Prognostic Factors For Prolonged Survival Research Articles

The effects of neutral argon plasma versus electrocoagulation on tissue in advanced-stage ovarian cancer: a case series

BackgroundThe aim of surgery for advanced-stage ovarian cancer is a complete cytoreduction, because this is the most important independent prognostic factor for prolonged survival. Yet this can be difficult to achieve when there are micrometastases on the intestinal mesentery or intestines. The PlasmaJet device is an instrument to remove these micrometastases, but little is known about the depth of damage in human tissue compared to electrocoagulation devices.MethodsA prospective study was performed for the ex-vivo comparison of the histological depth of thermal damage of neutral argon plasma (PlasmaJet®) and electrocoagulation devices, in a series of 106 histological slides of 17 advanced-stage ovarian cancer patients. Depending on the tissue types resected during complete cytoreductive surgery, samples were collected from reproductive organs (uterus, ovaries), intestines (ileum, colon, rectum) and omentum, intestinal mesentery and peritoneum.ResultsAverage thermal damage depth was 0.15 mm (range 0.03–0.60 mm) after use of neutral argon plasma and 0.33 mm (range 0.08–1.80 mm) after use of electrocoagulation (p < 0.001). Greater disruption of the tissue surface was often observed after electrocoagulation.ConclusionOur case series suggests that the use of neutral argon plasma during cytoreductive surgery produces significantly less thermal damage than electrocoagulation treatment. It is therefore considered a thermally safe alternative, aiding in the achievement of cytoreductive surgery.

Anaplastic thyroid carcinoma: a nationwide cohort study on incidence, treatment and survival in the Netherlands over 3 decades.

To perform a nationwide population based study in ATC on incidence, treatment and survival. Retrospective cohort study. All patients with primary ATC between 1989 and 2016 were identified in the Netherlands Cancer Registry (NCR). Of all these patients excerpts from the pathology reports from PALGA: Dutch Pathology registry were linked to the data of the NCR. Standardized incidences were calculated, survival was estimated using Kaplan-Meier method and univariable statistically significant factors were included in a multivariable regression model. In total, 812 patients were included. Mean standardized incidence rates were 0.18/100 000 (range 0.11-0.27/100 000) with a significant trend over the years with an estimated annual percentage change of 1.3% per year (95% CI 0.4-2.1%). Median overall survival was 2.2 months, and estimated 1-year survival was 12%. Patients without distant metastases at diagnosis had an estimated 1-year survival of 21.6%. Prognostic factors for prolonged survival were double or triple therapy, age below 65 years, M0-status and absence of bilateral lymph node metastases. ATC is rare, but often lethal, form of thyroid cancer, with a median survival of 2 months and 1-year survival of approximately 10%. The incidence is slightly rising in the Netherlands over the past 3 decades. There appears to be a subgroup of patients that survive longer, mainly those with relatively limited disease who underwent double or triple therapy. Further research is needed to define these patients more distinctively.

Lymphocyte-monocyte ratio as a predictive marker for pathological complete response to neoadjuvant therapy in esophageal squamous cell carcinoma.

