Overall Survival Curves Research Articles

Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma

ABSTRACT Background Talimogene laherparepvec (T-VEC) improves overall survival (OS) in unresectable stage IIIB/C-IV melanoma T-VEC may have synergistic effects with CTLA-4 inhibitors In the absence of a trial comparing T-VEC and ipilimumab (T-VEC + IPI) to T-VEC, we applied a novel indirect comparison method using extrapolated OS curves to estimate OS outcomes in a simulated trial comparing both regimens in stage IIIB/C-IV unresectable melanoma. Research Design and Methods Two trials with extractable OS curves for a T-VEC versus T-VEC + IPI comparison were identified. Outcomes were adjusted for heterogeneity in prognostic factors using a calculated adjustment factor. T-VEC and adjusted/unadjusted T-VEC+IPI curves were plotted with 95% CIs. Results Unadjusted indirect OS comparison of T-VEC versus T-VEC + IPI revealed no significant difference up to 15 months. Extrapolation beyond 15 months showed significant survival benefits for T-VEC + IPI over T-VEC, confirmed in adjusted analyses. The expected OS percentage at 48 months is 32.0% (95% CI = 26.6–37.3) for T-VEC, 60.0% (95% CI = 46.2–69.1) for unadjusted, and 81.1% (95% CI = 72.3–85.9) for adjusted T-VEC + IPI. Conclusions Our novel indirect comparison suggests that T-VEC + IPI may demonstrate a significantly improved OS versus T-VEC alone. Findings may portend a possible role for the addition of T-VEC to advanced melanoma treatment regimens in select patients as salvage therapy.

The Impact of Palliative Transurethral Resection of the Prostate on the Prognosis of Patients With Bladder Outlet Obstruction and Metastatic Prostate Cancer: A Population-Matched Study.

Objective: This study aimed to evaluate the survival outcomes of patients with bladder outlet obstruction (BOO) and metastatic prostate cancer (mPCa) after having a palliative transurethral resection of the prostate (pTURP) surgery.Methods: We identified patients with mPCa between 2004 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received pTURP and non-surgical therapy were identified. A propensity-score matching was introduced to balance the covariate. Kaplan–Meier analysis and COX regression were conducted to evaluate the overall survival (OS) and cancer-specific survival (CSS) outcomes.Results: A total of 36,003 patients were identified; 2,823 of them were in the pTURP group and 33,180 were in the non-surgical group. The survival curves of the overall cohort showed that the pTURP group was associated with worse outcomes in both OS (HR: 1.12, 95% CI: 1.07–1.18, p < 0.001) and CSS (HR: 1.08, 95% CI: 1.02–1.15, p = 0.004) compared with the non-surgical group. The mean survival time in the overall cohort of the pTURP group was shorter than the non-surgical group in both OS [35.13 ± 1.53 vs. 40.44 ± 0.59 months] and CSS [48.8 ± 1.27 vs. 55.92 ± 0.43 months]. In the matched cohort, the pTURP group had significantly lower survival curves for both OS (HR: 1.25, 95% CI: 1.16–1.35, p < 0.001) and CSS (HR: 1.23, 95% CI: 1.12–1.35, p < 0.001) than the non-surgical group. pTURP significantly reduced the survival months of the patients (36.49 ± 0.94 vs. 45.52 ± 1.23 months in OS and 50.1 ± 1.49 vs. 61.28 ± 1.74 months in CSS). In the multivariate COX analysis, pTURP increased the risk of overall mortality (HR: 1.19, 95% CI: 1.09–1.31, p < 0.001) and cancer-specific mortality CSS (HR: 1.23, 95% CI: 1.14–1.33, p < 0.001) compared with the non-surgical group.Conclusions: For mPCa patients with BOO, pTURP could reduce OS and CSS while relieving the obstruction.

Nomogram Based on Log Odds of Positive Lymph Nodes Predicting Cancer-Specific Survival in Patients With T3 and T4 Gallbladder Cancer After Radical Resection.

Background: The aim of this study based on log odds of positive lymph nodes (LODDS) is to develop and validate an effective prognostic nomogram for patients with T3 and T4 gallbladder cancer (GBC) after resection.Patients and Methods: A total of 728 T3 and T4 gallbladder cancer patients after resection from the Surveillance, Epidemiology, and End Results (SEER) database, randomly divided into training cohort and validation cohort according to 7:3. Another 128 patients from The Second Affiliated Hospital of Nanchang University for external validation. The nomograms were built by the Cox regression model and the Fine and Grey's model. Concordance index (C-index), calibration curve and the area under receiver operating characteristic (ROC) curve (AUC) were used to evaluate the nomogram and internal verification. The decision curve analysis (DCA) was used to measure clinical applicability.Result: LODDS was independent prognostic predictor for overall survival (OS) and cancer-specific survival (CSS), and established the nomograms on this basis. The nomogram we have established has a good evaluation effect, with a C-index of 0.719 (95%CI, 0.707–0.731) for OS and 0.747 (95%CI, 0.733–0.760) for CSS. The calibration curves of OS and CSS both showed good calibration capability, and the AUC for predicting 1-, 2-, and 3-year 0.858, 0.848 were and 0.811 for OS, and 0.794, 0.793, and 0.750 for CSS. The DCA of nomograms both showed good clinical applicability.Conclusion: The nomogram can provide effective OS and CSS prediction for patients with advanced gallbladder cancer after surgery.

