Significant Difference In Disease-specific Survival Research Articles

Long-term prognosis after endoscopic submucosal dissection for esophageal cancer in older adult patients

BackgroundThe validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients.MethodsThe clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed.ResultsThe mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p < 0.01). However, no significant difference in disease-specific survival was observed among the three groups.ConclusionsESD is safe for ESCC treatment in patients aged ≥ 65 years. However, additional treatments should be considered based on the patient’s general condition.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study

AimsTo evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). MethodsA retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. ResultsYolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I–II and stages III–IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1–2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). ConclusionDistinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

Efficacy of Recombinant Thrombomodulin for Sepsis-Associated Disseminated Intravascular Coagulation Caused by Urinary Tract Infections

Severe urinary tract infections occasionally cause sepsis and disseminated intravascular coagulation (DIC). We examined the efficacy of recombinant thrombomodulin (rTM) for treating DIC caused by urosepsis. We enrolled 40 patients who were diagnosed with DIC caused by urosepsis at our hospital between April 2018 and May 2022. Twenty-six patients were treated with rTM (rTM group), while 14 patients did not receive rTM (non-rTM group). The DIC score before treatment in the rTM group was significantly higher than that in the non-rTM group (P＜0.01). There was no significant difference in disease-specific survival between the two groups. There was a significant improvement in DIC scores on days 1-3 after administering rTM. However, the duration of DIC in the rTM group was significantly longer than that in the non-rTM group (P＝0.038). The administration of rTM may have benefits in patients with DIC caused by urosepsis.

Survival benefit of active surveillance for papillary thyroid carcinoma: a propensity score matching analysis based on SEER database.

Over-treatment of papillary thyroid microcarcinoma (PTMC) has become a common issue. Although active surveillance (AS) has been proposed as an alternative treatment to immediate surgery for PTMC, its inclusion criteria and mortality risk have not been clearly defined. The purpose of this study was to investigate whether surgery can achieve significant survival benefits in patients with larger tumor diameter of papillary thyroid carcinoma (PTC), in order to evaluate the feasibility of expanding the threshold for active surveillance. This study retrospectively collected data of patients with papillary thyroid carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The propensity score matching (PSM) method was used to minimize confounding factors and selection bias between the surgery and non-surgery groups, and to compare the clinical and pathological characteristics between the two groups based on the SEER cohort. Meanwhile, the impact of surgery on prognosis was compared using Kaplan-Meier estimates and Cox proportional hazard models. A total of 175,195 patients were extracted from the database, including 686 patients who received non-surgical treatment, and were matched 1:1 with patients who received surgical treatment using propensity score matching. The Cox proportional hazard forest plot showed that age was the most important factor affecting overall survival (OS) of patients, while tumor size was the most important factor affecting disease-specific survival (DSS) of patients. In terms of tumor size, there was no significant difference in DSS between PTC patients with tumor size of 0-1.0cm who underwent surgical treatment and those who underwent non-surgical treatment, and the relative survival risk began to increase after the tumor size exceeded 2.0cm. Additionally, the Cox proportional hazard forest plot showed that chemotherapy, radioactive iodine, and multifocality were negative factors affecting DSS. Moreover, the risk of death increased over time, and no plateau phase was observed. For patients with papillary thyroid carcinoma (PTC) staged as T1N0M0, AS is a feasible management strategy. As the tumor diameter increases, the risk of death without surgical treatment gradually increases, but there may be a threshold. Within this range, a non-surgical approach may be a potentially viable management strategy. However, beyond this range, surgery may be more beneficial for patient survival. Therefore, it is necessary to conduct more large-scale prospective randomized controlled trials to further confirm these findings.