BackgroundThe hematological markers of systemic inflammation has been proved to be significantly associated with clinical outcomes in esophageal cancer. This retrospectively study was to evaluate the value of the hematological markers in predicting pathological complete response (pCR) and overall survival (OS) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) who received neoadjuvant chemoradiotherapy (nCRT).MethodsA total of 87 patients with newly diagnosed LA-ESCC were retrospectively analyzed. The pretreatment lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were selected as hematological markers.ResultsAfter nCRT, 26 (29.9%) patients achieved pCR and 61 (70.1%) patients had non-pCR. The LMR was significantly higher in patients who achieved pCR compared to that in patients who did not achieve pCR (4.35±1.68 vs. 3.33±1.13, P=0.002). Based on the receiver operating characteristic (ROC) curve, the optimal cut off value of LMR that predicted pCR was 3.73 [area under the curve: 0.712; 95% confidence interval (CI): 0.594–0.830; P=0.002], with a sensitivity of 65.4% and specificity of 77.0%. The pCR rate of patients with LMR ≥3.73 was 53.1%, while the pCR rate of patients with LMR <3.73 was only 16.4% (P<0.001). The univariate and multivariate logistic regression analysis confirmed that LMR was an independent predictor of pCR [odds ratio: 5.093; 95% CI: 1.658–15.646; P=0.004]. However, in the prediction of OS, a multivariate Cox proportional hazard model revealed that only clinical stage [hazard ratio (HR): 1.970; 95% CI: 1.144–3.391; P=0.014] and pCR (HR: 0.469; 95% CI: 0.237–0.928; P=0.030) were independent prognostic factors.ConclusionsPre-treatment LMR may predict pCR in LA-ESCC patients who were treated with nCRT. Having pCR is an independent prognostic factor for prolonged survival.

Maintenance with Weekly Carfilzomib in Elderly Newly Diagnosed Multiple Myeloma (IFM 2012-03)

Background. Continuous therapy, such as maintenance approach, appears to be a major therapeutic change in multiple myeloma, improving response rate and overall survival. Novel agents widen the range of treatment options, still Lenalidomide (IMiD) is widely used in this indication. Even though usually well tolerated, it remains a daily treatment, and can lead to some side effects on a long term basis. Carfilzomib, a second generation PI, allows interesting response rate and prolonged survival, with manageable adverse events. Nevertheless, only few clinical trials focused on its use in maintenance rather than in first or second line treatment. We therefore thought to study the role of 1 year Carfilzomib exposure following KMP IFM 2012-03. Methods. IFM 2012-03 is a multicenter phase I study for eNDMM (patients aged 65 years old and more) that determined the maximal tolerated dose of weekly carfilzomib, associated with melphalan and prednisone (KMP), at 70mg/m². The following results will concern the second phase of the study using intravenous Carfilzomib monotherapy in maintenance. K was administered at 36 mg/m² for 13 cycles on an every 2 weeks schedule. Results. Thirty eNDMM were recruited in IFM 2012-03. Median age is 75, with 56% R-ISS 2 or 3 and 11% high-risk cytogenetic. With K weekly from 36 to 70mg/m², ORR is reported at 93.3%, including 46.7% ≥CR ; median PFS is 35.8 months and median OS was not reached. Twenty-two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36-months OS approximately 70%. Moreover, 3 patients (14%) improved their responses during maintenance. Conclusion. Carfilzomib monotherapy can be used safely in maintenance for 1 year in eNDMM, including for patients above 75 years. K maintenance may lead to deep response rate, certainly a most relevant prognostic factor for prolonged survival. Therefore, Carfilzomib maintenance, characterized with a simple administration modality, might be considered as an alternative to Lenalidomide and integrate the armamentarium of prolonged therapy in eNDMM. Further studies should still bring additional information in order to confirm our results. Disclosures Karlin: AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kolb:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: travel and registration for my participation to international medical congres (ASH). Jaccard:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria; Abbvie: Honoraria. Belhadj:Celgene: Other: personal fees from Celgene, personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, outside the submitted work. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Hulin:Janssen, AbbVie, Celgene, Amgen: Honoraria; celgene: Consultancy, Honoraria. Leleu:Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria.

Maintenance with weekly carfilzomib in elderly newly diagnosed multiple myeloma (IFM 2012-03).

