Single Metastatic Site Research Articles

Prognostic significance and optimal candidates of primary tumor resection in major salivary gland carcinoma patients with distant metastases at initial presentation: A population-based study

ObjectivesTo investigate the prognostic significance and identify optimal candidates of primary tumor resection (PTR) for patients with metastatic major salivary gland carcinoma (MaSGC) at diagnosis. Materials and methodsPatients with metastatic MaSGC were identified from the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic roles of PTR in the overall cohort and different subgroups. ResultsOverall, 255 patients were included in our study, among whom 80 (31.4%) received PTR. PTR was associated with decreased overall mortality (OM) and cancer-specific mortality (CSM) in the overall cohort (PTR vs No-PTR, HR: 0.363, 95%CI: 0.204–0.646, p = .001 for OM; HR: 0.439, 95%CI: 0.243–0.794, p = .006 for CSM). When we focused on site-specific metastases, receipt of PTR significantly reduced the risk of OM for patients with lung, bone or distant lymph node involvement (all p < .05), whereas this surgical procedure not only failed to bring survival benefit, but even seemed to insignificantly increase the mortality risk once liver metastases were presented (PTR vs No-PTR, HR: 1.109, 95%CI: 0.279–4.412 for OM; HR: 1.596, 95%CI: 0.364–7.004 for CSM). In addition, subgroup analyses showed that patients with stage T1-3 disease, younger age (<65), single-site metastases and high-risk pathologies might benefit from PTR. ConclusionOur study for the first time verifies the favorable prognostic impact of PTR for highly-selected patients with metastatic MaSGC at diagnosis and has the potential to be adopted in future clinical practice, although long-term prospective studies are warranted.

Up-front short-course radiotherapy and systemic chemotherapy for locally advanced rectal cancers with distant metastasis: Does it provide meaningful benefit?

778 Background: The optimal sequencing of treatment for locally advanced rectal cancer with distant metastasis (mLARC) is not well established. Methods: We retrospectively reviewed the records of mLARC patients receiving SCRT (25Gy/5#) and chemotherapy between July 2013 and December 2016. Patients were evaluated for surgery after SCRT and chemotherapy with the decision for further treatment being taken in a multidisciplinary team. Those patients who underwent surgery also received adjuvant chemotherapy as per the standard practice. Results: One hundred five consecutive mLARC patients were included in this study. Median age was 48 years (range 16-78) and 60 patients (57%) were male. Thirty-six patients (34%) had a single site of metastases. Sixty-one patients (58%) had obstruction at baseline and required stoma placement and another 19 patients (18%) had near obstructive lesions; these patients did not require stoma post SCRT and chemotherapy. With first line chemotherapy, objective response rate was 39% while 29% patients had stable disease. Twenty-four patients (23%) underwent definitive surgery. Median PFS and OS for entire cohort was 10.5 months (95% CI: 9.1-11.8) and 15.7 months (95% CI: 10.2-21.2), respectively. Median PFS was 23 months (95% CI: 18.7-27.7) for patients who could undergo surgery while it was 7.7 months (95% CI: 5.9-9.5, HR 5.0) (log rank &lt;0.001) for patients in whom surgery was not possible. Median OS was not reached for patients who underwent surgery while it was 10.9 months (95% CI: 9.6-12.3, HR 9.8) (log rank p&lt;0.001) for patients in whom surgery was not possible. OS at 3 years was 60% for patients who underwent surgery while it was only 7% in whom surgery was not possible. Conclusions: Upfront SCRT followed by systemic chemotherapy with delayed surgery in locally advanced rectal cancer with distant metastasis is an effective, feasible and attractive option. [Table: see text]

First line treatment of metastatic colorectal cancer: Are clinical trial results reproducible in real-life practice?

836 Background: Treatment of metastatic colorectal cancer (mCRC) has greatly advanced over the past decade, based on data from randomized controlled trials (RCTs). This raises the question whether results of RCTs, performed on selected patients (pts), do reflect outcomes in real-life practice. The aim of this study was to summarize our experience in the treatment of mCRC and compare it to data reported in RCTs. Methods: A retrospective single-institution study on consecutive mCRC pts treated with first-line bevacizumab-containing regimens in our institute between 2006 and 2014. Results: The study included 300 pts, of whom 54% were males. Median age was 67 years (range 28-90), 26% aged ≥ 75 years. ECOG performance status was ≤1 in 93%. The primary tumor site was right colon in 37%, left colon in 40%, rectal in 23% and 1% of pts had synchronous tumors. RAS status was available in 60%, of whom 55% had wild-type alleles. 46% of pts had a single metastatic site, including 27% with liver-limited disease, and 54% had multiple metastatic sites. Irinotecan-based chemotherapy was used in 66%, oxaliplatin-based chemotherapy in 29% and flouropyrimidine monotherapy in 5%. Curative metastasectomy during 1st line treatment was performed in 29%. Grade ≥3 hematological and non-hematological toxicities were reported in 24% and 38% of pts, respectively. Second and third line treatments were administered to 75% and 66% of pts, respectively; 73% of pts received both irinotecan and oxaliplatin through their treatment course and 76% of those with wild-type RAS were treated with anti-EGFR therapy. Overall response rate and disease control rate were 69% and 89%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 17 and 28 months, respectively. In a sub-group analysis on "RCT-like population", excluding pts ≥ 75 years, ECOG PS ≥ 3 and/or mutated/unknown RAS status, median PFS and OS were 15 and 29 months, respectively. Conclusions: The results of this study suggest that, if adhered to international clinical guidelines, outcomes reported in RCTs are indeed reproducible in routine clinical practice in unselected real-life pts. Additional data, with more pts and longer follow-up, will be presented.