Real-World Outcomes of Consolidative Autotransplant for High-Risk Large B-Cell Lymphoma

Background: Although there have been significant recent advances in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL), there remains a substantial unmet need to optimize the frontline management of high-risk LBCL. Patients with high International Prognostic Index (IPI) scores 4-5 have particularly poor progression-free survival (PFS) rates of ~50% with R-CHOP, and 2-year PFS may be as low as 10-25% for patients with positive interim PET scans. In the phase III DLCL04 and SWOG-9704 trials, the use of upfront consolidative autologous stem cell transplantation (ASCT) after R-CHOP resulted in significant improvements in PFS, with the latter study also demonstrating a significant improvement in overall survival (OS) in the age-adjusted high IPI subgroup. Furthermore, the GAINED trial demonstrated favorable outcomes using an interim PET-adapted strategy, where consolidative ASCT appeared to overcome the poor prognostic impact of a positive interim PET. However, there is only limited and conflicting data from prospective or retrospective studies concerning ASCT consolidation for the highest risk patients with LBCL and IPI score 4-5, particularly those with positive interim PET scans. Methods: This retrospective, multicenter study included consecutive patients with newly diagnosed LBCL and high IPI score 4-5 who received consolidative ASCT as a planned part of first-line therapy at the Tom Baker Cancer Centre and Cross Cancer Institute in Alberta, Canada. Patients were excluded if they had primary central nervous system (CNS) lymphoma, previously treated indolent B-cell lymphoma, or underwent ASCT for r/r LBCL. PFS, OS, and disease-specific survival (DSS) were determined using the Kaplan-Meier method. Results: We included 114 patients with median age 60 years (range 18-73) and median follow-up time 5.6 years. High-risk features at diagnosis included IPI score 4 in 81 (71%), IPI score 5 in 33 (29%), stage IV in 112 (98%), >1 extranodal site in 109 (96%), non-GCB cell of origin by Hans’ algorithm in 32 (28%), double-hit lymphoma in 26 (23%), and secondary CNS involvement in 15 (13%). The most common induction regimen was R-CHOP (n=102) and 25 (22%) patients received 1-3 cycles, 71 (62%) received 4 cycles, and 18 (16%) received 5-6 cycles of induction. Rituximab with dose-intensive cyclophosphamide, etoposide, and cisplatin (R-DICEP) was frequently used (n=69) to intensify induction and for peripheral blood stem cell mobilization. Interim PET was performed during induction for 45 patients and was positive (Deauville 4-5) in 24 (53%) and negative (Deauville 1-3) in 21 (47%). Pre-ASCT disease status was complete response (CR) in 68 (60%), partial response (PR) in 43 (38%), and unknown in 3 (3%) patients. The most common ASCT conditioning regimens were BEAM in 41 (36%), BuMel in 39 (34%), and TBM in 13 (11%) patients. At 2 years, PFS was 82% (95% CI 74-88%), OS was 86% (95% CI 78-91%), and DSS was 87% (95% CI 79-92%). At 5 years, PFS was 72% (95% CI 62-80%), OS was 74% (95% CI 64-81%), and DSS was 80% (95% CI 71-87%). Relapse occurred in 21 (18%) patients at median 284 days (range 168-2229) after ASCT. There was 1 (1%) death due to early transplant-related infection and 3 (3%) late deaths from pulmonary fibrosis and therapy-related myeloid neoplasms. There were no significant differences in DSS for patients with versus without CNS involvement (77% vs. 80%, p=0.62), double-hit lymphoma versus DLBCL NOS (85% vs. 78%, p=0.80), GCB versus non-GCB cell of origin (78% vs. 80%, p=0.89) and positive versus negative interim PET (83% vs. 74%, p=0.51). Discussion: In this study of 114 selected patients with high-risk LBCL with IPI score 4-5, consolidative ASCT was associated with excellent outcomes with long-term disease-specific survival in 80%. Importantly, the efficacy of consolidative ASCT appeared to be independent of adverse prognostic factors including CNS involvement, double-hit status, non-GCB cell of origin, and interim PET positivity. The results of our study are consistent with those of previous clinical trials and provide real-world evidence confirming that consolidative ASCT can be considered a reasonable treatment option for eligible patients with high-risk LBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The modified vermilion border-marionette line approach: A management for buccal cancer with wider indications and higher satisfaction.