8029 Background: Prolonged treatments have significantly improved survival in newly diagnosed multiple myeloma (NDMM). Lenalidomide (IMiDs), is currently approved in this indication, but remains a daily treatment, although oral, and may favor side effects in the long run. Furthermore, the use of a proteasome inhibitor (PI) is warranted in certain type of MM, such as high-risk. Carfilzomib, a second generation PI, has proved active combined with an acceptable security profile but its added benefit when given continuously is unknown. We thought to study maintenance Carfilzomib for elderly NDMM (eNDMM). Methods: The IFM 2012-03 multicenter phase I KMP (Carfilzomib, Melphalan, Prednisone) weekly study for eNDMM (≥ 65 years old) determined the maximal tolerated dose of weekly Carfilzomib at 70mg/m². We focus herein on the second part of the study with IV Carfilzomib monotherapy given at 36mg/m² for 13 cycles maintenance on an every 2 weeks schedule. Results: Thirty eNDMM were recruited in IFM 2012-03. Median age is 75, with 56% R-ISS 2 or 3 and 11% high-risk cytogenetic. With K weekly from 36 to 70mg/m², OS is reported at 93.3%, including 46.7% ≥CR; median PFS is 35.8 months and median OS was not reached. Twenty-two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36-months OS approximately 70%. Conclusions: Carfilzomib monotherapy can be used safely in maintenance for 1 year in eNDMM, including for patients above 75 years. K maintenance may lead to deep response rate, certainly a most relevant prognostic factor for prolonged survival. Therefore, Carfilzomib maintenance, characterized with a simple administration modality, might be considered as an alternative to Lenalidomide and integrate the armamentarium of prolonged therapy in eNDMM. Clinical trial information: NCT02302495.

Abstract A113: Harnessing lymphoid organ neogenesis as a novel prognostic biomarker and therapeutic target

Abstract Lymphoid organ neogenesis takes place in chronically inflamed tissues including cancer and yields the development of tertiary lymphoid structures (TLS). TLS are ectopic lymphoid organs that activate antigen specific T-cells and B cells in infection and autoimmunity and correlate with prolonged survival in various cancer types. This suggests that TLS contribute to protective anti-tumor immunity. Therefore, promoting the development of tumor-associated TLS could be a novel immunotherapeutic approach. However, the molecular and cellular mechanisms of TLS development in human cancer or how TLS contribute to survival are largely not understood. Here we used multiparameter immunofluorescence and digital pathology to quantify TLS and to characterize their cellular composition and tissue context in cohorts of lung squamous cell carcinoma (LSCC, n=138), colorectal cancer (CRC, n=111), clear cell renal cell carcinoma (ccRCC, n=50) and bladder cancer (BC, n=33) patients. Furthermore, we established an experimental model to characterize TLS development and its impact on tumor-specific immunity. We discovered that TLS development and maturation followed the same steps in all analyzed tumor types as well as in the lungs of mice in our experimental model. First, B and T lymphocytes accumulated around blood vessels. Second, a network of follicular dendritic cells developed within the lymphocytic aggregate, and third, a germinal center (GC) reaction was activated. Additionally, we identified a niche of CXCL13+ perivascular stroma and CXCL12+LTB+ and PD-L1+ epithelial cells that were associated with TLS in LSCC. We found that the number of tumor-associated TLS was an independent prognostic factor for prolonged survival in untreated LSCC, CRC and BC, but not in ccRCC patients or in LSCC and BC patients who were treated with neoadjuvant chemotherapy. By comparing the chemotherapy-treated and untreated cohorts we observed that the number of TLS was not changed but TLS maturation (i.e. GC formation) was significantly impaired after chemotherapy. This difference was at least partially dictated by corticosteroids, which are commonly used to treat the side effects of chemotherapy of LSCC patients. We further studied the mechanisms underlying TLS development using the experimental model. We identified a combination of stimuli that induces the development of mature TLS in the lungs of mice. Besides inflammatory stimuli, a foreign antigen was necessary to achieve a significant increase in TLS numbers and maturation stage, suggesting that cognate interactions are crucial for lymphoid organ neogenesis. This is further supported by our observation that CRC patients with microsatellite instability, which presumably results in more neoantigens, had an increased proportion of mature TLS. The negative impact of corticosteroids on TLS development was confirmed in this model. In summary, we propose that GC+ TLS represent the relevant TLS phenotype contributing to survival in different tumor types. Lymphoid organ neogenesis is negatively affected by corticosteroids, which might impair the spontaneous as well as therapy-induced anti-tumor immunity. The established experimental model will allow investigation of the mechanisms of TLS development and function in cancer and assessment of their therapeutic potential. Citation Format: Karina Silina, Alex Soltermann, Chiara Burkhardt, Farkhondeh Movahedian Attar, Ruben Casanova, Alessandra Curioni-Fontecedro, Holger Moch, Florian Posch, Thomas Winder, Nick van Dijk, Charlotte Voskuilen, Michiel van der Heijden, Maries van den Broek. Harnessing lymphoid organ neogenesis as a novel prognostic biomarker and therapeutic target [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A113.

