whole genome array studies. Fusions associated with Ph-like ALL were detected in 56 (44%) patients, of whom 38 were carrying CRLF2r. Compared with other non–Ph-like ALL (n = 71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P = .008), were less likely to carry high-risk cytogenetics (P < .001), and were more likely to receive blinatumomab prior to HCT (P = .019). With the median followup of 3.5 years, patients with Ph-like ALL fusions had comparable posttransplant outcomes compared with other B-cell ALL: 3-year relapse-free survival (RFS) (41% vs 44%; P = .36), overall survival (OS) (51% vs 50%; P = .59), and relapse (37% vs 31%; P = .47). In multivariable analysis, age (P = .023), disease status at the time of transplant (P < .001), and donor type (P = .015) influenced OS. RFS (primary endpoint) was significantly influenced by disease status (P < .001) and conditioning regimen intensity (P = .014). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.

Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab.

BackgroundStandard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes.MethodsWe performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma.Results199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p<0.001) and OS (HR: 0.12, 0.05-0.32; p<0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p<0.001) and OS (HR: 0.07, 0.03-0.14; p<0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965).ConclusionsEarly interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.

Distant metastasis without regional progression in non-muscle invasive bladder cancer: case report and pooled analysis of literature

BackgroundNon-muscle invasive bladder cancer (NMIBC) represents the majority of bladder neoplasms. It is unusual for NMIBC metastasizing distantly without regional progression, namely metastatic NMIBC (mNMIBC), which is still poorly understood and easily omitted based on current management policies. So far, description of mNMIBC is limited to a few case reports.MethodsWe reported a 70-year-old man with NMIBC who suffered from cervical metastasis without pelvic recurrence at 41 months after initial diagnosis. Then we performed a collective analysis of this case together with published mNMIBC cases searched from PubMed, Embase, and Web of Science, aiming to illustrate baseline clinicopathologic parameters, metastatic patterns, and treatment outcomes of these patients and analyze associated influencing factors.ResultsAfter scrupulous review, 45 cases previous reported and the one from our center were incorporated into the aggregated cohort of mNMIBC, including 34 males and 12 females. Primary tumors from 46.7% of patients were high-grade (HG) or grade 3 (G3) and 65.1% had T1 lesions. Aberrant biomarker expression was found in tumors of some cases. Most (40/46) metastases of mNMIBC occurred at a single site, mainly in lung, bone and lymph nodes. Apart from three cases of de novo mNMIBC, the mean metastasis-free survival (MFS) interval of metachronous mNMIBC was 42.5 months, which was obviously longer than conventional metastatic bladder cancer. Shortened MFS interval was associated with old age, T1 or HG/G3 primary tumors, and non-lung metastases. Systemic chemotherapy and metastasectomy or radiotherapy for oligometastatic lesion were main therapeutic approaches of mNMIBC, and immunotherapy was adopted for the case from our center. Lung and bone metastases correlated with relatively favorable and unfavorable survival outcomes, respectively. Compared with monotherapy, chemotherapy, or immunotherapy combined with local cytoreduction got more favorable outcomes.ConclusionAlthough rare, mNMIBC occurs more in tumors with high-risk features. Usually, mNMIBC metastasizes later than conventional metastatic bladder cancer and manifests as solitary lesion. Outcomes of mNMIBC would be influenced by metastatic site and post-metastatic treatment. Systemic treatment combined with local cytoreduction may render survival benefit in selected patients.

Ferroptosis-Associated Molecular Features to Aid Patient Clinical Prognosis and Therapy Across Human Cancers.

