Median Overall Survival Period Research Articles

Novel Treatment Strategies for Low-Risk Metastatic Castration-Sensitive Prostate Cancer.

The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan-Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w.

Craniospinal irradiation for leptomeningeal metastasis of solid tumors: survival analysis and prognostic factors.

We conducted a study to examine the treatment outcomes and prognostic factors for patients who underwent craniospinal irradiation (CSI) for leptomeningeal metastasis of solid tumors. This retrospective study included patients who received CSI for leptomeningeal metastasis at a single institute between 2010 and 2021. Data from clinical records and the radiation information system were obtained and analyzed. A total of 25 patients were included in the study. Eighteen patients (72%) completed the scheduled CSI. The median overall survival (OS) period was 4.8months (95% confidence interval (CI): 3.2-10.0months). Symptom relief was achieved in four out of 23 symptomatic patients (17%). Non-hematological adverse events occurred in 12 patients (48%), with 1 patient (4%) developing Grade 3 bacterial meningitis and the other patients having Grade 1-2 events. Twenty patients (80%) had hematological adverse events of Grade 3 or higher. Grade 4 hematologic toxicities occurred in 3 patients (12%) due to neutropenia and in 11 patients (44%) due to lymphopenia. In multivariate Cox regression analysis, the systemic immune-inflammation index (SII) was identified as the only significant parameter for predicting OS. The median OS periods for patients with SII < 607 and SII ≥ 607 were 6.1 and 2.1months, respectively (P = 0.003). In conclusion, this study showed the treatment outcomes of CSI for leptomeningeal metastasis of solid tumors. It was shown that a high baseline SII was associated with shorter OS after CSI. The findings will contribute to the evaluation of prognosis after CSI.

Prognosis and recurrence of spontaneously ruptured hepatocellular carcinoma treated after hepatectomy: A single institution experience.

Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11-32) and 23 (17-38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8-37, P = .099) and 33 (12-51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis

BackgroundSystemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy.MaterialsWe retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups.ResultsIn total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed.ConclusionThe combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Radiation-induced angiosarcoma of the breast: individual participant meta-analysis of Japanese population.

Radiation-induced angiosarcoma (RIAS) of the breast is a very rare and poor prognostic disease. According to previous studies, the efficacy of chemotherapy for RIAS is still controversial. However, no study has assessed the prognosis of RIAS and the prognostic impact of preoperative or postoperative chemotherapy in Japanese patients. Our study aimed to assess them in Japanese people using publication data with our three patients. Thirty-nine patients diagnosed with RIAS, including 36 patients from 34 published case series, and three patients from our hospital were used for analysis. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Among the 39 patients, 36 patients (92.3%) underwent surgery. The median DFS and OS periods were 14months (range 1-75months) and 23months (range 4-84months), respectively. Chemotherapy with taxane-based regimen was administered in 13 cases (33.2%) pre- or post-operatively. DFS was significantly improved with chemotherapy in addition to surgery (p = 0.037). However, addition of chemotherapy to surgery did not improve DDFS (p = 0.09) and OS (p = 0.878). In multivariate analysis, age ≥ 70years was an independent but poor prognostic factor of DFS. Additionally, a lack of chemotherapy showed a trend to be associated with worse DFS. There was no independent variable contributing to DDFS and OS. Chemotherapy may have reduced the recurrence rate of RIAS in Japanese patients but did not improve OS. Further data are needed to confirm the efficacy and proper regimen of chemotherapy.

Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients Treated with Definitive Chemoradiotherapy for Locally Advanced Oesophageal Squamous Cell Carcinoma.