Outcomes and Prognostic Factors of Small Cell Lung Cancer: A Retrospective Study

Background: Small cell lung cancer (SCLC) is a high grade neuroendocrine tumor, and has aggressive nature, so the majority of cases are presented with extensive disease. SCLC was staged into 2 categories: limited-stage disease (LS-SCLC) and extensive disease (ES-SCLC). Despite SCLC is sensitive to ra-diotherapy and chemotherapy, SCLC has high tendency for rapid dissemina-tion to regional and distant sites. Median survival time ranged from 2 - 4 months in patients with untreated SCLC. Multiagent chemotherapy was the primary treatment for SCLC. Aim of the work: This retrospective study was conducted to evaluate and analyze clinical features, treatment outcome, sur-vival and prognostic factors affecting survival in patients with SCLC presented to Clinical Oncology and Nuclear Medicine department, Chest department and Medical oncology unit in Mansoura Oncology Centre during the period from 2000-2015. Methods: Data of patients were collected from their files. The information obtained included demographic features, treatment received; its toxicity and outcome, survival and its prognostic factors. Demographic data were: age, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), smoking status, stage of disease. Data also included disease presentation and metastatic sites. Several factors affecting survival were analysed as age, sex, stage, PS, smoking status and LDH. Results: Sixty-three patients were enrolled in this study. Median age was 56.2 ± 6. Strong male predominance (92.1%) was observed; 84.1% of them were smoker. Thirty six patients (57.2%) were of ECOG-PS of 0 - 1. ES-SCLC was reported in 65% of cases and LDH was high (>1.5 xN) in 47.6%. The most common symptom was chest pain (38.1%) followed by cough (31.8%), weight loss (30%). Fifteen patients had single metastatic site (23.8%) and bone was the most common site of metastasis (reported in 8 patients) followed by brain, lung and liver. 2-year overall survival rate was 35% with median survival time of 14 months. On multivariate analysis, there were significantly higher survival in patients aged < 65 years (P = 0.03), female gender (P = 0.04), LD-SCLC (P = 0.03), good performance status (P = 0.04), low LDH level (P = 0.02) and non-smoker (P = 0.04). Conclusion: This clinico-epidemiologic study provides multiple prognostic factors that have important impact on survival as age, sex, LDH level, stage, smoking and performance status. Larger number of patients and prospective studies are needed to clarify more prognostic factor.

Analysis of A Single Para-Aortic Lymph Node Metastasis in Endometrial Cancer

Objective: To determine the indication for lymph node dissection in patients with endometrial cancer, we investigated the incidence and distribution of single metastatic lymph nodes in patients who underwent systematic pelvic and para-aortic lymph node dissection.Methods: This study involved 910 patients with endometrial cancer who were treated at the Cancer Institute Hospital, Japan, between January 1994 and December 2015. All patients underwent an open hysterectomy with bilateral salpingo-oophorectomy and pelvic and para-aortic lymph nodes dissection.Results: Lymph node metastasis was observed in 199 patients (21.9%), 45 (5%) of whom had single lymph node metastasis. Single lymph node metastasis accounted for 22.6% of all metastatic cases. Myometrial invasion >50% was observed in 30 patients, whereas 15 patients had <50% myometrial invasion. When mapping single lymph node metastatic sites, the para-aortic area had a frequency of 31.1% (14 cases). The distribution of single metastatic lymph nodes spanned a wide area between the pelvic and para-aortic regions. Considering single metastatic nodes and myometrial invasion, 8 patients (53.3%) who had myometrial invasion <50% had a single metastatic node in the para-aortic region. Four of 9 patients (45%) considered low-risk (endometrioid Grade 1-2, invasion depth <50%, no lymphovascular space invasion) showed metastasis to the para-aortic areas.Conclusion: Single metastatic lymph nodes were widely distributed between the pelvic and para-aortic regions, suggesting that detection of a sentinel lymph node in patients with endometrial cancer could be problematic.

