Metastasis Recurrence-free Survival Research Articles

Efficacy of high-dose-rate brachytherapy with different radiation source activities among cervical cancer patients and risk factors for long-term outcomes: A 6-year retrospective study

PURPOSEThis study aimed to assess the impact of dose rates due to natural decay of Iridium-192 sources and the risk factors of clinical outcomes for cervical cancer patients treated with high-dose-rate (HDR) brachytherapy. METHODS AND MATERIALSFour ninety-four patients were divided into relatively-high-radioactive (rHR), relatively-medium-radioactive (rMR), and relatively-low-radioactive (rLR) groups for retrospective treatment response comparison. The short-term outcomes were evaluated using the 1-month /3-month follow-up results based on RECIST 1.1. Local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS) were selected as long-term outcomes. A class of transformation models with adaptive lasso was applied to assess the risk factors of long-term outcomes. RESULTSNo significant difference was identified in short- or long-term outcomes of different radioactive groups. Subgroup analyses demonstrated similar findings. In multivariate factor analysis, advanced stage was significantly associated with higher risk of local recurrence and metastatic recurrence (HR = 1.66, 95%confidence interval [CI] = 1.14–2.43, p = 0.008; HR = 1.57, 95%CI = 1.23–2.00, p < 0.001). Significant associations were observed between local recurrence and pathology, and between metastatic recurrence and pre-treatment serum indices, respectively (HR = 8.62, 95%CI = 2.28–32.60, p = 0.002; HR = 1.98, 95%CI=1.20–2.26, p = 0.008). CONCLUSIONSOverall, there was no significant difference in long- or short-term efficacy of the HDR brachytherapy among the groups with different levels of activity of radiation sources. Stage, pathology, and pretreatment serum indices were crucial factors that affected the long-term outcomes.

Prognostic Factors Analysis of Metastatic Recurrence in Cervical Carcinoma Patients Treated with Definitive Radiotherapy: A Retrospective Study Using Mixture Cure Model.

This study aims to identify prognostic factors associated with metastatic recurrence-free survival of cervical carcinoma (CC) patients treated with radical radiotherapy and assess the cure probability of radical radiotherapy from metastatic recurrence. Data were from 446 cervical carcinoma patients with radical radiotherapy for an average follow up of 3.96 years. We applied a mixture cure model to investigate the association between metastatic recurrence and prognostic factors and the association between noncure probability and factors, respectively. A nonparametric test of cure probability under the framework of a mixture cure model was used to examine the significance of cure probability of the definitive radiotherapy treatment. Propensity-score-matched (PSM) pairs were generated to reduce bias in subgroup analysis. Patients in advanced stages (p = 0.005) and those with worse treatment responses in the 3rd month (p = 0.004) had higher metastatic recurrence rates. Nonparametric tests of the cure probability showed that 3-year cure probability from metastatic recurrence was significantly larger than 0, and 5-year cure probability was significantly larger than 0.7 but no larger than 0.8. The empirical cure probability by mixture cure model was 79.2% (95% CI: 78.6-79.9%) for the entire study population, and the overall median metastatic recurrence time for uncured patients (patients susceptible to metastatic recurrence) was 1.60 (95% CI: 1.51-1.69) years. Locally advanced/advanced stage was a risk factor but non-significant against the cure probability (OR = 1.078, p = 0.088). The interaction of age and activity of radioactive source were statistically significant in the incidence model (OR = 0.839, p = 0.025). In subgroup analysis, compared with high activity of radioactive source (HARS), low activity of radioactive source (LARS) significantly contributed to a 16.1% higher cure probability for patients greater than 53 years old, while cure probability was 12.2% lower for the younger patients. There was statistically significant evidence in the data showing the existence of a large amount of patients cured by the definitive radiotherapy treatment. HARS is a protective factor against metastatic recurrence for uncured patients, and young patients tend to benefit more than the elderly from the HARS treatment.