The neutrophil-to-lymphocyte ratio (NLR) has been shown to have prognostic value in several common cancers. This study aimed to investigate the prognostic value of NLR in patients with advanced oesophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). A retrospective analysis was performed on 158 patients with advanced ESCC who received dCRT from January 2012 to December 2018. The NLR for different treatment stages was calculated based on laboratory test results. The Kaplan-Meier (KM) method and Cox proportional regression model were used to analyse the relationship between NLR and overall survival (OS). The mean NLR of 158 patients with ESCC was 3.403 ± 2.479. The pre-treatment NLR cut-off was 4.839, and patients were divided into the low NLR group (NLR < 4.839) and the high NLR group (NLR ≥ 4.839). NLR in patients with ESCC was related to N stage (P < 0.05). The KM analysis showed that the median OS of all enrolled patients was 29.3 months, the median OS periods of patients in the high and low NLR groups were 15.6 and 35.8 months, respectively, and the OS of the low NLR group was better than that of the high NLR group (P < 0.001). In the multivariate analysis, NLR was an independent prognostic factor that affects the prognosis of patients with ESCC receiving dCRT. Furthermore, patients who maintained a high NLR before and after treatment showed worse clinical outcomes than the other groups. Our findings suggest that NLR can effectively assess the prognosis of patients with advanced ESCC undergoing dCRT.

Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study.

To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.

Abstract P3-23-07: Radiation induced angiosarcoma of the breast: Chemotherapy for radiation induced angiosarcoma of the breast - An individual participant data meta-analysis of Japanese population

Abstract Background: Radiation-induced angiosarcoma (RIAS) of the breast is a very rare disease. Previous studies from other countries have been reported that patients having RIAS has a poor prognosis, and the efficacy of chemotherapy is still controversial. However, the prognosis of RIAS and the prognostic impact of pre- or postoperative chemotherapy for RIAS in Japanese population are not well known. Our study aimed to assess them in Japanese population using publication data with the cases from our institute. Methods: We obtained 36 Japanese patients data from thirty-four original articles from 2007 to 2020 and 3 patients from our database. Clinicopathological data including age at diagnosis of RIAS, surgery for RIAS, pre- or postoperative chemotherapy for RIAS, regimen of chemotherapy, tumor size, stage for primary breast cancer, and systematic treatment for breast cancer were collected. We assessed disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) using Kaplan-Meier survival curves and log rank test. Hazard ratios were estimated from Cox models. Results: The median age at diagnosis of RIAS was 73.0 years (range, 32-89 years). A median follow-up period was 22 months (range, 6-84 months). RIAS developed on the breast in 36 patients (92.3%) and on chest wall in 3 patients (7.7%). Thirty-six patients (92.3%) underwent surgery. Chemotherapy was administered to 13 cases (33.2%); preoperatively in 3 patients and postoperatively in 10 patients. All patients had received taxane-based chemotherapy. The median size of tumor in pathological examination was 43.5 mm (range, 9-100 mm). There was no difference of patient’s characteristics between patients with or without chemotherapy. The median DFS period was 14 months (range 1-75 months), and the median OS period was 22 months (range, 6-84 months). Chemotherapy in addition to surgery significantly improved DFS period (19 vs 12 months, p=0.027), and DDFS tended to be prolonged by adding chemotherapy (p=0.06). However, chemotherapy did not improved OS (p=0.878). In multivariate analysis, age ≥ 70 years and no chemotherapy for RIAS were the independent poor prognostic factors for DFS. Conclusions: Our study showed that chemotherapy might reduce recurrence rate of RIAS in Japanese patients but did not improve OS. Further studies are warranted to confirm the prognostic impact and proper regimen of chemotherapy for RIAS. Citation Format: Yuri Takehara, Naoko Matsuda, Daiki Kobayashi, Atsushi Yoshida, Junko Takei, Hiroko Tsunoda, Naoki Kanomata, Hideko Yamauchi, Naoki Hayashi. Radiation induced angiosarcoma of the breast: Chemotherapy for radiation induced angiosarcoma of the breast - An individual participant data meta-analysis of Japanese population [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-23-07.

Symptomatic Recurrence and Survival Outcomes After Curative Treatment of Gastric Cancer: Does Intensive Follow-up Evaluation Improve Survival?

