5-year Metastasis-free Survival Research Articles

70-Gene Signature as an Aid to Treatment Decisions in Early Breast Cancer: Updated Results MINDACT

Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival (DMFS) of 94·7% (95%CI 92·5-96·2) in clinical high (C-High)/genomic low (G-Low) risk patients who did not receive chemotherapy. Long-term follow-up is presented. Methods: 6693 patients were enrolled 2007 to 2011. We reassessed DMFS rate at 5 years in C-High/G-Low patients not receiving chemotherapy (n=644) (primary analysis), updated DMFS and overall survival in C-High/G-Low patients receiving chemotherapy or not (n=749 and 748, respectively) (secondary analysis), and examined a potential age effect ( 50y) for women with HR+/HER2- disease. Findings: At a median follow-up of 8·7 years, the updated 5-year DMFS rate for C-High/G-Low patients receiving no chemotherapy is 95·1% (95%CI 93·1-96·6), above the predefined non-inferiority boundary of 92%, proving MINDACT as a positive de-escalation trial.The 5-year and 8-year outcome of C-High/G-Low patients show a respective 0·9% (SE ±1·1) 2·6% (SE ±1·6) difference in DMFS for chemotherapy versus no chemotherapy (HR 0·66; 95%CI 0·48-0·92), without differences in overall survival (95·7% vs 94·3%).The same comparisons confined to HR+/HER2- disease (91% of patients) generate different gain estimates from chemotherapy administration for DMFS according to age: 5% (SE ±2·8%) in women ≤50 years versus 0·2% (SE ±2·3%) in women > 50 years. Interpretation: The clinical utility of a low risk 70-gene signature for foregoing adjuvant chemotherapy in the presence of a high clinical risk (and up to 3 positive nodes) remains proven. In C-high/G-low patients > 50 years chemotherapy did not improve outcome across the whole follow-up trajectory. At longer follow-up in younger women, while underpowered, a clinically relevant benefit of about 5% was observed, possibly due to chemotherapy-induced ovarian function suppression, and should be part of informed, shared decision-making. Trial Registration: ClinicalTrials.gov number, NTC00433589; EudraCT number, 2005-002625-31. Funding Statement: Funded by the European Commission Sixth Framework Programme and other grants. Declaration of Interests: None to declare. Ethics Approval Statement: All patients gave written informed consent. The ethics committees of all participating sites approved the study, which involved collaboration of seven member groups under the Breast International Group umbrella.

Clinical Outcomes of High-Dose Palliative Radiotherapy for Elderly Patients with Localized Prostate Cancer

While men may live for many years with prostate cancer, symptoms associated with local extension and metastatic disease limit quality of life. Radical treatment for localized prostate cancer in elderly patients, age greater than 70, can sometimes lead to morbidity with less survival benefit. To mitigate this risk, androgen deprivation therapy-based approaches are often employed. At the study institution, a common clinical practice over the study period (>10 years) was to offer these patients palliative radiotherapy (RT) with doses up to 5000cGy in an attempt to control local disease, delay progression, and delay subsequent use of hormonal therapy. This study aimed to report on the benefits and toxicities associated with this RT treatment and whether it interrupted use of hormonal therapy. Using a patient information system, patients were identified with birthdate(s) on or before September 1, 1948, and having received radiotherapy treatment to the prostate with doses between 4000cGy and 5000cGy. Ethics approval was obtained and chart review performed to determine duration of hormonal treatment, radiation-related toxicity, PSA kinetics, and overall survival. 54 patients meeting the inclusion criteria for the study were identified. 53 (98%) had a pathologic confirmation of prostate cancer. Median time from pathologic diagnosis to administration of radiotherapy was 13 (13-31) months. Of the cohort, 36 (67%) patients did not receive continuous hormonal therapy. These patients had a median duration of combined neoadjuvant and adjuvant hormonal therapy of 18 months and a median time to re-initiation of hormonal therapy after radiotherapy of 20 months. No patients encountered CTCAE Grade 3 toxicities. There were no reported skin toxicities; 13 (24%) reported CTCAE Grade 1 Genitourinary (GU) toxicity, 3 (6%) CTCAE Grade 2 GU toxicity; and 9 (17%) reported CTCAE Grade 1 Gastrointestinal (GI) toxicity and 0% CTCAE Grade 2 GI toxicity. Kaplan-Meier estimated 5-year metastasis-free survival was 56%, and 5-year overall survival was 78%. Palliative radiotherapy to the prostate of up to 5000cGy was well tolerated in this cohort of elderly patients. In several patients, treatment breaks from androgen deprivation were achieved.