Study of the relationship between EGFR mutation status and bone metastasis in advanced lung adenocarcinoma

To investigate the relationship between EGFR gene status and bone metastasis in lung adenocarcinoma, we collected the data of 331 patients with advanced lung cancer, and the status of EGFR mutation was detected by RT-PCR. Follow-ups of these patients were performed. In these patients, the EGFR mutation rate was 52.2%. The incidence of bone metastases (54.9%) and brain metastases (29.4%) with EGFR mutant patients was higher than that of the wild-type EGFR patients. Compared with the number of metastases, EGFR mutant bone metastases were more than 2 and more, and the proportion of wild type single-site metastasis was more. The median survival of bone metastases in advanced lung adenocarcinoma was 14.7 months. Mutant EGFR group, bone metastasis group median survival in 18.2 months, no bone metastasis group median survival in 21.8 months. In the wild-type group, the median survival of the bone metastases group was 11.5 months, and the median survival in the non-bone metastases group was 15.5 months. EGFR mutations are more likely to develop bone metastasis and brain metastasis in patients with advanced lung adenocarcinoma.

Prognostic value of site-specific metastases and therapeutic roles of surgery for patients with metastatic bladder cancer: a population-based study.

BackgroundWe aimed to evaluate the prognostic value of site-specific metastases in patients with metastatic bladder cancer and analyze the roles that surgeries play in the treatment of this malignancy.Materials and methodsA population-based retrospective study using Surveillance, Epidemiology and End Results dataset was performed and metastatic bladder cancer patients were classified according to the sites of metastases (bone, brain, liver, lung and distant lymph nodes). Kaplan–Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 1862 patients with metastatic bladder cancer from 2010 to 2014 were identified. Bone, lung and distant lymph nodes were the most common metastatic sites. Patients with bone, brain, liver and lung involvement had worse OS and CSS compared to patients without the corresponding sites of metastases. Multivariate analysis showed that bone, brain, liver and lung metastases were independent prognostic factors for both OS and CSS, while distant node metastasis was not. Moreover, patients with a single metastatic site had more favorable OS (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single-site metastatic patients, distant nodes and liver metastases represented the best and the worst prognosis, respectively. Moreover, radical cystectomy was an independent predictor for better OS and CSS, while in patients with liver metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in patients with a single metastatic site, metastasectomy seemed to be associated with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006) and for muscle-invasive bladder cancer patients (p=0.031).ConclusionDistant metastatic sites have differential impact on survival outcomes in patients with metastatic bladder cancer. Surgeries, including radical cystectomy and metastasectomy, might still lead to survival benefits for highly selected patients.

P3.01-003 Study of the Relationship between EGFR Mutation Status and Bone Metastasis in Advanced Lung Adenocarcinoma

To investigate the relationship between EGFR mutation status and bone metastasis in lung adenocarcinoma. We collected the data of 331 patients with advanced lung adenocarcinoma, and the status of EGFR mutation was detected by RT-PCR. Follow-up with these patients was performed. 331 cases of advanced lung adenocarcinoma, EGFR mutation rate was 52.2%. The incidence of bone metastases (54.9%) and brain metastases (29.4%) with EGFR mutant patients was higher than that wild type. Compared with the number of metastases, EGFR mutant bone metastases were more than 2 and more, and the proportion of wild type single-site metastasis was more. The median survival of bone metastases in advanced lung adenocarcinoma was 14.7 months. EGFR gene mutant group, bone metastasis group median survival in 18.2 months, no bone metastasis group median survival in 21.8 months. In the wild-type group, the median survival of the bone metastases group was 11.5 months, and the median survival in the non-bone metastases group was 15.5 months. EGFR mutations in patients with advanced lung adenocarcinoma are more likely to develop bone metastasis and brain metastasis.

Abstract 2927: Proteogenomic heterogeneity in metastatic lung adenocarcinoma revealed from rapid/warm autopsy