Intensive surveillance after treatment of gastric cancer patients with curative intent may lead to an earlier diagnosis of disease recurrence, but its impact on survival is uncertain. This study aimed to evaluate whether early diagnosis of disease recurrence among asymptomatic patients was associated with long-term survival. This retrospective study analyzed patients with stages 1 to 3C gastric adenocarcinoma treated between 1999 and 2018. All recurrence events were classified as symptomatic or asymptomatic (detected by follow-up tests), and their clinicopathologic characteristics, patterns of recurrence, and survival were analyzed. The cohort consisted of 669 patients treated with a total gastrectomy in 48.6% and a D2-lymphadenectomy in 88.8% of the cases. Most of the tumors were pT3-4 (46.5%), with 45.5% involving lymph node metastases and 42.3% manifesting a diffuse histology. During a median follow-up period of 80.1 months (95% confidence interval [CI], 75.3-84.8 months), 166 patients had recurrences (24.8%), 65.7% of which were symptomatic. The peritoneum was the main site of recurrence (37.2%), and peritoneal recurrence was associated with worse overall survival (OS) (hazard ratio, 1.69; 95%CI, 1.2-2.37). The median disease-free, post-recurrence survival, and OS periods in the asymptomatic and symptomatic groups were respectively 13.4 versus 17.2 months (p = 0.04), 11.9 versus 4.7 months (p < 0.001), and 29.9 versus 26.4 months (p = 0.21). When OS was analyzed among the patients with non-peritoneal recurrence, no difference was observed between the two groups (31.3 vs 31.1 months; p = 0.46). Early diagnosis of asymptomatic disease recurrence did not affect the OS of the gastric cancer patients treated with curative intent. The use of intensive surveillance strategies in this scenario still requires further evidence.

Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who completed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: Multicenter, real-world data (KCSG LU20-11).

BackgroundImmune checkpoint inhibitors (ICIs) have shown significant improvements in patients with advanced non–small cell lung cancer (NSCLC). One of the major issues with ICIs is determining the optimal treatment duration.MethodsThis multicenter, retrospective study analyzed clinical outcomes in patients with NSCLC who completed 2 years of ICI therapy or were treated for more than 6 months and then discontinued ICIs without disease progression at 11 medical centers in Korea between August 2017 and December 2020.ResultsNinety‐six patients who completed 2 years of ICIs were reviewed. The median durations of treatment and follow‐up were 24.0 and 33.9 months, respectively. The objective response rate (ORR) was 85.4%. The median progression‐free survival (PFS) and overall survival (OS) periods were not reached. After completion, the PFS and OS rates were 81.1% and 96.4%, respectively, at 12 months. Forty‐three patients were identified who discontinued ICIs without disease progression: 26 (60.5%) for adverse events and 17 (39.5%) for other causes. The median durations of treatment and follow‐up were 10.5 and 21.2 months, respectively. The ORR was 90.7%. The median PFS and OS periods were not reached. After discontinuation, the PFS and OS rates were 71.0% and 90.0%, respectively, at 12 months.ConclusionsA significantly high proportion of patients who completed 2 years of ICI therapy continued to experience long‐term PFS. Even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long‐term survival.Lay Summary The optimal treatment duration for immune checkpoint inhibitors (ICIs) remains to be determined.This study reports the long‐term outcomes of patients with non–small cell lung cancer who completed 2 years of ICI therapy or achieved a durable response after the discontinuation of ICIs without disease progression in real‐world practice.A significantly high proportion of patients who completed 2 years of ICIs continued to experience long‐term progression‐free survival.In addition, even if ICIs are discontinued after 6 months in patients without disease progression, they may achieve a durable response and facilitate long‐term survival.

Long-Term Survival Effect of the Interval between Postoperative Chemotherapy and Radiotherapy in Patients with Completely Resected Pathological N2 Non-Small-Cell Lung Cancer.