Hospital-Based Registry Analysis of Staging Efficacy and Proposed Substaging for HPV Positive Oropharynx Cancers

The American Joint Committee on Cancer (AJCC) introduced the 8th edition staging for cancer in 2017, which provided separate staging for HPV+ oropharyngeal cancer (OPC). This update simplified staging with the intent of restoring prognostic discrimination between stages with regard to disease-specific survival. However, it also altered implications for treatment as many patients formerly classified as group stage I-IVA in the 7th edition, treated with either single or multimodality therapy including chemoradiation, were now classified as stage I. We used the National Cancer Database (NCDB) to study the efficacy of AJCC staging in a modern cohort of HPV+ OPC in the years prior to the introduction of AJCC 8th edition, and explore substaging of the AJCC 8th edition in order to provide better guidance for treatment.We queried the NCDB for patients with HPV+ OPC as their first primary cancer diagnosis, with known radiotherapy, surgery, and chemotherapy treatment status and without mortality within 90 days of surgery. Clinical T, N, and M stages per AJCC 7th edition were converted to AJCC 8th edition staging. Kaplan-Meier estimates were generated for overall survival (OS) at 5 years and compared using log-rank testing. Cox-proportional hazards models were generated to test for significant predictors of overall survival which were then used to generate substages for AJCC 8th edition stage I patients.A total of 8249 patients diagnosed from 2010-2016 met search criteria. Median age was 57 years (22-90). By AJCC 7th edition, 6% (470) of patients were group stage I, 10% (839) stage II, 23% (1913) stage III, 58% (4755) stage IVA, and 3% (272) stage IVB/C. A Cox-proportional hazards model including AJCC 7th edition T and N stage as covariates was generated using 5933 patients with clinical T1-2N0-2b staging, showing significant association of cT2 and cN2b status with OS (P = < 0.001, HR of 1.7 [95% CI 1.4-2.1] and 1.4 [95% CI 1.2-1.8] respectively). These results were used for substaging of AJCC 8th edition group stage I: cT1N0-2a were designated stage IA, cT2N0-2a and cT1N2b as stage IB, and cT2N2b as stage IIA. Using this substaging, log-rank testing between substages showed significant differences between the respective curves for OS at 5 years (P < 0.01 for all comparisons).Substaging of AJCC 8th edition group staging for HPV+ OPC provided significant hazard stratification for patients currently classified as group stage I, with subclassification by cT2 and cN2b (7th ed stage) showing significant association with OS at 5 years. Substaging by these factors not only maintains prognostic risk stratification, but also may provide better guidance in treatment decision making. For example, stage IA patients could be treated with either with surgery or radiation alone, stage IB with either single or multimodality therapy, and stage IIA and above would be treated with multimodality therapy. Further validation of this staging is warranted.

Prognostic implications of staging right heart failure in patients with significant tricuspid regurgitation undergoing tricuspid valve surgery