The purpose of this study is to explore the effects of modified vermilion border-marionette line (MVBML) approach on postoperative facial scar, nerves injury, and prognosis of patients with buccal squamous cell carcinoma (BSCC). This is a single-center, prospective cohort study that enrolled 80 patients with BSCC from June 2015 to December 2020. According to the different surgical approaches, the patients were divided into two groups: the lower lip median (LLM) approach group and the MVBML approach group. The results showed that the appearance (p=0.003), scar consciousness (p < 0.001) and satisfaction with appearance (p=0.001) of patients in the MVBML group were significantly better than those in the LLM group, and the difference was more obvious in elderly group. Statistical analysis of postoperative nerves injury showed that the MVBML group had a lower risk of facial and mental nerves injury than the LLM group, and there was a significant statistical difference in mental nerve injury between the two groups (p < 0.001). Through Kaplan-Meier survival analysis, we found no significant difference in disease-specific survival (p=0.47) or disease-free survival (p=0.70) between the LLM approach group and the MVBML approach group. The MVBML surgical approach is worthy of advancement for the surgical treatment of BSCC.

Survival comparison between endoscopic and surgical resection for non-ampullary duodenal neuroendocrine tumor (1–2 cm)

The treatment plan for non-ampullary duodenal neuroendocrine tumors (d-NETs) with diameters 1–2 cm remains controversial. We therefore aimed to compare the prognostic effects of endoscopic treatment and surgical resection on non-ampullary d-NETs with 1–2 cm diameters. A total of 373 eligible patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to match patients 1:1 according to clinicopathological characteristics. Disease-specific survival (DSS) and overall survival (OS) were calculated. Before PSM, there was no significant difference in DSS or OS (all P > 0.05), but the T stage, N stage, and TNM stage were significantly different between the two surgical methods (all P < 0.05). After 1:1 PSM, the differences in clinicopathological characteristics were significantly reduced (all P > 0.05). Survival analysis showed that tumor grade was correlated with DSS and that age was correlated with OS (all P < 0.05); however, the surgical method and other clinicopathological characteristics were not correlated with prognosis (all P > 0.05). Subgroup survival analysis of patients with T2N0M0 disease and tumors invading the lamina propria or submucosa showed that the 5-year DSS and OS rates were not significantly different according to the surgical approach (all P > 0.05). The surgical approach has no significant effect on the prognosis of patients with non-ampullary d-NETs with 1–2 cm diameters, especially those with T2N0M0 disease. This suggests that endoscopic treatment may be a preferred option for these patients.

Long-term outcomes of patients with multifocal intraductal papillary mucinous neoplasm following pancreatectomy

BackgroundThe decision to perform surgery is complicated by the presence of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs), which are characterized by two or more cysts located in different areas of the pancreas. ObjectivesWe aimed to establish a suitable treatment strategy and surgical indications in patients with MF-IPMNs. MethodsThis single-center retrospective study included patients with IPMNs who underwent pancreatic resection from 2006 to 2020. Patients with distant metastasis and patients with IPMNs of the main pancreatic duct were excluded from the analysis. ResultsAfter excluding 22 patients, 194 patients were included. One hundred thirteen patients (58.2%) had unifocal IPMNs, while 81 patients (41.8%) had MF-IPMNs. There were no significant differences in the 5-year disease-specific survival (DSS) rate (92.3% vs. 92.4%, p = 0.976) and the 5-year disease-free survival rate (88.6% vs. 86.5%, p = 0.461). The multivariate analysis identified high-risk stigmata, invasive carcinoma, and lymph node metastasis as independent predictors of DSS. The presence of cystic lesions in the pancreatic remnant was not a predictor of survival. Even in the MF-IPMN group, there were no significant differences in DSS when stratified by procedure (total pancreatectomy vs. segmental pancreatectomy, p = 0.268) or presence of cystic lesions in the pancreatic remnant (p = 0.476). The multivariate analysis identified lymph node metastasis as an independent predictor of DSS in the MF-IPMN group. ConclusionsIn patients with MF-IPMNs, each cyst should be evaluated individually for the presence of features associated with malignancy.

