Cancer Carcinomatosis Research Articles

Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer

Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA levels of SIP1 and other EMT regulators by real-time reverse transcription PCR in gastric tissue samples of 134 gastric cancer patients, and in five gastric cancer cell lines. SIP1 gene knockdown by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cells. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa. Although the mRNA expression of the other EMT regulators tested (Snail, Slug, and Twist) was not correlated with clinicopathological factors, increased SIP1 expression was an independent prognostic factor and an independent risk factor for peritoneal dissemination. In addition, SIP1 expression was significantly positive and correlated with vimentin expression. For intestinal type gastric cancer in particular, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p<0.05). In vitro, cell proliferation, migration, invasion, and resistance to anoikis were significantly inhibited in SIP1 siRNA-transfected MKN7 cells compared to control siRNA. SIP1 appears to play an important role in progression to peritoneal carcinomatosis and may be a therapeutic target for patients with intestinal type gastric cancer.

Usefulness of Dual-Time Point Imaging After Carbonated Water for the Fluorodeoxyglucose Positron Emission Imaging of Peritoneal Carcinomatosis in Colon Cancer

Fluorodeoxygluose (FDG) positron emission/computed tomography (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal carcinomatosis (PC). In this study, we assessed whether dual-time point imaging can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal cancer (CRC). Thirty-nine patients with past history of CRC were evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If one or more focal areas of increased FDG uptake (standardized uptake value, SUV max>2.5) were found in the abdomen, 1 L of carbonated water was orally administered to patients and a delayed scan of the abdominal region was acquired at 2 hours. The SUV max and the mean Delta (Δ) SUV were calculated. The scintigraphic results were compared with the results of colonoscopy and histology and with the clinical follow-up. Thirteen out of the 39 patients did not show any significant area of FDG uptake at the whole-body scan. The remaining 26 patients showed an overall number of 27 sites of focal increased uptake, showing a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11 cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall number of 16 sites) with SUV max of 15.6+4 and mean Δ SUV of +26.3%±7.5%. In these cases, final diagnosis was PC in 10 patients (according to cytology or histology) and dysplastic polyp in 5 cases. No significant difference in Δ SUV was found between patients with PC and those with polypoid formations. According to our results, dual-time point imaging after carbonated water may increase the accuracy of FDG PET/CT for the imaging of PC in patients affected by CRC.

Office-based Denver peritoneovenous shunt for malignant ascites: A feasibility study

expectation, unresponsive to diuretic treatment, and requiring paracentesis at least twice a week were evaluated for shunt placement. Of these, 98 patients (8 with breast cancer carcinomatosis, 5 with pancreatic cancer carcinomatosis, 30 with ovarian cancer carcinomatosis, 15 with gastric cancer carcinomatosis, 30 with colorectal cancer carcinomatosis, 5 with abdominal mesothelioma, 5 with carcinomatosis of other origin) with a cardiac ejection fraction >40 and Karnofsky Performance Status >80 received a Denver peritoneojugular shunt as an outpatient procedure under local anesthesia and mild sedation. Jugular vascular access was achieved via ultrasound-guided venipuncture.

P-0183 Outcomes of Patients With Colorectal Cancer With Peritoneal Carcinomatosis Who Underwent Cytoreductive Surgery and Intraperitoneal Chemotherpy Versus Palliative Chemotherapy