High intratumoral CD8+ T-cell infiltration is associated with improved survival in prostate cancer patients undergoing radical prostatectomy.

A high density of CD8+ tumor infiltrating lymphocytes (TILs) is associated with improved survival in multiple cancers, but its prognostic role in prostate cancer remains controversial. The aim of our study was to evaluate the prognostic value of CD8+ TILs in prostate cancer patients undergoing radical prostatectomy (RP). We hypothesized that elevated density of CD8+ TILs in the RP specimen would correlate with improved clinical outcomes. This information may be helpful for future immunotherapy clinical trial design and treatment selection. Tumor microarrays constructed from 230 patients with localized prostate cancers who underwent RP from 2006 to 2012 at Roswell Park Comprehensive Cancer Center were analyzed retrospectively using immunohistochemistry. CD8+ cell density was evaluated using a computerized scoring system. The cohorts were separated by CD8+ TIL density at the 25th percentile (i.e., low<quartile 1 and high≥quartile 1). The quartile 1 threshold was chosen through a "minimal pvalue approach" based on overall survival with correction of significance to adjust for multiple testing. Clinical outcomes were compared in the high versus low CD8+ TIL density groups. One hundred and forty-nine(65%) patients had high risk diseases (Gleason>7 or pT3/4). The median follow-up time was 8.4 years. High CD8+ TIL density was associated with improved 5-year overall survival (98% vs.91%, p = .01) and prostate cancer-specific survival (99% vs. 95%, p = .04) compared withpatients with low CD8+ TIL density. There was a trend toward higher 5-year biochemical recurrence-free survival and metastasis-free survival in the cohort of patients with high CD8+ TIL density (52% vs. 38% and 86% vs. 73%, respectively), although the difference did not reach statistical significance (p = .18 and p = .05, respectively). In a multivariate analysis high CD8+ TIL density was an independent favorable prognostic factor for overall survival (hazards ratio = 0.38; 95% confidenceinterval:0.17-0.87;p = .02). In contrast to the prognostic value of CD8+ TIL density, the CD8+ cell density in the matched normal prostate tissue was not associated with any clinical outcomes. Intratumoral CD8+ T-cell infiltration in the RP specimen is independently associated with improved survival after RP in this high-risk prostate cancer cohort. Pre-RP immunomodulation that promotes intratumoral CD8+ cytotoxic T-cell infiltration may be beneficial for this population.

Oncological outcomes of pathologically organ-confined, lymph node-positive prostate cancer after radical prostatectomy

BackgroundThe aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP). MethodsWe retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment. ResultsOf 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]). ConclusionPatients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9

Clinical characteristics and survival outcomes of ascending, descending and mixed types of nasopharyngeal carcinoma in the non-endemic areas of china: A propensity score matching analysis.

PurposeTo compare the clinical characteristics and survival outcomes of patients with ascending type (type A), descending type (type D), and mixed type (type AD) of nasopharyngeal carcinoma (NPC) in non‐endemic areas.Materials and methodsThe cohort included 628 patients diagnosed with type A, type D, and type AD of NPC between January 2009 and December 2014. Type A was defined as T3‐4 N0‐1, type D as T0‐1 N2‐3, and type AD as T3‐4 N2‐3. Propensity score matching (PSM) was performed to balance clinical factors and match patients. Kaplan‐Meier methods and Cox proportional hazards models were used to evaluate the impact of different NPC types on survival outcomes.ResultsThere were 145 patients with type A, 194 with type D, and 289 with type AD. However, after PSM, there were only 130 patients with each type. Compared with patients with type A, those with type D had lower 5‐year disease‐specific survival (96.9% vs 91.5%) and distant metastasis‐free survival (92.3% vs 77.7%) and higher local relapse‐free survival (88.5% vs 96.9%) (p < 0.05 for all). Patients with type AD may have an increased risk of disease progression (progression‐free survival, 56.9% vs 74.6% and 66.2%) and death (overall survival [OS], 76.9% vs 85.4% and 85.4%) (p < 0.05 for all) compared to patients with the other two types of tumors.We further analyzed the metastasis trend. Similar metastasis patterns were observed in types AD and D, and types AD and A had similar recurrence trends. The mortality rate of patients with types AD and D in the first 3 years after metastasis was remarkably higher than that of patients with type A.ConclusionsIn non‐endemic areas of China, metastases and recurrence patterns differed across tumor types. Type AD has the worst OS, and the clinical process is more radical. Type D has a lower recurrence rate, higher metastasis, and disease‐related mortality rates, and poorer prognosis after metastasis than type A.