Locally Advanced or Metastatic Pancreatic Adenocarcinoma: Easily Available Factors of Predictive Prolonged Survival Under Gemcitabine.

Prognosis of patients with locally advanced or metastatic pancreatic adenocarcinoma is poor. In this study, we assessed the predictive value of easily available baseline factors for prolonged survival. We conducted a retrospective study on patients who received gemcitabine between 1999 and 2010 for locally advanced or metastatic pancreatic adenocarcinoma. The primary end-point was the 12-month survival rate. We included 195 patients. The median age was 62.9 years; the performance status was 0-1 in 80 and 2-3 in 92 patients. The median number of metastatic sites was one. A total of 73 patients (37.4%) were alive 12 months after beginning chemotherapy. In multivariate analysis, no liver metastasis, CA19-9 level <250 IU/ml and localized or locally advanced cancer at diagnosis were good prognostic factors. According to a clinical score based on these features, overall survival was 7.7, 13.5, 19.7 and 21.0 months, respectively (p<0.001). We identified easily available prognostic factors for prolonged survival in patients treated with gemcitabine.

Treatment of Gastric Cancer With Paraaortic Lymph Node Metastasis

Patients with gastric cancer and paraaortic lymph node (PAN) metastasis suffered poor prognosis. The median survival time of the patients who received palliative chemotherapy was only about 12.8 months. However, the standard treatment strategy for patients with gastric cancer and PAN metastasis was controversial. This study aimed to evaluate the survival benefit of conversion chemotherapy followed by surgery in patients with gastric cancer and radiologically suspicious PAN metastasis compared with palliative chemotherapy alone. Twenty-four patients (19 males and 5 females) between January 1, 2008 and December 31, 2013 were analyzed. Fifteen patients received conversion chemotherapy followed by gastrectomy with D2 lymphadenectomy, and 9 received palliative chemotherapy. The median follow-up was 16.5 months (range: 3–50 months). The estimated median overall survival (OS) of patients who underwent the operation was longer than those who received palliative chemotherapy (44.0 versus 13.0 months; P = 0.007). Cox proportion hazard analysis indicated that surgery was a good prognostic factor for prolonged survival compared with that of palliative chemotherapy (hazard ratio: 0.211; 95% confidence interval, 0.061–0.732; P = 0.014). Moreover, the 1-year OS rate of surgical patients whose PAN shrank to &amp;lt;1 cm was better than those who received palliative chemotherapy (87.5 versus 55.6%; log-rank P = 0.008). In conclusion, patients with gastric cancer and radiologically suspicious PAN metastasis obtained a survival benefit from conversion chemotherapy followed by gastrectomy plus D2 lymphadenectomy.

Adult hepatoblastoma: a review of 47 cases.