Abstract Introduction Mortality of tricuspid valve (TV) surgery for severe secondary tricuspid regurgitation (TR) remains relatively high. Current guidelines advise surgery in patients with symptomatic severe TR as a concomitant procedure to left-sided valve surgery. Right ventricular (RV) dysfunction is an important prognostic marker and may appear late in the natural history of TR. How a staging algorithm of right heart failure (RHF) may impact on TV surgery outcomes has not been evaluated. Purpose To evaluate the impact of staging RHF on survival of patients with significant TR undergoing TV surgery. Methods Patients diagnosed with significant (moderate and severe) TR who subsequently underwent TV surgery, were staged into 4 groups of progressive disease according to the diagnosis of RV dysfunction and the presence of RHF: stage 1, at risk for RHF; stage 2, RV dysfunction without clinical symptoms of RHF; stage 3, RV dysfunction with symptoms of RHF, and stage 4, RV dysfunction with refractory symptoms of RHF (Figure 1). The study endpoint was all-cause mortality. Results A total of 279 patients (mean age 64±12 years, 49% male), were included in the analysis, of which 20 patients (7%) were in stage 1, 14 patients (5%) were in stage 2, 141 patients (51%) were in stage 3 and 104 patients (37%) were in stage 4. The majority of the patients (266 patients, 95%) underwent TV annuloplasty. Most patients had TV surgery concomitant to left-sided valve surgery or coronary artery bypass grafting (254 patients, 91%). In per-group analysis, patients in stage 4 had significantly larger left ventricular (LV) and RV dimensions, lower LV ejection fraction and more severe diastolic dysfunction than patients in other RHF stages. During a median follow-up of 65 [15 - 106] months after TV surgery, 145 deaths (52%) occurred. The cumulative survival rates were 88%, 77% and 60% at 1 month, 1 year and 5 years, respectively. The Kaplan-Meier curves for overall survival according to RHF stage are shown in Figure 2. Survival rates at 5 years were significantly worse in more advanced stages of RHF: 71% (stage 1 and 2), 66% (stage 3) and 49% (stage 4); log-rank chi-square: 11.302; p=0.004. Right heart failure stage was independently associated with all-cause mortality following adjustment for age, gender, LV ejection fraction, kidney function, TV annulus diameter, concomitant mitral valve surgery and time delay from diagnosis until surgery (p=0.021). Conclusion Patients diagnosed with significant TR may benefit from earlier referral for surgical intervention, before presenting with RV dysfunction and before the onset of symptoms of RHF. Funding Acknowledgement Type of funding sources: None. Figure 1. Stages of right heart failureFigure 2. Kaplan-Meier curves for overall survival

Cost-effectiveness analysis of the first‐line EGFR‐TKIs in patients with advanced EGFR-mutated non-small-cell lung cancer

ABSTRACT Aim To evaluate the cost-effectiveness of first-line treatments, such as erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib, for patients diagnosed with stage IIIB/IV NSCLC harboring EGFR mutations. Materials & methods A partitioned survival model was developed to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER) from the perspective of the Spanish National Health System. Two Bayesian NMAs were performed independently, by using the polynomial fraction method to fit Kaplan–Meier curves for overall survival and progression-free survival. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. Results The ICER was calculated for the four first-line treatments by comparing them with gefitinib, and the ratios obtained were as follows: €166,416/QALY for osimertinib, €183,682/QALY for dacomitinib, €167,554/QALY for afatinib, €36,196/QALY for erlotinib. It was seen that patients who received osimertinib presented higher QALYs (0.49), followed by dacomitinib (0.33), afatinib (0.32), erlotinib (0.31), and gefitinib (0.28). Conclusions Gefitinib is the most cost-effective treatment. In terms of QALYs gained, Osimertinib was more effective than all other TKIs. Nevertheless, with a Spanish threshold of €24,000/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 70%, to obtain a cost-effectiveness alternative.

MA09.05 PD1-Positive Tertiary Lymphoid Structure as a Predictive Factor of Durable Clinical Effect in Immunotherapy for NSCLC

There is urgent need for accurate biomarkers in immunotherapy (IO) for advanced or recurrent lung cancer. In 2020, tertiary lymphoid structure (TLS) of cancer tissue was reported to be related with IO response and is attracting attention as a new biomarker. In the current study, we investigated whether TLS and its lymphocyte distribution are associated with durable clinical effect (DCR) by IO in postoperative recurrent non-small cell lung cancer (NSCLC) patients. Between 2016 and 2019, 55 patients were treated with IO for recurrent NSCLCs. Tumor pathology and TLS were evaluated by H&E and immunohistochemical staining. DCR was defined as ‘tumor maintaining stable disease or better for more than one year after IO’, and the patients were divided to DCR and non-DCR group. Their clinicopathological factors, the number of TLS or tumor infiltrating lymphocytes (TIL) and lymphocytic subset in TLS were compared between the two groups. The median age of all 55 patients was 68 years and 43 (78%) of them were men. Histological types of their tumors were 39 (71%) adenocarcinomas, 8 (15%) squamous cell carcinomas, and 3 (6%) large cell neuroendocrine carcinomas. DCR was observed in 14 (26%) patients, and included significantly younger patients (70 years old or less), more PD-L1 expression scores (TPS), more CD8-positive TIL, more PD1-positive TLS (PD1+TLS) and more immune-related adverse event (irAE, Grade 3 and more) than non-DCR group. There were not significant differences in pathological findings including histological type, pathological stage, pleural invasion, vessel invasion, predominant subtypes in adenocarcinoma. Multivariate analysis revealed that age, PD1+TLS and irAE were independent predictive factors of DCR. In DCR group, 1- and 3-year overall survival (OS) rate after IO treatment was 100 and 81%, respectively, while those in non-DCR group were 37 and 7%, respectively. Their post-IO OS curves were significantly different (p <0.01). We explored predictive factors for DCR in IO-treated recurrent NSCLC patients. PD1+ TLS was an independent positive factor of DCR.