Simple SummaryIn patients with completely resected stage III pN2 non-small cell lung cancer (NSCLC), adjuvant chemotherapy of 4–6 cycles was recommended prior to post-operative radiotherapy (PORT). However, some were given concurrently or early-sequentially with PORT. The objectives of this study were to verify the benefit of adjuvant sequential chemotherapy and radiotherapy (SCRT) relative to that of concurrent chemoradiotherapy (CCRT) in an Asian population and to identify the optimal timing of initiation of PORT as part of adjuvant SCRT. A longer interval (>104 days and <180 days) between the initiation of adjuvant chemotherapy and PORT was associated with improved OS compared with CCRT. No locoregional recurrence-free survival (LRFS) difference related to the interval between the initiation of adjuvant chemotherapy and PORT was observed. In older patients (aged >60 years), the benefit of delayed PORT initiation was more significant. We suggest that PORT should be postponed in the completed-resected pN2 elderly patients.(1) Purpose: To investigate the effects of the time interval between initiation of adjuvant chemotherapy and radiotherapy on survival outcomes in patients with completely resected stage IIIA pN2 non-small-cell lung cancer (NSCLC); (2) Methods: Data on 2515 patients with completely resected stage IIIA pN2 NSCLC in 2007–2017 were extracted from the Taiwan Cancer Registry Database. The survival outcomes in patients who underwent concurrent chemoradiotherapy (CCRT) and sequential chemotherapy and radiotherapy (SCRT) with either a short (SCRT1) or long (SCRT2) interval between treatments were estimated using Kaplan–Meier, Cox regression, and propensity score matching (PSM); (3) Results: Multivariate analyses of OS showed that SCRT2 (hazard ratio [HR] 0.64, p = 0.017) was associated with improved overall survival (OS). After PSM, the median OS periods were 64 and 75 months in the SCRT1 and SCRT2 groups, respectively, which differed significantly from that of 58 months in the CCRT group (p = 0.003). In elderly patients, SCRT2 significantly improved survival relative to CCRT before PSM (p = 0.024) and after PSM (p = 0.002); (4) Conclusions: A longer interval between initiation of adjuvant chemotherapy and postoperative radiotherapy (PORT; SCRT2) improved OS relative to CCRT; the benefits were greater in elderly patients (age >60 years).

Cytoreductive Surgery for Selected Patients Whose Metastatic Gastric Cancer was Treated with Systemic Chemotherapy.

The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90days. The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n=25,690), metastasectomy alone (n=1170), gastrectomy alone (n=2248), and CRS (n=620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p<0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9±13.4 vs 62.0±13.1years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p<0.001 for all). The medianOS for the propensity-matched patients who underwent CRS (n=615) was longer than for those with NS (16.4 vs 9.3months; p<0.001), including inthose with clinical M1 stage (n=210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p<0.001). In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA

BackgroundBeta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time. ObjectiveTo report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA. Design, setting, and participantsTwenty-six patients were treated under a compassionate use protocol. The eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy, progression after Lu-177-PSMA, and positive PSMA-ligand uptake. The median number of previous mCRPC regimens was 6. Ac-225-PSMA-617 was given every 8 wk until progression/intolerable side effects. Outcome measurements and statistical analysisProstate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS), overall survival (OS), and toxicity were measured. Results and limitationsSixty-one cycles of Ac-225-PSMA-617 (median number of cycles 2; median activity 9 MBq) were administered. A PSA decline of ≥50% was achieved in 17/26 patients. The median PSA-PFS, cPFS, and OS periods were 3.5 (95% confidence interval [CI] 1.8–11.2), 4.1 (95% CI 3–14.8), and 7.7 (95% CI 4.5–12.1) mo, respectively. Liver metastases were associated with shorter PSA-PFS (median 1.9 vs 4.0 mo; p = 0.02), cPFS (median 1.8 vs 5.2 mo; p = 0.001), and OS (median 4.3 vs 10.4 mo; p = 0.01). Hematological grade 3/4 toxicities were anemia (35%), leucopenia (27%), and thrombocytopenia (19%). All patients experienced grade 1/2 xerostomia. Two and six patients stopped due to hematological toxicity and xerostomia, respectively. A limitation is the retrospective design. ConclusionsAc-225-PSMA-617 showed measurable antitumor effect after Lu-177-PSMA failure in late-stage mCRPC. Grade 3/4 hematological side effects were observed in up to one-third of patients, and xerostomia led to treatment halt in a relevant number of patients. Patient summaryAc-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy showed substantial antitumor effect in late metastatic castration-resistant prostate cancer after Lu-177-PSMA failure. However, dry mouth is a common side effect that caused about a quarter of patients to stop therapy.

Prognostic Nomogram for Patients with Hepatocellular Carcinoma After Thermal Ablation.

