e14687 Background: Gastroesophageal cancer is a major cause of cancer-related mortality. HER2 is overexpressed in ~ 7-34% of gastroesophageal (GE) adenocarcinomas. The ToGA study, established the benefit of trastuzumab in combination with chemotherapy in HER2 positive metastatic GE tumours. In this study, 22% of patients were HER2 positive {immunohistochemistry (IHC)3+ or fluorescence insitu hybridization (FISH)(+)}. Potential heterogeneity of HER2 amplification, overexpression, and incomplete membrane staining of HER2 by IHC leaves some ambiguity in HER2 testing and definition of HER2 positive GE tumours. We report a multi-center Irish experience by examining HER2 status by IHC and FISH in GE tumours. Methods: HER2 testing was performed on adenocarcinoma biopsy or resection specimens of patients with early stage and metastatic GE tumors between 2008 - 2011. We defined HER2 positive as IHC3+ or FISH(+) {HER2:17ch ≥ 2}. In addition, age, gender, smoking history, histology, stage of disease, treatment, and survival data were recorded. Results: A total of136 Caucasian patients with early stage and metastatic GE cancers were identified. Median age was 69 yrs (ranging from 25 – 96). Data available for analysis was conducted from 111 patients with 10% FISH(+). There are 73 patients with early stage and 38 with metastatic disease. Five metastatic cases (13%) were FISH(+) (of whom 3 IHC3+, 1 IHC2+, 1 IHC1+), 33 cases were FISH(-). Sites of metastatic disease in the FISH(+) cohort were liver, peritoneal, and bone metastasis. In the FISH(-) group, sites of metastatic disease were predominantly liver. Interestingly CNS disease is seen exclusively in the FISH(-) cohort. Of the early stage patients, only 6 patients (8.2%) were FISH(+) (of whom 3 IHC3+, 2 IHC2+, 1 IHC1+). With respect to tumour heterogeneity of HER2 amplification, in IHC3+, 82% were FISH(+), IHC2+, 17% were FISH(+) and IHC1+, 6% were FISH(+). There was 100% concordance between IHC0 and FISH(-). Conclusions: HER2 positive GE adenocarcinomas in the analyzed cohort displays similar pattern of heterogeneity in IHC staining and FISH positivity but with lower incidence (10%) of HER2 amplification than was reported in the ToGA study. Further data on location, histological pattern and survival will be reported.
2062 Background: GBM is the most common and aggressive primary brain tumor. The neutrophil to lymphocyte ratio (NLR) gives a measure of systemic inflammatory response and lymphopenia, both of which are poor prognostic factors in many malignancies. No published study has assessed the prognostic impact of NLR in GBM. Methods: Patients treated for GBM at our regional referral centre with assessable complete blood count at first presentation (prior to corticosteroid therapy or surgery) were identified. Medical notes were reviewed to extract demographic and treatment data. Survival curves were estimated via Kaplan-Meier method and compared via log-rank method. Multivariate analysis was performed via Cox proportional hazards regression modelling. Results: A total of 86 patients were identified, of which 65(76%) were male. Median age at diagnosis was 58 years (range: 18–76). At the time of analysis all patients still alive had ≥ 2 years follow-up. Median overall survival (OS) was 9.3 months (range: 1-82). 57% completed the standard adjuvant Stupp protocol and 43% discontinued early due to disease progression or treatment toxicity. Median OS was 11.2 months in patients with NLR<4 and 7.5 months in patients with NLR>4 (HR 0.59, p=.04). Other significant prognostic factors based on univariate analysis were consistent with published data (Table). After correcting for known prognostic factors NLR remained a significant predictor of survival (Table). Conclusions: Recent advances in immunotherapy have highlighted the importance of the immune system in the treatment and prognosis of cancer patients. Many GBM patients are on corticosteroids for a significant proportion of their disease course which may abrogate the effects of host immunity on outcome. Nevertheless, we have shown that NLR at diagnosis is an independent predictor of survival in GBM patients. Investigation of therapies which harness the immune response are warranted in this disease. [Table: see text]
e15196 Background: Definitive chemoradiotherapy (CRT) is an established treatment option in localised esophageal cancer. While most patients are treated with cisplatin and fluorouracil, alternative chemotherapy regimens have been used. The combination of carboplatin and paclitaxel (CP) has been validated in a neoadjuvant CRT trial by the CROSS study. There has also been a phase II study (v. Meerten, ASCO 2010, e14508) showing efficacy and tolerability of this regimen in the definitive setting with radiation doses of 50.4Gy/28#. We report our experience using this strategy in two Irish centres. Methods: Patients treated with weekly CP and definitive radiation between Jan 2010 and Oct 2012 were identified from our pharmacy database. Clinicopathologic details were obtained from electronic medical records. The group contains patients with locally advanced unresectable disease, or those medically unfit for esophagectomy. Results: Between Jan 2010 and Oct 2012, we identified 22 patients. Thirteen patients had squamous histology, while 9 had adenocarcinoma. Staging was performed with CT, EUS, and PET/CT – 1 patient had T2 disease, while the remainder had T3/T4, and 10 patients had positive nodes. Reasons for not pursuing surgical resection were extent of disease and poor performance score. In total, 86% of patients received full dose treatment, with reasons for dose delay/reduction being grade 3 sepsis, grade 3 gastrointestinal toxicity, and decline in performance status. Overall 5 (23%) patients needed hospital admission during treatment. At a median follow up of 14 months (range 9-23months), 19 patients are alive with no evidence of disease, 2 patients have died of disease, and 1 patient is alive with relapsed disease. Our 1-year recurrence free survival rate is 86%. Conclusions: Definitive CRT with CP is a tolerable regimen that can be administered on an outpatient basis, and provides a treatment option in those who are unsuitable for surgical resection or Herskovic type CRT. Our results compare favorably with previous studies in this population. Further investigation is warranted in a prospective study to validate the efficacy of this approach.