Treatment outcomes after definitive radio(chemo)therapy for 17 lacrimal sac squamous cell carcinoma.

Tumors of the lacrimal sac are rare and life-threatening. Because of their rarity, no extensive clinical data on their management and prognosis exist. We investigated the application of definitive radiation therapy and its outcome in patients with lacrimal sac squamous cell carcinoma (LSSCC). We retrospectively studied 17 patients with LSSCC at a single institution between 2003 and 2017. All the patients were treated with definitive radiotherapy, and 11 patients were delivered with cisplatin-based chemotherapy. The patients' clinical records were reviewed for symptoms, pathological types, the volume and dosimetry of the tumors and their adjacent structures, radiation coverage of lymph node drainage areas, treatment outcomes, and complications from definitive radiotherapy. Median follow-up was 38.9 months, and age at diagnosis was 48 years.The 2-year and 5-year overall survival, progression-free survival, locoregional control, and disease metastasis-free survival rates were 94.1 and 84.7%, 88.2 and 73.5%, 93.8%, 94.1, and 78.4%, respectively. A total dose of 6600-7000 cGy was prescribed to the tumor. Levels Ⅰb, Ⅶa, Ⅷ, and Ⅸ were covered with the clinical target volume regardless of lymph involvement. Acute Grade 3 radiation dermatitis occurred in seven patients (17.6%), but no acute Grade 4 or Grade 5 toxicity of any type occurred. Seven (41.2%, 7/17) of the treated eyes had moderated vision impairments; 17.6% (3/17) of patients developed cataracts, and glaucoma and radiation retinopathy were found in 5.9% (1/17) of patients. Definitive radiotherapy could be a treatment option for those who refuse surgery or have unresectable LSSCC. Radiation alone is a treatment option for LSSCC.

Functional and oncological outcome of percutaneous cryoablation versus laparoscopic partial nephrectomy for clinical T1 renal tumors: A propensity score-matched analysis

PurposeTo evaluate the clinical trifecta of percutaneous cryoablation (PCA) vs. laparoscopic partial nephrectomy (LPN) for cT1 renal tumors. Patients and methodsWe retrospectively analyzed the records of patients who had undergone 2 types of nephron sparing surgeries (NSS) PCA or LPN for cT1 renal tumors between November 2011 and December 2019. The cohorts were matched by one-to-one propensity scores based on patient demographics, renal function, and tumor complexity. Perioperative and oncological outcomes and preservation of renal function following surgery were compared. ResultsAfter matching, a total of 180 patients who had undergone NSS for de novo renal tumors were evaluable: 90 for PCA and 90 for LPN. No statistically significant differences were noted among the measured baseline characteristics in the propensity score-matched cohorts. Overall perioperative complication rates were 5.5% in the PCA and 11.1% in the LPN groups (P = 0.28). The rate of eGFR preservation 1 to 3 months after surgery was significantly higher for PCA than for LPN (92.8 ± 11.5% vs. 88.5 ± 14.6%, P = 0.03). Median follow-up was 33 months for PCA and 18 months for LPN (P < 0.001). Three residual and 4 recurrent tumors were later diagnosed in the PCA group and 1 recurrent tumor in the LPN group. The 5-year local recurrence-free survival was lower for PCA than LPN (90.2% vs. 98.5%, P = 0.36). The 5-year metastasis-free survival rate was similar in both groups (98.4% vs. 100%, P = 0.38). The 5-year overall and cancer-specific survival rates were comparable in both groups (91.7% vs. 98.9%, P = 0.53, and 95% vs. 100%, P = 0.55, respectively). ConclusionsClinical T1 RCC patients are better treated with LPN if technically possible. Though PCA had a higher local recurrence rate, medium-term local control was not inferior to LPN. Additionally, PCA patients tended to retain renal function without severe complications. PCA appears to be a reasonable option for patients with high comorbidity at presentation.