Short- and long-term survival outcomes among never smokers who developed lung cancer

BackgroundLung cancer is the leading cause of cancer death in the US. While an extensive literature exists detailing lung cancer risk factors and mortality among patients with a history of tobacco use, the data are more limited among individuals who have never smoked. The purpose of this investigation is to compare survival rates between the two groups and evaluate potential risk factors among never smokers. MethodsThis retrospective study included 3380 smokers and 334 never smokers who were diagnosed with lung cancer at Stony Brook University Hospital between 2003 and 2016. 1-, 3-, 5- and 10-year survival outcomes, stratified by smoking status, were compared and Kaplan-Meier curves for overall survival are provided. Cox Proportional Hazard models were used to evaluate factors influencing survival among never smokers. ResultsNever smokers with lung cancer were more likely to be female, be diagnosed with adenocarcinoma histology, and had fewer comorbidities than lung cancer patients who smoked. Although 60% of patients were diagnosed at a later stage of disease development, regardless of smoking status, overall short- and long-term survival was significantly higher among never smokers compared to those with a history of tobacco use. In addition to age and stage at diagnosis, a history of diabetes was found to be a significant prognostic factor for decreased survival among never smokers (HR=3.15, 95% CI (1.74, 5.71)). ConclusionsData from the present investigation suggest that, regardless of smoking status, approximately three of every five lung cancer patients are diagnosed at a later stage, and that both short- and long-term survival outcomes are significantly better among never smokers compared to those with a history of tobacco use. Additional studies are required to validate these findings and better explain the mechanistic drivers for the improved outcomes among never smokers.

Epidemiologic Trends of and Factors Associated With Overall Survival for Patients With Gastroenteropancreatic Neuroendocrine Tumors in the United States

Although the incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have been thought to have increased during the past decades, updated epidemiologic and survival data are lacking. To conduct an epidemiologic and survival analysis of the largest cohort of patients with GEP-NETs using the latest data and to establish a novel nomogram to predict the survival probability of individual patients with GEP-NETs. In this cohort study, 43 751 patients with GEP-NETs diagnosed from January 1, 1975, to December 31, 2015, were identified from the Surveillance, Epidemiology, and End Results Program. Associated data were used for epidemiologic and survival analysis, as well as the establishment and validation of a nomogram to predict the survival probability of individual patients with GEP-NETs. The study cutoff date was December 31, 2018. Statistical analysis was performed from February 1 to April 30, 2020. Incidence, factors associated with overall survival, and a nomogram model for patients with GEP-NETs. A total of 43 751 patients received a diagnosis of GEP-NETs from 1975 to 2015 (22 398 women [51.2%], 31 976 White patients [73.1%], 7097 Black patients [16.2%], 3207 Asian and Pacific Islander patients [7.3%], 270 American Indian and Alaska Native patients [0.6%], and 4546 patients of unknown race [10.4%]; mean [SD] age at diagnosis, 58 [15] years). The age-adjusted incidence rate of GEP-NETs increased 6.4-fold from 1975 to 2015 (annual percentage change [APC], 4.98; 95% CI, 4.75-5.20; P < .001). Furthermore, among site groups, the incidence of GEP-NETs in the rectum increased most significantly (APC, 6.43; 95% CI, 5.65-7.23; P < .001). As for stage and grade, the incidence increased the most in localized GEP-NETs (APC, 6.53; 95% CI, 6.08-6.97; P < .001) and G1 GEP-NETs (APC, 18.93; 95% CI, 17.44-20.43; P < .001). During the study period, the mean age at diagnosis for localized disease increased by 9.0 years (95% CI, 3.3-14.7 years; P = .002), which remained unchanged for regional and distant cases. On multivariable analyses, age, sex, marital status, and tumor size, grade, stage, and site were significantly associated with overall survival for patients with GEP-NETs (eg, patients with distant vs localized disease: hazard ratio, 10.32; 95% CI, 8.56-12.43; G4 vs G1 GEP-NET: hazard ratio, 6.37; 95% CI, 5.39-7.53). Furthermore, a nomogram comprising age, size, grade, stage, and site was established to predict the 3-year and 5-year survival probability, with the concordance indexes of 0.893 (95% CI, 0.883-0.903) for the internal validations and 0.880 (95% CI, 0.866-0.894) for the external validations. The receiver operating characteristic curve demonstrated that the nomogram exhibited better discrimination power than TNM classification (area under the curve for 3-year overall survival, 0.908 vs 0.795; for 5-year overall survival, 0.893 vs 0.791). In this study, the incidence and prevalence of GEP-NETs have continued to increase over 40 years, especially among patients with rectal GEP-NETs. In addition, this study suggests that a nomogram with 5 prognostic parameters may accurately quantify the risk of death among patients with GEP-NETs, indicating that it has satisfactory clinical practicality.