Ferroptosis is a new non-apoptotic form that regulates cell death and is mainly dependent on iron-mediated oxidative damage and subsequent cell membrane damage. Ferroptosis may be a potential therapeutic strategy for immunotherapy, chemotherapy, and radiotherapy in human cancers. Numerous studies have analyzed ferroptosis-correlated signatures or genes, but a systematic landscape of associations among tumor ferroptosis, clinical outcomes, tumor microenvironment, and therapies in human cancers is lacking. Here, we developed a relative ferroptosis level (RFL) combined with drive/suppress regulators and validated it in the Gene Expression Omnibus datasets of ferroptotic drug treatment. Based on this effective evaluation method, we classified about 7,000 tumor samples into high and low RFL groups in each cancer type and observed that high RFL cases demonstrate favorable survival outcomes in nine cancer types from The Cancer Genome Atlas. Then, several RFL-correlated candidate genes that have not been reported to be ferroptosis-related were selected and experimentally validated in five cancer cell lines using Erastin treatment. We further showed that both immunostimulatory and immunosuppressive phenotypes were observed in high RFL tumors, suggesting that the consideration of ferroptosis could be a potential strategy in cancer immunotherapy. Moreover, we found that high RFL cases/cells showed responder or sensitivity to chemotherapy and radiotherapy. Our study provides a comprehensive molecular-level understanding of ferroptosis and may have practical implications for clinical cancer therapies, including immunotherapy, chemotherapy, and radiotherapy.

Abstract 5546: Inflamed lymph nodes mark active tumor immune response in colorectal cancer patients

Abstract Background Tumor-infiltrating lymphocytes (TILs) can be used to predict immune response in multiple tumors. Currently, the evaluation of TILs relies on pathological and molecular examine on resected tumor samples. Enlarged regional lymph nodes could be attributed to tumor involvement or local inflammation with active immune response. We therefore aimed to investigate the role of inflamed lymph nodes in distinguishing the hot tumor from cold tumor. Methods Fresh-frozen tumor samples from pathologically-confirmed node-negative colorectal cancer patients with inflamed nodes (n= 22) and non-inflamed nodes (n= 23) were used to generate the genome-wide DNA methylation profile using Infinium Methylation EPIC BeadChip. The inflamed and non-inflamed nodes were defined as the pathologically-confirmed negative regional lymph nodes with enlarged size (≥ 5mm) and normal size (&amp;lt; 5mm) in radiological imaging, respectively. A MeTIL algorithm that integrates CD3+ T cell-specific differentially methylated positions was constructed and validated by immunohistochemical assay to evaluate TIL-based tumor immune response in bulk tumor samples. Results The baseline characteristics were balanced between patients with inflamed and non-inflamed nodes. The high abundance of TILs was significantly associated with inflamed nodes (P= 0.025). In addition, we identified a subgroup of superhot tumors characterized by inflamed nodes, enriched TILs and favorable overall survival outcomes (HR 0.53, 95% CI: 0.36-0.97; P = 0.032). Conclusions Inflamed regional lymph nodes in radiological imaging indicate potential active immune response in tumor. Our findings provide an easily accessible biomarker for cancer immunotherapy. Citation Format: Dingcheng Shen, Xiaolin Wang, Meijin Huang, Yanxin Luo, Huichuan Yu. Inflamed lymph nodes mark active tumor immune response in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5546.

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

Local therapy (LT) could potentially prolong the survival of patient with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitors (TKIs) and harboring oligometastatic/oligoprogressive disease (OMD/OPD). However, the optimal imaging method for identifying patients with OMD/OPD remains controversial. The objective of this study was to investigate the clinical value of incorporating PET/CT in detecting patients with OMD/OPD. Consecutive cases with metastatic EGFR-mutant NSCLC undergoing first-line EGFR-TKI treatment were retrospectively screened and those receiving baseline PET/CT and brain magnetic resonance imaging (MRI) or complete conventional imaging (CIM), including brain MRI, chest computed tomography (CT), abdomen ultrasound or CT and bone scintigraphy were included. OMD/OPD was defined as metastases/progressions documented at a maximum of five lesions and three organs, otherwise was defined as multiple metastatic/progressive disease (MMD/MPD). Progression-free survival (PFS) and overall survival (OS) were analyzed. Of the 392 patients evaluated, baseline OMD was detected in 22.7% (53/233) of patients by PET/CT and in 18.2% (29/159) of patients by CIM (p = 0.171). Among the patients evaluated with baseline PET/CT, patients with OMD had longer PFS (p = 0.016) and tendency of improved OS (p = 0.058) than those with MMD. However, this result was not observed with patients evaluated using baseline CIM. With a median follow-up of 24.2 (range, 1.1-124.6) months, 297 patients had their first disease progression (FPD), of whom 164 (55.2%) had adequate imaging scans to analyze the tumor distributions at FPD comprehensively. OPD was detected in 63.0% (34/54) and 35.0% (39/110) of patients among the PET/CT and CIM assessed group (p = 0.003), respectively. Among the PET/CT assessed group, patients with OPD had significantly longer post-progressive overall survival (OS2) than those with MPD (p = 0.011). However, no significant difference of OS2 in the CIM assessed group was found. Patients with OMD/OPD, evaluated by PET/CT but not CIM, generally had more favorable survival outcomes than those with MMD/MPD among patients with metastatic NSCLC undergoing first-line EGFR-TKI treatment. PET/CT seems to affect the survival of patients under first-line EGFR-TKI treated metastatic NSCLC with OMD/OPD.