What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities?

Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. Level II, prognostic study.

Long-term outcomes of active surveillance for clinically localized prostate cancer in a community-based setting: results from a prospective non-interventional study

PurposeTo report on long-term outcomes of patients treated with active surveillance (AS) for localized prostate cancer (PCa) in the daily routine setting.MethodsHAROW (2008–2013) was a non-interventional, health service research study about the management of localized PCa in the community setting, with 86% of the study centers being office-based urologists. A follow-up examination of all patients who opted for AS as primary treatment was carried out. Overall, cancer-specific, and metastasis-free survival, as well as discontinuation rates, were determined.ResultsOf 329 patients, 62.9% had very-low- and 21.3% low-risk tumours. The median follow-up was 7.7 years (IQR 4.7–9.1). Twenty-eight patients (8.5%) died unrelated to PCa, of whom 19 were under AS or watchful waiting (WW). Additionally, seven patients (2.1%) developed metastasis. The estimated 10-year overall and metastasis-free survival was 86% (95% CI 81.7–90.3) and 97% (95% CI 94.6–99.3), respectively. One hundred eighty-seven patients (56.8%) discontinued AS changing to invasive treatment: 104 radical prostatectomies (RP), 55 radiotherapies (RT), and 28 hormonal treatments (HT). Another 50 patients switched to WW. Finally, 37.4% remained alive without invasive therapy (22.2% AS and 15.2% WW). Intervention-free survival differed between the risk groups: 47.8% in the very-low-, 33.8% in the low- and 34.6% in the intermediate-/high-risk-group (p = 0.008). On multivariable analysis, PSA-density ≥ 0.2 ng/ml2 was significantly predictive for receiving invasive treatment (HR 2.55; p = 0.001).ConclusionEven in routine care, AS can be considered a safe treatment option. Our results might encourage office-based urologists regarding the implementation of AS and to counteract possible concerns against this treatment option.

Conditional Survival in Uveal Melanoma

To investigate conditional survival in patients with uveal melanoma in the United States. Cohort study. Patients were identified using International Classification of Disease for Oncology, Third Edition, codes for both morphologic features (melanoma, 8720-8790) and site (retina, C69.2; choroid, C69.3; and ciliary body, C69.4) from 1975 through 2011 using the Surveillance, Epidemiology, and End Results (SEER) database SEER18. Observed metastasis-free survival (MFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Conditional metastasis-free survival (cMFS) and conditional overall survival were calculated based on the observed MFS and OS. Relative survival also was calculated using the actuarial method. Survival to 5 and 10 years after diagnosis were calculated, conditioned on various numbers of years already survived. Conditional MFS, conditional OS, and conditional relative survival. A total of 6863 cases of uveal melanoma were identified. Median follow-up among survivors was 11 years. During follow-up, 3883 patients died of any cause, and of these, 2131 deaths were the result of metastatic uveal melanoma. The nonconditional 5-year MFS was 80%. After surviving 1, 2, 3, or 4 years after diagnosis, the 5-year cMFS estimates increased to 82%, 87%, 92%, and 96%, respectively. The nonconditional MFS at 10 years was estimated to be 69%. After having survived 5, 6, 7, 8, or 9 years after diagnosis, the 10-year cMFS estimates increased to 87%, 90%, 93%, 96%, and 98%, respectively. This result pattern was confirmed with estimates of relative survival. Conditional survival estimates of uveal melanoma improve with time since primary diagnosis. Among patients who already have survived for at least 5 years, 10-year conditional survival rates are high. Conditional survival analysis can provide specific guidance for counselling patients.

Development and Validation of a Novel TP53 Mutation Signature That Predicts Risk of Metastasis in Primary Prostate Cancer.

