5-year RFS Research Articles

Outcome and Molecular Measurable Residual Disease Monitoring in Adult B-Cell Acute Lymphoblastic Leukemia Patients with MEF2D Fusions

Oncogenic gene fusions caused by chromosomal rearrangements are the major hallmarks of B-cell acute lymphoblastic leukemia (B-ALL). With the application of next-generation sequencing technologies, several non-scarce recurrent fusion genes have been identified in B-ALL, and MEF2D fusions is the one. More clinical data is needed to clarify the incidence and prognosis. Furthermore, the prognostic significance of measurable residual disease (MRD) monitored by the quantitative detection of MEF2D fusions remains absent to date. A total of 357 adult Ph-negative B-ALL cases who were consecutively diagnosed and received treatment in our institute from 2009 to 2021, and have available bone marrow cDNA samples at diagnosis were retrospectively screened MEF2D fusions. All patients have been tested common fusion transcripts at the time of diagnosis. MEF2D fusions were tested by the multiplex TaqMan-based real time quantitative polymerase chain reaction technology. A total of 7 fusion partners were included. The split-out real time PCR was performed to identify the partner. Totally 16 patients were identified MEF2D fusions with the incidence of 4.5% in Ph-negative BCP-ALL. The distributions were as follows: 7 MEF2D-BCL9, 7 MEF2D-HNRNPUL1, 1 MEF2D-DAZAP1 and 1 MEF2D-FOXJ2. Their median transcript levels were 65.0% (range, 20.9%-335.5%) at diagnosis. The median age of these 16 patients were 30 (range, 17-60) years and 10 of them were male (63%). The median follow-up time of 16 patients with MEF2D fusions was 26 months (range, 8-156 months). 9 (61.1%) patients were alive at the last follow-up. 14 and 2 patients individually achieved complete remission (CR) after 1 and 2 courses of CODP ± L regimen for induction. Thereafter, 8 patients received hyper-CVAD-based chemotherapy alone and all of them relapsed after 1-6 cycles of consolidation, then 2 relapsed patients received allogeneic hematologic stem cell transplantation (allo-HSCT) as salvage treatment after achieving the 2nd CR (CR2); the remaining 8 patients received chemotherapy followed by allo-HSCT (matched sibling donor, n = 3; haploidentical related donor, n = 5) in CR1. The median follow-up time after HSCT was 19 (6-148) months, and 5 patients (4 CR1, 1 CR2) relapsed at a median of 9 (range 6-15) months post-HSCT. The 3-year relapse free survival [RFS] and overall survival (OS) rates of all 16 patients were 30.0% (95% confidence interval [CI]: 10.2%-53.0%) and 54.6% (95% CI: 23.9%-77.5%) (Fig 1). Bone marrow samples serially collected after treatment were retrospectively tested MEF2D fusion transcript for MRD monitoring. 58.3% (7/12) and 50.0% (6/12) of patients were PCR-negative at the time of achieving CR1 and after one cycle of consolidation, respectively. PCR-negative at the above both time-points was not related to relapse (P=1.0 and 0.45). For patients receiving allo-HSCT, the scheduled monitoring time-points were 0, 1, 2, 3, 4.5, 6, 9, 12, 18, 24 months post-HSCT then every 12 months thereafter. There was a tendency that PCR-negative at the time of receiving HSCT was related to a lower relapse rate (post-HSCT 2-year RFS rate, 75.0% [95% CI, 12.8%-96.1%] vs 20.0% [95% CI, 0.8%-58.2%], P=0.13). 5 patients who were in continuous CR were tested MEF2D fusion transcript at a median of 9 (range, 3-11) time-points after HSCT, 38 (97.4%) samples were PCR-negative. 5 patients who relapsed post-HSCT were tested MEF2D fusions at a median of 5 (range, 4-7) time-points before relapse, they all were in continuous PCR-negative from 1 to 2-6 months post-HSCT, then all became PCR-positive before the occurrence of relapse. Their intervals between the 1st PCR-positive and relapse were 1.5-6 months. As a result, occurrence of PCR-positive post-HSCT was significantly related to relapse (post-HSCT 2-year RFS rate, 100.0% (95% CI, 100%-100%) vs 33.0% (95% CI, 4.3%-67.2%), P=0.039, Fig 2). In conclusion, MEF2D fusions confer adverse prognostic significance to adult B-ALL, and relapse is a treatment challenge. PCR-negative of MEF2D fusion transcript at the time of achieving CR and after the 1st consolidation could not predict long-term CR, whereas PCR-positive after HSCT predict relapse. The benefit of urgent allo-HSCT after achieving CR and MEF2D fusion transcript levels directed intervention post-HSCT remains to be investigated. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcome of autologous stem cell transplantation in patients with favorable-risk acute myeloid leukemia in first remission

ObjectiveTo evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission.MethodTwenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed.ResultsUntil last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively.ConclusionThe outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients.

Preoperative voice analysis and survival outcomes in papillary thyroid cancer with recurrent laryngeal nerve invasion.