SURGICAL MANAGEMENT OF APPENDIX TUMORS: A SINGLE-CENTER REVIEW OF 15 YEARS

Objective: Primary neoplasms of the appendix are rare and most clinicians are unfamiliar with them. The selected approach may differ, ranging from appendectomy to cytoreductive surgery. We aimed to present our clinical experience with the surgical management of appendix tumors. Materials and Methods: 4,450 patients with a history of appendectomy from January 2006 to February 2021 were analyzed retrospectively. Patients diagnosed with “serrated lesion/polyp, low/high-grade appendiceal mucinous neoplasm (LAMN/ HAMN), mucinous/non-mucinous/goblet cell adenocarcinoma, neuroendocrine tumor (NET)” were included in the study. Histological evaluations, surgical procedures, follow-up data, and survival outcomes were evaluated. Results: Among 132 [F:87 (65.9%)] patients diagnosed with appendix tumors, 27 (20.5%) were in the benign group (Group A), 61 (46.2%) were in the borderline group (Group B), and 44 (33.3%) were in the malignant group (Group C). Appendectomy and right hemicolectomy were performed as the initial operations in 105 (79.5%) and 27 (20.5%) patients, respectively. Seventeen patients (12.9%) with a previous history of appendectomy received right hemicolectomy (n=9; due to surgical margin positivity) and Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) (n=8; due to recurrence) as redo surgery during the follow-up period. Appendectomy was sufficient for 88 (66.6%) patients. Adenocarcinoma was revealed as a statistically significant factor for recurrence-free survival (RFS) (HR=7.28, p=0.049). Malignancy (HR=3.76, p=0.036) and age (≥60) (HR=3.86, p=0.006) were significant factors of overall survival (OS). Conclusion: Appendectomy is efficient in the treatment of appendix tumors for selected cases considering low morbidity of the procedure and favorable survival outcomes. For advanced-stage tumors, extended resections combined with chemotherapy should be the preferred approach.

Associations of Education Level With Survival Outcomes and Treatment Receipt in Patients With Gastric Adenocarcinoma.

BackgroundIt remains largely unclear how education level, an important socioeconomic factor, affects prognoses for patients with gastric adenocarcinoma (GAC). We aimed to demonstrate the associations between education level and clinical outcomes in patients with GAC.MethodsWe included a total of 30,409 patients diagnosed with GAC from the Surveillance, Epidemiology, and End Results 18 registry database. Education level, household income, unemployment rate, poverty rate, insurance status, and marital status were selected as sociodemographic variables for the comprehensive analysis. Cox and logistic regression models, Kaplan–Meier curves, and subgroup analyses were the primary statistical methods employed.ResultsA low level of education was correlated with less income, higher unemployment rates, and higher poverty rates (all p < 0.001). The multivariate Cox analysis indicated that a high education level was significantly associated with superior overall survival rates and cancer-specific survival rates in patients with GAC (both p < 0.001). We also corroborated favorable survival outcomes by high education level within almost every clinical and demographic subgroup. Furthermore, chemotherapy combined with surgery could markedly prolong the survival for all patients, including patients of stage IV cancer (both p < 0.001). By using multivariable logistic models, patients in counties with high education levels had a higher probability of chemotherapy receipt (p < 0.001). Contrarily, those in the counties with low levels of education were less likely to receive chemotherapy or undergo surgery (p < 0.001).ConclusionsEducation level was identified and confirmed as an independent predictor of treatment and survival for GAC patients. Efforts are needed to provide effective interventions for those whose educational status is adverse.

Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: A contemporary single-institution experience.

Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity. A single-center, retrospective study was conducted of patients age ≥18 years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses. Fifty-nine patients met criteria, with median age of 25 years (range 18-62 y) and median follow-up of 6.5 years (range 0.7-23.1 y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6 Gy (relative biological effectiveness [RBE]), median total dose was 54.0 Gy (RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5 year PFS and OS were 86.5% and 95.8%, respectively; 10 year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (P = .04). Among eight recurrences, 25% presented after 5 years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (P = .05). Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

LINC-04. Optic pathway gliomas in children: an 18-year experience in a middle-income country

Abstract BACKGROUND: Optic pathway gliomas (OPGs) have favorable survival outcomes, but can have significant morbidity, from the tumor or from its treatment. This retrospective study sought to describe the clinical presentation and outcomes of children with OPGs at a tertiary center in a middle-income country. METHODS: Patients younger than 18 years diagnosed with OPGs between 2002-2020 at the Hospital Civil de Guadalajara in Mexico, were included. Survival analyses and logistic regression were used to determine risk factors for progression. RESULTS: Thirty patients were identified with a median age of six years. Common clinical characteristics at presentation included: visual accuracy impairment (40%), headache (23.3%), nystagmus (20%), endocrine disturbances (16.6%), and diencephalic syndrome (13%). Neurofibromatosis-1 was present in 23.3% of the patients. Eight patients underwent resection at diagnosis, 7 of them had secondary complications. One died during surgery due to catecholamine-resistant shock, and the other developed neuro-infection and died due to septic shock after surgery. Five children developed neurological or endocrine sequelae. Fifteen total patients received chemotherapy as their first line treatment. The 5-year progression-free survival was 77.9±10% and overall survival was 89.5±5%. Patients who received chemotherapy or targeted therapy as the first line of treatment had higher PFS compared to those who received other therapies (p=0.03). The patients who received surgery as first-line treatment had a 3.1 times greater risk of achieving a Lansky/Karnofsky score of fewer than 90 points 6 months after diagnosis (p=0.006). Ten patients had pre- and post-treatment ophthalmologic assessment, either visual acuity or visual evoqued potentials. Five had no changes and 5 showed improvement after treatment. CONCLUSIONS: These results show inferior outcomes compared to high-income countries, influenced importantly due to morbidity after surgical resection. These data can be used to prospectively optimize treatment at our institute and other middle-income countries through a multidisciplinary neuro-oncology team.

Neoadjuvant chemotherapy plus tislelizumab followed by concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A single-arm, phase II trial.

6068 Background: Neoadjuvant treatment with gemcitabine plus cisplatin (GP) prior to concurrent chemoradiotherapy (CCRT) has favorable survival outcomes with acceptable toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC), 10% of whom achieved complete response (CR) after neoadjuvant treatment. Immune checkpoint blockade therapy plus GP regimen has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of neoadjuvant treatment with GP plus tislelizumab, an anti-PD-1 monoclonal antibody, in previously untreated LANPC. Methods: In this phase II, single-armed Simon two-stage study, eligible patients are of age 18-70, with adequate haematological, renal, and hepatic function, diagnosed with staged III-IVa（AJCC 8th） non-keratinizing LANPC. Enrolled patients received intravenous gemcitabine (1000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and tislelizumab (200mg) on day 1 every 3 weeks for 3 cycles followed by standard CCRT. The primary endpoint was CR rate after neoadjuvant treatment, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. The secondary endpoints included pathology complete response (pCR) rate, 2-year progress-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), and toxicity. This study is registered with ClinicalTrials.gov, NCT04833257, all enrolled patients have finished their treatment and the follow-up is ongoing. Results: From April 14th 2021 to August 5th, 2021, a total of 63 patients (median age 46y, 74.6% male) were enrolled at Sun Yat-sen University Cancer Center. As of January 31st, 2022, the median follow-up is 7.37 months, no patients had disease progression. The CR rate after neoadjuvant treatment was 41.3% (95% CI, 28.8% to 53.8%). The ORR and pCR rate were 88.9% (95% CI, 80.9% to 96.9%) and 75.8% (95% CI, 64.8% to 86.8%), respectively. The incidence of acute treatment-related AEs (trAEs) and immune-related adverse events (irAEs) of grade 3 or 4 was 69.8% and 3.2%, respectively. All of irAEs for grade 3 or 4 were hepatotoxicity and skin rash. Long-term efficacy is awaited. Conclusions: Neoadjuvant treatment with GP plus tislelizumab achieved impressive CR rate and pCR rate with manageable toxicities. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04833257.