Overall Survival of Patients Receiving Cisplatin or Carboplatin for Primary Metastatic Urothelial Carcinoma of the Bladder: A Contemporary Dutch Nationwide Cohort Study

BackgroundCisplatin is preferred to carboplatin when treating metastatic urothelial carcinoma of the bladder (mUCB), despite its greater toxicity. Randomised studies underpinning this have been performed in noncontemporary populations with limitations in sample sizes and analyses, affecting their validity in current clinical practice. ObjectiveTo estimate overall survival (OS) and assess the benefit of cisplatin-based regimens over carboplatin-based regimens in a contemporary cohort of patients with mUCB. Design, setting, and participantsA nationwide retrospective cohort study was conducted in patients diagnosed with de novo mUCB in the Netherlands between 2016 and 2019, who underwent first-line treatment with cisplatin- or carboplatin-based chemotherapy, based on the data from the Netherlands Cancer Registry. Outcome measurements and statistical analysisA propensity model for receiving cisplatin-based chemotherapy based on age, sex, age-adjusted Charlson Comorbidity Index, renal function, performance status, serum haemoglobin, and the presence of visceral and bone metastases was used to produce inverse probability weighting (IPW) per patient. Unadjusted and IPW-adjusted Kaplan-Meier OS curves of both chemotherapy groups were compared by restricted mean survival time (RMST). Results and limitationsOf the 1041 patients with mUCB, 359 received either cisplatin (n = 170; 47%) or carboplatin (n = 189; 53%) as first line. The cisplatin group was younger, had fewer comorbidities, and had better performance status and renal function. The median OS in the cisplatin and carboplatin groups was 13.1 and 11.5 mo, respectively. After IPW adjustment, prognostic factors were balanced between the two chemotherapy groups (standardised differences <0.1), and differences in RMST were <2.0 mo and not statistically significant up to 24 mo. ConclusionsAfter accounting for all known prognostic factors, we found no significant survival benefit for cisplatin over carboplatin as first-line chemotherapy in mUCB. Patient summaryIn this study, we compared the survival benefits of cisplatin- and carboplatin-based chemotherapy for patients with metastatic bladder cancer.

Effects of 225Ac-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis.

Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, has become a popular target for radionuclide-based theranostic applications in the advanced stages of prostate cancer. We conducted a meta-analysis of the therapeutic effects of PSMA-targeting α-therapy (225Ac-PSMA radioligand therapy [RLT]) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: A systematic search was performed using the keywords "mCRPC," "225Ac-PSMA," and "alpha therapy." Therapeutic responses were analyzed as the pooled proportions of patients with more than a 50% prostate-specific antigen (PSA) decline and any PSA decline. Survival outcomes were analyzed by estimating summary survival curves for progression-free survival and overall survival. Adverse events were analyzed as the pooled proportions of patients with xerostomia and severe hematotoxicity (anemia, leukocytopenia, and thrombocytopenia). Results: Nine studies with 263 patients were included in our meta-analysis. The pooled proportions of patients with more than a 50% PSA decline and any PSA decline were 60.99% (95% CI, 54.92%-66.83%) and 83.57% (95% CI, 78.62%-87.77%), respectively. The estimated mean progression-free survival and mean overall survival were 9.15 mo (95% CI, 6.69-11.03 mo) and 11.77 mo (95% CI, 9.51-13.49 mo), respectively. The pooled proportions of patients with adverse events were 62.81% (95% CI, 39.34%-83.46%) for xerostomia, 14.39% (95% CI, 7.76%-22.63%) for anemia, 4.12% (95% CI, 0.97%-9.31%) for leukocytopenia, and 7.18% (95% CI, 2.70%-13.57%) for thrombocytopenia. Conclusion: In our study, around 61% of patients had more than a 50% PSA decline and 84% of patients had any PSA decline after 225Ac-PSMA RLT. The common adverse events in 225Ac-PSMA RLT were xerostomia in 63% of patients and severe hematotoxicity in 4%-14% of patients.

A Real-World, Population-Based Retrospective Analysis of Therapeutic Survival for Recurrent Localized Renal Cell Carcinoma After Nephrectomy.