To investigate the clinicopathological characteristics of papillary thyroid cancer (PTC) and identify risk factors for postoperative recurrence of PTC with recurrent laryngeal nerve (RLN) involvement. In total, 171 patients (112 women and 59 men, age: 18-80 years, and 65 patients aged ≥ 55) with T4a PTC with RLN involvement, treated at Beijing Tongren Hospital, Capital Medical University, from January 2006 to December 2020, were retrospectively examined. Clinicopathological characteristics, including voice analysis results, and survival outcomes were assessed. The Mann-Whitney U and Kruskal-Wallis H tests were used to analyze differences in acoustic parameters. The Kaplan-Meier method was used to calculate the overall survival (OS) and recurrence-free (RFS) rates. Univariate and multivariate Cox regression analyses were performed of the clinical data. The postoperative follow-up period ranged from 12 to 196 months (mean: 66.18 months). Of the 171 patients, 16 had recurrence and 8 died of thyroid-related diseases. The 5-year OS rate was 95.22%. The 5-year RFS rate was 89.38%. Jitter and shimmer were higher and maximum phonation time was shorter in patients with preoperative vocal cord paralysis (VCP) than in those without RLN involvement, and in those with RLN involvement but without preoperative VCP. Acoustic parameters were similar in patients with no preoperative VCP and those without RLN involvement. Voice analysis results did not differ between cases with RLN adhesion and RLN invasion. Univariate analysis showed that age at onset ≥ 55 years, preoperative RLN palsy, and esophageal invasion were risk factors for postoperative recurrence of PTC with RLN involvement. Multivariate analysis showed that onset age ≥ 55 years (OR 4.52, 95% confidence interval: 1.44-14.19, P = 0.010) was an independent risk factor for recurrence. PTC patients with RLN invasion can achieve good outcomes. Preoperative voice analysis may offer insights into RLN function. Age of onset ≥ 55 years is an independent risk factor for postoperative recurrence in T4a PTC patients.

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women with FIGO Stage II Uterine Endometrioid Carcinoma

<h3>Purpose/Objective(s)</h3> To explore the prognostic significance of the depth of cervical stromal invasion (CSI) on survival endpoints in women with FIGO stage II uterine endometrioid adenocarcinoma. <h3>Materials/Methods</h3> A total of 117 patients were included in this retrospective review. Between 1990 and 2021, all patients with FIGO stage II endometrial cancer (EC) underwent hysterectomy and oophorectomy at our institution, with or without lymph node dissection. Patients with synchronous ovarian or breast cancer, as well as those who had undergone adjuvant systemic chemotherapy for EC, were excluded from the study. Pathologic slides were retrieved for these patients and were reviewed by a gynecologic pathologist to determine stromal thickness and the depth of CSI. The depth of CSI was then measured as a percentage of invasion (% CSI) and used in the analysis as a continuous or dichotomous variable (< 50% vs > = 50%). Patients' demographics, pathologic, and treatment characteristics were analyzed using univariate and multivariate analysis to calculate recurrence-free (RFS) and disease-specific (DSS) rates. <h3>Results</h3> The median age for the study cohort was 65 years (range, 34–96), and the median follow-up was 131 months (range, 9–334). A total of 90 patients (77%) had lymph node dissection, with a median of 8 examined lymph nodes (range 0-18). Adjuvant radiation therapy (RT) with pelvic or vaginal cuff HDR brachytherapy, or a combination of the two, was completed in 92 patients (79 percent). The median % CSI was 27% (range, 1-100) with 68% of patients having ≥ 50% CSI. While there was a trend for a worse 5-year RFS and DSS for women with ≥ 50% CSI (69% vs. 83%, p = 0.093) and (78% vs. 91%, p = 0.034), respectively, the depth of CSI was not statistically significant as an independent predictor of 5-year RFS, DSS, or OS. The depth of CSI was not associated with a difference in the recurrence pattern (vaginal cuff, pelvic, paraaortic, or distant). In multivariate analysis, FIGO grade was the only predictor of 5-year OS. FIGO grade and the presence of lympho-vascular space invasion (LVSI) were independent predictors of 5-year RFS and DSS. <h3>Conclusion</h3> Deep cervical stromal invasion does not appear to be an independent predictive factor for survival endpoints in women with stage II uterine endometroid cancer, according to our findings. The presence of LVSI and tumor grade were both independent predictors of recurrence-free and disease-specific survival. Pooled data analysis may be needed to validate our study findings.

Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC – Is it the exception to the rule?

BackgroundAlthough primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. MethodsAll eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence–free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS. ResultsA total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98). ConclusionsIn contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

278. SHORT- AND LONG-TERM OUTCOME AFTER UPFRONT SURGERY OR NEOADJUVANT CHEMOTHERAPY FOLLOWED BY SURGERY IN ELDERLY PATIENTS WITH RESECTABLE ESOPHAGEAL CANCER