Breast and colorectal cancer recurrence-free survival estimates in the US: Modeling versus active data collection

BackgroundA modeling method was developed to estimate recurrence-free survival using cancer registry survival data. This study aims to validate the modeled recurrence-free survival against “gold-standard” estimates from data collected by the National Program of Cancer Registries (NPCR) Patient-Centered Outcomes Research (PCOR) project. MethodsWe compared 5-year metastatic recurrence-free survival using modeling and empirical estimates from the PCOR project that collected disease-free status, tumor progression and recurrence for colorectal and female breast cancer cases diagnosed in 2011 in 5 U.S. state registries. To estimate empirical recurrence-free survival, we developed an algorithm that combined disease-free, recurrence, progression, and date information from NPCR-PCOR data. We applied the modeling method to relative survival for patients diagnosed with female breast and colorectal cancer in 2000–2015 in the SEER-18 areas. ResultsWhen grouping patients with stages I-III, the 5-year metastatic recurrence-free modeled and NPCR-PCOR estimates are very similar being respectively, 90.2 % and 88.6 % for female breast cancer, 74.6 % and 75.3 % for colon cancer, and 68.8 % and 68.5 % for rectum cancer. In general, the 5-year recurrence-free NPCR-PCOR and modeled estimates are still similar when controlling by stage. The modeled estimates, however, are not as accurate for recurrence-free survival in years 1–3 from diagnosis. ConclusionsThe alignment between NPCR-PCOR and modeled estimates supports their validity and provides robust population-based estimates of 5-year metastatic recurrence-free survival for female breast, colon, and rectum cancers. The modeling approach can in principle be extended to other cancer sites to provide provisional population-based estimates of 5-year recurrence free survival.

Efficacy of Organ Preservation Strategy by Adjuvant Chemoradiotherapy after Non-Curative Endoscopic Resection for Superficial SCC: A Multicenter Western Study.

In case of high risk of lymph node invasion after endoscopic resection (ER) of superficial esophageal squamous cell carcinoma (SCC), adjuvant chemoradiotherapy (CRT) can be an alternative to surgery. We assessed long-term clinical outcomes of adjuvant therapy by CRT after non-curative ER for superficial SCC. We performed a retrospective multicenter study. From April 1999 to April 2018, all consecutive patients who underwent ER for SCC with tumor infiltration beyond the muscularis mucosae were included. A total of 137 ER were analyzed. The overall nodal or metastatic recurrence-free survival rate at 5 years was 88% and specific recurrence-free survival rates at 5 years with and without adjuvant therapy were, respectively, 97.9% and 79.1% (p = 0.011). Independent factors for nodal and/or distal metastatic recurrence were age (HR = 1.075, p = 0.031), Sm infiltration depth > 200 µm (HR = 4.129, p = 0.040), and the absence of adjuvant CRT or surgery (HR = 11.322, p = 0.029). In this study, adjuvant therapy is associated with a higher recurrence-free survival rate at 5 years after non-curative ER. This result suggests this approach may be considered as an alternative to surgery in selected patients.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator-guided intensity modulated radiotherapy boost in patients with bulky cervical tumour.

To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). A retrospective cohort study. Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China. Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited. This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6and 5Gy per fraction for five fractions, respectively. Mean HR-CTV was 65.8 ± 23.6ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6Gy and 78.1 ± 2.5Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3and 56.7 ± 8.7Gy, respectively. Median follow-up was 85 months (47.9-124.2months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

HYPOFRACTIONATEDRADIOTHERAPY OF BREAST CANCER IN ELDERLYWOMEN

Introduction:Breast cancer remains the first malignantpathology in women and itsdiagnosis in elderlywomenislate. The aim of ourworkis to evaluate the effectiveness of hypofractionatedradiotherapy in the treatment of breast cancer in elderlywomen. Material And Methods: This is a retrospectivestudy of 171 patients aged over 65 yearsfollowed for invasive breast cancer and whoreceived adjuvant hypofractionatedradiotherapy at the radiotherapydepartment of CHU Hassan II Fez fromJanuary 2012 to December 2016. Results: The frequency of breast cancer in womenaged over 65 yearswas 7.31%. The averageage of our patients was 70 years (65-88 years) of which 40% wereolderthan 70 years. 8.5% of patients had a familyhistory of breast cancer. The delay of consultation was 10 months. A breast nodule was the revealingsign in all patients withinflammatorysigns in 4.6%axillaryadenopathywasfound in 20% of patients. All cancers werehistologicallyproven. The cancer wasinfiltratingductal in 90% of cases. 27% of the tumorswereScarff-Bloom and Richardson grade I, 45% grade II, 30% grade III. Hormone receptorswereexpressed in 77% and HER positive in 10% of patients. 83% underwentmastectomywithlymphnode dissection followed by adjuvant radiotherapyaccording to the hypo-fractionatedprotocol: total dose of 42Gy on the wall, of which 32% of patients alsoreceivedlymphnode irradiation, fractionation 2.8Gy/Fr in 15 sessions, spread over 19 days 17% of the patients had conservative surgeryassociatedwith adjuvant externalradiotherapy on the breastaccording to the sameschemewith a boost of 11.8Gy on the tumorbed, spread over 25 days.After a medianfollow-up of 5 years, overallsurvivalwasestimated at 84.2%, locoregionalrecurrence-free survival at 84.7% and metastaticrecurrence-free survival at 83%. Acute toxicityconsisted of radiodermatitis in 81% of patients, and post-radiation fibrosis in 15%, and no long-termcardiac or pulmonarytoxicitywasobserved. Conclusion: For elderly patients, adjuvant hypofractionated irradiation seems to be a good alternative, with a good rate of local control, and withoutincreasedtoxicity.