Abstract Introduction: Intratumor heterogeneity has been characterized among multiple cancer types. However, in lung adenocarcinoma, recent work has been limited to early stage primary tumors and intertumor heterogeneity has not been well-studied. Most importantly, an integrated tumor heterogeneity analysis at the level of somatic variants, copy number, transcript and protein expression, and the phosphoproteome is outstanding. Methods: In order to characterize both intra-tumor and inter-tumor heterogeneity of metastatic lung adenocarcinoma, we applied whole exome sequencing, RNA-seq, CNV-seq and mass spectrometry-based proteomic analyses on 33 tumor regions from metastatic sites including lung, liver and kidney, obtained by rapid/warm autopsy from 4 patients with Stage IV lung adenocarcinoma. The autopsy procedure was initiated between 2-4 hours of death. Results: We found considerable intertumor heterogeneity with organ-specific, branched evolution that was consistent across DNA, RNA and protein analyses. Intratumor heterogeneity differed depending on oncogene-status: oncogene-negative tumors (without RTK/RAS/RAF mutations or known fusion gene) had significantly higher genomic intratumor heterogeneity than oncogene positive tumors. The degree of heterogeneity at the genomic and proteomic level was patient-specific. The proteomic analysis complemented genomic variants-based clonal evolution analysis. High-confidence driver mutations (KRAS, EGFR, TP53, CTNNB1) uniformly occurred early in the evolution of metastatic lung adenocarcinoma consistent with the concept of these mutations as likely ‘founders’. In contrast, other known driver mutations occurred more often in later stages among specific organ branches. Notably, oncogene-negative tumors carried significantly more driver mutations than oncogene-positive tumors suggesting that genomic alterations may have a larger role in the metastatic process versus the early evolution of lung adenocarcinoma in oncogene-negative vs. oncogene-positive tumors. Among all patients, lung cancer specific focal copy number alterations frequently occurred within metastatic branch points. Single metastatic site biopsies would therefore be unlikely to capture all significant driver mutations and copy number alterations, particularly among oncogene-negative tumors. Conclusion: Metastatic lung adenocarcinoma evolves through a branched, organ-specific, process with acquisition of significant driver mutations and copy number changes, particularly among oncogene-negative tumors. The branched evolution is ultimately influenced by proteomic and phosphoproteomic alterations affecting key signaling pathways that may not be always a result of genomic changes. Citation Format: Nitin Roper, Tapan K. Maity, James Gao, Abhilash Venugopalan, Xu Zhang, Romi Biswas, Constance Cultraro, David Kleiner, Stephen Hewitt, Javed Khan, Guha Udayan. Proteogenomic heterogeneity in metastatic lung adenocarcinoma revealed from rapid/warm autopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2927. doi:10.1158/1538-7445.AM2017-2927

Upfront short course radiotherapy (SCRT) in metastatic rectal cancer (mRC): A way forward.

3570 Background: To evaluate the feasibility and efficacy of SCRT followed by chemotherapy (CT) in locally advanced metastatic rectal cancer (LAmRC). Methods: Between May 2012 and August 2015, 70 patients having LAmRC with or without circumferential resection margin (CRM) positive disease treated with SCRT (25Gy/5#) followed by 3-6 cycles of capecitabine/5-FU, oxaliplatin or irinotecan based CT were assessed. Results: Fifty one had single site metastases (23 liver, 16 lung, 10 retroperitoneal lymph nodes and 2 peritoneum), 9 had combined lung and liver metastases and 10 had combined nodal and organ metastases. Sixty five (93%) patients could complete planned SCRT and 3-6 cycles of chemotherapy (starting 7-10 days after RT completion) with dose reduction in 21 (32%) patients owing to CT induced toxicities. Local tumor down-staging was achieved in 43 (61.4%) patients and the rest had a stable primary disease. Radiologically, CRM was free in 25 (46.3%) patients out of 54 initially involved. Surgery of the primary was planned in 38 (58%). R0 resection in 26 (40%), R1 in 7 (pCRM positive). Five refused surgery in spite of being resectable. Rest of the 27 (41%) received palliative CT due to progression of distant disease. Metastatectomy along with primary surgery was done in 16 (25%) patients. Median follow up was 29 months. Overall survival (OS) of entire cohort at 2 years was 40%. Median progression free survival (PFS) and OS of patients with resected primary was 17 (10-24) and 37 (28-45) months, respectively, which is significantly better than those who were not resected (p = &lt; 0.001). Of these 33 resected patients, 13 (39.4%) are disease free and 20 have progressed (16 distant, 2 loco-regional and 2 local and systemic). Conclusions: Upfront SCRT followed by systemic CT in an unresectable group of metastatic rectal cancer patients is safe and feasible and is having encouraging results in terms of downstaging and resectability of the primary. [Table: see text]

Fulvestrant 500 milligrams as endocrine therapy for endocrine sensitive advanced breast cancer patients in the real world: the Ful500 prospective observational trial.