ABSTRACT Introduction Patients with advanced colorectal cancer and peritoneal carcinomatosis (PC) have a poor prognosis with median survival ranging from 6 to 8 months. Novel treatment strategies have emerged combining cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with improved outcomes. The aim of this retrospective analysis is to evaluate the outcomes in patients with advanced colorectal cancer with PC who had undergone CRS with peritonectomy and HIPEC versus those who underwent resection of primary and palliative chemotherapy. Methods From our institutional database, we identified 43 patients with colorectal cancer with metastasis isolated to the peritoneum. 21 patients received local resection of the primary colonic tumour and chemotherapy. 22 patients received CRS with peritonectomy and HIPEC. Demographic data, treatment and survival data were collated and analysed. Results All patients had good performance status with ECOG less than or equal to 1. The median follow up of all patients still alive was 20.7 months. The median time from detection of peritoneal metastasis to peritonectomy was 4.6 months. The progression free survival for patients who underwent peritonectomy and HIPEC was 9.6 months (95% CI 6.6-12.6). From time of detection of peritoneal metastasis, overall survival for patients who underwent peritonectomy versus those who did not was 47 months and 18 months respectively (HR 0.18; 95% CI: 0.05-0.67, p =0.01). However there is substantial selection bias with the peritonectomy group comprising younger patients with mean age of 49 years old versus 59 years old in the non - peritonectomy group (P=0.02). All the patients who did not undergo peritonectomy were stage IV at diagnosis whereas in the group who underwent peritonectomy, only 45.4% were stage IV at diagnosis. Conclusion In well selected group of patients with advanced colorectal cancer and peritoneal carcinomatosis, good long term survival outcomes with cytoreductive surgery with peritonectomy and HIPEC can be achieved.

Intracranial Meningeal Carcinomatosis in Metastatic Castration Resistant Prostate Cancer: Will Extension of Survival Increase the Incidence?

Case Report We present an 81-year-old man with a history of prostate cancer and leptomeningeal metastases. He was diagnosed to have CRPC with extensive bone metastases coupled with a prostate-specific antigen (PSA) 894 ng/mL diagnosed 18 months earlier. He had received docetaxel in combination with prednisone for 6 cycles in conjunction with zoledronic acid. Upon progression, he was offered a clinical trial evaluating a novel autologous antigen-presenting cell-based vaccine. He experienced an improvement in pain during the trial and progressed approximately 6

Intestinal obstruction due to malign breast neoplasm and peritoneal carcinomatosis: a case report

Peritoneal carcinomatosis due to breast cancer is rare and gastrointestinal tract involvement is also unusual. Symptoms are unspecific and can begin many years after the primary tumor. Investigation of carcinomatosis origin is mandatory as breast cancer carcinomatosis can relieve partially or totally with chemo and hormonal therapy. A case of colonic obstruction due to carcinomatosis secondary to breast cancer is reported, emphasizing its diagnostic aspects and treatment.

Risk factors for peritoneal carcinomatosis in gastric cancer patients, and outcomes following resection and hyperthermic intraperitoneal chemotherapy (HIPEC).

e14656 Background: Gastric cancer (GC) contributes significantly to the burden of cancer death in the United States. Unfavorable prognosis in patients with gastric cancer and peritoneal carcinomatosis (GCPC) is well-documented. In this study, a model predictive of GCPC is proposed, and outcomes in patients with GCPC treated with surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are assessed. Methods: A single-institution analysis of 112 patients treated for GC between the years 2000 and 2011 was performed. Demographic and clinical-pathologic criteria were entered into univariate and multivariate analyses, to identify criteria independently predictive of GCPC. Overall survival in each cohort was determined via Kaplan-Meier analysis. Results: GCPC developed in 28/112 (25%) of GC patients. Several variables were associated with GCPC by univariate analysis (age, p = 0.018; tumor stage, p = 0.004; tumor location, p = 0.046), but only age (≤60) and tumor stage (T3/T4) were independently predictive of GCPC by multivariate analysis (HR = 3.949, p = 0.024; HR = 3.942, p = 0.049, respectively). Intermediate-term survival was not significantly impacted in nine GCPC patients treated with HIPEC (65% 1-year, 39% 3-year without HIPEC; vs. 73% 1-year, 39% 3-year with HIPEC, p = NS). Conclusions: A model to identify gastric cancer patients at highest risk for GCPC is proposed. Although intermediate term survival in a small number of GCPC patients (9) treated with HIPEC is not significantly improved, emerging experience with increased follow-up with HIPEC in larger cohorts is needed. Earlier application of HIPEC targeted at patients at highest risk may be feasible in utilizing a model predictive of GCPC.

