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Background: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs. Methods: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI = neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of the overall survival (OS) and progression-free survival (PFS) were performed according to various factors. Results: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (P < 0.001, P = 0.008, P = 0.027, P = 0.013, and P < 0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (P = 0.007, P = 0.008, and P = 0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio: 2.16, P = 0.006). Conclusion: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

Objective eribulin, an anticancer agent that inhibits microtubule growth, along with trabectedin and pazopanib, has been approved for the treatment of advanced soft tissue sarcoma (STS). However, there has been no consensus on the optimal second-line therapy among these three agents following treatment failure with doxorubicin. Recently, the effects of eribulin on the tumor microenvironment and immunity have been reported in breast cancer, and peripheral blood immune markers have also been reported to be a predictor of eribulin efficacy, though this remains unverified in STS. We aimed to evaluate the predictive value of various peripheral blood immune markers in STS patients treated with eribulin. Methods we retrospectively reviewed the medical records of STS patients treated with eribulin and examined whether peripheral blood immune markers at different time points could be prognostic factors for STS patients treated with eribulin. Results several peripheral blood immune markers were significantly associated with progression-free survival (PFS), specifically neutrophil-to-lymphocyte ratio (NLR) prestart (NLR before the initial administration of eribulin) (P = 0.019) and absolute lymphocyte count (ALC)8D (ALC on Day 8 of the first administration of eribulin) (P = 0.037). NLR prestart (P = 0.001) was significantly associated with overall survival. The combination of NLR prestart and ALC8D determined the PFS of STS patients treated with eribulin. Conclusions the combined indicator of low NLR prestart and high ALC8D predicted the survival of patients treated with eribulin as well as the histology of L-sarcoma. Though further validation was needed, this finding would provide valuable prognostic factor that help treatment decision in the absence of consensus on the optimal second-line therapy following doxorubicin treatment in STS patients.

Enzalutamide is a potent inducer of cytochrome P450 substrates. Hence, it induces major metabolizing enzyme effects in some of the concomitant drugs, raising the possibility of decreased efficacy. We investigated the actual status of drugs for which precautions for co-administration are indicated during concomitant use with enzalutamide.We retrospectively investigated the duration of enzalutamide use, concomitant medications, laboratory values, and events using the medical records of patients prescribed enzalutamide for castration-resistant prostate cancer at the National Cancer Center Hospital from May 2014 to May 2017.The median age of the 107 studied patients was 74 years[range: 53-93], median duration of enzalutamide prescriptions was 120 days[range: 14-1,008], and the median number of concomitant medications(components)was 6[range: 0-16]. Sixty nine patients(64%)were taking drugs that could be affected by enzyme induction. The medications listed in the concomitant use section of the package insert were warfarin(3 patients) and omeprazole(2 patients). In this study, 4 patients(except for 1 on warfarin)were taking other drugs that could be affected by enzyme induction. Events considered to possibly reduce their efficacy during concomitant use with enzalutamide were elevated blood pressure and blood clots.When enzalutamide is used in combination with other drugs, there exists the possibility that the effect of concomitant medications may be weakened by enzyme induction.

The prognostic factors of retroperitoneal soft tissue sarcoma (STS) have been explored but not yet certain. This study evaluated the prognostic impact of various preoperative clinical parameters and inflammatory indices in primary STS, with a particular focus on the transition of inflammatory index before and after tumor resection in de-differentiated liposarcoma (DD-LPS).The clinical data of 113 patients with primary retroperitoneal STS receiving tumor resection were reviewed. Six variables (neutrophils, platelets, C-reactive protein (CRP), lymphocytes, albumin, and hemoglobin) in the blood samples were measured and nine inflammatory indices (neutrophil-lymphocyte ratio (NLR), CRP-lymphocyte ratio (CLR), platelet-lymphocyte ratio (PLR), neutrophil-albumin ratio (NAR), CRP-albumin ratio (CAR), platelet-albumin ratio (PAR), HALP (hemoglobin, albumin, lymphocyte and platelet), prognostic nutrition index (PNI), and modified Glasgow Prognostic Score (mGPS)) were calculated. The prognostic value of the indices was analyzed by univariate and multivariate analyses.Elevated NLR, CLR, PLR, NAR, CAR, PAR, and mGPS were associated with a worse overall survival (p = 0.0124, 0.0011, 0.049, 0.0047, 0.0085, 0.0332, and 0.0086, respectively) in univariate analysis. Multivariate analysis showed that elevated CLR and DD-LPS were associated with poor overall survival (p = 0.0267 and 0.0218, respectively) in all retroperitoneal STS. In DD-LPD, patients with preoperative high CLR, whose postoperative CLR was normalized, demonstrated a favorable survival rate similar to those with preoperative low CLR.Elevated CLR before surgery as well as DD-LPS were poor prognostic markers for overall survival in primary retroperitoneal STS. Perioperative CLR normalization may be related to a favorable prognosis in DD-LPS.