The observational prospective trial herein presented aimed at evaluating the efficacy of fulvestrant 500 mg in the treatment of endocrine sensitive advanced breast cancer patients from the real world setting. The primary end point was clinical benefit rate (CBR). Secondary end points were overall survival (OS), progression free survival (PFS) and tolerability. One hundred sixty three patients were enrolled. At a median follow up of 20 months, the 61% of patients reached CBR, whose median duration was 10.8 months. Median PFS and OS were 7 and 35 months, respectively. Endocrine sensitive patients showed better PFS and OS. No relevant toxicity appeared when analyzing safety data. In multivariate analysis, visceral involvement, endocrine sensitivity and previous endocrine therapy were prognostic factor for PFS, whereas endocrine sensitivity and metastasis at diagnosis had prognostic relevance for OS. Estrogen receptor expression >50%, single metastatic site, and no prior endocrine therapy for advanced disease were predictive of CBR. In this prospective trial, fulvestrant 500 mg appeared to be a safe and active treatment and confirmed its efficacy in the daily clinical practice. A high percent expression of estrogen receptors (above 50%) was associated with higher CBR. Treatment was very well tolerated. Endocrine sensitivity had a major impact on treatment outcome. As expected, patients who had received first-line endocrine therapy for advanced disease exhibited worse outcome and a lower CBR.

MP34-20 CAN RADICAL CYSTECTOMY BE PERFORMED SAFELY IN THE METASTATIC SETTING? LOCATION OF METASTATIC BLADDER CANCER AS A DETERMINANT OF IN-HOSPITAL MORTALITY

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2017MP34-20 CAN RADICAL CYSTECTOMY BE PERFORMED SAFELY IN THE METASTATIC SETTING? LOCATION OF METASTATIC BLADDER CANCER AS A DETERMINANT OF IN-HOSPITAL MORTALITY Emanuele Zaffuto, Marco Moschini, Sami-Ramzi Leyh-Bannurah, Stephanie Gazdovich, Paolo Dell'Oglio, Raisa S. Pompe, Shahrokh F. Shariat, Francesco Montorsi, Alberto Briganti, Fred Saad, and Pierre I. Karakiewicz Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Sami-Ramzi Leyh-BannurahSami-Ramzi Leyh-Bannurah More articles by this author , Stephanie GazdovichStephanie Gazdovich More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Raisa S. PompeRaisa S. Pompe More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Fred SaadFred Saad More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1037AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A recent study within a highly-select patient cohort suggested a survival benefit when local treatment is delivered in patients with metastatic bladder cancer (BCa). We relied on a similar patient cohort to examine in-hospital mortality (IHM) rates according to presence, absence and location of metastatic disease in BCa patients treated with radical cystectomy (RC). METHODS We identified 25,004 BCa patients treated with RC between 2004 and 2013 from the hospital claims data in the National Inpatients Sample database. Using International Classification of Diseases, 9th edition (ICD-9-CM) diagnostic codes, we identified 5,049 patients with metastatic disease. Metastatic BCa patients were stratified according to the presence of non-regional lymph node metastases (NRNM) in absence of distant organ involvement vs. presence of distant organ metastases (DM), regardless of nodal status. We tested postoperative IHM rates according to presence of metastases, as well as location of metastatic disease (NRNM vs. DM). Logistic regression analyses were adjusted for age, gender, race, comorbidities, length of hospitalization, hospital location, teaching status, hospital surgical volume and bed size. RESULTS Overall, 3,323 patients (13.3%) had NRNM, 1,726 (6.9%) had DM, and 19,965 (79.8%) had non-metastatic disease. Virtually all metastatic patients had a single metastatic site involvement (n=4,458; 88.5%), while only a small proportion of individuals had metastatic involvement in 3 or more sites (n=57; 1.1%). The most common metastatic sites were lymph nodes (76.0%; n=3,830), other urinary organs (23.2%; n=1,168), intestine (4.7%; n=235) and retroperitoneum (4.1%; n=209). Interestingly, bone and liver metastases represented only 1.6% (n=81) and 1.1% (n=55) of cases, respectively. IHM rates were 1.5% (n=51), 3.5% (n=60) and 2.0% (n=404) for NRNM, DM and non-metastatic patients, respectively. The difference in IHM rates between DM and non-metastatic BCa patients was statistically significant (p<0.001). Conversely, NRNM patients did not exhibit different mortality rates than their counterparts without metastatic disease (p=0.07). In multivariable logistic regression analyses, DM patients (OR: 1.68; 95% CI: 1.26-2.20; p<0.001), but not NRNM patients (OR: 0.84; 95% CI: 0.62-1.11; p=0.2), were at increased risk of IHM. CONCLUSIONS DM patients are at an increased risk of IHM, compared to NRNM or non-metastatic patients. If at all indicated, RC in metastatic setting should be limited to patients with NRNM. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e435 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Emanuele Zaffuto More articles by this author Marco Moschini More articles by this author Sami-Ramzi Leyh-Bannurah More articles by this author Stephanie Gazdovich More articles by this author Paolo Dell'Oglio More articles by this author Raisa S. Pompe More articles by this author Shahrokh F. Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Fred Saad More articles by this author Pierre I. Karakiewicz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The prognostic value of histological subtype in patients with metastatic bladder cancer.