Abstract In Japan, the standard therapeutic strategy for resectable advanced esophageal cancer (R-AEC) is neoadjuvant chemotherapy (NAC) followed by surgery. However, there is no strong evidence of the strategy for the elderly patients, thus the efficacy of NAC for the elderly patients with R-AEC remains controversial. Here we studied the efficacy of NAC for R-AEC in the patients aged 75 or older. This study included the patients aged 75 or older who diagnosed with R-AEC and underwent esophagectomy in our institution from 2005 to 2021. Among the total of 59 cases with R-AEC, the cases who received neoadjuvant chemoradiotherapy or who had poor follow-up were excluded, and the remaining 42 cases were enrolled in this cohort. Among 42 patients with R-AEC, 33 patients underwent UFS and 9 patients underwent NAC followed by surgery. The short- and long-term outcome was evaluated between upfront surgery (UFS) group and NAC group. There was a difference in historical background: patients in UFS group were more in 2012 or before, and patients in NAC group were more later than 2013. There was no significant differences in age, PS, Charlson comorbidity index and clinical characteristics such as TNM disease stage between two groups. The short-term outcome, the frequency of postoperative complications, curability, etc., was similar in two groups. In UFS group, only 5 cases (15.2%) underwent adjuvant chemotherapy. NAC improved 2-year RFS (UFS: 51.4% vs. NAC 76.2%, not significant), and 2-year OS (UFS 60.1% vs. NAC 71.1%, not significant). This study showed the likelihood of the benefits of NAC on the long-term outcomes without increasing the postoperative complications in patients with R-AEC aged 75 or older. There were some limitations in this study, single-institutional and retrospective study with small number of cases. The further study will be needed to clarify the efficacy of NAC in elderly patients with R-AEC.

Pathologic Implications of Radial Resection Margin and Perineural Invasion to Adjuvant Chemotherapy after Preoperative Chemoradiotherapy and Surgery for Rectal Cancer: A Multi-Institutional and Case-Matched Control Study.

Simple SummaryThe significance of the role of adjuvant chemotherapy in patients with rectal cancer treated with neoadjuvant chemoradiation and surgery has yet to be been determined. In this multi-center and case-matched analysis, we evaluated 1799 patients with rectal cancer who received adjuvant chemotherapy after neoadjuvant chemoradiation and total mesorectal excision. Positive surgical margin and perineural invasion were poor prognostic factors after neoadjuvant chemoradiotherapy and curative surgery. Adjuvant chemotherapy significantly decreased recurrences in patients with positive margin or perineural invasion. The role of adjuvant chemotherapy in rectal cancer patients without positive margin and perineural invasion after neoadjuvant chemoradiotherapy and surgery could be limited.We assessed the exact role of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CRT) and surgery in rectal cancer patients with positive surgical margin or perineural invasion (PNI). This multi-institutional study included 1799 patients with rectal cancer at cT3-4N0-2M0 stages. Patients were divided into two groups. The high-risk group had a positive margin and/or perineural invasion. The low-risk group showed no positive margin or PNI. Propensity-score matching analysis was performed, and a total of 928 patients, with 464 in each arm, were evaluated. The high-risk group showed significant differences in overall survival (OS, 73.4% vs. 53.9%, p < 0.01) and recurrence-free survival (RFS, 52.7% vs. 40.9%, p = 0.01) at five years between the adjuvant chemotherapy arm and observation arm. The low-risk group showed no significant differences in 5-year OS (p = 0.61) and RFS (p = 0.75) between the two arms. Multivariate analyses showed that age, pathologic N stage, and adjuvant chemotherapy were significantly correlated with OS and RFS in the high-risk group (all p < 0.05). Adjuvant chemotherapy improved OS and RFS more significantly in rectal cancer patients with positive surgical margin or PNI than in those with negative surgical margin and PNI.

Variables associated with hematological remission and survival in patients with acute myeloid leukemia after induction failure and relapse

Objective: This study aimed to explore variables associated with remission rate and survival in patients with acute myeloid leukemia (AML) after induction failure and relapse. Methods: Data of 373 consecutive patients with AML were analyzed after induction failure and relapse. Binary logistics and the Cox model regression were used to identify variables associated with remission rate and outcomes. Results: In patients with AML after induction failure and relapse, the total CR+CRi rates were 50.6% and 40.3%, respectively; among those who achieved CR/CRi, the 3-year RFS rates were 34.4% and 30.4%, respectively, and the 3-year overall survival rates were 40.1% and 31.6%, respectively. In the multivariate analyses, using CLAG or FLAG regimen as a re-induction chemotherapy regimen, age <39 years and SWOG low-risk were significantly associated with higher remission rates in patients with induction failure. Male, secondary AML, SWOG high-risk, the interval from the first remission to relapse within 12 months, and bone marrow blasts ≥20% at the time of relapse were significantly associated with lower remission rates in relapsed patients. Transplantation was significantly associated with prolonged relapse-free survival and overall survival in patients achieving hematologic remission; the SWOG low-risk group was significantly associated with longer overall survival in those with induction failure; and achieving CR (not CRi) or having female gender was associated with longer RFS or overall survival in relapsed patients. Conclusion: Reinduction chemotherapy regimen, age, gender, SWOG risk, secondary AML, the interval from the first remission to relapse, and bone marrow blast percentage at the time of relapse were significantly associated with remission rates in the patients with AML after induction failure and relapse. Transplantation, SWOG low-risk, achieving CR, or female gender were associated with longer survivals in those achieving remission.

Clinical utility of psoas muscle volume in assessment of sarcopenia in patients with early-stage non-small cell lung cancer.