We retrospectively analyzed therapeutic strategies and risk factors for overall survival (OS) in disease recurrence following curative nephrectomy for localized renal cell carcinoma (loRCC) using the Korean National Cancer Registry Database. We selected 1295 recurrent loRCC patients who underwent either partial or radical nephrectomy from 2007–2013. Patients were excluded for age <19 years, secondary RCC, multiple primary tumors, other SEER stages except for a localized or regional stage, postoperative recurrence within 3-month, and non-nephrectomized cases. Four therapeutic groups were statistically analyzed for OS and risk factors: surgery (OP, 12.0%), other systemic therapy (OST, 59.5%), radiotherapy (RT, 2.8%), and targeted therapy (TT, 25.8%). The overall mortality rate for recurrent loRCC was 32.5%, including 82.4% for RCC-related deaths. The baseline comparison among groups showed statistical differences for the diagnostic age of cancer and the SEER stage (p<0.05). Multivariate analysis of OS showed significance for the TT (hazard ratio [HR]: 6.27), OST (HR: 7.05), and RT (HR: 7.47) groups compared with the OP group, along with significance for the sex, SEER stage, and the time from nephrectomy to treatment for disease recurrence (p<0.05). The median OS curve showed a significantly better OS in the OP group (54.9 months) compared with the TT, OST, and RT groups (41.7, 42.9, and 38.0 months, respectively; p<0.001). In conclusion, the surgery-treated group had the best OS among the different therapeutic strategies for recurrent loRCC after nephrectomy, and the importance of the time from nephrectomy to secondary treatment was a significant prognostic factor.

MP24-04 LONG-TERM OUTCOMES OF PHASE 1 STUDY ON CYTOREDUCTIVE RADICAL PROSTATECTOMY: IS CURE POSSIBLE?

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-04 LONG-TERM OUTCOMES OF PHASE 1 STUDY ON CYTOREDUCTIVE RADICAL PROSTATECTOMY: IS CURE POSSIBLE? Joshua Sterling, Arnav Srivastava, Bertram Yuh, Seok Soo Byun, Shigeo Horie, and Isaac Kim Joshua SterlingJoshua Sterling More articles by this author , Arnav SrivastavaArnav Srivastava More articles by this author , Bertram YuhBertram Yuh More articles by this author , Seok Soo ByunSeok Soo Byun More articles by this author , Shigeo HorieShigeo Horie More articles by this author , and Isaac KimIsaac Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Roughly 4% of new prostate cancer (Pca) patients will be diagnosed with metastatic disease. Traditional treatments for these patients have focused on symptomatic relief and prevention of skeletal events. The dogma that there is no role for surgery in this population has started to be questioned. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy. METHODS: This is a multicenter phase 1 trial (NCT02458716). The major inclusion criteria was biopsy proven Pca with evidence of metastasis by MRI, CT, bone scan, or histologic confirmation. Primary end point was the major complication rate. Secondary outcomes were biochemical progression and overall survival. RESULTS: The patient characteristics of the 33 patients are included in this analysis are shown in table 1. With the median follow-up of 46 months, 25 out of the 33 patients (75%) are still alive at time of last contact. Kaplan Meier curve for overall survival is seen in figure 1. 15 patients still have an undetectable PSA. Among these men, seven were switched to intermittent androgen deprivation therapy and five remain free of any evidence of disease after more than two years off all systemic therapy and normalization of testosterone. Long term pad-free rate was 30.3%. CONCLUSIONS: Overall survival with a median follow-up of 46 months was 75% following cytoreductive radical prostatectomy. Importantly, 15% remain free of any evidence of disease off all systemic therapy for more than two years with normalization of testosterone. This observation suggest that the combination of surgery with systemic therapy may be curative in a minority of men who present with metastatic prostate cancer. However, long-term continence rate was only 30.3%. Source of Funding: This work is supported in part by the cancer center support grant from the National Cancer Institute (P30CA072720) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e412-e413 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Sterling More articles by this author Arnav Srivastava More articles by this author Bertram Yuh More articles by this author Seok Soo Byun More articles by this author Shigeo Horie More articles by this author Isaac Kim More articles by this author Expand All Advertisement Loading ...

Bioinformatic analysis of differentially expressed genes and pathways in idiopathic pulmonary fibrosis.