We aim to evaluate the prognostic effect of the histological sub-type in patients with metastatic bladder cancer based on the Surveillance Epidemiology and End Results database. A total of 2634 eligible patients were included. The histological subtypes were: transitional cell carcinoma (TCC; 75.2%); adenocarcinoma (3.3%); squamous cell carcinoma (SQCC; 4.1%); and small cell carcinoma (4.3%). A significant association of adenocarcinoma with better survival outcomes (P < 0.015), and that of SQCC with worse outcomes (P < 0.001) was observed. On multivariate analysis, adenocarcinoma was significantly associated with longer and SQCC with shorter survival time as compared to TCC. Overall, 1331 (50.5%) patients had a single metastatic site and 523 (19.9%) had multiple sites involved. Single-site metastasis had a better survival outcome than multiple metastases (P < 0.001). Histological sub-type and presence of multiple metastatic sites are independent predictors of survival time. Prospective, in-depth research is needed to determine optimal therapeutic strategies for different histological subtypes of bladder cancer with different metastatic patterns.

Randomized phase II trial of sipuleucel-T immunotherapy preceded by sensitizing radiation therapy and sipuleucel-t alone in patients with metastatic castrate resistant prostate cancer.

222 Background: Sipuleucel-T (sip-T) is an autologous cellular vaccine indicated for patients (pts) with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC). Since radiation therapy (RT) can suppress the bone marrow function and immune response, previous studies evaluating sip-T excluded pts who received RT less than or equal to 28 days prior to sip-T therapy. Recent evidence suggests that RT may act synergistically with immunotherapy to enhance and broaden antitumor immune response. Methods: Pts who met standard criteria for sip-T were randomized to receive sip-T alone (Arm A) or sip-T initiated 1 week after completing sensitizing RT to single metastatic site (Arm B). RT was delivered at 300cGy/day to 3000 cGy total. The primary endpoint was the ability to safely combine sip-T preceded by RT and generate sip-T product with adequate immune activation parameters. Secondary endpoints included the measurement of immune responses to prostatic acid phosphatase (PAP) and PA20204 (recombinant fusion protein utilized in the generation of sip-T). Results: 51 pts were enrolled, 2 did not receive any sip-T because of vascular access problems and were excluded. 24 were treated on Arm A, 25 on Arm B. 47/49 pts received all 3 sip-T infusions. Median age was 66 yrs (range 45-90). Sip-T product parameters including: total nucleated cell (TNC) count, antigen presenting cell (APC) count and APC activation were similar in both groups. 2 pts on Arm A demonstrated PSA response. Median progression free survival (PFS) was 3.0 months on Arm A and 4.6 months on Arm B (p = 0.19). Both arms showed similar increases in humoral responses to PA2024 and PAP. IFN-ƴ ELISPOT T-cell activation responses to PA20204 were observed in both arms, but were more robust in the Arm A (p = 0.04). Both arms were well-tolerated, with fatigue as the most common grade 2 adverse event (1 pt in Arm A and 3 pts in Arm B). Conclusions: Sensitizing RT completed 1 week before generation of sip-T did not affect product parameters and the ability to deliver sip-T therapy. RT did not enhance the humoral and cellular responses associated with sip-T therapy. Clinical trial information: NCT01807065.

Response rate and survival for patients with metastatic colorectal cancer from right-sided versus left-sided tumors, treated with first-line triplet chemotherapy with bevacizumab.

801 Background: Recent data have shown that right sided colonic cancer represent a molecularly different class of tumors from the left sided ones with worse survival in patients treated with doublets systemic chemotherapy. We report the result of response and survival on patients treated with triplet chemotherapy according to the primary tumor location. Methods: Medical records of patients treated with triplet chemotherapy (capecitabine, oxaliplatin and irinotecan) in combination with bevacizumab on a prospective clinical trial (clinicaltrial.gov: NCT01311050), were retrospectively reviewed for the location of primary tumor. Right sided tumors: from cecum to hepatic flexure. Left sided tumors: from splenic flexure to and including the rectum. Transverse colon were excluded. Patients who had multiple primaries were considered right sided if at least one of them was right sided. Results: Fifty-three patients treated with above triplet therapy. Eleven were right sided and 42 were left sided. Characteristics for right vs left sided tumors were as follow: Median age: 46 (range 24-55 years) vs 53 ( 32-74 years), male: 5 (46%) vs 23 (55%), performance status 0-1: 9 (82%) vs 37 (88%), KRAS wild: 3 (27) vs 12 (29%), single metastatic site: 5 (46%) vs 14 (33%) and Prior adjuvant chemotherapy: none vs 6 (14%). Response rate (complete and partial) were 6 (54%) in right sided tumors and 24(57%) in left sided tumors. Progression free and overall survival for right sided tumors was 22 (95% confidence interval (CI) 12.3-31.7) and 22 months (95% CI 16.6-27.4) and for left sided tumors were 12 (95% CI 3.5-20.5) and 28 months (95% CI 22.7-33.2) respectively. Conclusions: First-line triplet chemotherapy with bevacizumab may overcome the poor prognosis of metastatic right sided colonic cancer. Clinical trial information: NCT01311050.