e11569 Background: Resection of a single brain metastasis (SBM) in metastatic cancer has been shown to improve overall survival (OS). A previously reported series from MD Anderson of breast cancer patients undergoing SBM resection reported a median overall survival of 19 months. We report our experience of SBM resection for breast cancer. Methods: Retrospective observational study of patients who underwent resection of SBM from breast cancer brain in a tertiary referral centre from 2000-2011. Results: 20 patients underwent SBM resection from 2000-2011. All patients received WBRT after surgery. 2 patients had progressive metastatic disease presenting as brain metastases. Median time from original breast cancer diagnosis to development of SBM was 53 months (range:1-286months). 9 patients had solitary brain metastases (no metastases elsewhere) and 11 patients had synchronous metastases elsewhere. Regarding the primary breast tumour: 41% of patients were ER+, 57% were HER2+ and 25% were triple negative. 1 patient had discordance of ER status between the primary tumour and brain metastasis (changed from ER- to ER+). Median overall survival was 9 months (95% CI: 5-18 months) with 1 year OS of 50%, 2 year OS of 15% and 3 year OS of 5%. Patients treated between 2006-2011 had better median OS than those treated 2000-2005(18 months vs 6 months – p-value not significant). Patients with a solitary brain metastasis had better median OS than those with synchronous extracranial disease (13 months vs 6 months – p-value not significant). An additional 2 patients underwent craniotomy for presumed breast cancer metastasis but histology revealed glioblastoma multiforme. Conclusions: We report on a cohort of patients undergoing metastatectomy for single brain metastasis from breast cancer. Median OS was 9 months but there was a trend towards better survival in patients treated in recent years when compared with those treated from 2000-2005. Improved systemic therapies may account for this difference. Also of note 2 patients undergoing resection for presumed brain metastases were found to have GBM, highlighting the role of tissue diagnosis in patients presenting with a solitary brain lesion.
e19059 Background: Ipilimumab (Ipi) is a potent anti CLA-4 immunotherapy recently shown to improve overall survival (OS) in a phase III study in patients (pts) with previously-treated, unresectable or metastatic malignant melanoma. Ipilimumab (3 mg/kg) has been available on compassionate grounds to pts in Ireland since June 2010. Methods: In this retrospective observational study we examine the Irish experience with ipilimumab specifically regarding patient-factors, treatment toxicity, and outcomes including response rate and survival. Results: Between June 2010 and December 2011, a total of 93 patients received ipilimumab. Data available for analyses was conducted in 46patients. Median age of patients was 56 yrs (ranging 28 – 84). M1c disease was identified in 40 patients (83.3%). Median number of prior lines of chemotherapy is 1 (ranging from 1-4). 22 (47.8%) patients received all four planned induction doses of ipilimumab. All patients received full doses of treatment and on schedule. There are no grade 4 toxicities reported and 13% (n= 6) had grade 3 adverse events. This included renal autoimmune toxicity (n=3), diarrhoea (n=1) elevated AST/ALT (n=1), ocular toxicity (n=1) and skin (n=1). Grade 3 adverse events occurred in 3 patients who received all 4 cycles of Ipilimumab. No intestinal perforations or hypophysitis were noted. There were no drug-related deaths. From available survival follow-up data there are 22 reported deaths. Due to paucity of the data, surrogate marker for response of treatment was expressed as absence of disease progression at the time of assessment. Among the 11 (23.9%) patients who responded to treatment, 45.5% of these patients received 4 cycles of ipilimumab. Conclusions: Ipilimumab was well tolerated with a manageable side effect profile. Response rates to ipilimumab in metastatic melanoma in an Irish population are in keeping with internationally reported figures. Comprehensive survival data will be reported as well as correlation of response with hematologic and biochemical blood tests.
Effective communication is a prerequisite to the delivery of good palliative care. The increasing use of web-based technologies and social media challenges us to reassess traditional communication styles and to define appropriate applications of evolving technologies. The use of Skype, blogging and webcams by patients in our hospitals and hospices is increasing. As illustrated in this case, the availability of such technology enables patients and families to communicate across wide geographical boundaries. This has particular advantages in situations where family members cannot routinely attend at the hospital because of other commitments or distance. The authors report on the varying use of Skype video-telephony over the course of a cancer patient's illness from the initial treatment phase through to the final days and hours of life. The benefits and challenges of using such technologies in a hospital setting and particularly in end-of-life circumstances are discussed.
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