Interim analysis from the first large-scale post-marketing surveillance study of eribulin treatment for soft tissue sarcomas (STSs) showed antitumor activity in both common and rare subtypes of STS (NCT03058406)., Background Although eribulin is used to treat soft tissue sarcomas (STSs), treatment data for rare subtypes are limited. We conducted a post-marketing surveillance study to assess safety and efficacy of eribulin in STS patients stratified by subtype. Methods Japanese patients (n = 256) with advanced or metastatic STS receiving eribulin treatment were monitored for treatment status, adverse events, diagnostic imaging, and clinical outcomes at 3 months and 1 year. Interim analysis was performed. Patients will be monitored up to 2 years. Results Interim analysis included 3-month (n = 255), imaging (n = 226), and 1-year (n = 105) data. STS subtype distribution was normal. Median number of eribulin cycles was 3.0 (range: 1–17 cycles). Among patients with imaging data, best overall tumor response (12 weeks) was partial response, 7.5% (n = 17); stable disease, 34.5% (n = 78); and stable disease ≥11 weeks, 10.2% (n = 23). Overall response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) for all patients were 7.5%, 42.0% and 17.7%, respectively. ORR, DCR, and CBR were 10.3%, 32.0% and 16.5%, respectively, for patients with STS subtypes other than liposarcoma and leiomyosarcoma and included responses from patients with rare STS subtypes. Adverse drug reactions (ADRs) occurred in 211 (82.7%) patients (42 [16.5%] patients had serious ADRs), and none led to death. ADRs leading to drug withdrawal and dose reduction occurred in 27 (10.6%) and 55 (21.6%) patients, respectively. Conclusion Eribulin was generally well tolerated and showed antitumor activity against STSs, including rare subtypes that currently have few treatment options. Clinical trial number NCT03058406 (ClinicalTrials.gov)

Objectives To evaluate whether the extent of seminal vesicle invasion of prostatic adenocarcinoma can stratify the risk of biochemical recurrence after radical prostatectomy. Methods We carried out radical prostatectomy for 1309 patients with prostatic adenocarcinoma between 2006 and 2019; 135 (10.3%) patients had seminal vesicle invasion. After excluding patients with neo-/adjuvant therapy, we reviewed 105 patients. We analyzed the correlation of the extent of seminal vesicle invasion and biochemical recurrence-free survival after prostatectomy and adjusted by various clinicopathological factors in multivariate analyses. Seminal vesicle invasion was stratified into three groups; the proximal part from the base was defined as level 1, followed by level 2 and the distal part as level 3. Results Among the 105 patients, 30 (29%), 54 (51%) and 21 patients (20%) had seminal vesicle invasion at levels 1, 2 and 3, respectively. Median times to biochemical recurrence were 110, 67 and 12 months in patients with levels 1, 2 and 3, respectively (P = 0.002). The extent of seminal vesicle invasion was the independent risk factor for biochemical recurrence in univariate (level 3 vs 1, P = 0.001; level 3 vs 2, P = 0.015) and multivariate analyses (level 3 vs 1, P = 0.025; level 3 vs 2, P = 0.030). Conclusions The extent of seminal vesicle invasion might be a significant predictor of biochemical recurrence in prostate cancer patients undergoing radical prostatectomy.