Combining pembrolizumab and palliative radiotherapy in gastroesophageal cancer to enhance anti-tumor T-cell response and augment the abscopal effect.

TPS220 Background: Pembrolizumab has demonstrated encouraging preliminary evidence of activity in small cohorts of gastroesophageal cancer patients (pts) when selected for tumor PD-L1 overexpression. Strategies should be further developed to enhance the potency of PD-1 inhibitors, even in pts whose tumors are not considered to have detectable PD-L1 expression. The abscopal effect is a rarely observed though well annotated clinical phenomenon in cancer radiotherapy (RT), in which non-irradiated metastatic lesions are noted to regress after radiation to the primary tumor site. In preclinical models, this phenomenon has been attributed to immune-mediated effects, while RT has been observed to increase tumor PD-L1 expression. This lends credence to ongoing efforts to combine RT and immune checkpoint inhibition. We present the study design for a phase II trial combining pembrolizumab and palliative RT in metastatic gastroesophageal squamous cell and adenocarcinoma pts. Methods: A target accrual of 14 pts will be assigned to palliative RT of 30 Gy over 10 fractions for symptoms from their primary tumor or a single target metastatic site in combination with fixed dose pembrolizumab 200 mg every 3 weeks. Symptomatic brain metastases will be excluded. Pembrolizumab will be continued until disease progression, intolerable toxicity, or 35 administrations (~2 years). Pts will be required to undergo sequential biopsies of a non-target metastatic site (inclusive of malignant ascites) with timepoints occurring pre-treatment and ~21 days after completion of RT. Biomarkers of immune response and overall response rate (RECIST1.1, irRECIST) will be a composite primary endpoint; progression-free and overall survival, and toxicities will be secondary endpoints. Quantitative spatial image analyses of biopsy samples will be performed to examine changes in tumor cell-stromal interactions inclusive of CD4, CD8, Treg, and MDSC populations as well as tumor PD-L1/PD-1 expression levels. The results will assist in determining mechanisms of response and resistance to combination RT and PD-1 targeting strategies. Clinical trial information: NCT02830594.

Therapeutic role of axillary lymph node dissection in patients with stage IV breast cancer: a population-based analysis.

To assess the clinical value of axillary lymph node (ALN) dissection in stage IV breast cancer. Patients with a diagnosis of stage IV breast cancer from 1990 to 2010 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of ALN dissection and ALN status on breast cancer-specific survival (BCSS) and overall survival (OS). A total of 11,645 patients were identified. Of these, 7358 (63.2%) patients underwent ALN dissection, and 6168 (83.8%) patients showed nodal positivity. During this time, the rate of ALN dissection increased. Patients with delayed diagnosis, age <50years, poorly/undifferentiated disease, larger tumor size (>2cm), and married women were more likely to undergo ALN dissection. ALN dissection was associated with improved BCSS and OS in multivariate analysis. ALN dissection improved the survival in patients with bone and liver metastasis, and patients with single site of distant metastasis also had survival benefit by ALN dissection. Lymph node staging based on the number of positive lymph nodes was the independent prognostic factor for BCSS and OS in multivariate analysis; patients with advanced lymph node staging had a poor survival. ALN dissection may improve survival in patients with stage IV breast cancer who received primary tumor surgery, especially in patients with bone, liver, and single site of distant metastasis. The lymph node staging was also the prognostic factor in patients with stage IV breast cancer.

D11 - A multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer (mCRC)