Peritoneal Colorectal Carcinomatosis Treated with Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy

Background-Aims: Peritoneal colorectal carcinomatosis is a potentially curative disease. The purpose of the study is the retrospective analysis of survival of the patients with peritoneal colorectal carcinomatosis that underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy and the identification of prognostic variables of the disease. Patients-Methods: Patients with primary or recurrent colorectal cancer and peritoneal carcinomatosis were included in the study. Clinical variables were correlated to survival, recurrence, hospital mortality, and morbidity. Results: From 2000-2010, 28 patients underwent 33 cytoreductive operations. The hospital mortality and morbidity rate was 9.1% and 45.5% respectively. The overall 5-year and median survival time was 29.2% and 19 months respectively. The extent of peritoneal carcinomatosis (p = 0.0003) and the completeness of cytoreduction (p = 0.0002) were related to survival. The completeness of cytoreduction (p = 0.003) was the single prognostic variable of survival. The recurrence rate was 42.4% and the use of systemic chemotherapy was identified as the single prognostic variable of recurrence (p = 0.047). Conclusions: Patients with limited extent of peritoneal colorectal carcinomatosis who undergo complete cytoreduction may be offered long-term survival.

Interferon γ improves the vaccination potential of oncolytic parvovirus H-1PV for the treatment of peritoneal carcinomatosis in pancreatic cancer

Oncolytic viruses with their capacity to specifically replicate in and kill tumor cells emerged as a novel class of cancer therapeutics. Rat oncolytic parvovirus (H-1PV) was used to treat different types of cancer in preclinical settings and was lately successfully combined with standard gemcitabine chemotherapy in treating pancreatic ductal adenocarcinoma (PDAC) in rats. Our previous work showed that the immune system and particularly the release of interferon-gamma (IFNγ) seem to mediate the anticancer effect of H-1PV in that model. Therefore, we reasoned that the therapeutic properties of H-1PV can be boosted with IFNγ for the treatment of late incurable stages of PDAC like peritoneal carcinomatosis. Rats bearing established orthotopic pancreatic carcinomas with peritoneal metastases were treated with a single intratumoral (i.t.) or intraperitoneal (i.p.) injection of 5x108 plaque forming units of H-1PV with or without concomitant IFNγ application. Intratumoral injection proved to be more effective than the intraperitoneal route in controlling the growth of both the primary pancreatic tumors and peritoneal carcinomatosis, accompanied by migration of virus from primary to metastatic deposits. Concomitant i.p. treatment of H-1PV with recIFNγ resulted in improved therapeutic effect yielding an extended animal survival, compared with i.p. treatment with H-1PV alone. IFNγ application enhanced the H-1PV-induced peritoneal macrophage and splenocyte responses against tumor cells while causing a significant reduction in the titers of H1-PV-neutralising antibodies in ascitic fluid. Thus, IFNγ co-application together with H-1PV might be considered as a novel therapeutic option to improve the survival of PDAC patients with peritoneal carcinomatosis.

Leptomeningeal Carcinomatosis in Esophageal Cancer: Case Report and Review of Literature

Leptomeningeal carcinomatosis (LCM), also known as carcinomatous meningitis or neoplastic meningitis, is the infiltration and multifocal seeding of leptomeninges by malignant cells originating from a solid tumor or lymphomatous or leukemic meningitis [1]. It occurs in approximately 5% of all cancer patients, but the incidence is on the rise due to availability of newer diagnostic modalities and improved systemic treatment [2]. The incidence of LCM is 1–5% in patients with solid tumors and 5–15% in patients with leukemia [3]. The most common solid tumor as a cause of LCM is the breast cancer (41%) followed by lung cancers (24%), gastrointestinal tract malignancies (13%), and melanoma (12%) [4]. In this report, we present two cases of LCM arising from esophageal adenocarcinoma located at gastroesophageal (GE) junction followed by review of the current medical literature.