BackgroundUsing bioinformatic methods to explore the differentially expressed genes (DEGs) of human idiopathic pulmonary fibrosis (IPF) and to elucidate the pathogenesis of IPF from the genetic level.MethodsThe GSE110147 gene expression profile was downloaded from the GEO database. The data of lung adenocarcinoma (LUAD) samples, lung squamous cell carcinoma (LUSC) samples and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. DEGs between IPF patients and healthy donors were analyzed using the GEO2R tool. Use the “clusterprofiler” package in R software to perform gene ontology (GO) and KEGG pathway enrichment analysis, and then perform function annotation and protein-protein interaction (PPI) network construction in the STRING online tool. The Genome Browser tool of the university of california santa cruz (UCSC) online website was used to predict transcription factors (TFs) of genes. In the final, the results were analyzed synthetically.ResultsA total of 9,183 DEGs were identified, of which 4,545 genes were down-regulated, and 4638 were up-regulated. MMP1, SPP1, and BPIFB1 were the top three DEGs with the highest significant up-regulation. These DEGs played an important role in the occurrence of IPF through the MAPK (mitogen-activated protein kinase) signaling pathway. Furthermore, 50 DEGs were enriched in the expression of PD-L1 and the PD-1 checkpoint pathway in cancer, of which 11 genes were re-enriched in the pathway of non-small cell lung cancer. The expression of the 11 genes were extensively regulated by CTCFL, SP2 and ZNF341. Most of them were differentially expressed between lung cancers and normal lung tissues. The overall survival (OS) curve of LUAD were significantly stratified by AKT2, KRAS, PIK3R1, meanwhile the OS curve of LUAC was significantly stratified by MAPK3.ConclusionsBioinformatics analysis revealed that DEGs including MPP1 might be potential targets and biomarkers of IPF, and the MAPK signaling pathway is related to the occurrence and development of IPF. The development of IPF lung cancer complications may be related to the activation of genes enriched in PD-L1 expression and PD-1 checkpoint pathway, which provides clues to the pathogenesis of IPF combined with lung cancer.

Combined 177 Lu-PSMA-617 PRLT and abiraterone acetate versus 177 Lu-PSMA-617 PRLT monotherapy in metastatic castration-resistant prostate cancer: An observational study comparing the response and durability.

The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients. The mCRPC patients who received at least one cycle of 177 Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only 177 Lu-PSMA PRLT and Group 2 received combined 177 Lu-PSMA PRLT + AA therapy. Therapeutic dose of 177 Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging (68 Ga-PSMA-11 and 18 F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first 177 Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ2 or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p < 0.05 significant). A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of 177 Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables. In the present study, the combination of 177 Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to 177 Lu-PSMA-617 PRLT monotherapy.

Antidepressants use is associated with overall survival improvement of patients with gastric cancer after surgery and adjuvant chemotherapy in Taiwan: A large population-based cohort study.

To determine whether exposure to antidepressants (ATDs) results in improved overall survival (OS) of patients with gastric cancer (GC) after surgery, we conducted a large cohort study and considered confounding factors that might affect the research outcomes.Patients who received a new diagnosis of GC and received surgery and chemotherapy between 1999 and 2008 were recruited and were classified into different groups based on the ATD level used. The association between the OS of patients with GC after surgery with different levels of ATD use, and the hazard ratio with comorbidities at different ATD use levels were compared.According to Kaplan–Meier method, the more of an ATD was taken, the longer the OS and a dose-dependent relationship was discovered in the OS curve; the adjusted HRs were 0.76 (95% confidence interval [CI] = 0.68–0.84) and 0.48 (95% CI = 0.41–0.57) for ATD users taking a cumulative defined daily dose (cDDD) of 28–167 and ≧168, respectively. Sensitivity analyzes were performed to investigate the effect of various comorbidities on OS with different degrees of ATD use and the results remained consistent among the varying models. Additionally, the effect of ATD use still exhibited a dose-dependent relationship in distinct stratifications for sex and age.The OS for patients with GC after surgery and chemotherapy improved with ATD use, and a dose-dependent relationship was discovered in this study. Further studies on the association between OS of GC and ATD use are required.

Tumor Expression Profile Analysis Developed and Validated a Prognostic Model Based on Immune-Related Genes in Bladder Cancer.

Background: Bladder cancer (BLCA) ranks 10th in incidence among malignant tumors and 6th in incidence among malignant tumors in males. With the application of immune therapy, the overall survival (OS) rate of BLCA patients has greatly improved, but the 5-year survival rate of BLCA patients is still low. Furthermore, not every BLCA patient benefits from immunotherapy, and there are a limited number of biomarkers for predicting the immunotherapy response. Therefore, novel biomarkers for predicting the immunotherapy response and prognosis of BLCA are urgently needed.Methods: The RNA sequencing (RNA-seq) data, clinical data and gene annotation files for The Cancer Genome Atlas (TCGA) BLCA cohort were extracted from the University of California, Santa Cruz (UCSC) Xena Browser. The BLCA datasets GSE31684 and GSE32894 from the Gene Expression Omnibus (GEO) database were extracted for external validation. Immune-related genes were extracted from InnateDB. Significant differentially expressed genes (DEGs) were identified using the R package “limma,” and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for the DEGs were performed using R package “clusterProfiler.” Least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the signature model. The infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The performance of the model was evaluated with receiver operating characteristic (ROC) curves and calibration curves.Results: In total, 1,040 immune-related DEGs were identified, and eight signature genes were selected to construct a model using LASSO regression analysis. The risk score of BLCA patients based on the signature model was negatively correlated with OS and the immunotherapy response. The ROC curve for OS revealed that the model had good accuracy. The calibration curve showed good agreement between the predictions and actual observations.Conclusions: Herein, we constructed an immune-related eight-gene signature that could be a potential biomarker to predict the immunotherapy response and prognosis of BLCA patients.