To develop an effective prognostic nomogram for patients with hepatocellular carcinoma (HCC) after thermal ablation. A total of 772 patients with intrahepatic primary or recurrent HCC who underwent radiofrequency ablation or microwave ablation between March 2011 and October 2016 were included. 602 patients (mean age, 56.0 ± 11.9years; 495 male/107 female) were included in the primary cohort to establish a prognostic nomogram. Significant prognostic factors for overall survival (OS) identified by Cox univariate and multivariate regression analyses were used to construct the nomogram. The remaining 170 patients (mean age, 55.9 ± 11.9years; 145 male/25 female) were used to validate the predictive accuracy of the nomogram. During a mean follow-up period of 26months (range 1-85months), the median OS periods were 48.6months and 44.0months for the primary and validation cohorts. The 1-, 3-, and 5-year OS rates were 85.5%, 61.4%, and 43.3% in the primary cohort and 84.7%, 59.6%, and 43.3% in the prospective validation cohort, respectively. Multivariate analysis found that pre-ablation treatment, AFP, CEA, CA19-9, ALBI grade, tumor number, and tumor size (hazard ratio > 1, P < 0.05) were independent risk factors for OS. A nomogram was developed based on these seven variables. The calibration curve for predicting the probability of survival showed a good agreement between the nomogram and actual observation both in the primary (concrete index: 0.699) and validation cohorts (concrete index: 0.734). This simple nomogram based on seven variables including ALBI grade offers personalized prognostic data for HCC patients after ablation. Level 4, case series.

Skeletal muscle density as a positive predictive factor for nivolumab therapy in patients with metastatic renal cell carcinoma.

e17107 Background: Immunotherapy has shown promising clinical responses in patients with metastatic Renal Cell Carcinoma (mRCC) at second-line therapy. Since objective response rates are highly variable, it is utmost important to identify patients who may benefit from immunotherapy to avoid unnecessary adverse effects and costs. Therefore, predictive as well as prognostic markers need to be studied extensively. To our knowledge, none of the body composition measurements such as fat content or skeletal muscle density have been assessed for this purpose. The objective of the current study is to analyze whether skeletal muscle (either muscle mass or muscle density) and adipose tissue play a prognostic role in patients with mRCC who were treated with immunotherapy at second line. Methods: We retrospectively analyzed 14 patients with mRCC who were progressed after tyrosine kinase inhibitor therapy and treated with Nivolumab between March 2016 and September 2019. Skeletal muscle density (SMD), skeletal muscle and adipose tissue were assessed with computed tomography imaging. Overall Survival (OS) and Progression Free Survival (PFS) were estimated by using the Kaplan-Meier method. Results: The median OS was 13,1 months and it was strongly associated with SMD; the median OS was significantly longer in patients with high SMD compared to patients with low SMD (6,9 months vs 18,5 months; P &lt; 0,05). Also in our analysis, SMD separated the intermediate-risk group into 2 groups with different median OS periods, ranging from 8,1 months (95% confidence interval [95% CI], 5,1 months-11,1 months) in patients with intermediate-risk Heng score and low SMD to 21,5 months (95% CI, 14 months-27 months) in patients with an intermediate-risk Heng score and high SMD. Other parameters calculated for adipose tissue or skeletal muscle did not cause any significant change in survival analysis. Conclusions: High SMD appears to be associated with improved outcome in our small patient population. It could be a predictive factor when immunotherapy, Nivolumab, is considered for therapy of mRCC patients at second line.

Deferred Cytoreductive Nephrectomy in Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma

BackgroundThe use of cytoreductive nephrectomy (CN) selectively for patients who show a favorable response to upfront systemic therapy may be an approach to select optimal candidates with metastatic renal cell carcinoma (mRCC) who are most likely to benefit. ObjectiveWe sought to characterize outcomes of deferred CN (dCN) after upfront sunitinib, outcomes relative to sunitinib alone, and outcomes of CN followed by sunitinib. Design, setting, and participantsWe used the prospectively maintained International mRCC Database Consortium (IMDC) database to identify patients with newly diagnosed mRCC (2006–2018). InterventionSunitinib alone, upfront CN followed by sunitinib, sunitinib followed by dCN. Outcome measurements and statistical analysisOutcomes were overall survival (OS) and time to sunitinib treatment failure (TTF). Kaplan-Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results and limitationsWe evaluated 1541 patients, of whom 651 (42%) received sunitinib alone, 805 (52%) underwent CN followed by sunitinib, and 85 (5.5%) received sunitinib followed by dCN, at a median of 7.8 mo from diagnosis. Median OS periods for patients treated with sunitinib alone, CN followed by sunitinib, and sunitinib followed by dCN were 10, 19, and 46 mo, respectively, while the median TTF values were 4, 8, and 13 mo, respectively. In multivariable regression analyses, sunitinib followed by dCN was significantly associated with improved OS (hazard ratio [HR] = 0.45, 95% confidence interval [CI] 0.33–0.60, p < 0.001) and TTF (HR = 0.62, 95% CI 0.46–0.85, p = 0.003) versus sunitinib alone. Among CN-treated patients, sunitinib followed by dCN was associated with improved OS (HR = 0.52, 95% CI 0.39–0.70, p < 0.001) and TTF (HR = 0.71, 95% CI 0.56–0.90, p = 0.005) compared with upfront CN followed by sunitinib. In various sensitivity analyses, dCN remained significantly associated with improved OS and TTF. ConclusionsPatients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. Patient summaryWe characterized benchmark survival outcomes for patients with metastatic kidney cancer treated with sunitinib alone, nephrectomy (kidney removal) followed by sunitinib, and sunitinib followed by nephrectomy. Patients who had their nephrectomy after an initial course of sunitinib had prolonged survival.

MP14-05 A HIGHER CONTROLLING NUTRITIONAL STATUS (CONUT) SCORE IS AN ADVERSE PROGNOSTIC FACTOR IN METASTATIC RENAL CELL CARCINOMA TREATED WITH NIVOLUMAB

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Apr 2020MP14-05 A HIGHER CONTROLLING NUTRITIONAL STATUS (CONUT) SCORE IS AN ADVERSE PROGNOSTIC FACTOR IN METASTATIC RENAL CELL CARCINOMA TREATED WITH NIVOLUMAB Kosuke Takemura*, Ryo Fujiwara, Takeshi Yuasa, Junji Yonese, Yasukazu Nakanishi, Masaya Ito, Madoka Kataoka, Hiroaki Suzuki, Noriyuki Iida, Honoka Fuse, and Fumitaka Koga Kosuke Takemura*Kosuke Takemura* More articles by this author , Ryo FujiwaraRyo Fujiwara More articles by this author , Takeshi YuasaTakeshi Yuasa More articles by this author , Junji YoneseJunji Yonese More articles by this author , Yasukazu NakanishiYasukazu Nakanishi More articles by this author , Masaya ItoMasaya Ito More articles by this author , Madoka KataokaMadoka Kataoka More articles by this author , Hiroaki SuzukiHiroaki Suzuki More articles by this author , Noriyuki IidaNoriyuki Iida More articles by this author , Honoka FuseHonoka Fuse More articles by this author , and Fumitaka KogaFumitaka Koga More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000839.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The controlling nutritional status (CONUT) score, consisting of serum albumin, lymphocytes, and cholesterol, is an efficient tool for nutritional assessment. We explored the prognostic impact of malnutrition evaluated by the CONUT score on metastatic renal cell carcinoma (mRCC). METHODS: Between 2013 and 2019, 64 patients with mRCC were treated with nivolumab at two cancer centers. Of these, 60 patients with mRCC were subjects of this retrospective study, with four patients excluded due to missing data. Clinical variables collected from medical records were as follows: Age, gender, Karnofsky performance status (KPS), body mass index, histology, metastatic sites, treatments given, and laboratory data including CONUT score at the start of nivolumab. CONUT scores were interpreted as normal (0-1 points), light malnutrition (2-4 points), and moderate/severe malnutrition (≥5 points) according to the original definition of the undernutrition degree. Kaplan-Meier curves and associations of clinical variables with overall survival (OS) were analyzed by log-rank test and Cox proportional hazard model, respectively. RESULTS: The median (range) CONUT score was 2 (0-10). A higher CONUT score was associated with poorer KPS (P=0.015) and lower hemoglobin (P<0.001). During follow-up periods (median=22.1 months), 14 (23%) patients died. The median OS periods for patients with normal, light, and moderate/severe malnutrition were 26.5, 21.1, and 9.8 months, respectively (P=0.002). Univariable analysis revealed a higher CONUT score (≥2 points) to be a significant adverse prognostic factor (malnutrition vs normal, hazard ratio [HR]=14.49, P=0.011), along with poorer KPS (HR=7.45, P=0.003) and absence of prior nephrectomy (HR=7.85, P<0.001). Incorporation of a higher CONUT score into established prognostic models, the MSKCC and IMDC models, increased their Harrell's C-indices from 0.680 to 0.787 and from 0.684 to 0.789, respectively. CONCLUSIONS: The present study for the first time demonstrated the prognostic significance of the CONUT score in patients with mRCC treated with nivolumab. The CONUT score indicates patients’ general conditions from the aspect of nutritional status and appears to be a useful prognosticator. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e196-e197 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kosuke Takemura* More articles by this author Ryo Fujiwara More articles by this author Takeshi Yuasa More articles by this author Junji Yonese More articles by this author Yasukazu Nakanishi More articles by this author Masaya Ito More articles by this author Madoka Kataoka More articles by this author Hiroaki Suzuki More articles by this author Noriyuki Iida More articles by this author Honoka Fuse More articles by this author Fumitaka Koga More articles by this author Expand All Advertisement PDF downloadLoading ...