Comparison of triweekly cisplatin regimens in definitive chemoradiotherapy for locally advanced head and neck cancer: A propensity score matching analysis.

e18007 Background: Concurrent chemoradiotherapy (CCRT) with cisplatin (CDDP) is a standard treatment for locally advanced head and neck cancer (LAHNC) in the definitive setting. Three cycles of 100 mg/m2 CDDP for every three weeks (Q3W) are now recommended but compliance with CCRT is relatively low due to its severe toxicity. Therefore, the potential de-escalation strategies for LAHNC have been discussed to decrease the therapeutic toxicity. Methods: Patients with LAHNC who underwent definitive CCRT with CDDP between 2012 and 2018 at The Cancer Institute Hospital of Japanese Foundation for Cancer Research were analyzed. Patients were classified into two groups based on the planned CDDP dose: (A) 100 mg/m2 and (B) 80 mg/m2 Q3W for three times. One-to-one propensity score matching was performed to minimize bias between two groups. After patients in two groups were matched by using propensity score, the overall survival (OS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), and metastatic recurrence-free survival (MRFS) were analyzed by the Kaplan-Meier method with the Cox proportional hazards model. The follow-up term was set as two years to evaluate the early survival benefit. The dose and density of CDDP and the objective adverse events were also assessed. Results: A total of 304 patients were included with the median age of 62 (Interquartile range [IQR]: 54-67) years. Among them, 249 patients (82%) were male. Patients were treated with 100 mg/m2 CDDP (n = 145) and 80 mg/m2 CDDP (n = 159) regimens. After the propensity score matching, 119 patients were included in each group, respectively. There were no significant differences in baseline characteristics between two propensity-matched cohorts. The median follow-up time was 24 months in each group. Two-year OS was 93.0% (95% confidence interval [CI]: 88.4-97.8) in group A and 94.9% (91.0-99.0) in group B. Two-year RFS was 86.5% (80.6-92.9) in group A and 83.1% (76.6-90.1) in group B, respectively. No significant difference was observed in OS (Hazard ratio [HR] = 1.42, 95% CI: 0.49-4.08, p = 0.52), RFS (HR = 0.81, 95% CI: 0.42-1.57, p = 0.54), LRFS (HR = 0.57, 95% CI: 0.24-1.36, p = 0.20), and MFS (HR = 1.32, 95% CI: 0.52-3.35, p = 0.56). The median cumulative dose of CDDP was significantly higher in group A (300 mg, interquartile range [IQR]: 240-300) than in group B (240 mg, IQR:160-240) but the frequency of hematological, hepatic, renal, electrolytic, and grade 3-5 any adverse events was not significantly different between two groups. Conclusions: Our study showed no survival difference at 2-year follow-up between 100 mg/m2 and 80 mg/m2 CDDP regimens of definitive CCRT for LAHNC. This result could support the tide of the de-escalation strategy in head and neck cancer treatment. Longer follow-up is necessary and further prospective trials comparing CDDP dosage are warranted.