Prostate tumors with TP53 gene mutations are molecularly heterogenous, and the presence of TP53 gene mutations has been linked to inferior outcomes. We developed an RNA-based gene signature that detects underlying TP53 gene mutations and identifies wild-type prostate tumors that are analogous to TP53-mutant tumors. Using genomic expression profiles from The Cancer Genome Atlas, we developed a mutation signature score to predict prostatic tumors with a molecular fingerprint similar to tumors with TP53 mutations. Area under the receiver operating characteristic curve assessed model accuracy in predicting TP53 mutations, and Cox regression models measured association between the signature and progression-free survival and metastasis-free survival (MFS). The TP53 signature score achieved an area under the receiver operating characteristic curve of 0.84 in the training and 0.82 in the validation cohorts for predicting an underlying mutation. In three retrospective cohorts, a high score was prognostic for poor 5-year MFS: 46% versus 81% (hazard ratio [HR], 3.05; P< .0001; Johns Hopkins University cohort), 64% versus 83% (HR, 2.77; P< .0001; Mayo Clinic cohort), and 71% versus 97% (HR, 6.8; P= .0001; Brigham and Women's Hospital cohort). The signature also identified TP53 wild-type tumors molecularly analogous to TP53 mutant tumors, wherein high signature score correlated with worse 5-year MFS (50% vs. 82%; HR, 3.05; P< .0001). This novel mutational signature predicted tumors with TP53 mutations, identified TP53 wild-type tumors analogous to mutant tumors, and was independently associated with poor MFS. This signature can therefore be used to strengthen existing clinical risk-stratification tools.

Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer.

Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression-free survival (BPFS) over RP alone. Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS). In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, -0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone. The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term androgen deprivation therapy for very high-risk prostate cancer.

To estimate the outcomes of high-dose-rate brachytherapy combined with hypofractionated external beam radiotherapy in prostate cancer patients classified as very high risk by the National Comprehensive Cancer Network. Between June 2009 and September 2015, 66 patients meeting the criteria for very high-risk disease received high-dose-rate brachytherapy (2 fractions of 9Gy) as a boost of external beam radiotherapy (13 fractions of 3Gy). Androgen deprivation therapy was administered for approximately 3years. Biochemical failure was assessed using the Phoenix definition. The median follow-up period was 53months from the completion of radiotherapy. The 5-year biochemical failure-free, distant metastasis-free, prostate cancer-specific and overall survival rates were 88.7, 89.2, 98.5 and 97.0%, respectively. The independent contribution of each component of the very high-risk criteria was assessed in multivariable models. Primary Gleason pattern5 was associated with increased risks of biochemical failure (P=0.017) and distant metastasis (P=0.049), whereas clinical stage ≥T3b or >4 biopsy cores with Gleason score8-10 had no significant impact on the two outcomes. Grade3 genitourinary toxicities were observed in two (3.0%) patients, whereas no grade ≥3 gastrointestinal toxicities occurred. The present study shows that this multimodal approach provides potentially excellent cancer control and acceptable associated morbidity for very high-risk disease. Patients with primary Gleason pattern5 are at a higher risk of poor outcomes, indicating the need for more aggressive approaches in these cases.

684 - External validation of genomic classifier based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer

To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP). We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan–Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis. The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92–0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients. Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients’ classification in future clinical trials.

The Impact of Hypertension on the Clinicopathological Outcome and Progression of Renal Cell Carcinoma.

Hypertension is a risk factor for occurrence of renal cell carcinoma; however, it remains unclear whether hypertension affects development and prognosis of renal cell carcinoma. This study evaluated the impact of hypertension on the progression of renal cell carcinoma. Renal cell carcinoma patients who were treated from October 2007 to December 2018 at our Institution were retrospectively analyzed. Of 462 patients, the number of patients with and without hypertension was 234 (including 227 treated with anti-hypertensive agents) and 228, respectively. The tumor size was significantly smaller in the hypertension group than in the non-hypertension group (median 32 and 45 mm, respectively, p=0.010). The 5-year cancer-specific and metastasis-free survival in the hypertension group were significantly better than those in the non-hypertension group (93.6% and 80.4%, and 84.6% and 73.0%, respectively, p=0.021 and p=0.017). Propensity score matching revealed significantly better metastatic-free survival in the hypertension group than the non-hypertension group (p=0.022). Renal cell carcinoma patients with hypertension show better prognosis with low metastasis possibility.

Long-term outcome of endoscopic resection for intramucosal esophageal squamous cell cancer: a secondary analysis of the Japan Esophageal Cohort study.