Prognostic value of transcriptional expression of fibronectin type III domain-containing 4 (FNDC4) in head and neck carcinoma patients treated with chemoradiotherapy

PurposeFNDC4 gene encodes the fibronectin type III domain-containing 4 protein. Elevated expression of FNDC4 has been associated with poor prognosis in several types of cancer. There are no studies that have evaluated the prognostic capacity of FNDC4 in patients with head and neck cancer (HNSCC). The aim of our study was to analyze the relationship between the transcriptional expression of FNDC4 and prognosis in HNSCC patients.MethodsWe determined the transcriptional expression of FNDC4 in 67 patients with advanced-stage HNSCC (III–IV) treated with chemoradiotherapy. The FNDC4 expression was categorized according to the disease-specific survival with a recursive partitioning analysis.ResultsThere were significant differences in disease-specific survival as a function of the level of FNDC4 transcriptional expression. The 5-year disease-specific survival for patients with high FNDC4 expression (n = 44, 65.7%) was 32.9% (95% CI: 16.5–49.3%), and for patients with low expression (n = 23, 34.3%) it was 85.4% (95% CI: 70.2–100%) (P = 0.0001). Patients with a high FNDC4 expression had poorer local (P = 0.097), regional (P = 0.008), and distant (0.034) recurrence-free survival. The results of a multivariate analysis showed that patients with a high FNDC4 expression had a 6.15-fold increased risk of death as a consequence of the HNSCC (95% CI: 1.71–22.06).ConclusionFNCF4 transcriptional expression was significantly related to the disease-specific survival of HNSCC patients treated with chemoradiotherapy. Patients with elevated FNDC4 expression had a significant decrease in disease-specific survival.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12094-022-02870-3.

Radiation therapy for pelvic recurrent colorectal or gynecological cancer: is whole pelvic irradiation necessary?

Preoperative whole pelvic radiation therapy (RT) is used commonly for rectal cancer and is the standard field postoperatively in gynecological cancer. However, the ideal field (local vs. whole pelvis) has not been determined for local recurrence of these cancers. We retrospectively reviewed the data for 52 patients who developed local tumor recurrence of rectal or gynecological cancer treated from 2013 to 2021. The initial treatment for all patients was total excision of the primary tumors without radiation therapy. Radiation therapy targets were surgical stumps, perianastomosis sites, and pelvic lymph nodes, classified according to the pelvic nodal volume atlas for radiation therapy. Patients were divided into the local recurrent tumor only radiation therapy group and the whole pelvis radiation therapy group. Whole pelvis radiation therapy included the common iliac lymph nodes or prophylactic lymph nodes below the L5/S1 junction. We recorded second recurrence after RT and the affected site(s) in each group. We also compared disease-specific survival using uni- and multivariate analyses. We found no significant differences between the groups regarding second recurrence or regarding the site(s) of recurrence. We also found no significant differences in disease-specific survival between the two RT groups. However, patients who did not receive chemotherapy after the initial surgery and before RT had significantly longer survival (P=0.015). In patients with locally recurrent rectal or gynecological cancer, we found no significant difference in second recurrence or survival between the local tumor only RT field and the whole pelvic RT field.

Validation of the Prognostic Stage from the American Joint Committee on Cancer 8th Staging Manual in Luminal B-Like Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PurposeThe 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer.MethodsA total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan–Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups.ResultsThe 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ2 = 4.366, p = 0.037) and OS (χ2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ2 = 7.724, p = 0.021) but no significant differences in OS (χ2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ2= 0.159, p = 0.690) or OS (χ2 = 0.099, p = 0.753).ConclusionThe 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.