Adult hepatoblastoma is a very rare and aggressive neoplasm. The aim of this study was to review the cases of adult hepatoblastoma patients. A search of all case reports about adult hepatoblastoma from 1958 to 2016 by medical database was performed. Data about demographic information, clinical symptoms and signs, laboratory test and imaging examination, treatment and clinical outcomes were extracted and analysed. A total of 43 English articles including 47 cases of adult hepatoblastoma patients were collected. The median age was 39 years (range: 18-84 years), including 25 males and 22 females. Hepatitis B virus tests were positive in seven patients. Alpha-fetoprotein was positive in 18 patients. Liver cirrhosis was confirmed in six cases. The median size of main tumour nodule was 15 cm (range: 6-42 cm) in 30 patients with details. Hepatectomy was undertaken in 28 cases, exploratory laparotomy in seven cases and chemoembolization and chemotherapy in two cases. Follow-up data were available in 33 patients including 23 patients with liver resection and the median survival time was 8 months (range: 0-151 months) and the 1-year survival rate was 39.2%. For 23 patients with liver resection, the median survival time was 15 months (range: 0.5-151 months) and the 1-year survival rate was 54.2%. In Cox multivariate analysis, liver resection was indentified as an independent prognostic factor for prolonged survival (P = 0.001). Curative liver resection can prolong survival of adult hepatoblastoma. More effective systemic therapies may need to provide a great survival benefit.

Independent prognostic factors for posttransplant survival in hepatocellular carcinoma patients undergoing liver transplantation.

The aim of this study was to investigate longitudinal trends in locoregional therapy (LRT) use in hepatocellular carcinoma (HCC) patients listed for transplant, and evaluate independent prognostic factors for overall survival (OS) in HCC patients undergoing orthotopic liver transplantation (OLT). The United Network for Organ Sharing (UNOS) database was used to identify HCC patients listed for liver transplantation from 1988 to 2014, and longitudinal rates of bridging LRT were calculated. OLT recipients listed from 2002 to 2013 and transplanted up to 2014, with ≥1 year of follow‐up were further analyzed. OS was compared between patients receiving bridging LRT versus none, high versus low wait times (HWT vs. LWT), and by geographic region. Bridging LRT use in the US has increased dramatically over 25 years, with more than 50% of listed patients receiving at least 1 LRT in 2014. Of 17,291 HCC patients listed for LT from 2002 to 2013, 14,511 received OLT, mean age 57.4 years, 76.8% male; 3889 received bridging LRT. Comparison groups were similar for gender, race, body mass index (BMI), HCC etiology, and biological MELD scores (P > 0.05). Significant differences in mean OS in regions with HWT/high LRT (122.4 months), HWT/low LRT (104.5 months), LWT/high LRT (104.2 months), and LWT/low LRT (102.3 months) were observed, P = 0.0006. Recipient age, donor age, bridging LRT, and longer wait times were independent prognostic factors of survival from OLT. Increasing longitudinal trends in bridging LRT for HCC patients were observed. Younger age, younger donor age, high wait times, and bridging LRT were significant independent prognostic factors for prolonged survival from transplant.

Results of surgical treatment of patients with multiple brain metastases

Objective: to evaluate the results of surgical treatment ofpatients with multiple brain metastases and to determine prognostic factors. Material and methods. 57 patients with multiple brain metastases were operated, 146 metastatic foci were removed. All metastases were removed in 42 persons; only large clinically significant metastases were removed in 15 patients. Whole brain radiation therapy was applied in 37patients, alone or in combination with chemotherapy, 20 patients after surgery received only corticosteroid and symptomatic therapy. Results. Median survival time of the whole group was 7.3 months; for patients, who received adjuvant whole brain radiation therapy - 11.6 months. Two-year survival was 8.8 %. The number of patients with Karnofsky performance score ≥ 70 increased from 12 persons (21,1%) at admission to the hospital to 38 (66.7 %) at 9-1th day after surgery. Median survival time for patients with complete resection was 9,2 months, with partial resection - 3,7 months. Prognostic factors were Karnofsky performance score and RPA class, estimated before operation, but after the corticosteroid therapy: median survival time for patients with RPA-class I was 19.5 monthsversus 5.6 months for patients with RPA- class II and III. Conclusions. Surgery rapidly improves the condition of patients with multiple brain metastases and saves the time for postoperative adjuvant treatment. Median survival time for patients who received adjuvant whole brain radiation therapy reaches 11.6 months. Favorable prognostic factors for prolonged survival are total resection of all lesions, RPA-class I and adjuvant whole brain radiation therapy.