MMP-2 as a Putative Biomarker for Carcinomatosis in Gastric Cancer

We evaluated matrix metalloproteinase (MMP)-2 and -9 as novel biomarkers in the body fluid of advanced gastric cancer with peritoneal and pulmonary metastasis. MMPs activity from zymography was quantified with ELISA to determine the cut-off expression levels of MMPs. The expression of MMPs in patient samples were evaluated with ELISA and compared with clinical parameters. Ascitic CEA (aCEA) and pleural CEA (pCEA) were measured by chemiluminescent enzyme immunoassay. MMP-2 and -9 cut-off levels were 8.6ng/mL and 0.14ng/mL, respectively. Ascitic fluid cytology of 93 patients revealed a positivity of 55.9% while for MMP-2 it was 93.3%, for MMP-9 35.2% and for aCEA 86.7%. Combining biomarkers, the positivity increased to 99.1% in patients with MMP-2 or aCEA expression. We found a negative correlation between MMP-2 expression and survival when a new prognostic cut-off of 22.6ng/mL was used. Patients with high MMP-2 expression (≥22.6ng/mL) had a median survival of 45 days and those with low MMP-2 expression (<22.6ng/mL) had a median survival of 69 days (p<0.01). These results suggest that MMPs could be used as diagnostic markers in body fluid and MMP-2 might be a prognostic marker in ascites of advanced gastric patients with disseminated metastasis.

The strengths and limitations of routine staging before treatment with abdominal CT in colorectal cancer

BackgroundAdvanced colorectal cancer (CRC), either locally advanced, metastasized (mCRC) or both, is present in a relevant proportion of patients. The chances on curation of advanced CRC are continuously improving with modern multi-modality treatment options. For incurable CRC the focus lies on palliation of symptoms, which is not necessarily a resection of the primary tumor. Both situations motivate adequate staging before treatment in CRC. This prospective observational study evaluates the outcomes after the introduction of routine staging with abdominal CT before treatment.MethodsIn a prospective observational study of 612 consecutive patients (2007-2009), the ability of abdominal CT to find liver metastases (LM), peritoneal carcinomatosis (PC) and T4 stage in colon cancer (CC) was analysed.ResultsAdvanced CRC was present in 58% of patients, mCRC in 31%. The ability to find LM was excellent (99%), cT4 stage CC good (86%) and PC poor (33%). In the group of surgical patients with emergency presentations, the incidences of both mCRC (51%) and locally advanced colon cancer (LACC) (69%) were higher than in the elective group (20% and 26% respectively). Staging tended to be omitted more often in the emergency group (35% versus 12% in elective surgery).ConclusionsThe strengths of staging with abdominal CT are to find LM and LACC, however it fails in diagnosing PC. On grounds of the incidence of advanced CRC, staging is warranted in patients with emergency presentations as well.

A rare presentation of Pulmonary Lymphangitic Carcinomatosis in cancer of lip: case report

Squamous cell carcinoma of lip is a common malignancy in Indian subcontinent. Metastatic spread is infrequent. Although advanced tumours spread to lymph nodes in the neck, it does not typically present with lung metastasis or with lymphangitic carcinomatosis. We describe a patient who developed cough and increasing dyspnoea while on treatment for carcinoma of lip. Chest x-ray and computed tomography were consistent with lymphangitic carcinomatosis. Lymphangitic carcinomatosis occurs with many different primary tumours and can rarely occur in oral cancers. This is the first report from carcinoma of lip.

Neoadjuvant intraperitoneal chemotherapy with paclitaxel for the radical surgical treatment of peritoneal carcinomatosis in ovarian cancer: a prospective pilot study

The admitted benefits of intraperitoneal chemotherapy during postoperative administration for the treatment of peritoneal carcinomatosis from ovarian origin are limited by their associated morbidity and restricted diffusion by the presence of multiple intra-abdominal adherences. The purpose of the study was to evaluate the security, effectiveness, and cytoreduction optimization of intraperitoneal paclitaxel administration previously to radical surgery/peritonectomy/HIPEC (hyperthermic intraoperative intraperitoneal chemotherapy) either in monotherapy or combined with intravenous carboplatin. Prospective pilot study of 10 patients with ovarian peritoneal carcinomatosis in stage IIIc-FIGO without previous treatment. After staging of the diseases by laparoscopy, five patients received paclitaxel by weekly intraperitoneal administration (60mg/m(2), 10 cycles), and other five patients additionally received intravenous carboplatin every 21days (AUC 6, 4 cycles). Subsequently radical surgery/peritonectomy with HIPEC was performed. The presence of moderate abdominal pain was the most common (70%) side effect associated with neoadjuvant paclitaxel intraperitoneal administration. The intravenous carboplatin administration was not associated with significant increase in adverse effects. It boosted intraperitoneal paclitaxel-associated antitumoral activity with a high average decrease in Index Cancer Peritoneal (21.2 vs. 14.4, P=0.066) and CA 125(1,053 vs. 346, P=0.043). All the patients who received combined neoadjuvant chemotherapy obtained R0 cytoreduction. Five-year overall survival was 62%. The intraperitoneal paclitaxel weekly administration combined with intravenous carboplatin administration prior to radical surgery/peritonectomy with HIPEC is a safe and effective option in the treatment of ovarian peritoneal carcinomatosis. This study shows the possibility to investigate other forms of intraperitoneal chemotherapy and their combinations thoroughly.