Anastomotic Suturing Techniques and Their Association With Post-Lung Transplantation Complications.

Currently, standard practice is to use the continuous suturing technique on the bronchial anastomosis during lung transplantation. This study used a large cohort to investigate and contrast continuous and interrupted suturing techniques, comparing survival outcomes and occurrence of postoperative bronchial complications to examine if utilization of interrupted suturing has merit. Survival outcomes of 740 single-center lung transplant recipients over 8y (February 2012-March 2020) were compared by suturing techniques: either continuous or interrupted at the bronchial anastomosis. Clinical parameters and demographics were compared between two suturing groups, with P values<0.05 considered significant. The groups were compared for postoperative morbidity, including need for bronchial interventions. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox regression analysis was run with statistically significant variables to study association with survival. Of the 740 patients, 462 received the continuous suturing technique and 278 received the interrupted suturing technique. Most demographic and clinical data were not statistically significant between the two groups, and those that were significant were not associated with worse survival outcomes, with the exception of the variable diagnosis. Bronchial complications were comparable between the continuous and interrupted groups (12.6% versus 10.4%, P=0.382). Extracorporeal membrane oxygenation (ECMO) use did not differ significantly between the two groups (P=0.12). The Kaplan-Meier curve showed comparable survival between groups (P=0.98), and Cox regression analysis showed that only diagnosis, bronchial complications, and ECMO utilization were associated with different survival outcomes. Chronic obstructive pulmonary disorder was shown to be associated with more favorable survival outcomes as opposed to idiopathic pulmonary fibrosis and the category "other". The need for ECMO and the occurrence of a bronchial complication were also associated with worse survival outcomes. Both techniques showed reasonable post-transplant outcomes, as our study demonstrated similar survival outcomes and bronchial complication rates.

Phase 2 study of trastuzumab deruxtecan in the neoadjuvant treatment for patients with HER2-positive gastric and gastroesophageal junction adenocarcinoma (EPOC2003).

TPS4161 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate consisting of an anti-HER2 antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. DESTINY-Gastric01 study showed significantly higher objective response rate with T-DXd than physician's choice of chemotherapy (51.3%, vs. 14.3%, Shitara K, et al. NEJM 2020) as well as prolonged overall survival (median 12.5 vs. 8.4 months, hazard ratio 0.59). Considering that high response rate or major pathological response (MPR), which is defined as the proportion of subjects with &lt; 10% residual tumor may be associated with favorable survival outcomes after preoperative chemotherapy, T-DXd could be a promising neoadjuvant treatment for patients with gastric and gastroesophageal junction (GEJ) cancer. However, to our knowledge, there is no currently ongoing study of T-DXd as a neoadjuvant setting for patients with gastric and GEJ cancers. Methods: This is an open-label, single-arm, multicenter, investigator initiated phase 2 trial to evaluate antitumor activity of T-DXd as the neoadjuvant treatment for patients with HER2 positive gastric and GEJ adenocarcinoma. Eligible patients should have previously untreated locally advanced gastric and GEJ adenocarcinoma with clinical stage of T2-4 and/or N+ without distant metastasis. The main cohort will enroll patients with HER2 overexpression defined as immunohistochemistry （IHC）3+ or IHC2+/ in situ hybridization（ISH）+ by local assessment. According to the results of exploratory biomarker analysis of DESTINY-Gastric01 study (Shitara K, et al. ESMO-GI2021), patients with HER2-low expression (IHC1+ or 2+ with ISH negative) with HER2-extra cellular domein (ECD) higher than 11.6 ng/ml also will be enrolled into the exploratory cohort. Patients will receive 3 cycles of T-DXd (6.4mg/kg) by intravenous infusion every 3 weeks followed by surgery at 3 to 8 weeks after last T-DXd infusion.The primary endpoint is MPR rate. The threshold in the main cohort is defined as 20%, and the expected MPR rate was set at 45%. The minimum sample size of this trial is 23 patients in the main cohort (α- and β-error probabilities, 0.1 and 0.15, respectively). Total number of patients will be increased up to 27 patients depending on the enrollment. In addition, 10 patients will be recruited into the exploratory cohort. Secondary endpoints are pathologic complete response (pCR) rate, curative resection rate, and adverse event rate. Biomarker analyses including whole exome sequencing, RNA sequencing, proteomics, and ctDNA changes will also be conducted using pre- and post-treatment tumor and blood samples. Enrollment is ongoing at six sites in Japan from November 2021. Clinical trial information: NCT05034887.