Trends in incidence, treatment and survival of small bowel adenocarcinomas between 1999 and 2013: a population-based study in The Netherlands

Background: We conducted a population-based study to establish the incidence, treatment and overall survival over time of patients with small bowel adenocarcinoma.Material and methods: All patients diagnosed with small bowel adenocarcinoma in the Netherlands between 1999 and 2013 were included (n = 1775). Age-standardized incidence rates were calculated per 100 000 person-years using the European standardized population rate. The influence of patient and tumor characteristics on the administration of chemotherapy was analyzed by means of a multivariable logistic regression analysis. The Cochran-Armitage trend test was conducted to evaluate trends in treatment and survival and the Cox proportional hazards model was used to identify prognostic factors of overall survival.Results: The incidence of small bowel adenocarcinomas increased, mainly due to an almost twofold increase of duodenal adenocarcinomas. Patients with locoregional duodenal tumors were less likely to undergo surgery (58%), towards 95% of the locoregional jejunal and ileal tumors (p < 0.0001). The use of chemotherapy doubled for adjuvant (7–15%) and palliative chemotherapy (19–37%). Median overall survival of patients with locoregional disease increased from 19 to 34 months (p = 0.0006), whereas median overall survival of patients with metastatic disease remained 4–5 months. Favorable prognostic factors for prolonged survival in locoregional disease, identified by multivariable survival analysis, included age <60 years, tumor stage I or II, diagnosis in 2009–2013, surgical treatment and chemotherapy. Favorable prognostic factors for prolonged survival in metastatic disease were age <50 years, jejunal tumors, surgical treatment and chemotherapy.Conclusion: Small bowel adenocarcinomas are rare tumors with an increasing incidence. The administration of adjuvant and palliative chemotherapy doubled, but median overall survival only increased for patients with locoregional disease. Given the rarity and dismal prognosis, it is important to develop international studies to determine the optimal treatment for these patients.

Yttrium-90 radioembolization for the treatment of chemorefractory colorectal liver metastases: Technical results, clinical outcome and factors potentially influencing survival

Background: The purpose of this study was to retrospectively assess the technical and clinical outcomes, overall survival and prognostic factors for prolonged survival after yttrium-90 (90Y) radioembolization as a salvage therapy for patients with chemorefractory liver-only or liver-dominant colorectal metastases.Material and methods: From January 2005 to January 2014, all the patients selected for 90Y radioembolization to treat chemorefractory colorectal liver metastases were identified. Demographic, laboratory, imaging and dosimetry data were collected. Post-treatment technical and clinical outcomes were analyzed as well as overall survival; finally several factors potentially influencing survival were analyzed.Results: In total 88 patients were selected for angiographic workup; 71 patients (81%) finally underwent catheter-directed 90Y microsphere infusion into the hepatic artery 25 days (standard deviation 13 days) after angiographic workup. Median infused activity was 1809 MBq; 30-day toxicity included: fatigue (n = 39; 55%), abdominal discomfort (n = 33; 47%), nausea (n = 5; 7%), fever (n = 14; 20%), diarrhea (n = 6; 9%), liver function abnormalities and elevated bilirubin (transient) (n = 3; 4%). Gastric ulcer was found in five patients (7%). A late complication was radioembolization-induced portal hypertension (REIPH) in three patients (4%). Median time to progression in the liver was 4.4 months. Estimated survival at six and 12 months was 65% and 30%, respectively, with a 50% estimated survival after 8.0 months in this group of chemorefractory patients. Prognostic factors for worse survival were high preprocedural bilirubin, alkaline phosphatase and tumor volume levels.Conclusion: 90Y microsphere radioembolization for chemorefractory colorectal liver metastases has an acceptable safety profile with a 50% estimated survival after 8.0 months. Pretreatment high bilirubin, alkaline phosphatase and tumor volume levels were associated with early death.