Thyrotropin suppression therapy using levothyroxine does not negatively affect breast cancer prognosis

IntroductionBreast cancer (BC) and thyroid dysfunction are common in females, yet the relationship between thyroid hormone and BC is unclear. To search for the connection between thyrotropin and BC, we contradistinguished BC patients with or without synchronous second primary thyroid cancer (TC) with surgery using data from the Surveillance, Epidemiology, and End Results (SEER) database. Theoretically, according to the ATA (American Thyroid Association) guidelines, all TC patients were treated with thyrotropin suppressive therapy only from 2010 to 2015. Materials and MethodsData from BC patients with a synchronous second TC with surgery (BC2TC) and only BC patients (1BC) during 2010–2015 were extracted from the SEER database. Differences in the clinicopathological characteristics between BC2TC and 1BC patients were analyzed by chi-square tests. Comparisons of the disease-specific survival (DSS) and overall survival (OS) curves between these two groups were performed with the log-rank (Mantel-Cox) test. ResultsWithin this dataset, we identified 134 BC2TC patients during the period from 2010 to 2015. Significant differences between the BC2TC and 1BC groups were found only for different ages and TNM (tumor-node-metastasis status) stages. There were no significant differences in DSS between the two cohorts (P = 0.060). The same tendencies in OS or DSS were observed for the different age groups and different TNM groups, even the stage I, N0 (without metastases to lymph nodes), and ER (+) (estrogen receptor (ER)-positive) groups. ConclusionsThere were no remarkable differences in survival between the BC2TC and 1BC groups, and thyrotropin suppression therapy using levothyroxine did not negatively affect BC prognosis.

Favorable Outcomes with Thiotepa/Busulfan-Based Conditioning and Autotransplant for Patients with Aggressive B-Cell Lymphoma and Secondary CNS Involvement

Introduction: Central nervous system (CNS) relapse is a devastating complication affecting ~5% of patients with diffuse large B-cell lymphoma (DLBCL). The optimal management is unknown and survival rates are ~20% in contemporary series. Thiotepa/busulfan-based high-dose chemotherapy (HDT) and autotransplant (ASCT) has demonstrated efficacy in primary CNS lymphoma, but there have been fewer studies of this conditioning regimen in secondary CNS lymphoma (SCNSL).Methods: This multicenter retrospective study included all consecutive patients ≥18 years old with aggressive B-cell lymphoma and secondary CNS involvement treated with thiotepa/busulfan-based HDT/ASCT at the University of Calgary and University of Alberta since 2005. Kaplan-Meier curves were used to estimate progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) from the time of ASCT. Data collection is underway for all consecutively diagnosed SCNSL patients at our institutions to evaluate frequency and predictors of HDT/ASCT use.Results: This study included 57 patients with DLBCL (n=45), double-hit lymphoma (n=6), high-grade B-cell lymphoma NOS (n=2), intravascular large B-cell lymphoma (n=2), or T-cell/histiocyte-rich large B-cell lymphoma (n=2). Two (4%) had previously treated indolent B-cell lymphoma and 1 (2%) had multiply relapsed DLBCL. Median International Prognostic Index was 4 (range 0-5) at DLBCL diagnosis and median time to CNS relapse was 4 months (range 0-139). Median age was 58 years (range 20-73) and median ECOG was 3 (range 0-4) at diagnosis of SCNSL. CNS involvement was present at initial diagnosis in 20 (35%) patients or developed during frontline treatment in 10 (18%) or after completion of treatment in 27 (47%). For those without SCNSL at diagnosis, isolated CNS relapse occurred in 31 (84%) patients while 6 (16%) had concurrent CNS and systemic relapse.Most patients (n=54, 94%) received high-dose methotrexate (HD-MTX)-based multiagent induction chemotherapy (median HD-MTX doses 4, range 1-5) followed by peripheral blood stem cell mobilization with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in 41 (72%). HDT conditioning regimens were thiotepa, busulfan, melphalan, rituximab (TBMR, n=52, 91%) or thiotepa, busulfan, cyclophosphamide (TBC, n=5, 9%). Median time from SCNSL diagnosis to ASCT was 116 days (range 7-201). Median time to neutrophil engraftment was 10 days (range 7-15) and to platelet engraftment 16 days (range 9-93).Overall response rates (ORR) for systemic/CNS disease were 93%/89% pre-ASCT and 95%/100% post-ASCT. Combined ORR pre-ASCT was 88%, with complete response in 21% and partial response in 67%. Two (4%) patients who developed CNS relapse immediately prior to ASCT achieved long-term remission after TBMR conditioning without any other systemic chemotherapy. With a median follow-up time of 4.0 years (range 0.1-15.9), PFS was 75% (95% CI 61-85%), OS was 76% (95% CI 62-86%), and DSS was 79% (95% CI 64-88%) at 4 years after ASCT. Lymphoma recurred in 9 (16%) patients at median 88 days (range 54-346) after ASCT with CNS relapse (n=4), systemic relapse (n=3), or both (n=2). There were 2 (4%) deaths due to peri-transplant toxicity and 1 (2%) death at 1.5 years due to therapy-related acute myeloid leukemia; no other unexpected toxicities of HDT/ASCT were observed. Among the 45 (79%) patients achieving long-term disease-specific survival, none were treated with CNS radiation therapy and only 1 (2%) had persistent neurocognitive impairment. There were no significant differences in DSS with respect to timing of CNS relapse, concurrent presence of systemic disease, or TBMR versus TBC conditioning (78% vs 80%, p=0.87).Conclusion: In one of the largest studies of this conditioning regimen in SCNSL to date, we found that high-dose thiotepa/busulfan-based conditioning with ASCT is associated with favorable outcomes for patients with aggressive B-cell lymphoma and secondary CNS involvement, with 4-year OS ~75% in this study. Although SCNSL has been historically associated with a poor prognosis, an increasing proportion of patients may achieve long-term survival after intensive therapy with HD-MTX-based induction and thiotepa/busulfan-based HDT and ASCT. [Display omitted] DisclosuresChua: Eisai: Honoraria; Pfizer: Honoraria; Merck: Honoraria; Gilead: Honoraria. Stewart: Novartis: Honoraria; AstraZeneca: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Roche: Honoraria; Sandoz: Honoraria; Teva: Honoraria.