Sarcopenia influences postoperative outcomes of patients with non-small cell lung cancer (NSCLC). Imaging tools for evaluating and diagnosing sarcopenia have developed, and a novel method of psoas volume index (PVI) obtained by measuring bilateral psoas major muscle volume has been reported. However, the relationship between sarcopenia based on PVI and clinical outcomes has not been fully investigated for patients with early-stage NSCLC. This study aimed to clarify the utility of PVI values in assessing the relationshipe between sarcopenia and clinical outcomes. This study included 645 patients with stage I-II NSCLC who underwent curative lung resection between 2012 and 2017. Bilateral psoas major muscle volumes were calculated semi-automatically using a three-dimensional workstation. The cutoff value of PVI for defining sarcopenia was < 60.5cm3/m3 for men and < 43.6cm3/m3 for women. The avrage time to obtaine PVI was only 25s with the 3D system, and interobserver agreements for evauating sarcopenia on PVI was 1. A total of 159 patients (24.7%) were preoperatively diagnosed with sarcopenia. On multivariate analysis, sarcopenia was an independent prognostic factor for overall survival (OS, p < 0.001), recurrence-free survival (RFS, p < 0.001), and lung cancer-specific survival (LCS, p < 0.001). The 5-year OS, RFS, and LCS were significantly worse in sarcopenic patients than non-sarcopenic patients (88.8 vs. 72.4%, p < 0.001; 80.1 vs. 65.0%, p < 0.001; 92.4 vs. 78.9%, p < 0.001, respectively). Sarcopenia diagnosed using PVI is an independent prognostic predictor of OS, RFS, and LCS in early-stage NSCLC.

Prognosis and treatment of uterine sarcoma found incidentally after myomectomy (147)

Objectives: This study aimed to determine prognosis and factors associated with survival of women with uterine sarcoma found incidentally after myomectomy. Methods: We performed a retrospective study for patients who had previously undergone myomectomy at the time of initial surgery for presumed benign uterine fibroid disease and were found to have uterine sarcoma after surgery. Survival outcomes were evaluated by using Kaplan-Meir survival analysis according to the type of initial myomectomy. Results: Overall, 50 patients were identified from 2007 to 2020. Of these patients, 22 (44.0%) had leiomyosarcomas (LMS), 25 (50.0%) had low-grade endometrial stromal sarcomas (LG-ESS), and two (4.0%) patients had adenosarcomas. All these patients had their primary myomectomy performed at an outside institution and then referred to our center. Twenty-three patients had their myomectomy performed through minimal invasive surgery: laparoscopic (Lap, n=22, 44.0%) or transvaginal (TV, n=1, 2.0%) approach; while 24 (48.0%) and three (6.0%) patients had myomectomy through abdominal (Abd) or hysteroscopic (Hys) approach, respectively. The median age of occurrence was 37.5 years (range: 21-61 years), the majority (94.0%) of women diagnosed with uterine sarcoma before age 50. None of the 50 patients had documented evidence of extra-uterine disease at the time of primary surgery. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 43 days (range: 15-90 days). Seventeen patients had remnant sarcoma on the remaining uterus, and six patients had disseminated disease after re-exploration. The FIGO 2009 distribution by stage was: stage I in 44 patients, stage II in four patients, and stage III in two patients. The median follow-up duration was 67.2 months (range: 9.9-178.7 months). Ten (20.0%) patients experienced recurrence, and four (8.0%) patients died during follow-up. The 5-year RFS and 5-year OS for the entire cohort were 79.4% and 88.0%, respectively. For stage I disease, patients who received initial myomectomy through laparoscopic/transvaginal (Lap/TV group) approach had a worse 5-year PFS compared with those through abdominal/hysteroscopic approach (Abd/Hys group) (58.3% vs 95.7%, p=0.009). No difference in OS was found between the two groups (p=0.121). Conclusions: Most uterine sarcomas are found incidentally after myomectomy or hysterectomy for uterine fibroid disease. Re-exploration to complete the staging operation is highly likely to detect remnant or disseminated sarcoma after primary surgery. Patients with uterine sarcoma who received primary laparoscopic/transvaginal myomectomy may have worse survival. Objectives: This study aimed to determine prognosis and factors associated with survival of women with uterine sarcoma found incidentally after myomectomy. Methods: We performed a retrospective study for patients who had previously undergone myomectomy at the time of initial surgery for presumed benign uterine fibroid disease and were found to have uterine sarcoma after surgery. Survival outcomes were evaluated by using Kaplan-Meir survival analysis according to the type of initial myomectomy. Results: Overall, 50 patients were identified from 2007 to 2020. Of these patients, 22 (44.0%) had leiomyosarcomas (LMS), 25 (50.0%) had low-grade endometrial stromal sarcomas (LG-ESS), and two (4.0%) patients had adenosarcomas. All these patients had their primary myomectomy performed at an outside institution and then referred to our center. Twenty-three patients had their myomectomy performed through minimal invasive surgery: laparoscopic (Lap, n=22, 44.0%) or transvaginal (TV, n=1, 2.0%) approach; while 24 (48.0%) and three (6.0%) patients had myomectomy through abdominal (Abd) or hysteroscopic (Hys) approach, respectively. The median age of occurrence was 37.5 years (range: 21-61 years), the majority (94.0%) of women diagnosed with uterine sarcoma before age 50. None of the 50 patients had documented evidence of extra-uterine disease at the time of primary surgery. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 43 days (range: 15-90 days). Seventeen patients had remnant sarcoma on the remaining uterus, and six patients had disseminated disease after re-exploration. The FIGO 2009 distribution by stage was: stage I in 44 patients, stage II in four patients, and stage III in two patients. The median follow-up duration was 67.2 months (range: 9.9-178.7 months). Ten (20.0%) patients experienced recurrence, and four (8.0%) patients died during follow-up. The 5-year RFS and 5-year OS for the entire cohort were 79.4% and 88.0%, respectively. For stage I disease, patients who received initial myomectomy through laparoscopic/transvaginal (Lap/TV group) approach had a worse 5-year PFS compared with those through abdominal/hysteroscopic approach (Abd/Hys group) (58.3% vs 95.7%, p=0.009). No difference in OS was found between the two groups (p=0.121). Conclusions: Most uterine sarcomas are found incidentally after myomectomy or hysterectomy for uterine fibroid disease. Re-exploration to complete the staging operation is highly likely to detect remnant or disseminated sarcoma after primary surgery. Patients with uterine sarcoma who received primary laparoscopic/transvaginal myomectomy may have worse survival.