Background: Bevacizumab is a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, approved in combination with chemotherapy in the treatment of mCRC. It is proposed that the schedule of administration might be critical and that giving bevacizumab before chemotherapy might improve treatment efficacy. Methods: mCRC patients, ≤ 75 years old, ECOG PS ≤1, with at least one measurable lesion according to RECIST, having received no more than one line of treatment for metastatic disease, were randomized (1:1) to receive standard concomitant administration of bevacizumab (5mg/kg every 2 weeks) with chemotherapy (mFOLFOX/OXXEL regimen for 12 cycles) vs experimental bevacizumab given 4 days before chemotherapy (same dose), at each cycle. Patients could receive maintenance bevacizumab (7.5 mg/kg every 3 weeks) until disease progression or unacceptable toxicity in both arms. Primary end point was the objective response rate (ORR). With 80% power and 2-tailed alpha 0.05, 230 patients were planned to verify an increase of response rate of 20% between the standard and the experimental arm. With 163 events, the study has 80% power to detect a progression-free survival (PFS) improvement with a hazard ratio (HR) of 0.64. Analyses are based on intention to treat. Results: From May 2012 to Dec 2015, 230 patients were randomised to experimental (n = 115) and standard arm (n = 115). Median age was 62 (IQ range 53-68), 79% were PS 0, 93% were not pretreated, 53% had a single metastatic site. Median numbers of chemotherapy cycles was 12 in both arms, 73% received the FOLFOX regimen. In the experimental arm, the median time between bevacizumab and chemotherapy administration per cycle was 4 (interquartile range 4-4) days. ORR was 57.4% (95% CI 47.8-66.6) in both arms (p = 1.00). With a median follow-up of 21.1 months, 173 PFS events were reported. Median PFS was 12.0 and 10.4 (HR 0.84, 95% CI: 0.63-1.14; log rank p = 0.27) months in the experimental and standard arm, respectively. In a multivariate Cox regression model including PS, previous treatment and number of metastatic sites as covariates, the difference remained not significant (HR 0.83, 95% CI: 0.62-1.12; p = 0.23). Conclusion: the OBELICS trial shows that anticipating bevacizumab to chemotherapy does not improve ORR nor significantly prolongs PFS. Correlative studies on biomarkers and FDG-PET are ongoing. The trial was supported by of the Italian Ministry of Health. ClinicalTrials.gov NCT01718873.

Prognostic effect of liver metastasis in lung cancer patients with distant metastasis.

Because the need of clinical prognostic evaluation by specific metastatic organ, we aim to analyze the prognostic factors in lung cancer patients with M1b disease with Surveillance Epidemiology and End-Results database (SEER). This retrospective study evaluated lung cancer patients of adenocarcinoma (AD), squamous cell carcinoma (SQCC), and small cell lung cancer (SCLC) selected from SEER. We provided the prognostic correlates of overall survival (OS) and lung cancer-specific survival (LCSS) in this population. 23,679 eligible patients were included. Bone was the most common metastatic site in AD (63.1%) and SQCC (61.1%), while liver was the most prevalent site (61.9%) in SCLC. Single site metastasis was significantly associated with better outcome compared to multiple sites metastases in all patients. Among patients with single site metastasis, OS and LCSS were longer for AD and SCLC if involving brain or bone, with median survival time of 5 to 7 months, comparing to 3 months if invloving liver (all p-values < 0.001). Similarly, among patients with multiple metastases, better outcomes were observed in AD patients (4 vs 3 months; OS and LCSS, p < 0.001) and SCLC patients (6 vs 4 months; OS, p = 0.017; LCSS, p = 0.023) without liver metastasis compared to those with liver metastasis. In conclusion, we estimated multiple survival outcomes by histology of primary tumor and sites of metastasis. Liver metastasis is found to be the worst prognostic factor for AD and SCLC patients with distant metastasis. More in-depth research is warranted to identify patients who are prone to develop distance metastasis, especially to liver.

35P Unemployment risk among lung cancer survivors: A population based study

department of Clinical Oncology and Nuclear medicine in Ain Shams University hospitals. Methods: All patients with pathologically proven primary NSCLC in the period from 2012 to 2014 were included for analysis. Data from records of 195 cases were available for clinicopathological evaluation during the study period. Treatment received and outcome was collected. Results: The mean age at diagnosis of the study population was 59 years, Male to female ratio was 3.6:1, 71.2% of cases were current or x-smokers, 44.6% of patients had ECOG performance status 1. The most common symptom at presentation was dyspnea and right upper lobe was the most common tumor site. Adenocarcinoma was the most common histological subtype representing 62% of cases. Most common stage at diagnosis was stage IV (56.4%) and the most common site of metastasis was bones. Statistically significant improvement in overall survival rate and progression free survival rate was found in the following groups: female sex, PS 1 or 2, never smokers, grade II tumors, lower tumor size, less lymph nodal stations involvement, lower stage at diagnosis, single versus multiple metastatic sites and response to definitive treatment. Conclusions: The present analysis suggested that lung cancer incidence in Egypt is less than most of the western countries. Patients presented at younger age compared to other areas of the world. Most of the patients had advanced disease at presentation. Adenocarcinoma was the most common histological subtype. Female sex, better performance status, never smokers, smaller tumors, less lymph nodal affection, earlier stage at diagnosis, fewer metastatic sites and response to definitive treatment have a statistically significant better OS and PFS. Legal entity responsible for the study: Ain Shams Hospitals Funding: Ain Shams Hospitals Disclosure: All authors have declared no conflicts of interest.