The treatment goal for visceral metastatic nonseminomatous germ cell tumor (NSGCT) is to remove any residual teratoma or viable NSGCT after chemotherapy. However, this provides no therapeutic benefit to patients whose metastases necrotize on their own. This study therefore analyzed NSGCTs with pulmonary metastases to determine preoperative factors that predict necrosis and could help identify patients who might be treated with monitoring rather than surgery. The study retrospectively analyzed 41 patients (135 metastatic pulmonary nodules) treated from 1997 to 2016 for NSGCT who showed tumor marker normalization after chemotherapy. Relationships between clinicopathologic characteristics and necrosis in resected pulmonary specimens were analyzed. Receiver operating characteristic analysis of the pulmonary nodules showed 9 mm to be the optimal cutoff length for predicting necrosis. The logistic regression model showed that absence of teratoma components in the primary tumor and all pulmonary nodules shorter than 10 mm after chemotherapy both were independent predictors of pathologic necrosis in pulmonary specimens. No patients experienced late recurrence (i.e., > 2 years afterward). The presence of teratoma components in primary tumors and nodular size after chemotherapy predict the pathology of residual pulmonary nodules. Patients whose residual nodules all are shorter than 10 mm and who have no primary-tumor teratoma components might be candidates for careful monitoring before pulmonary resection.

Highlights • ALK-rearranged inflammatory myofibroblastic tumor(IMT) of the bladder is a rare tumor. • No standard therapeutic strategy for locally advanced cases has been established. • Crizotinib is a promissing treatment for unresectable IMT with ALK rearrangements. • Bladder-preserving surgery following neoadjuvant crizotinib is a preferred approach., Introduction Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that involves various organs, but has a predilection for the urinary bladder in the genitourinary tract. Given that approximately half of all IMT cases have anaplastic lymphoma kinase (ALK) rearrangements, the ALK inhibitor crizotinib is suggested as a promising treatment for unresectable cases. No reports on neoadjuvant crizotinib therapy for locally advanced IMT of the bladder are available. Presentation of case We report a case of a 17-year-old Japanese boy referred to our institution for painful urination and increased urinary frequency. He was diagnosed with ALK-positive IMT via transurethral resection of the bladder tumor. Computed tomography (CT) revealed a 5-cm mass and extramural invasion at the bladder dome. The diagnosis was locally advanced IMT of the bladder. We decided that partial cystectomy can be performed if neoadjuvant crizotinib therapy reduced the tumor size. After 2 months of administration, CT showed that the longest tumor diameter was reduced by 48%. Thus, we performed partial cystectomy, and the surgical margin was negative. No recurrence developed for over 1 year. Discussion IMT has intermediate malignant potential because its clinical course is relatively indolent with low risk of distant metastasis. As this patient is young and IMT of the bladder has good prognosis after surgical resection, bladder-preserving surgery is the most preferred approach. Conclusion Neoadjuvant crizotinib therapy may be effective for large, locally advanced, and difficult to resect tumors.

