Palliative Systemic Chemotherapy Research Articles

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in pancreatic cancer patients with peritoneal metastasis

Introduction: The median survival in pancreatic cancer (PC) patients with synchronous peritoneal metastasis (PM) is six weeks, and the effect of palliative systemic chemotherapy is limited. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has shown promising results in patients with PM of different origin, but data in patients with PM from PC are sparse. We present prospective data on PIPAC treatment in nine PC patients with PM. Methods: Between January 2016 and January 2018, PC patients with isolated PM were included. Objective response evaluation was based on the Peritoneal Regression Grading Score (PRGS) in repeated biopsies from PM. Survival data, prior chemotherapy, number and complications of PIPAC procedures were collected. Results: Nine patients (5M/4F, median age 62 years (range 46-72)) were included. Six patients had synchronous PM, whereas three patients developed PM after initial resection. Patients had received between 2 and 12 (median 9) cycles of systemic chemotherapy prior to inclusion. Twenty-four PIPAC procedures (median 2, range 1-5) were performed, without significant complications. The median survival was 11 months (range 8-25) after diagnosis of PM and 6 months (range 2-16) after the first PIPAC. Based on the PRGS score in six patients who received > 1 PIPAC, four patients responded and two had stable disease. One patient died before the second PIPAC (disease progression), two patients received no further PIPAC since PM could not be bioptically verified. Conclusions: PIPAC is safe in pancreatic cancer patients with peritoneal metastasis, and PIPAC may induce an objectively measureable treatment response.

Metastatic gastric cancer: Does the site of metastasis make a difference?

Metastatic gastric cancer has a poor prognosis. We aim to study how clinical features and prognosis differs between different metastatic sites, and to identify prognostic factors for overall survival. We retrospectively reviewed patients with metastatic gastric adenocarcinoma managed at a tertiary referral cancer center over a 5-year period. We divided our cohort into three groups based on the site(s) of metastasis at presentation-peritoneal metastasis only (P), distant metastasis only (D), and peritoneal and distant metastases (PD). We studied 470 patients with 175 (37.2%), 193 (41.1%) and 102 (21.7%) patients in the P, D and PD groups, respectively. Patients with peritoneal disease (both P and PD) had higher proportions of patients experiencing chemotherapy disruption due to unplanned hospitalizations, which were also of a longer average duration. The P group had the longest overall median survival of 8.9 months compared to the PD and D groups with 7.4 and 5.5 months, respectively (P<0.001). On multivariate Cox regression analysis, the presence of ≥1 metastatic site (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.23-2.28; P = 0.001) was significantly associated with increased overall mortality, whereas palliative systemic chemotherapy (HR 0.29; 95% CI, 0.22-0.37; P<0.001) and palliative gastrectomy (HR 0.24; 95% CI, 0.15-0.39; P<0.001) were significantly associated with decreased overall mortality. Metastatic gastric cancer represents a heterogeneous disease, with specific disease complications and treatment outcomes unique to different metastatic sites. We can consider novel multimodality therapies for patient subgroups with isolated metastatic disease and good prognostic factors in a bid to improve long-term survival.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with standard of care chemotherapy in primarily untreated chemo naïve upper gi-adenocarcinomas with peritoneal seeding - a phase II/III trial of the AIO/CAOGI/ACO.