Locally advanced or metastatic pancreatic adenocarcinoma (PA): Prognostic factors for prolonged survival.

e15134 Background: Prognosis of pts with locally advanced or metastatic PA is poor, with median survival of 6-9 months. Yet, since the use of gemcitabine, some patients survive more than one year. Recently, FOLFIRINOX regimen yielded better results in selected patients, but with more toxicity. We assessed the value of baseline predictive factors of prolonged survival in non-selected pts treated with gemcitabine. Methods: We conducted a monocentric, retrospective study (1999 to 2010) on all pts treated for locally advanced or metastatic PA. Demographical, clinical, tumoral and biological variables were included into the analysis. The primary end-point was the 12 months survival. All parameters were assessed in univariate and multivariated analyses. We then built a prognostic scoring system integrating the independent prognostic factors. Results: The study was performed on 160 pts: median age 61.1 years, sex ratio (M/F) 93/67, ECOG 0-1/2-3: 60/98, jaundice 62 (38.8%), initially resectable : 36 (22.5%), intra-pancreatic primary location: head: 110 (68.8%), body: 19 (11.9%), tail: 27 (16.9%). The adenocarcinoma was histologically document in 124 cases (77.5%). The median number of metastasis sites was 1 (71.3% liver). The median Ca 19-9 concentration was 925 IU/ml. 155 pts (96.9%) received chemotherapy, of which 124 (80.0%) with gemcitabine in first line. Fifty-two patients (32.5%) were alive 12 months after diagnosis. In univariate analysis, male gender, PS, initial stage, differentiation, primary tumor location, Ca 19-9 were prognostic factors. In multivariate analysis, male gender, head or body locations and low Ca 19-9 concentration (&lt; 111 IU/ml) were associated with a better prognosis. The score with a cut-off between 2 and 3 points was discriminant, with positive and negative predictive values of 64.7% IC-95% [59.2-70.2] and 75.3% IC-95% [74.4-76.2], respectively. The rate of correctly classified pts was 73.6% IC-95% [72.8-74.4]. Conclusions: Male gender, pancreatic head or body location, and Ca 19-9 &lt; 111 are independent prognostic factors for prolonged survival. Further analyses are needed to determine more accurately pts suitable for gemcitabine or the more recently validated regimen FOLFIRINOX.

Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P=0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P=0.047) and cN2-3 single station metastasis (P=0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.

Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Drugs

The treatment of multiple myeloma (MM) is changing rapidly. During the last 10 years, higher rates of complete response (CR) and prolonged progression-free and overall survival have been seen with high-dose chemotherapy plus autologous stem-cell transplantation (HDT-ASCT). Achievement of CR and good partial response have been shown to be key prognostic factors for prolonged survival, with eradication of minimal residual disease seeming crucial to long-term disease-free survival. Until recently, high rates of CR and other major responses were primarily seen with HDT-ASCT, but insights into the biology of MM have led to the development and approval of new drugs with significant activity, and new induction regimens based on these novel agents are offering improved responses. Thalidomide, bortezomib, and lenalidomide have been combined with corticosteroids, alkylators, and anthracyclines in front-line MM treatment. Phase II studies have indicated that high rates of response and CR may be achieved. The substantial activity seen with these new drug combinations has prompted a re-examination of the role of SCT in MM treatment. Will achievement of major responses with these new regimens translate into improved survival after consolidation with transplantation? Will these improved induction regimens reduce the need for tandem transplantation, or does achievement of CR obviate the need for front-line transplantation altogether? To help address these questions, randomized trials are needed, as well as tests with improved sensitivity to better define depth of remission.