Preoperative Free Ferrous Protoporphyrin and Reactive Oxygen Species Status of Voided Urine Predicts Potential Recurrence Risk in NMIBC.

PurposeThis study aimed to assess the relationship between the preoperative reactive oxygen species and free ferrous protoporphyrin (ROS and FH) combined test and the risk of recurrence in a pathologically confirmed non-muscular invasive bladder cancer (NMIBC) patients.Patients and MethodsThe retrospective study included 218 patients, newly diagnosed with NMIBC between January 2019 and February 2022. According to the results of FH and ROS combined test of voided urine, all patients were classified as FH(-)/ROS(-), FH(+)/ROS(-), or FH(+) /ROS(+). We reviewed demographic information, pathological results, and the FH and ROS combined test status. The clinicopathological characteristics were evaluated, and the survival rates of each group were compared. Finally, we also analyzed the association between preoperative free ferrous protoporphyrin and reactive oxygen species status and the tumor stage and grade.ResultsThis study included 218 NMIBC patients with a median age of 68 years (interquartile range [IQR] 60–76 years). The number and proportion of patients in FH(-)/ROS(-), FH(+)/ROS(-) and FH(+) /ROS(+) were 95(43.6%), 79(36.2%) and 44(20.2%), respectively. And the pathological stages for those with FH(+) and ROS(+), FH(+) and ROS(-), FH(-) and ROS(-) at diagnosis were 0.5% Tis, 6.4% Ta, 13.3% T1; 2.3% Tis, 20.6% Ta, 13.3% T1; 5.5% Tis, 28.9% Ta, 9.2% T1, respectively. After adjusting for clinical factors, including tumor grade, tumor stage and FH/ROS status were independent risk factors for RFS In the multivariate Cox regression analysis. Through logistics regression analysis, FH(+)/ROS(+) were found to be corelated with high grade and more high stage (T1). Kaplan–Meier analysis showed that 1-year RFS of FH(+)/ROS(+), FH(+)/ROS(-) and FH(-)/ROS(-) were 46.0%, 87.8% and 93.4%, respectively (P=0.000).ConclusionIn newly diagnosed NMIBC patients, the status of FH(+)/ROS(+) has an association with a higher risk in recurrence. Furthermore, FH(+)/ROS(+) at diagnosis was correlated with high grade and higher stage (T1). Hence, the FH/ROS combined test can help specify treatment options for patients diagnosed with NMIBC.

Relevance of flow cytometric categorization and end-of-induction measurable residual disease assessment in pediatric and adult T-lymphoblastic leukemia patients.

BackgroundT-lymphoblastic leukemia (T-ALL) patients expressing myeloid/stem cell antigens are classified as early T-cell precursor lymphoblastic leukemia (ETP-ALL) or near-ETP-ALL.MethodsClinico-laboratory profiles, flow cytometric end-of-induction measurable residual disease (EOI-MRD), and survival of treatment naïve T-ALL patients were analyzed according to their immunophenotypic subtypes.ResultsAmong 81 consecutive T-ALL patients diagnosed, 21% (N=17) were ETP-ALL and 19% (N=15) were near-ETP-ALL. EOI-MRD was detectable in 39% of the 59 samples tested (31.6% of pediatric samples and 52.4% of adult samples). The frequency of EOI-MRD positivity was significantly higher among ETP-ALL (75%, P=0.001) and near-ETP-ALL (71%, P=0.009) patients compared to that in conventional-T-ALL (con-T-ALL) patients (22.5%). CD8 (P=0.046) and CD38 (P=0.046) expressions were significantly upregulated in the EOI blasts of con-T-ALL and ETP-ALL samples, respectively. The 2-year rates of overall (OS), relapse-free (RFS), and event-free survival (EFS) among the T-ALL patients (pediatric vs. adult) was 79.5% vs. 39.8% (P<0.001), 84.3% vs. 60.4% (P=0.026), and 80.3% vs. 38% (P<0.001), respectively. Univariate analysis revealed that 2-year EFS and RFS of pediatric T-ALL patients was independent of T-ALL subtype and was influenced only by EOI-MRD status. However, 2-year OS, RFS, and EFS among adult T-ALL patients were EOI-MRD independent and influenced only by the near-ETP-ALL phenotype.ConclusionTwo-year survival among pediatric and adult T-ALL patients is attributed to EOI-MRD status and near-ETP-ALL phenotype, respectively.