Treatment Results for Stage III Laryngeal Cancer: Analysis of a Populational Database Using Propensity Scores.

Introduction Treatment of stage III laryngeal cancer suffered a major paradigm change with surgery being substituted by radiation therapy with chemotherapy. Objective To evaluate the oncological outcome of different treatment modalities for stage III laryngeal cancer using a population database. Methods A population database representing patients treated in the state of São Paulo, Brazil, was analyzed. Demographic, clinical and treatment variables were included, and the outcomes of interest were disease-specific and overall survival. Propensity score with nearest neighbor matching was used to compensate for imbalances in treatment groups. Results We retrieved data from 1,804 patients. In multivariate analysis, age, female gender, payment source, clinical N stage (cN) stages, and treatment modality were significant for disease-specific and overall survival. Patients submitted to surgery treatment had a significantly better disease-specific ( p < 0.001) and overall survival ( p < 0.001) compared with chemoradiation. Propensity score matching was based on cN stage, gender, age, topography, and payment modality, and allowed the pairing of 685 patients from each treatment modality. There was a significant difference in disease-specific survival favoring surgery-based treatment ( p = 0.017). Conclusion The treatment choice has a significant impact on survival in patients with stage III laryngeal cancer with surgery-based treatment being superior to chemoradiotherapy (CRT).

Differential Characteristics of Patients With Squamous Cell Carcinoma of the Head and Neck According to Gender

ObjectiveTo analyse the trend in the percentage of patients with squamous cell carcinoma of the head and neck (SCCHN) of female gender over the last decades, and differences in survival according to gender. Material and methodsRetrospective study of 5828 SCCHN diagnosed during the period 1985–2019. In the survival analysis we only included only patients with more than two years of follow-up. ResultsThe proportion of tumours in female patients increased significantly over the study period. There was greater increase of tumours located in the oral cavity, oropharynx and larynx in the percentage of female patients. When considering the total number of patients, there were no significant differences in disease-specific survival according to gender. We observed a variable behaviour of disease-specific survival according to gender depending on the primary location of the tumour. For tumours of the larynx and oropharynx the female patients had a disease-specific survival significantly higher than that of men, while for tumours of the oral cavity, the female patients had a significant reduction of disease-specific survival. ConclusionsIn our setting, the percentage of female patients with HNSCC has been increasing steadily over recent decades. There were differences in disease-specific survival according to gender depending on the location of the primary tumour.