Palliative treatment by high–dose-rate intraluminal brachytherapy in patients with advanced esophageal cancer

Purpose The aim of this work was to analyze the results of palliative HDR brachytherapy in patients with advanced esophageal cancer. Methods and materials Ninety-one patients with unresectable, advanced esophageal cancer were treated palliatively by HDR brachytherapy. All patients received a total dose of 22.5 Gy in three fractions per week. Remissions of dysphagia and other clinical and radiological factors were assessed in the first month posttreatment, and then in the third, sixth, and twelfth months. The survival rate was compared with some chosen clinical factors using a log-rank test and the Kaplan–Meier method. Results The median survival time among all patients was 8.2 months. The median survival time according to the obtained remission was 14.6, 7.2, and 3.8 months (log-rank p = 00001, F Cox p = 0.00001) for complete remission (CR), partial remission (PR), and lack of remission (NR), respectively. A longer median survival time was observed when tumor size was less then 5 cm (12.1 months), than between 5 and 10 cm (7.8 months), or longer than 10 cm (6.4 months) (log-rank p = 0.002). Longer median survival times were observed in clinical stage II (14.1 months), compared with clinical stage III (7.7 months) and IV (7.2 months) (log-rank p = 0.01). Significant correlations were found between survival and the Karnofsky Performance Status, grade of dysphagia, and age. Conclusions HDR brachytherapy for advanced esophageal cancer allowed for improvement of dysphagia in most patients. The complete or partial remission, the older age of patients, and the lower grade of dysphagia observed in first month posttreatment were the most important prognostic factors allowing for prolonged survival (confirmed by a multivariate analysis). In the univariate analysis, important prognostic factors for prolonged survival were: a higher Karnofsky Performance Status, a lower clinical stage and a small tumor size.

Outcomes of Patients Undergoing Surgical Resection of a Brain Metastasis: A Cancer Care Nova Scotia Project

Brain metastases pose a formidable and increasingly common challenge in contemporary cancer care. Current evidence suggests that surgical resection of single brain metastases affords a survival advantage over mainstay treatment of brain metastases with radiotherapy and corticosteroids. Despite advances attained by surgical resection, median survival times remain short, however, and most patients succumb to systemic progression of their cancer within a year following resection. Patients with a single or solitary, tissue-proven brain metastasis obtained by surgical resection were retrospectively reviewed. Of eligible patients that met inclusion criteria, the mean age at diagnosis of the brain metastasis was 57. Lung cancer was the most common type of cancer producing metastasis to the brain. The most common histologies were adenocarcinoma (17/41; 41.5%) and unspecified carcinoma (12/41; 29.3%). Following resection, the overall median survival was 33.3 weeks. Good performance status and small brain metastasis size were favourable prognostic factors for prolonged survival in this series. The median survival times of patients in this series were slightly inferior, yet comparable to more stringently selected patients in randomized control trials of surgical resection of brain metastases. These comparable results add further support for the use of surgical resection in the treatment of a brain metastasis.

Predictive factors of response to cisplatin-based chemotherapy and the relation of response to survival in patients with metastatic urothelial cancer

To identify pretreatment variables predicting overall and complete response to cisplatin-based chemotherapy for metastatic urothelial cancer, and to study the relation between response and the duration of survival. A total of 119 evaluable patients with recurrent locally advanced or metastatic urothelial cancer received cisplatin-based combination chemotherapy in four consecutive phase II studies from 1987 to 1997. The relationship of pretreatment variables and response was evaluated with logistic regression, and prognostic factors for survival were analyzed with Cox's multivariate model. Response was achieved in 49% of the patients with a complete response rate of 15%. Good performance status and absence of bone metastases were independently predictive of overall response. Good performance status and normal hemoglobin were independently predictive of complete response. Median survival was 8.9 months. Performance status, alkaline phosphatase, s-creatinine, liver and bone metastases were independent prognostic factors for survival. Median survival was 12.4 months in responding patients and 6.3 in nonresponding patients. Response to chemotherapy was included in the multivariate model and was the strongest prognostic factor for survival. The presence of bone metastases, low hemoglobin or poor performance status predicts decreased chance of response to chemotherapy. Response to chemotherapy is an independent prognostic factor for prolonged survival in patients with metastatic urothelial cancer.