Metastatic acral melanoma treatment outcomes: a systematic review and meta-analysis.

Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBASE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan-Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa Scale. Nineteen nonrandomized studies were included, comprising 646 patients with acral melanomas and 1609 patients with nonacral melanomas treated with systemic therapy including chemotherapy, KIT-targeted drugs, as well as anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy. Thirteen studies included Kaplan-Meier curves for progression-free survival or overall survival and 11 studies reported treatment responses. Patients with acral melanomas had worse prognosis than nonacral cutaneous melanoma (acral overall survival: median 15 months, 95% CI, 13.7-16.3 months; nonacral cutaneous: median 24 months, 95% CI, 22.6-25.4 months, P < 0.001). Acral melanoma patients treated with anti-PD-1 monotherapy had higher overall survival at 12 months (53%) compared with anti-CTLA-4 monotherapy (34%; P < 0.001). This study provides estimates of treatment response for metastatic acral melanoma, demonstrating low activity across a breadth of approved drug therapies, including anti-PD-1, the most active therapy in melanoma to date. Further research into treatments for metastatic acral melanoma is needed.

Overall Survival in Patients with Hepatocellular Carcinoma Treated with Sorafenib: A Polish Experience.

BackgroundThe mortality caused by hepatocellular carcinoma is expected to rise in the upcoming decade. Sorafenib has become the preferred systemic treatment option in patients with unresectable HCC. This study aimed to present the median overall survival (OS) in a group of patients with advanced HCC, treated with sorafenib in Poland between 2011 and 2019.Material/MethodsThe analyzed group of patients was qualified for treatment with sorafenib, financed by the National Health Fund, based on the guidelines of the Polish Drug Program.Kaplan-Meier method was used to plot the OS curves, and the log-rank test was used for testing. Multivariate assessment of factors (sex and age) related to the time to death of the patient was done using Cox regression.ResultsOf the 2072 treated patients, 75% were men (1556) and 25% were women (516). The minimum age of patients in the trial group was 18 years and the maximum age was 90 years.Among the 1556 analyzed cases in males, 27.44% (427) did not end with death (by the date of completing the analysis). The percentage of one-year survival for this population was 58.16%, and the 2-, 3-, and 5-year survival rates were 34.45%, 21.81%, and 9.72%, respectively.The percentage of censored cases in the 516 females was 25.78% (133). The 1-2-, 3-, and 5-year survival for this population was 59.30%, 36.27%, 22.47%, and 11.34%, respectively. Statistical tests did not reveal a significant difference in the curve profiles by sex. There were no associations between OS and age.ConclusionsSystemic treatment with sorafenib in accordance with the presented criteria allows for very good results, comparable to the results of selected groups of patients presented by other authors.

Prognostic Impact of Lateral Pelvic Node Dissection on the Survival of Patients in Low Rectal Cancer Subgroups Based on Lymph Node Size.

Lateral pelvic node (LPN) dissection (LPND) is considered a promising technique for treating low rectal cancer; however, there is insufficient evidence of its prognostic value. Using centrally reviewed preoperative pelvic magnetic resonance (MR) images, this study aimed to find the patient population who has benefited from LPND. MR images of patients from 69 institutes with stage II-III low rectal cancer were reviewed by experienced radiologists. Recurrence-free survival (RFS), overall survival (OS), and short-term outcomes were measured. In total, 731 preoperative MR images were reviewed (excluding patients with short-axis LPN ≥ 10 mm). Of these, 322 underwent total mesorectum excision (TME) without LPND (non-LPND group), and 409 underwent TME with LPND (LPND group). Preoperative treatment was performed for 40% and 25% of patients in the non-LPND and LPND groups, respectively. The incidence of postoperative complications was higher in the LPND group (44.5%) than in the non-LPND group (33.2%; P = 0.002). Among patients with LPNs < 5 mm, OS and RFS curves were not significantly different between the groups. Among patients with LPNs ≥ 5 mm, the LPND group had significantly higher 5-year OS and RFS than the non-LPND group (OS: 81.9% versus 67.3%; RFS: 69.4% versus 51.6%). On multivariate analysis of LPN ≥ 5 mm cases, LPND was independently associated with RFS. Despite the high incidence of postoperative complications, this study showed the prognostic impact of LPND on low rectal cancer patients with LPNs (≥ 5 mm, < 10 mm short axis) measured by experienced radiologists. Trial registration UMIN-ID: UMIN000013919.