CD3+, CD8+, CD4+ and FOXP3+ T Cells in the Immune Microenvironment of Small Bowel Neuroendocrine Tumors.

The role of inflammation in neuroendocrine tumors is poorly known. The purpose of this study was to characterize the densities of CD3+, CD8+, CD4+ and FOXP3+ T cells in small bowel neuroendocrine tumors (SB-NETs), SB-NET lymph node metastases and gastric neuroendocrine tumors (G-NETs) to assess the prognostic role of immune cell infiltrates in SB-NETs. The final cohort included 113 SB-NETs, 75 SB-NET lymph node metastases and 19 G-NETs from two Finnish hospitals. CD3+- and CD8+-based immune cell score (ICS), and other T cell densities were evaluated. Survival analyses of SB-NETs and SB-NET lymph node metastases were performed with the Kaplan-Meier method and Cox regression adjusted for confounders. The primary outcome was disease-specific survival (DSS). No significant difference in DSS was seen between low and high ICS groups in SB-NETs at 5 years (92.6% vs. 87.8%) or 10 years (53.8% vs. 79.4%), p = 0.507, or in SB-NET lymph node metastases at 5 years (88.9% vs. 90.4%) or 10 years (71.1% vs. 59.8%), p = 0.466. Individual densities of the examined T cell types showed no correlation with prognosis either. SB-NETs and lymph node metastases had similar inflammatory cell profiles, whereas in G-NETs CD3+ and CD8+ T cells were particularly more abundant. In SB-NETs, ICS or T cell densities showed no correlation with prognosis.

Características diferenciales de los pacientes con carcinomas escamosos de cabeza y cuello en función del género

ObjectiveTo analyse the trend in the percentage of patients with squamous cell carcinoma of the head and neck of female gender over the last decades, and differences in survival according to gender. Material and methodsRetrospective study of 5,828 squamous cell carcinoma of the head and neck diagnosed during the period 1985-2019. In the survival analysis we only included only patients with more than two years of follow-up. ResultsThe proportion of tumours in female patients increased significantly over the study period. There was greater increase of tumours located in the oral cavity, oropharynx and larynx in the percentage of female patients. When considering the total number of patients, there were no significant differences in disease-specific survival according to gender. We observed a variable behaviour of disease-specific survival according to gender depending on the primary location of the tumour. For tumours of the larynx and oropharynx the female patients had a disease-specific survival significantly higher than that of men, while for tumours of the oral cavity, the female patients had a significant reduction of disease-specific survival. ConclusionsIn our setting, the percentage of female patients with squamous cell carcinoma of the head and neck has been increasing steadily over recent decades. There were differences in disease-specific survival according to gender depending on the location of the primary tumour.

Malignant tumours of temporomandibular joint

BackgroundMalignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed.MethodsA retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973–2016).ResultsData for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P < 0.05). In the multivariate survival analysis, age > 44 years and AJCC stage III and IV were associated with poor DSS.ConclusionMTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient’s age and AJCC stage was independent predictor of DSS.

Abstract B23: FGFR3 mutations and their relation to FGFR3 expression and clinical outcome in a large radical cystectomy cohort: Implications for anti-FGFR3 bladder cancer treatment?