Homogeneity of pathological response (PR) and histopathological growth pattern (HGP) in resected colorectal liver metastases (CRLM) are associated with favorable survival outcome after surgery.

3596 Background: Surgical resection of CRLM aims to maximize patient survival. However, recurrence rates remain high post-surgery. We previously reported the prognostic relevance of tumor regression grading (TRG) and HGP of resected CRLM. Several studies reported the association of tumoral heterogeneity with anti-cancer drug resistance and prognosis. This study aims to explore tumoral heterogeneity for TRG and HGP in patients resected for CRLM and its prognostic implication. Methods: Tumor homogeneity for PR and HGP was evaluated in 2 independent cohorts. Cohort 1 included 57 patients (159 CRLMs) resected after chemotherapy/bevacizumab (prospective BEV-ONCO trial). Cohort 2 included 221 patients (582 CRLMs) operated after preoperative treatment or not. TRG (1 to 5 according complete to no response), HGP (desmoplastic, pushing, replacement or mixed) were evaluated for each CRLM. Max-TRG (higher TRG among all the CRLM) was used to define PR. Homogenous TRG (TRG-h) and HGP (HGP-h) was defined when all CRLMs had the same TRG or HGP pattern. HGP homogeneous desmoplastic (HGP-hd) was defined when all CRLM had a desmoplastic HGP. TRG-h, HGP-h and HGP-hd were combined into a homogeneity score (H-score: 0 to 3, 1 point given for each parameter and summed-up). Overall survival (OS for both cohorts), progression-free survival (PFS for cohort 1) and time to relapse (TTR for cohort 2) were estimated using the Kaplan–Meier method and compared by log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. Results: Patient and disease characteristics were comparable in both cohorts excepted for preoperative treatment. In cohort 1, TRG-h and HGP-h were significantly associated with a longer PFS (HR = 0.21; 95CI:0.10-0.43, p &lt; 0.001; HR = 0.27; 95CI = 0.14-0.54, p &lt; 0.001) and better OS (HR = 0.23; 95CI = 0.07-0.70, p = 0.010; HR = 0.32; 95CI = 0.10-0.93, p = 0.037). Interestingly, the same significant results were observed in cohort 2 for TTR (TRG-h: HR = 0.60; 95CI = 0.43-0.85, p = 0.004; HGP-h: HR = 0.68; 95CI = 0.49-0.94, p = 0.017) and OS (TRG-h: HR = 0.51;95CI = 0.33-0.80, p = 0.003; HGP-h: HR = 0.63; 95CI = 0.41-0.97, p = 0.034). HGP-h reported a significant association with TRG-h, a Max-TRG &lt; = 3, the absence of HGP replacement and mixed, a desmoplastic pattern, and the absence of sinusoidal obstruction syndrome in both cohorts. H-score was significantly associated with TTR (score 1-2: HR = 0.57; 95CI = 0.38-0.85, p = 0.004; score 3: HR = 0.4; 95CI = 0.24-0.64, p &lt; 0.001) and OS (score 3: HR = 0.31; 95CI = 0.15-0.64, p &lt; 0.001) in univariate analysis and with OS (HR = 0.74; 95CI = 0.59-0.94, p = 0.011) in multivariate analysis (cohort 2). Conclusions: TRG-h and HGP-h are strongly associated with patient’s survival. H-score could be an easy morphological and prognostic score to assess. Validation studies are needed.

Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001). RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Chromobox 4 (CBX4) promotes tumor progression and stemness via activating CDC20 in gastric cancer

The Chromobox homolog 4 (CBX4) has been found to be overexpressed in multiple malignancies. However, the associations between CBX4 and gastric cancer (GC) have remained unclear. This study aimed to determine the biological roles of CBX4 in GC and identify effective therapeutic targets. The 3-(4,5-dimethylthiazol-2-yl) (MTT) assays were used to screen CBX family members. Differential analysis was utilized to evaluate the CBX4 levels. Kaplan-Meier analysis was used to perform prognostic analysis. Western blotting assay, quantitative polymerase chain reaction (qPCR) assay and immunohistochemistry (IHC) were used to assess CBX4 expressions. Colony formation assay, Cell Counting Kit-8 (CCK-8) assay, and Transwell assay were used to assess progression features of cells. The tail vein injection model was utilized to determine the metastatic efficacy of GC cells. Tumor sphere formation assay was used to assess tumor stemness maintenance ability. Chromatin immunoprecipitation (ChIP)-qPCR assay was used to evaluate the associations between CBX4 and CDC20. A subcutaneous tumor model was used to assess the in vivo growth ability of GC. The MTT assay revealed that only CBX4 inhibition could lead to notable restriction of GC growth, as compared to others. Differential analysis suggested that CBX4 was upregulated in tumor samples relative to normal tissues. Less favorable overall survival (OS) outcomes were noticed in GC patients with high CBX4 in comparison to those with low CBX4. High CBX4 could notably enhance cell proliferation capacity, migration ability, and in vivo metastatic efficacy. Gene set enrichment analysis (GSEA) indicated the relationships between CBX4 and GC stemness, and CBX4 overexpression could remarkably elevate self-renewal ability of GC cells. In addition, CBX4 could mainly promote CDC20 messenger RNA (mRNA) levels, and targeting CBX4 suppressed the relative CDC20 levels. The ChIP-qPCR assay further demonstrated that CBX4 coordinated with H3K4me3 to bind at the CDC20 promoter region. Additionally, CBX4 depended on CDC20 to drive GC growth. Lastly, downregulated CBX4 could notably inhibit the growth of GC in vivo. This study highlights the oncogenic roles of CBX4 in GC. CBX4 activates CDC20 to maintain stemness features of GC, thereby creating therapeutic vulnerabilities in the treatment of GC.

Impact of perioperative chemotherapy on survival outcome of advanced colorectal cancer patients treated with cytoreduction and hyperthermic intraperitoneal chemotherapy: A retrospective study.

e15570 Background: Colorectal cancer (CRC) with peritoneal carcinomatosis (PC) is generally associated with poor prognosis. The present study aims to assess potential value of perioperative systemic chemotherapy in patients treated with cytoreductive surgery with HIPEC (CRS/HIPEC) in a single institute in Saudi Arabia. Methods: We included CRC with PC who underwent CRS/ HIPEC from January 2012 till December 2019. Different clinicopathological, treatment-related factors and dates of relapse/death, were retrospectively assessed. We checked the distribution of these factors in addition to survival outcome in those who received perioperative chemotherapy vs. none. Results: We recruited 127 eligible patients (79 patients [62.2%] received systemic chemotherapy). Patients with no perioperative chemotherapy were more likely to have grade 1 tumours (62.5% vs. 25.3%, p &lt; 0.0001), mucinous adenocarcinoma (41.7% vs. 12.7%, p = 0.002), normal CEA ≤5 ng/dl (70.2% vs. 47.4%, p = 0.016) and peritoneal-only metastasis (66.7% vs. 45.6%, p = 0.021). Median PFS and OS were 34 and 62.2 months, respectively. Patients with no perioperative systemic chemotherapy had significantly better PFS and OS (median PFS: not reached vs. 19 months, HR = 0.29, 95% CI = 0.15-0.59, p &lt; 0.0001, OS :HR = 4.3, 95% CI 1.3-14.3, p = 0.009). After adjustment of different prognostic factors, there was no significance difference in OS between the two groups (HR = 3.8, 95% CI = 0.98-14.71, p = 0.053), while PFS was still significantly better in the no chemotherapy group (HR = 2.52, 95% CI = 1.13-5.63, p = 0.024). Conclusions: CRS/HIPEC provided favourable survival outcome in our study cohort especially in patients with more favourable prognostic features. No survival benefit with perioperative chemotherapy could be demonstrated.