BackgroundPeritoneal metastasis is a common and dismal evolution of several gastrointestinal (GI) tumors, including gastric, colorectal, hepatobiliary, pancreatic, and other cancers. The therapy of peritoneal metastasis is largely palliative; with the aim of prolonging life and preserving its quality. In the meantime, a significant pharmacological advantage of intraperitoneal chemotherapy was documented in the preclinical model, and numerous clinical studies have delivered promising clinical results.MethodsThis is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy vs. intravenous systemic chemotherapy alone on patients with metastatic upper GI tumors with a peritoneal seeding. Upper GI-adenocarcinomas originated from biliary tract, pancreas and stomach, or esophago- gastric junction are eligible. Patients in the study are treated with standard of care systemic palliative chemotherapy (mFOLFOX6) vs. PIPAC with intravenous (i.v.) chemotherapy (mFOLFOX6). Patients in first line with first diagnosed peritoneal seeding are eligible. Primary outcome is progression free survival (PFS).ConclusionsPIPAC-procedure is explicit a palliative method but it delivers cytotoxic therapy like in hyperthermic intraperitoneal chemotherapy (HIPEC)-procedure directly to the tumor in a minimally invasive technique, without the need for consideration of the peritoneal-plasma barrier. The technique of PIPAC is minimally invasive and very gentle and the complete procedure takes only round about 45 min and, therefore, optimal in a clearly palliative situation where cure is not the goal. It is also ideal for using this approach in a first line situation, where deepest response should be achieved. The symbiosis of systemic therapy and potentially effective surgery has to be well-planned without deterioration of the patient due to aggressive way of surgery like in cytoreductive surgery (CRS)+HIPEC.Trial registrationEudraCT: 2018-001035-40.

Real-World Effectiveness of Chemotherapy in Elderly Patients With Metastatic Bladder Cancer in the United States

Background:Outcomes for patients with metastatic bladder cancer (mBC) are generally poor and progressively worse following first-line (1L) chemotherapy.Objective:To evaluate treatment patterns, survival outcomes, and characteristics of a large, real-world US population of elderly patients with advanced mBC receiving 1L and second-line (2L) treatment retrospectively.Methods:We identified patients with advanced mBC (aged ≥66 years)—newly diagnosed between January 1, 2004, and December 31, 2011—in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program–Medicare linked database and assessed their palliative systemic chemotherapy treatments and survival outcomes.Results:Of 1703 eligible patients, 42% received 1L chemotherapy; 1L-treated patients tended to be younger and healthier than nontreated patients. Only 27% of 1L-treated patients received cisplatin-based chemotherapy, most commonly cisplatin-gemcitabine. Cisplatin-treated patients were younger and had fewer comorbidities than non-cisplatin–treated patients. Thirty-five percent of 1L-treated patients subsequently received 2L chemotherapy. Patients received a variety of 2L agents as combination chemotherapy (52%) or single-agent chemotherapy (39%). Median overall survival durations in 1L-treated and 2L-treated patients were 8.5 and 7.9 months, respectively.Conclusions:Results from this retrospective SEER-Medicare database analysis underscore the historical inadequacies of 1L and 2L treatments in elderly patients with advanced mBC. Few patients were treated with 1L chemotherapy, a minority of whom received 1L cisplatin-based chemotherapy, and even fewer received 2L chemotherapy. These findings highlight the disconnect between 1L treatment in clinical trials and treatment in the real-world setting and the lack of standard approaches to 2L treatment in the United States.

Downstaging of unresectable intrahepatic or hilar cholangiocellular carcinoma by selective intra-arterial floxuridine and systemic cisplatin and gemcitabine. A dose finding single center phase IIa study.

478 Background: Patients with unresectable cholangiocarcinomas (CCC) have a poor prognosis even if palliative systemic chemotherapy is offered. A combined approach of systemic and intrahepatic chemotherapy may improve local control rates and allow downstaging. The aim of the study was to determine the maximum tolerated dose (MTD) of systemic intravenous gemcitabine in combination with intravenous cisplatin and hepatic arterial infusion with floxuridine in patients with unresectable intrahepatic or hilar CCC. Safety, toxicity, response rates and resectability rates after 3 months of combination treatment are reported. Methods: 12 patients were treated within a 3+3 dose escalation algorithm with 600, 800 or 1000 mg/m2 gemcitabine and a fixed dose of cisplatin 25 mg/m2 systemic chemotherapy on day 1, 8 every 3 weeks for 4 cycles and floxuridine 0,2 mg/kg on day 1-14 continous hepatic intra-arterial chemotherapy every 4 weeks for 3 cycles. PET/CT and/or CT scan was performed after 12 weeks. Results: The MTD of gemcitabine was 800 mg/m2 in this setting. Dose-limiting toxicities were recurrent biliary tract infections (n = 1) and neutropenic fever (n = 1). Response rates were: 27% partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, 3-year-overall survival (OS) was 33%, median OS 21,9 months (1-49) and median progression-free survival 10,5 months (2-40). Conclusions: Combination of systemic gemcitabine and cisplatin plus intraarterial floxuridine is feasible and appears effective in disease control, but achievement of resectability seems challenging. Randomized trials comparing this combination to gemcitabine/cisplatin alone are warranted. Clinical trial information: NCT01692704.