Abstract Objective: Fibroblast growth factor receptor 3 (FGFR3) is a potentially actionable target in bladder cancer (BC). FGFR3 mutations are associated with favorable prognosis in non-muscle invasive (NMI) BC and MIBC. Overexpression of FGFR3 was reported in up to 40% of FGFR3 wild-type MIBC. p53 alterations rarely coincide with FGFR3 mutations. We analyzed FGFR3 mutations and protein-expression of FGFR3 and p53 and assessed their prognostic value in a multicenter, multilaboratory setting. Methods: We included 1,000 cN0M0, chemotherapy-naive patients who underwent radical cystectomy (RC) with pelvic node dissection. Specimens were reviewed by eight uropathologists. At seven laboratories, FGFR3 mutation status was examined using PCR-SNaPshot. p53 and FGFR3 expression were determined by immunohistochemistry (IHC). FGFR3 mutation status, p53 and FGFR3 protein expression were correlated to each other, clinicopathologic parameters, and disease-specific survival (DSS). Results: FGFR3 mutations were found in 107/1,000 RCs (11%), of which 67 were S249C. Overexpression of FGFR3 was found in 279/1,000 (28%) of tumors. p53 overexpression (cut-off&amp;gt;10%) was found in 638/926 (69%) of available cases. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression. Among FGFR3 wild-type tumors, 22% had FGFR3 overexpression. FGFR3 mutations were associated with lower pT-stage (P&amp;lt;0.001), lower grade (G2-WHO 1973) (P&amp;lt;0.001), absence of CIS (P=0.009), pN0 (P&amp;lt;0.001), normal p53 (P&amp;lt;0.001), and prolonged DSS (Plog-rank=0.001). FGFR3 overexpression was associated with lower pT-stage (P&amp;lt;0.001) and G2 (P&amp;lt;0.001) but not with absence of CIS (P=0.860), pN0 (P=0.230), normal p53, (P=0.330) nor prolonged DSS (Plog-rank=0.204). We found no significant difference in DSS for patients with FGFR3 mutant tumors comparing normal vs. overexpression of FGFR3 (Plog-rank=0.444). Furthermore, we also found no significant difference in DSS for patients with FGFR3 wild-type tumors comparing normal vs. overexpression of FGFR3 (Plog-rank=0.754). Conclusions: FGFR3 mutations identified patients with favorable BC with fewer p53 alterations at RC. FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. Our results suggest that FGFR3 mutations (driver effect) have a distinct functional role than FGFR3 overexpression (passenger effect). Hence, patients with FGFR3 mutations may be more likely to benefit from anti-FGFR3 therapy than patients with only overexpression of FGFR3. Citation Format: Bas van Rhijn, Laura Mertens, Roman Mayr, Peter Bostrom, Mirari Marques, Geert van Leenders, Stefanie Gotz, Michiel van der Heijden, Michael Jewett, Francisco Real, Robert Stohr, Alexandre Zlotta, Markus Eckstein, Yanish Soorojebally, Max Burger, Wolfgang Otto, Francois Radvanyi, Damien Pouessel, Theo van der Kwast, Nuria Malats, Arndt Hartmann, Yves Allory, Deric van der Schoot, Ellen Zwarthoff, Tahlita Zuiverloon. FGFR3 mutations and their relation to FGFR3 expression and clinical outcome in a large radical cystectomy cohort: Implications for anti-FGFR3 bladder cancer treatment? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B23.

Characteristics of Japanese elderly patients with pulmonary arterial hypertension

Previous nationwide Japanese data suggested that pulmonary arterial hypertension (PAH) predominantly affects young women. However, the number of elderly patients diagnosed with PAH has been increasing in western countries. There have been no reports on elderly PAH patients in Asian countries. This study aimed to investigate the clinical characteristics of elderly PAH patients in a Japanese cohort. Idiopathic/heritable PAH (I/H-PAH) was included in the national research project on intractable diseases. The patients were required to submit a clinical research form completed by their attending physicians. We analyzed the characteristics of Japanese I/H-PAH using the newly registered forms in 2013 (Study 1, n = 148). Also, we did a retrospective, observational cohort study at Chiba University Hospital (Study 2, n = 42). We compared the characteristics of elderly PAH patients (≥65 years old) with younger patients (<65) in both studies. Study 1 revealed a predominance of males (51% male), better hemodynamics and poorer exercise capacity in the elderly group (n = 72), compared with the younger group (n = 76) in study 1. In Study 2, elderly patients showed a male predominance (63% male), a higher ratio of smokers, a lower % carbon monoxide diffusing capacity, and poorer exercise tolerance. Elderly patients in Study 2 showed less improvement in hemodynamics with therapy. There was no significant difference in disease-specific survival between elderly and younger patients. Japanese elderly patients with I/H-PAH showed poorer exercise capacity and impaired gas exchange, but better pulmonary hemodynamics than younger patients.