Prospectively collected long-term data of patients undergoing endoscopic resection for superficial esophageal squamous cell carcinoma (ESCC) are limited. The aim of this study was to determine the prospectively collected long-term outcomes of endoscopic resection for ESCC as a secondary analysis of the Japan Esophageal Cohort (JEC) study. Patients who underwent endoscopic resection of intramucosal ESCC at 16 institutions between September 2005 and May 2010 were enrolled in the JEC study. All patients underwent endoscopic examination with iodine staining at 3 and 6 months after resection, and every 6 months thereafter. We investigated clinical courses after endoscopic resection, survival rates, and cumulative incidence of metachronous ESCC. 330 patients (mean age 67.0 years) with 396 lesions (mean size 20.4 mm) were included in the analysis. Lesions were diagnosed as high-grade intraepithelial neoplasia in 17.4 % and as squamous cell carcinoma in 82.6 % (limited to epithelium in 28.4 %, to lamina propria in 55.4 %, and to muscularis mucosa in 16.2 %). En bloc resection was achieved in 291 (73.5 %). The median follow-up period was 49.4 months. Local recurrences occurred in 13 patients (3.9 %) and were treated by endoscopic procedures. Lymph node metastasis occurred in two patients (0.6 %) after endoscopic resection. The 5-year overall, disease-specific, and metastasis-free survival rates were 95.1 %, 99.1 %, and 94.6 %, respectively. The 5-year cumulative incidence rate of metachronous ESCC was 25.7 %. Our study demonstrated that endoscopic resection is an effective treatment for intramucosal ESCC, with favorable long-term outcomes.

Contact with renal sinus is associated with poor prognosis in surgically treated pT1 clear cell renal cell carcinoma.

To investigate the prognostic significance of contact with the renal sinus in patients with clear cell renal cell carcinoma. A total of 787 pT1N0M0 clear cell renal cell carcinoma patients who had undergone radical or partial nephrectomy were reviewed retrospectively. A tumor in contact with the renal sinus was defined as a tumor radiologically attached to the renal sinus. Metastatic-free survival rates were analyzed in the total and propensity score-matched cohorts. A risk score model for metastasis after surgery was developed. Of the 787 patients, 411 (52.2%) had tumors in contact with renal sinus. The contact with renal sinus group showed poorer metastatic-free survival in both total and matched cohorts. In multivariate analysis, contact with renal sinus was an independent prognostic factor of metastasis, as well as Fuhrman grade, microvascular invasion and age. The scoring model likewise consisted of Fuhrman grade, microvascular invasion, age and contact with renal sinus. Metastasis-free survival curves were clearly stratified according to risk, with 5-year metastasis-free survival rates of 95.7% and 65.2% in the low- and high-risk groups, respectively (P<0.001). Contact with the renal sinus is a significant risk factor for metastasis in T1 clear cell renal cell carcinoma after surgery. More intensive follow up should be recommended for patients with renal cell carcinoma that is in contact with the renal sinus.

Performance of a prognostic 31-gene expression profile test in patients with node-negative cutaneous melanoma.

e22071 Background: The National Comprehensive Cancer Network guidelines recommend considering sentinel lymph node biopsy (SLNB) for cutaneous melanoma (CM) patients with a 5-10% risk of SLN positivity and offering it to those with &gt; 10% risk. However, SLNB limitations include identification of only 1/3 of patients who end up with distant metastasis and a regional metastasis false negative rate ranging from 5-21% indicating a need to detect the risk of metastasis in patients with a negative SLNB. The 31 gene expression profile (31GEP) test uses the molecular biology of the primary tumor to predict 5-year recurrence-free (RFS), distant metastasis-free (DMFS), melanoma-specific (MSS), and overall survival (OS). Therefore, the objective of this study is to determine whether the 31GEP can stratify risk for patients with SLN-negative results to help guide CM management. Methods: 607 primary CM tumors were collected from patients with SLN-negative status who were enrolled in multi-center IRB-approved studies. Tumors were staged according to the AJCC 8th edition and analyzed by 31GEP testing to differentiate low-risk (Class 1A), intermediate-risk (Class 1B/2A), and high-risk (Class 2B) tumor biology. Clinical data were recorded and Kaplan-Meier (KM) and Cox regression analyses were performed to assess the relationship between 31GEP class and patient outcomes including RFS, DMFS, MSS, and OS. Results: KM analysis for 5yr RFS, DMFS, MSS, and OS stratified by 31GEP class are listed in Table. Multivariate Cox regression analysis demonstrated that the 31GEP Class 2B status was an independent predictor of RFS, DMFS, MSS, and OS with hazard ratios of 4.4 (95% CI, 2.7-7.2; p &lt; 0.001), 4.4 (95% CI, 2.3-8.5; p &lt; 0.001), 15.6 (95% CI, 3.4-71.2; p &lt; 0.001), and 5.4 (95% CI, 2.6-10.9; p &lt; 0.001), respectively. Conclusions: The results indicate that the 31GEP can stratify risk for a subset of patients with SLNB-negative results with the highest 5-year survival rates being associated with a Class 1A result. Moreover, GEP Class 2B is a significant independent predictor of metastatic risk in patients who are node negative. [Table: see text]