Prognostic significance of the controlling nutritional status (CONUT) score in advanced urothelial carcinoma patients

Introduction & ObjectivesThe controlling nutritional status (CONUT) score, consisting of serum albumin, total lymphocyte count, and total cholesterol, is a validated and objective tool for nutritional assessment. Cancer-bearing patients often suffer from malnutrition in association with cachexia. We explored the prognostic role of malnutrition evaluated by the CONUT score in advanced urothelial carcinoma (aUC) patients. Materials & MethodsBetween 2003 and 2018, 201 aUC patients with cT4 and/or metastases to lymph nodes/distant organs were treated at a single cancer center. Of these, 185 were subjects of this retrospective study, with 16 excluded due to missing data. Clinical variables examined included age, sex, performance status (PS), body mass index (BMI), primary tumor site, lymph node/visceral metastasis, treatments before and after the diagnosis of aUC, hemoglobin, lactate dehydrogenase, alkaline phosphatase (ALP), C-reactive protein (CRP) and the CONUT score. Associations between clinical variables and overall survival (OS) were examined using the Cox proportional hazards model. ResultsThe median (range) CONUT score was 2 (0–8). A higher CONUT score was associated with poorer PS (P < 0.001), lower BMI (P = 0.007), lower hemoglobin (P < 0.001), higher ALP (P = 0.005), and higher CRP (P < 0.001). During follow-up (median 12.3 months), 133 (72%) patients died. The median OS periods for patients with CONUT scores of 0 to 1, 2 to 3 and ≥4 were 19.3, 13.3, and 7.7 months, respectively (P < 0.001). Multivariate analysis revealed a higher CONUT score to be an independent and significant adverse prognostic factor (2–3 vs. 0–1, hazard ratio [HR] 1.57, P = 0.024; ≥4 vs 0–1, HR 2.94, P < 0.001), along with greater age (P = 0.003), poorer PS (P = 0.006), lower BMI (P = 0.008), primary tumor site in the upper tract (P = 0.004), higher CRP (P < 0.001), no usage of pembrolizumab (P = 0.005), and no curative treatment after the diagnosis of aUC (P = 0.035). ConclusionThis study showed the prognostic significance of the CONUT score in aUC patients. The CONUT score indicates a patient's general condition from the aspect of nutritional status, and appears to be independent of PS as a prognosticator.

Randomized, phase II trial of sequential hepatic arterial infusion chemotherapy and sorafenib versus sorafenib alone as initial therapy for advanced hepatocellular carcinoma: SCOOP-2 trial

BackgroundThe efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC.MethodsPatients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety.ResultsFor the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0–18.8) in the HAIC group and 15.2 months (95% CI, 8.2–19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7–5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3–6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group.ConclusionsSequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution.Trial registrationUMIN ID 000006147, registration data: August 11, 2011.

P1.12-02 Phase II Study of Amrubicin Monotherapy in Elderly or Poor-Risk Patients with Extensive Disease of Small Cell Lung Cancer

Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1–6 cycles). ORR was 52.8% [95% confidence interval (CI), 37–69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4–6.6 months) and 9.4 months (95% CI, 5.2–13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027). Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMI11055 www.clinicaltrials.gov).