Impact of radiation source activity on short- and long-term outcomes of cervical carcinoma patients treated with high-dose-rate brachytherapy: A retrospective cohort study

ObjectiveHigh-dose-rate (HDR) afterloading brachytherapy using Iridium-192 source involves large radiation activity varieties due to fast decay. It was unknown but clinically desirable to evaluate its impacts on patient outcomes to support more informed decisions. MethodsData of 510 cervical carcinoma (CC) patients were retrospectively included. High-radioactive (HR) and low-radioactive (LR) groups were statistically defined per patient-specific average mean-dose-rate (MDR) of all fractions. The cutoffs were calculated using R-3.6.1 packages based on significance of correlation with binary outcome or survival time. Categorized 1-month and 3-month follow-up results were analyzed as short-term outcomes. Long-term outcomes were evaluated using local recurrence-free survival (LRFS) and metastatic recurrence-free survival (MRFS). Propensity-score-matched (PSM) pairs were generated to reduce bias. ResultsThe median follow-up time was 47.1 months (interquartile range: 33.9 months–66.4 months), involving MDR varieties of up to 9 folds ranging from 6059.99 cGy/h to 54013.66 cGy/h due to 17 source replacements at intervals ranging from 93 days–199 days. Both short-term (1-month: p = 0.22; 3-month: p = 0.79) and long-term (LRFS: p = 0.10; MRFS: p = 0.46) outcomes showed no significant difference between HR and LR. Subgroup analysis displayed significantly better results in LR for stage I–II (3-month, p = 0.02) and stage II (LRFS, p = 0.04) patients. Both LRFS and MRFS of LR were significantly non-inferior to HR (p ≤ 0.02). ConclusionsLR is clinically non-inferior or partially superior to HR for CC treatment using HDR, which dispels concerns of potentially undermined patient outcomes when source replacement is delayed.

Early esophageal squamous cell carcinoma in a western series is not associated with active HPV infection.

Few data are available concerning human papillomavirus (HPV) in early esophageal squamous cell carcinoma (ESCC) in Western population. Our study intended to determine the prevalence of HPV infection and the histological characteristics in such early tumors. A monocentric and retrospective study was conducted including 86 patients with early ESCC treated by endoscopic resection or esophagectomy, from 2012 to 2018. Histopathological prognostic criteria were evaluated. Immunohistochemistry for p16 and p53 and an HPV mRNA in situ hybridization were performed. The tumors were composed of 25 (29%) in situ carcinomas, 21 (24%) intramucosal carcinomas, and 40 (47%) submucosal carcinomas, of which 34 had a deep infiltration (> 200μm). Emboli, present in 12 cases, were associated with deep infiltration. P16-positive ESCC accounted for 21% of the patients. It was not correlated with active HPV infection as no cases were found to be positive in RISH analysis for RNA detection of this virus. However, there was a correlation between p16 expression and alcohol or tobacco consumption. The only histopathological criterion correlated with p16 positivity was marked inflammatory infiltrate. Local or distant neoplastic recurrence occurred in 25% of patients. Overall survival was 95.8% and local or metastatic recurrence-free survival was 75%. There was a correlation between positive resection margins and tumor recurrence. In contrast to oropharynx carcinoma, our study showed that ESCC were not associated with an active HPV infection, highlighting the negligible role of this virus in early ESCC carcinogenesis in the Western world.

867P - Multi-institutional evaluation of therapeutic management for oligometastatic cancer prostate recurrence with choline-PET/CT

BackgroundCholine Positron Emission Tomography – Computed Tomography (Choline PET/CT) allows for the diagnosis of oligometastatic (OM) Prostate Cancer (PCa) recurrence that could be treated with a curative intent. The aim of the study was to evaluate the different therapeutic approaches and outcomes for first OM recurrence. MethodsThis multi-institutional, retrospective study included patients with a hormone-sensitive biochemical PCa recurrence after an initial curative local treatment, and with at least 1 to 5 Choline PET/CT-diagnosed metastatic lesions. Primary endpoint was Biochemical Recurrence Free Survival (BRFS). Secondary endpoints were Metastatic Recurrence-Free Survival (MRFS) and Androgen Deprivation Therapy-Free Survival (ADT-FS). ResultsBetween October 2012 and December 2016, 177 patients were included. Sixty-eight patients (38.4%) received an ADT alone, 72 (40.7%) received an External Beam Radiation Therapy (EBRT) – ADT association, 28 (15.8%) received an EBRT, 6 (3.4%) received a surgery, and 2 (1.1%) received a surgery with ADT. Median follow-up was 49 months [95%CI, 44.3-53.4]. Among patients who received non-standard treatment, 55% avoided long-term ADT. Grade 3 acute and late toxicities were rare (0.8% and 2.5% respectively). The median BRFS, MRFS and ADT-FS were 42 [95%CI, 37-51], 61 [95%CI, 45-81], and 53 [95%CI, 45-60] months, respectively. In multivariate analysis, concomitant ADT with MDT and "regional" EBRT combined with MDT significantly improved BRFS (p<0.0001 and p=0.0113 respectively) and MRFS (p=0.0005 and p=0.0013 respectively). In multivariate analysis, a PSA-doubling time of>3 months had a statistically significant positive impact on MRFS (p=0.0496) and ADT-FS (p=0.0007). The overall and disease specific survivals were 87% and 97% respectively at 5 years. The median incidence of castration resistant PCa was 80 months. ConclusionsIn patients with hormone-sensitive OM PCa recurrence after initial local treatment, BRFS and MRFS were significantly improved when concomitant ADT and "regional" EBRT were combined with MDT. Clinical trial identificationOMPPC-IPC 2018-059. Legal entity responsible for the studyInstitute Paoli-Calmettes. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The long-term survival characteristics of a cohort of colorectal cancer patients and baseline variables associated with survival outcomes with or without time-varying effects

BackgroundColorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years.MethodsThe patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected.ResultsDuring the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that.ConclusionsThis study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

BackgroundThe outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.Patients and methodsctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).ResultsThe detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.ConclusionPre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.

Risk Factors and Predictive Value of Local Recurrence in Chinese Upper Tract Urothelial Carcinoma Patients: Implication for Postoperative Adjuvant Radiation Therapy

Lymph node dissection (LND) for UTUC at the time of radical nephroureterectomy (RNU) is not routine. Patients experienced local relapse rate after surgery, this ratio can reach up to 30% in advanced stage. There is little research about the risk factors of local recurrence in UTUC patients after surgery, especially in the Chinese population. This study aim to evaluate the influence of factors and the predictive value of local recurrence in patents with upper tract urothelial carcinoma (UTUC) after nephroureterectomy and found implications for postoperative adjuvant radiotherapy. We retrospectively analyzed the clinical and pathological data of the patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy between 2010 and 2016 in our center. Patients with postadjuvant radiation therapy were not enrolled in our study. We retrospectively analyzed the clinical data 330 patients after radical nephroureterectomy. With a median follow-up of 47 m (range: 4-110 months), local recurrence occurred in 73 patients (22.1%). The median interval of local recurrence was 39 months (range: 1-80 months). The probability of local recurrence-free survival at 12, 36, and 60 m was 96.2%, 90.9%, and 86.8%, respectively. Univariate and multivariate logistic regression analysis was used to address the prediction for local recurrence. In univariate analyses, statistically significant factors influencing the local recurrence were tumor multifocality, T stage, G grade, tumor location, LVI, and positive margin. In multivariate analysis tumor multifocality, T stage, G grade were significant risk factors influencing the local recurrence (P < 0.001). Local recurrence rate in T1-4 were 9.0%, 17.2%, 43%, and 37.5%. No patients experienced local recurrence in G1 grade, while 39.4% patients in G3 grade had local recurrence. Local recurrence rate was much higher in patients with multifocality (39.3% vs 18.6%, P < 0.001). Between the local recurrence group and non-local recurrence group there were statistically significant differences in 5-year metastasis recurrence-free survival (51.2% vs 93.9%, p < 0.01)and 5-year overall survival (47.1% vs 78.2%, p < 0.01). There were no significant differences in 5-year bladder recurrence survival between the two groups (66.5% vs 68.5%, P = 0.321). Local recurrence after RNU is a common event in patients with UTUC especially in T3 and T4 group. Patients with high Grade and multifocality were at high risk of recurrence. Patients with local recurrence tended to develop a metastasis recurrence and have a poor OS. This study implies some patients with high-risk local recurrence may benefit from postoperative adjuvant radiation therapy.

133P - The global forecast of prostate cancer drug-treatable populations eligible for targeted anticancer therapies (2017-2027)