Background In this study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node‐positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph nodes (LN). Methods We retrospectively analyzed the data from cN1 patients who were treated with definitive RT and androgen deprivation therapy (ADT) between June 2004 and February 2016. All patients received localized irradiation to the prostate region and whole pelvis irradiation. Some patients received intensity‐modulated radiation therapy with RT dose escalation to metastatic LN. Univariate analyses using log‐rank test were performed to find prognostic factors between patient subgroups. Results Fifty‐one consecutive patients were identified. The median follow‐up period for all patients was 88 (range 20‐157) months. Primary Gleason pattern and LN RT dose were statistically significant prognostic factors for relapse‐free survival (RFS) and distant metastasis‐free survival (DMFS). Especially, RT dose escalation (60 Gy or more) to metastatic LN significantly improved RFS and DMFS compared with standard dose RT (4‐year RFS 90.6% vs 82.1%, 7‐year RFS 90.6% vs 58.0%, P = .015; 4‐year DMFS 90.6% vs 82.1%, 7‐year DMFS 90.6% vs 62.8%, P = .023). The following factors were all statistically significant for biochemical relapse‐free survival (BRFS): T stage, LN RT dose, local RT dose, and ADT duration period. Any significantly different toxicity was not seen for each LN or local RT dose except for the incident rate of grade 2 or more acute urinary retention, which was significantly higher in the higher LN RT dose (60 Gy or more) group by the Chi‐square test. Conclusions RT dose escalation to metastatic LN in cN1 patients improves BRFS, RFS, and DMFS at 4 and 7 years, without increasing severe adverse events., In this retrospective study, we aim to present the clinical outcomes of radiotherapy (RT) in clinical pelvic lymph node‐positive prostate cancer (cN1) patients. We also analyze the prognostic factors with focus on RT dose escalation to metastatic lymph node (LN). RT dose escalation to metastatic LN in cN1 patients improves relapse‐free survival (RFS) and distant metastasis‐free survival (DMFS) at 4 and 7 years, without increasing severe adverse events.

e21511 Background: End-of-life discussion (EOLd) including information about incurability, prognosis, the site of death, and do-not-resuscitate (DNR) status is considered indispensable for advanced care planning (ACP). However, the preference for EOLd in cancer patients has not been elucidated. Objective: To clarify the preferences of EOLd in Japanese patients with newly diagnosed advanced or recurrent cancer. Methods: A multi-center questionnaire survey was conducted on Japanese adult patients with breast cancer, pancreatic cancer, or sarcoma, who were diagnosed as incurable within the past three months. We asked patients whether they would like to have EOLd with their physician at the time of survey. Factors related to preferences of EOLd were analyzed using chi-square or Mann-Whitney U-test. Results: For 1 year from August 2015, we distributed the questionnaire to 251 patients at five centers. Responses were obtained from 159 patients (45 males, 113 females) (response rate: 63%). The median age was 65 years (range: 29-86). 93 patients (59%) answered they would like to have EOLd, while 60 patients (38%) answered they would not. In univariate analyses, elderly patients (odds ratio [OR]: 1.03; p = 0.027), patients having worse performance status (OR: 1.988; p = 0.03), and with any physical symptoms (OR: 1.533; p = 0.044) preferred to have EOLd. On the other hand, patients who perceived “being able to sufficiently fight the disease” ( p = 0.021) and “living without being aware of the disease” ( p = 0.004) as important were reluctant to have EOLd. 114 patients (72%) answered they wanted to know their life-time prognosis. Employed patients preferred to know their prognosis (OR: 8.919; p = 0.004) while patients who had received chemotherapy did not (OR: 0.313; p = 0.009). Conclusions: Even just after the diagnosis as an incurable disease, more than half of patients with advanced cancer were willing to have EOLd with their treating physician. Patients’ preference of knowing about life-time prognosis was affected by their social and medical experience.

438 Background: Colorectal adenoma is a well-established precursor lesion of colorectal cancer, so the prevention of adenoma may also contribute to the prevention of cancer. Adipocyte secretes hormones, namely adipocytokines, some of which are likely to be associated with malignancies such as colorectal, breast, and prostate gland cancer. Among several adipocytokines, resistin and visfatin have been suggested to be associated with the progression of colon cancer, and they could therefore be good biomarkers for colorectal adenoma and cancer. Methods: Prior to any procedures, healthy volunteers provided their venous blood, from which we obtained the plasma to measure concentrations of adiponectin, visfatin, and resistin. We underwent total colonoscopy, and identified 776 adenoma cases (522 males, 254 females), 734 controls (478 males, 256 females) were selected from those without adenoma. An unconditional logistic regression model was used to estimate odds ratios for colorectal adenoma after adjustment for potential confounders, including body mass index (BMI). Results: We found no positive association between the presence of colorectal adenoma and the levels of either visfatin (P trend: male 0.24, female 0.87), or resistin (P trend: male 0.85, female 0.71). After adjusting for potential confounders, we still saw no association. On the other hand, adiponectin levels showed a correlation with both BMI (P: male