Abstract 772: Targeted cancer therapy with immunotoxins

Abstract The therapeutic options for patients with metastasis are generally limited and the need to develop better treatment modalities is obvious. Immunotoxins (ITs) represent a promising group of targeted therapeutics, consisingt of a cancer-specific antibody and a cell killing toxin. The number of IT protocols approved for treatment of cancer patients is expected to increase, as this type of treatment has several advantages compared to conventional strategies. Unfortunately, the clinical use of ITs has been hampered by liver toxicity and the induction of a strong anti-IT-antibody response. However, in an ongoing clinical phase I study with one of our ITs, targeting EpCAM, in combination with the immunosuppressor cyclosporin (CsA) we have demonstrated only transient liver toxicity and minimal/no anti-IT antibody response. We are now investigating the potential use of our-clinical grade BM7PE for patients with triple-negative breast cancer (TNBC) and peritoneal carcinomatosis from ovarian cancer, for whom standard treatment is no longer an option. This IT targets Mucin-1 which is over-expressed and aberrantly glycosylated in these cancer types. We have found that the combination of BM7PE and CsA caused a remarkable synergistic effect in killing the TNBC cell lines MDAMB468 and MDAMB231, as well as in the ovarian cell line B76, established from pleural effusion. The mechanisms underlying this synergism in vitro have been thoroughly studied in cell viability assays, western blot and PCR-arrays. Preliminary data show reduced Matrigel invasion, which was even more inhibited by the combination with CsA. This suggests that the IT treatment does regulate cellular migration and invasion. Further investigations are ongoing to identify molecular pathways involved in IT- (+/-CsA) induced cell death and invasion. In conclusion, the combination of BM7PE and CsA might constitute an important improvement and increase the possible clinical potential of IT in these patient groups. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 772. doi:10.1158/1538-7445.AM2011-772

Netrin-4 Delays Colorectal Cancer Carcinomatosis by Inhibiting Tumor Angiogenesis

A close relationship between tumor angiogenesis, growth, and carcinomatosis has been observed. Netrin-4 (NT-4) has been shown to regulate angiogenic responses. We aimed to examine the effects of NT-4 on colon tumor angiogenesis, growth, and carcinomatosis. We showed that NT-4 was expressed in human colon cancer cells (LS174). A 20-fold increase in NT-4 expression was stably induced by NT-4 pcDNA in LS174 cells. In vivo, a Matrigel angiogenesis assay showed that NT-4 overexpression altered vascular endothelial growth factor (VEGF)/basic fibroblast growth factor-induced angiogenesis. In nude mice with LS174 xenografts, NT-4 overexpression inhibited tumor angiogenesis and growth. In addition, these NT-4-involved inhibitory effects were associated with decreased tumor cell proliferation and increased tumor cell apoptosis. Using an orthotopic peritoneal carcinomatosis model, we demonstrated that NT-4 overexpression decreased colorectal cancer carcinomatosis. Moreover, carcinomatosis-related ascites formation was significantly decreased in mice transplanted with NT-4 LS174 cells versus control LS174 cells. The antiangiogenic activity of NT-4 was probably mediated by binding to its receptor neogenin. Netrin-4 had a direct effect on neither in vitro apoptosis and proliferation of cultured LS174 cells nor the VEGF-induced acute increase in vascular permeability in vivo. We propose that NT-4 overexpression decreases tumor growth and carcinomatosis, probably via an antiangiogenic effect, underlying the potential therapeutic interest in NT-4 in the treatment of colorectal cancer growth and carcinomatosis.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis arising from gastric cancer.