Background: Targeted anticancer therapies have been approved by the Food and Drug Administration for use in some men with metastatic castrate-resistant prostate cancer (MCRPC). This study aimed to forecast the first-line MCRPC drug-treatable populations (DTP) by global geographic/economic regions over the period 2017-2027. Methods: Using country-specific cancer registries, prostate cancer incidence was estimated for 45 countries, representing approximately 90% of world population in 2017. Observed correlations between gross domestic product (GDP), prostate cancer risk, and background survival were used to forecast incidence for lower-income countries under study over the next ten years. Diagnosed incident cases were stratified by Tumor Node Metastasis (TNM) stage and risk categories using National Comprehensive Cancer Network (NCCN) 2013 Guidelines. A GDP-based forecast was applied to TNM stage/NCCN risk at diagnosis based on expected improvements in prostate cancer screening for lower-income countries. Metastatic recurrence-free survival was forecast using a function of historical trends to account for improvements in cancer therapy. First-line MCRPC DTP represents the total number of cases eligible for drug treatment in the first-line MCRPC setting each year. Using estimates of stage- and risk-stratified incident cases, and recurrent cases as described above, annualized estimates of first-line MCRPC DTP were obtained. To estimate incident cases and DTP globally, aggregate estimates for each region were divided by the proportion of countries in that region for which direct estimates were made using the methods described above. Results: In 2017, there were an estimated 331,000 first-line MCRPC DTP worldwide. The first-line MCRPC DTP worldwide will increase by 30% over the period 2017-2027, with higher growth across lower-income countries (40%), than across high-income countries (14%). Conclusions: The first-line MCRPC DTP is expected to increase globally, primarily driven by increases in diagnosed incidence in conjunction with growing and aging populations in the lower-income regions. Legal entity responsible for the study: Decision Resources Group, Burlington, MA, USA Funding: Has not received any funding Disclosure: The author has declared no conflicts of interest.

Outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease

BackgroundThe present study evaluated clinical outcomes for patients with head and neck squamous cell carcinoma presenting with N3 nodal disease.MethodsA retrospective analysis of N3 head and neck squamous cell carcinoma patients was performed. Pearson chi-square and Wilcoxon signed-rank tests were used to analyze patient demographics, disease characteristics, and treatment variables. Survival was evaluated using Kaplan-Meier curves with the log-rank test. Univariate analysis using Cox proportional hazards models was used to define factors associated with overall survival. Patient and tumor characteristics associated with treatment assignments were analyzed by univariate multinomial logistic regression.ResultsWe identified 36 patients with radiographically-defined N3 disease. For the entire cohort, median follow-up was 23.6 (range 2.8–135.0) months, and overall survival was 60% at 2 years and 30% at 5 years. Overall survival was similar between patients receiving primary surgery, radiotherapy, or chemoradiotherapy (p = 0.10). Primary, regional, and distant control at 5 years was 71%, 66%, and 53%, respectively. There was a trend towards improved regional control with primary surgery (p = 0.07). Planned neck dissection following primary chemoradiotherapy did not improve regional control (p = 0.55). Patients with p16-positive tumors exhibited improved overall (p = 0.05) and metastatic recurrence-free survival (p < 0.05). There were no factors predictive of treatment assignment nor factors associated with overall survival, local and regional control, or distant metastases free-survival on univariate analysis.ConclusionsPatients with N3 head and neck squamous cell carcinoma exhibit 5-year overall survival rates of approximately 30% regardless of treatment modality. Planned neck dissection does not improve regional control in patients undergoing definitive chemoradiotherapy. p16-positive patients represent a favorable cohort. Distant failure comprises the major failure pattern and should be the focus of future studies in improving the outcome of this patient cohort.

Analysis of open and intracorporeal robotic assisted radical cystectomy shows no significant difference in recurrence patterns and oncological outcomes

ObjectivesTo report and compare early oncological outcomes and cancer recurrence sites among patients undergoing open radical cystectomy (ORC) and robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). Methods and materialsA total of 184 patients underwent radical cystectomy for bladder cancer. ORC cases (n = 94) were performed between June 2005 and July 2014 while iRARC cases (n = 90) were performed between June 2011 and July 2014. Primary outcome was recurrence free survival (RFS). Secondary outcomes were sites of local and metastatic recurrence, cancer specific survival (CSS) and overall survival (OS). ResultsMedian follow-up for patients without recurrence was 33.8 months (interquartile range [IQR]: 20.5–45.4) for ORC; and 16.1 months (IQR: 11.2–27.0) for iRARC. No significant difference in age, sex, precystectomy T stage, precystectomy grade, or lymph node yield between ORC and iRARC was observed. The ORC cohort included more patients with≥pT2 (64.8% ORC vs. 38.9% iRARC) but fewer pT0 status (8.5% ORC vs.vs. 22.2% iRARC) due to lower preoperative chemotherapy use (22.3% ORC vs. 34.4% iRARC). Positive surgical margin rate was significantly higher in the ORC cohort (19.3% vs. 8.2%; P = 0.042). Kaplan-Meir analysis showed no significant difference in RFS (69.5% ORC vs. 78.8% iRARC), cancer specific survival (80.9% ORC vs. 84.4% iRARC), or OS (73.5% ORC vs.vs. iRARC 83.8%) at 24 months. Cox regression analysis showed RFS, cancer specific survival and OS were not influenced by cystectomy technique. No significant difference between local and metastatic RFS between ORC and iRARC was observed. ConclusionThis study has found no difference in recurrence patterns or oncological outcomes between ORC and iRARC. Recurrent metastatic sites vary, but are not related to surgical technique.