Phase I study of hepatic arterial infusion (HAI) therapy with floxuridine (FUDR) combined with systemic gemcitabine and oxaliplatin in patients with locally advanced intrahepatic cholangiocarcinoma (ICC).

417 Background: The standard of care for unresectable ICC is palliative systemic chemotherapy with cisplatin and gemcitabine. HAI therapy with FUDR in ICC resulted in high response rates [Kemeny 2011]. The use of HAI FUDR with systemic chemotherapy may improve outcomes. We conducted a phase 1 study of HAI FUDR with systemic gemcitabine and oxaliplatin. Methods: We enrolled patients in 3 cohorts: FUDR 0.16mg/kg/day x 14 days (Cohort 1), FUDR 0.12 mg/kg/day x 14 days with gemcitabine 1000mg/m2 on days 1, 8, 15 (Cohort 2), and FUDR 0.10 mg/kg/day x 14 days with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15 (Cohort 3). The primary endpoint was the recommended phase 2 dose (RP2D) for Cohort 3. DLTs were assessed during cycle 1. Secondary objectives were response rate and survival. Results: We enrolled 24 patients, 6 male, age range 42-81 years (median 64). No DLTs were observed in Cohort 1 (FUDR). In Cohort 2 (FUDR + Gem), the addition of gemcitabine at 1000mg/m2 days 1, 8, 15 resulted in grade 3 LFT elevation in 2 patients; for subsequent patients, the gemcitabine dose was reduced to 800mg/m2, and no further DLT were noted. No DLT were observed in Cohort 3 (FUDR + GemOx). 10 patients experienced partial responses and conversion to resectable disease occurred in all cohorts. No other significant toxicities occurred. Conclusions: FUDR via HAI with systemic gemcitabine and oxaliplatin is well-tolerated in patients with unresectable cholangiocarcinoma, with a high rate of response and disease control, allowing for resection in some patients. Our RP2D is FUDR 0.10 mg/kg/day x 14 days, with gemcitabine 800mg/m2 days 1, 15 and oxaliplatin 85mg/m2 days 1, 15. Collaboration with MSKCC is ongoing. Clinical trial information: NCT01525069. [Table: see text]

Locally Advanced Pancreatic Cancer: A Review of Local Ablative Therapies.

Pancreatic cancer is typically characterized by its aggressive tumor growth and dismal prognosis. Approximately 30% of patients with pancreatic cancer present with locally advanced disease, broadly defined as having a tumor-to-artery interface >180°, having an unreconstructable portal vein or superior mesenteric vein and no signs of metastatic disease. These patients are currently designated to palliative systemic chemotherapy, though median overall survival remains poor (approximately 11 months). Therefore, several innovative local therapies have been investigated as new treatment options for locally advanced pancreatic cancer (LAPC). This article provides an overview of available data with regard to morbidity and oncological outcome of novel local therapies for LAPC.

Utilization and trends in palliative therapy for stage IV pancreatic adenocarcinoma patients: a U.S. population-based study.