Development and validation of metabolic scoring to individually predict prognosis and monitor recurrence early in gastric cancer: A large-sample analysis

PurposeTo develop and validate a simple metabolic score (Metabolic score, MS) for use in evaluating the prognosis of gastric cancer (GC) patients and dynamically monitor for early recurrence. MethodsWe retrospectively collected general clinicopathological data of patients who underwent radical gastrectomy for GC between September 2012 and December 2017 in the Department of Gastric Surgery of the Fujian Medical University Union Hospital. Using a random forest algorithm to screen preoperative blood indicators into the Least absolute shrinkage and selection operator (LASSO) model, we developed a novel MS to predict prognosis. ResultsData of 1974 patients were used to develop and validate the model. Total cholesterol (TCHO), bilirubin (TBIL), direct bilirubin (DBIL), and 15 other metabolic indicators had significant predictive value for the prognosis using the random forest algorithm. In the overall population, 533 patients (27.0%) had high and 1441 (73%) had low MS status. High MS status was related to tumor progression. The KM curves of 3-year OS and RFS for training set patients showed low MS had a better prognosis than high MS (OS: 79.4% vs 59.7%, P < 0.001; RFS: 76.0% vs 56.2%, P < 0.001). ConclusionsWe have developed and validated MS to predict the long-term survival of GC patients and allow early monitoring of recurrence. This will provide physicians with simple, economical, and dynamic tumor monitoring information.

Abstract CT546: A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection

Abstract Background: Surgical resection is one of the most important radical treatment in hepatocellular carcinoma (HCC). However, the 5-year recurrence rate of HCC after surgery is up to 70%, hampering further improvement in the prognosis of HCC patients. Risk factors for recurrence include microvascular invasion (MVI), multiple lesion and solitary tumor ≥ 5 cm, etc. Postoperative adjuvant treatment with transarterial chemoembolization (TACE) can reduce the recurrence rate and improve overall survival (OS) for patients with high risk of recurrence to some extent. TACE treatment promotes the release of tumor related antigen and the recruitment of immune cells by killing tumor cells, thereby promoting the anti-tumor immune response; it may have a potential synergistic effect with PD-1 blockade. Currently, there is no ongoing study on TACE combined with immunotherapy as postoperative adjuvant therapy for HCC. This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in HCC patients with high risk of recurrence after curative resection (NCT04981665). Trial design: Eligible patients are ≥18 y, ECOG PS 0 or 1, Child-Pugh class A, diagnosed with HCC confirmed by histopathology or cytology, with no prior systematic treatment and locoregional therapy for HCC, and have received a curative resection with high risk of recurrence fulfilling one of the following criteria: (1) a solitary tumor &amp;gt; 5 cm, (2) solitary tumor &amp;gt; 2 cm and ≤ 5 cm with MVI, (3) 2-3 lesions. 50 pts will receive TACE treatment once (4±1 w) after curative resection, then followed by tislelizumab 200 mg IV Q3W (5±2 d). Tislelizumab will be administered until disease recurrence, intolerable toxicity, death, withdrawal of consent or completion of a maximum of 17 cycles of tislelizumab. Primary endpoint is 2-year recurrence-free survival rate (2-year RFS rate). Secondary endpoints include RFS, time to recurrence, OS, 1-year RFS rate, 1-year and 2-year OS rate, and safety. Exploratory endpoints include biomarkers related to the response and prognosis of adjuvant TACE sequential tislelizumab therapy. Citation Format: Tingbo Liang, Zongli Zhang, Jinfang Zheng, Yijun Wang, Jialin Zhang, Bo Li, Tao Ma, Yunfei Xu, Changxiong Wu, Quan Sun, Yiman Meng, Xiaoli Yang. A phase 2, multicenter study to evaluate the efficacy and safety of TACE sequential tislelizumab as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection [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 CT546.

Survival data of PRADO: A phase 2 study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma.