Strong adverse effect of epidermal growth factor receptor 2 overexpression on prognosis of patients with invasive lobular breast cancer: a comparative study with invasive ductal breast cancer in Chinese population.

The data on the outcome of breast invasive lobular carcinoma (ILC) are conflicting. In addition, the prognostic effect of molecular subtypes on ILC remains unclear. In this study, the clinicopathological and prognostic data between 269 ILC and 816 invasive ductal carcinoma (IDC) cases in a Chinese population were extensively compared, with a median follow-up time of 7.8 years. Compared with the IDC group, ILC tumors had more lymph node invasion, hormonal receptor positivity, and human epidermal growth factor receptor 2 (HER2) negativity. ILC patients showed overall survival (OS) and recurrence/metastasis-free survival (RFS) rates similar to those of IDC patients but exhibited worse disease-free survival (DFS) rate because of the higher rate of contralateral breast cancer (BC). Further analysis showed that OS, RFS, and DFS were similar between ILC and IDC patients in the subgroups of luminal A and triple-negative BC with HER2 negativity but were worse in ILC patients than those in IDC patients in the subgroups of luminal B and HER2 overexpression with positive HER2 expression. Multivariate analysis indicated HER2 positivity as an independent risk factor for OS, RFS, and DFS of ILC patients, which increased the risk in the ILC group than that in IDC group. The interaction of HER2 and ILC was also defined as an independent risk factor for OS, RFS, and DFS of the entire population. In conclusion, overexpression of HER2 exhibited stronger negative effect on the prognosis of ILC patients than that in IDC patients, suggesting that treatment targeting HER2 is crucial for this BC subgroup.

Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.Patients and MethodsA total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC) cases were included. The clinical features, breast cancer-specific survival (BCSS) and recurrence/metastasis-free survival (RFS) of the patients were compared between these two groups.ResultsThe IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively) than patients with IDC (89.5% and 84.5%, respectively). Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%). In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034). A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001). However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.ConclusionsIn Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

Postoperative Chemoradiotherapy versus Postoperative Chemotherapy for Completely Resected Gastric Cancer with D2 Lymphadenectomy: A Meta-Analysis

BackgroundBoth chemoradiotherapy and chemotherapy are used in postoperative adjuvant therapy for resected gastric cancer. However, it is controversial whether chemoradiotherapy or chemotherapy is the optimal strategy for patients with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to provide more evidence on the relative benefits of adjuvant therapies in this setting.MethodsWe conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed meta-analysis to obtain the relative hazards of adjuvant chemoradiotherapy to chemotherapy on efficacy and toxicities.ResultsA total of 895 patients from 3 randomized controlled trials were identified for this meta-analysis. All patients were from Asian countries. Our results showed that postoperative chemoradiotherapy significantly improved locoregional recurrence-free survival [LRRFS: hazard ratio (HR) = 0.53, 95% CI = 0.32–0.87, p = 0.01] and disease-free survival (DFS: HR = 0.72, 95% CI = 0.59–0.89, p = 0.002); however, the improvement of distant metastasis recurrence-free survival (DMRFS: HR = 0.86; 95% CI = 0.66–1.11, p = 0.25) and overall survival (OS: HR = 0.79, 95% CI = 0.61–1.03, p = 0.08) were non-significant. The main grade 3 or 4 toxicities were equivalent between the two groups.ConclusionIn non-selected Asian patients with resected gastric cancer who underwent D2 lymphadenectomy, postoperative chemoradiotherapy improved LRRFS and DFS but might not improve OS compared to postoperative chemotherapy.

Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified

BackgroundFew studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database.MethodsA total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups.ResultsThere were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival.ConclusionsMBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.