Updated 5-year local control (LC), metastasis-free survival (MFS), and overall survival (OS) data from a phase I study of nilotinib plus radiation (RT) in high-risk chordoma.

e23505 Background: Chordomas are malignant tumors arising from remnant notochordal tissue. Despite improved local control with preoperative/postoperative RT, progression-free survival and OS remain poor in patients (pts) with high-risk features. Chordoma has been identified to express and activate platelet-derived growth factor receptor signaling. We conducted a phase 1 trial to identify the maximum tolerated dose (MTD), safety, and feasibility of nilotinib with RT as either preoperative or definitive treatment for patients with high-risk chordoma. Enclosed is an updated report on LC, MFS, and OS. Methods: We recruited 23 pts with nonmetastatic chordoma to the phase I and dose expansion arms of the study. High-risk was defined as the presence of any of the following: local recurrence after surgery, previous intralesional resection, unplanned incomplete resection, unresectable/marginally resectable disease, or declining surgery due to excessive morbidity. Pts were treated with nilotinib and concurrent RT to 50.4 Gy relative biological effectiveness (RBE) followed by surgery and postoperative RT to a cumulative dose up to 70.2 Gy RBE or definitively up to 77.4 Gy RBE without surgery. On completion of RT, pts were eligible to continue nilotinib until disease progression. Results: The dose escalation arm of the study identified nilotinib 200 mg daily as the maximum tolerated dose (MTD). Eighteen evaluable pts were treated with nilotinib plus RT at the MTD. The objective best response rate was 6% (1 of 18 pts). The 4 and 5-year LC rates were 94.3% (95% CI 83.2-100) and 70.7% (95% CI 20.8-100), respectively. The MFS rate was 74.3 at 4 and 5 years (95% CI 51.8-96.7). The 4 and 5-year OS rates were 70.2% (95% CI 44.4-95.9) and 54.6% (95% CI 20.5-88.6). Conclusions: In updated data from a cohort of high-risk chordoma pts nilotinib 200 mg/d with RT +/- surgery, with long-term follow-up, local control and distant metastasis free survival remains favorable. Clinical trial information: NCT01407198 . [Table: see text]

Efficacy of Adjuvant Systemic Chemotherapy Combined with Radical Surgery and Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer Treatment.

Evaluation of the efficacy of the combination of radical surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and adjuvant systemic chemotherapy (ACT) in reducing gastric cancer progression in patients with resectable serosa-invasive gastric cancer in a single institution. In 2015-2016, 19 patients with gastric cancer (stage IIB-IIIC) were included in the trial. The trial protocol comprised radical surgery, HIPEC (cisplatin 50mg/m2 + doxorubicin 50mg/m2, 42°C, 1hour), and 1-8cycles of ACT (oxaliplatin 100mg/m2 administered on day 1 of each cycle and oral capecitabine 1000mg/m2 (or tegafur 10-15 mg/kg) administered twice daily on days 1-14 of each cycle with an interval of 7days between cycles). Following the ACT treatment, the patients were divided into 2 subgroups-those who underwent up to 6 ACT cycles (1-6cycles, subgroup ≤ 6-8 patients) and those who underwent 7-8 ACT cycles (subgroup > 6-11 patients). Three-year metastasis-free survival (MFS) for the > 6 subgroup was 91 ± 9%. With a follow-up median of 17months, 3-year MFS for the ≤ 6 subgroup was not reached - p log-rank = 0.003. The trial showed that in managing advanced gastric cancer patients (pT4a-4bN0-3M0) by supplementing radical surgery with ACT-enhanced hyperthermic intraperitoneal chemotherapy, ACT proved to be highly effective when administered in its full mode of 7-8cycles compared with its truncated variant of 1-6cycles.