9501 Background: In the OpACIN-neo study, 2 cycles neoadjuvant (neoadj) IPI 1mg/kg + NIVO 3mg/kg (I1N3) have been identified as most favorable dosing scheme with a pathologic response rate (pRR) of 77% and 20% grade 3-4 irAEs. After 24.6 months median follow-up (FU), the 2-year (2y) RFS was 96.9% for patients (pts) with pathologic response versus 35.5% for non-responders (&gt;50% viable tumor; pNR). These data raised the question whether therapeutic lymph node dissection (TLND) could be safely omitted in pts achieving a major pathologic response (MPR; ≤10% viable tumor) in their index node (ILN; largest LN metastasis at baseline), and if additional adjuvant (adj) therapy could improve the outcome of pNR pts. Methods: PRADO is an extension cohort of the phase 2 OpACIN-neo study aiming to confirm the pRR and safety of neoadj I1N3 and to test response-driven subsequent therapy. Pts with stage III melanoma were included to receive 2 cycles neoadj I1N3 after marker placement in the ILN. ILN resection was planned at week 6. Pts that achieved MPR in the ILN did not undergo TLND; pts with partial response (pPR; &gt;10 – ≤50% viable tumor) underwent TLND; and pts with pNR underwent TLND and received adj NIVO or dabrafenib plus trametinib (D+T) for 52 weeks ±radiotherapy (RT). Primary endpoints were pRR in the ILN and RFS at 2y. The 2y RFS rates were calculated using a Kaplan Meier based method. Results: Between Nov 2018 and Jan 2020, 99 patients were enrolled and treated with at least 1 cycle of neoadj I1N3. We previously showed a pRR of 72% (95% CI 62 - 80), including 60 (61%) pts with MPR and 11 (11%) pts with pPR. TLND omission in MPR pts resulted in significant reduced surgical morbidity and improved quality of life. There were 27 non-responders of whom 6 developed distant metastasis before ILN resection. Of the other 21 pNR pts, 7 received adj NIVO, 10 adj D+T, 3 no adj therapy, and 1 was lost to FU. After a median FU of 27.9 months (data cutoff Jan 31, 2022), the estimated 2y RFS rate for MPR pts was 93.3% (95% CI 87.2 – 99.9), with 4/60 pts developing a regional relapse. Distant metastasis-free survival (DMFS) was 100%. Of the 11 pPR pts, 4 developed a relapse (all distant), resulting in a 2y RFS and DMFS rate of 63.6% (95% CI 40.7 – 99.5). The 2y RFS rate of the pNR pts was 71.4% (95% CI 54.5 – 93.6), and DMFS 76.2%. At data cutoff, relapse occurred in 2/7 pNR pts with adj NIVO and 3/10 with adj D+T. Final data cutoff is planned mid Feb, 2022. Conclusions: MPR pts in whom TLND was omitted showed a 2y RFS rate of 93.3% and DMFS of 100%, indicating that the ILN procedure and omitting adj therapy could become a safe approach in these pts. Adj systemic therapy in pNR pts seems to improve RFS as compared to historic control (OpACIN-neo), thus should be considered in this unfavorable pNR group. The DMFS rate of 63.6% observed in the pPR group advocates the consideration of adj therapy also for this subgroup in the future. Clinical trial information: NCT02977052.

Need for organ preservation in postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).

5031 Background: The aim ofPC-RPLND for advanced nonseminomatous germ cell tumors is to resect all remaining metastatic tissue. So far, the resection of adjacent visceral or vascular organs is also commonly performed to achieve complete resection of the residual mass. To determine the possibility of more organ preservation, we aimed to analyze the pathohistology of patients with adjunctive surgery as the frequency of metastatic involvement in those organs with teratoma or vital cancer is currently unknown. Methods: We reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 as a 2-center study and identified 242 (20.1%) cases of adjunctive surgery during PC-RPLND. We analysed the pathohistological presence of germ cell tumor elements in the resected organs: viable tumor (V), teratoma (T) or necrosis / fibrosis (N). Surgery associated complications were reported according to the Clavien-Dindo classification. Outcomes of subgroups were compared by using log-rank test. Results: V, T and N were present in 54 (22%), 94 (39%) and 94 (39%) of all patients with adjunct resected organs. In 242 patients, 325 adjunct organs were resected with 66 (27.3%) of these patients receiving a resection of multiple organs. The kidney was the most often resected organ (n = 77; V: 29% T: 39% N: 32%), followed by V. Cava (n = 67; V: 25% T: 36%, N: 39%) and partial liver resections (n = 50; V: 16%, T: 30%, N: 54%). Postoperative complications occurred in 30% of which 22% were Clavien grade III-V, showing no significant differences between V, T and N; p = 0.093. 27% of all patients suffered from a relapse during a median follow-up of 22 months [0-180]. Patients with T or V in the resected specimens had a significantly reduced 5-year RFS compared to patients with only N (39%, 81%, p &lt; 0.001). Conclusions: This study shows tremendous need for more organ preservation as 40% of all resections of adjunct organs are oncologically unnecessary due to the presence of N only in the pathological specimens. Therefore, in case of doubt, we should increase intraoperative frozen section to avoid oncologically unnecessary adjunctive surgeries, especially nephrectomies and vascular resections. Additionally, serological or image-based means for a more accurate presurgical workup are required to spare patients with N from PC-RPLND in general.

Splenic Volume, an Easy-To-Use Predictor of HCC Late Recurrence for HCC Patients After Hepatectomy.

PurposeThe high recurrence rate of hepatocellular carcinoma (HCC) has a poor impact on the quality of life and survival time of patients. Especially for late recurrence, poor data are available in analysis. We aim to evaluate whether the splenic volume (SV) measured from preoperative CT images could predict late recurrence in HCC patients after hepatectomy.Patients and MethodsA cohort of 300 HCC patients hospitalized at Xiangya Hospital of Central South University between January 2015 and June 2018 was retrospectively analyzed. The SV was calculated by using automated volumetry software from preoperative CT images. A total of 300 HCC patients were separated into the early recurrence cohort (n=167), the late recurrence cohort (n=39), and the no recurrence cohort (n=94) according to whether there is a recurrence and the recurrence time. Univariate and multivariate Cox analyses were performed to identify the independent risk factors of both early and late recurrence.ResultsAFP, Microvascular invasion (MVI), satellitosis, and BCLC staging were independent risk factors of HCC early recurrence. Splenic volume (HR=1.003, 95%CI:1.001-1.005, P<0.001) was the only predictor of HCC late recurrence. Based on X-tile software, 133 non-early recurrence patients were divided into two groups according to SV: low SV (<165ml, n=45) and high SV (≥165ml, n= 88). The low SV group had a significantly better RFS compared with the high SV group (P=0.015). Nomogram was built on the base of SV to get the probability of 3-year RFS, 4-year RFS, and 5-year RFS.ConclusionIn our study, we drew a conclusion that splenic volume was the only predictor of HCC late recurrence because of its association with portal hypertension and liver cirrhosis. High splenic volume often indicated a worse recurrence.