132 Background: Peritoneal carcinomatosis is a common sign of advanced tumor stage or disease recurrence in patients with gastric cancer. The prognosis of these patients is poor. There is some evidence that CRS and HIPEC may improve the oncological outcome of a highly selected part of patients with peritoneal carcinomatosis arising from gastric cancer. Nevertheless, the use of CRS and HIPEC as an additional therapeutic option is still controversial. Methods: Between 01/2005 and 09/2009 16 out of 256 patients underwent CRS and HIPEC for peritoneal carcinomatosis arising from gastric cancer at the University of Regensburg Medical Center. The mean age of patients at the time of surgery was 52 years (range 32-69). Four patients were female (25%). The mean follow-up time was 16.3 months. Results: Thirteen patients (81.25%) underwent complete macroscopic cytoreduction (CC-0/1). HIPEC was performed in all patients. The median hospital stay was 19.5 days (range 8-44) and the median stay on ICU 1 day (range 0-14), respectively. The median operating time was 342 minutes (range 49- 510). The perioperative grade 3/4 morbidity rate was 37.5%. Postoperative complications were pneumonia (2), pancreatitis (2), pneumothorax (2), intraabdominal abscess (2), renal insufficiency (1), urine bladder dysfunction (1) and wound infection (1). There was no operative mortality in our series. The 1-year survival rate was 68.7%. The mean survival of the ten patients that died during follow-up was 14.1 months (range 3.4-44.8). Conclusions: In highly selected patients with gastric cancer and peritoneal carcinomatosis CRS and HIPEC may lead to prolonged survival rates. However, the therapy should be integrated in an interdisciplinary multimodality treatment concept. Further prospective randomized trials are required to determine the role of CRS and HIPEC in the treatment of patients with gastric cancer. No significant financial relationships to disclose.

Indication for oophorectomy during cytoreduction for intraperitoneal metastatic spread of colorectal or appendiceal origin

The incidence of ovarian metastases at the time of peritoneal carcinomatosis, and the influence of such metastases on survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), are unknown. This retrospective analysis included 194 women subjected to CRS and HIPEC since 2001. The incidence of ovarian metastases, disease-free survival and disease-specific survival were analysed. The histological diagnosis was colorectal cancer carcinomatosis in 108 patients, peritoneal mucinous carcinomatosis (PMCA) in 23 and disseminated peritoneal adenomucinosis (DPAM) in 63. Ninety-nine patients underwent oophorectomy during the HIPEC procedure. Ovarian metastases were confirmed in at least 52 per cent of the patients. There was a significant difference in disease-free survival between women with or without ovarian metastases in both PMCA and DPAM groups (P = 0·044 and P = 0·010 respectively). No significant differences in survival were found in the group with colorectal cancer carcinomatosis. When peritoneal carcinomatosis of colorectal or appendiceal origin is confirmed, at least 52 per cent of ovaries will have synchronous metastases. Disease-free survival after a HIPEC procedure for PMCA or DPAM is significantly lower in women with ovarian metastases. Oophorectomy during CRS for peritoneal carcinomatosis should be strongly considered.

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

Leptomeningeal Carcinomatosis Presenting Early in Non-Small Cell Lung Cancer

Purpose: We present the case of a patient presenting with altered mental status on post-operative day seven after a diagnostic lung biopsy. The diagnosis of carcinomatous letomeningeal metastasis was confirmed. Methods: We discuss meningeal carcinomatosis in lung cancer, and describe challenges to diagnosis, therapy, and prognosis. Results: A review of the literature describing the clinical and oncologic principles of letomeningeal carcinomatosis in lung cancer is performed. Discussion: Leptomeningeal carcinomatosis (LC) occurs in approximately 5% of patients with non-small cell lung cancer and incurs a bleak prognosis. Presenting neurologic symptoms can be varied and diagnosis is confirmed via lumbar puncture and cerebrospinal fluid cytology. Few data exist regarding optimal treatment, although intrathecal chemotherapy has been shown to provide a modest improvement in median survival.