A Clinical-Radiomics Nomogram Based on the Apparent Diffusion Coefficient (ADC) for Individualized Prediction of the Risk of Early Relapse in Advanced Sinonasal Squamous Cell Carcinoma: A 2-Year Follow-Up Study

PurposeTo develop and validate a nomogram model combining radiomic features and clinical characteristics to preoperatively predict the risk of early relapse (ER) in advanced sinonasal squamous cell carcinomas (SNSCCs).MethodsA total of 152 SNSCC patients (clinical stage III-IV) who underwent diffusion-weighted imaging (DWI) were included in this study. The training cohort included 106 patients assessed at the headquarters of our hospital using MR scanner 1. The testing cohort included 46 patients assessed at the branch of our hospital using MR scanner 2. Least absolute shrinkage and selection operator (LASSO) regression was applied for feature selection and radiomic signature (radscore) construction. Multivariable logistic regression analysis was applied to identify independent predictors. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis (DCA). Furthermore, the patients were classified into high- or low-risk ER subgroups according to the optimal cutoff value of the nomogram using X-tile. The recurrence-free survival probability (RFS) of each subgroup was assessed.ResultsER was noted in 69 patients. The radscore included 8 selected radiomic features. The radscore, T stage and surgical margin were independent predictors. The nomogram showed better performance (AUC = 0.92) than either the radscore or the clinical factors in the training cohort (P < 0.050). In the testing cohort, the nomogram showed better performance (AUC = 0.92) than the clinical factors (P = 0.016) and tended to show better performance than the radscore (P = 0.177). The nomogram demonstrated good calibration and clinical utility. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (P < 0.001).ConclusionsThe ADC-based radiomic nomogram model is potentially useful in predicting the risk of ER in advanced SNSCCs.

30-Year Experience With 22 Cases of Malignant Transformation Arising From Ovarian Mature Cystic Teratoma: A Rare Disease.

ObjectiveTo investigate the clinical characteristics and survival outcomes of patients with malignant transformation arising from ovarian mature cystic teratoma (MT-MCT).MethodsThis retrospective study included patients with ovarian MCTs at Peking Union Medical College Hospital (PUMCH) during 1990.01-2020.12. When the pathologic histology was MT-MCT, detailed information was collected.ResultsOverall, 7229 ovarian MCT patients and 22 patients with MT-MCT were enrolled. The rate of malignant transformation of all ovarian MCTs was 0.30%. Most patients with MT-MCT were 51 (21–75) years old, and the tumor mass size was 10 (3–30) cm. The typical clinical symptoms were mainly abdominal pain and distension. The levels of tumor markers were elevated on preoperative examination. Early diagnosis could be made by ultrasonic examination, pelvic enhanced MRI and CT. Most patients underwent debulking surgery and adjuvant chemotherapy. The most common histological type to exhibit malignant transformation was squamous cell carcinoma (59.1%), followed by adenocarcinoma (13.6%), carcinoid (9.1%), and borderline tumor (18.2%). The 5-year RFS and OS rates were 54.5% and 81.8%, respectively. Patients with FIGO stage I had the best RFS (P=0.047) and OS (P=0.018), followed by those with FIGO stage II-IV.ConclusionMT-MCTs mainly occur in elderly females, are rare and have a poor prognosis. Advanced FIGO stage is a risk factor for survival. Although there is no standard treatment, cytoreductive debulking surgery and adjuvant chemotherapy could be considered. Perimenopausal and menopausal women with MCT should receive surgical treatment.

Clinical significance of panendoscopy in initial staging of oral squamous cell carcinoma and detection of synchronous second malignancies of the upper aerodigestive tract — Insights from a retrospective population-based cohort study

The aim of this study was to examine the prevalence of synchronous upper aerodigestive tract (UAT) tumors within oral squamous cell carcinoma (OSCC) patients, and to specify distinct risk groups who benefit from panendoscopy.Definite clinical and pathohistological characteristics, as well as overall and recurrence-free survival (OAS and RFS, respectively) of OSCC patients with and without synchronous second UAT tumors, carcinomas in situ, or higher-grade dysplasia/metaplasia, were evaluated based on a retrospective population-based cohort study, including alignment with cancer registry data.Out of 727 included OSCC patients, 465 cases (64.0%) received panendoscopy. Among these, 18 UAT tumors were detected, all of which were linked to patients with a positive history of nicotine abuse. Every synchronous UAT tumor was revealed by panendoscopy, which, analyzed as an independent staging procedure, was accompanied by a low complication rate (1.7%). When illuminating the impact of a second UAT tumor in OSCC patients, survival analysis revealed reduced 5-year OAS (63.9% vs 43.5%, p = 0.010) and RFS (57.1% vs 32.4%, p = 0.016) for patients with a second oncology diagnosis of the UAT.Within the limitations of the study, it seems that panendoscopy should be performed in the majority of patients suffering from OSCC, because most of them have a history of smoking and drinking, which correlates with an increased risk of developing synchronous UAT tumors.