Pancreatic adenocarcinoma is an aggressive malignancy, with most patients diagnosed with advanced or metastatic disease. Palliative therapies comprise an important, but underutilized, aspect of care. This aim of this study was to characterize the trends, factors, and outcomes associated with utilization of palliative therapies. Patients with stage IV pancreatic adenocarcinoma from the 2003-2011 U.S. National Cancer Database were identified and stratified by receipt of palliative therapy. Linear regression, multivariable logistic regression, and survival analyses using multivariate proportional hazards models were performed. Sixty-eight thousand and seventy-five patients with stage IV disease were identified, of which only 11,449 (16.8%) underwent designated palliative therapy. The majority received systemic chemotherapy (37.2%), followed by surgery (19.0%), pain management alone (15.3%), radiation (8.1%), referral alone (11.7%), or a combination thereof (8.7%). Utilization of palliative therapies increased from 12.9% in 2003 to 19.2% in 2011 (P<0.001). Patients were less likely to undergo palliation when older than 60 (OR 0.89, P<0.001), or of black or Hispanic race (OR 0.83, P<0.001; OR 0.80, P<0.001, respectively, vs. Caucasians). Presence of comorbidities increased the use of palliative therapy (OR 1.16 per comorbidity, P<0.001). Survival was improved in those receiving palliative systemic chemotherapy (HR 0.55, P<0.001) and palliative surgery (HR 0.94, P<0.001), although this may be due to selection bias. Despite the continued dismal prognosis of pancreatic cancer, palliation of symptoms remains underutilized in this country, particularly in non-Caucasian, older patients. Increased awareness of palliative options may help increase its utilization.

Treatment of Peritoneal Dissemination in Stomach Cancer Patients With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Rationale and Design of the PERISCOPE Study.

BackgroundPatients with gastric cancer and peritoneal carcinomatosis have a very poor prognosis; median survival is 3 to 4 months. Palliative systemic chemotherapy is currently the only treatment available in the Netherlands. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has an established role in the treatment of peritoneal carcinomatosis originating from colorectal cancer, appendiceal cancer, and pseudomyxoma peritonei; its role in gastric cancer is uncertain. Currently, there is no consensus on the choice of chemotherapeutic agents used in HIPEC for gastric cancer.ObjectiveThe main objectives of this study are (1) to investigate the safety, tolerability, and feasibility of gastrectomy combined with cytoreductive surgery and HIPEC after systemic chemotherapy, as a primary treatment option for patients with advanced gastric cancer with tumor positive peritoneal cytology and/or limited peritoneal carcinomatosis; and (2) to determine the maximum tolerated dose (MTD) of intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin.MethodsThe PERISCOPE study is a multicenter, open label, phase I-II dose-escalation study. The MTD of docetaxel will be studied using a 3+3 design. Patients with locally advanced (cT3-cT4) gastric adenocarcinoma are eligible for inclusion if the primary gastric tumor is considered resectable, tumor positive peritoneal cytology and/or limited peritoneal carcinomatosis is confirmed by diagnostic laparoscopy/ laparotomy, and prior systemic chemotherapy was without disease progression. At laparotomy, cytoreductive surgery (complete removal of all macroscopically visible tumor deposits) and a total or partial gastrectomy with a D2 lymph node dissection is performed. An open HIPEC technique is used with 460mg/m2 hyperthermic oxaliplatin for 30 minutes (41°C to 42°C) followed by normothermic docetaxel for 90 minutes (37°C) in a dose that will be escalated per 3 patients (0, 50, 75, 100, 125, 150 mg/m2). The primary endpoint is treatment related toxicity.ResultsPatient accrual is ongoing and the first results are expected in 2017.ConclusionsThe PERISCOPE study will determine the safety, tolerability, and feasibility of gastrectomy combined with cytoreduction and HIPEC using oxaliplatin in combination with docetaxel after systemic chemotherapy as primary treatment option for gastric cancer patients with tumor positive peritoneal cytology and/or limited peritoneal carcinomatosis. This study will provide pharmacokinetic data on the intraperitoneal administration of oxaliplatin and docetaxel, including the MTD of intraperitoneal-administered docetaxel. These data are a prerequisite for the safe conduct of future HIPEC studies in patients with gastric cancer.Trial RegistrationNetherlands Trial Registration (NTR): NTR4250; http://www.trialregister.nl/trialreg/admin/ rctview.asp?TC=4250 (Archived by WebCite at http://www.webcitation.org/6rWJONgkt)

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

BackgroundAlthough anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown.Case presentationWe discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size.ConclusionsTo the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.

P-145 - Understanding the hepatocellular carcinoma (HCC) patient landscape: Results of the first global survey of people living with HCC

Introduction: A global survey, the first of its kind, was undertaken to understand the experience of patients living with hepatocellular carcinoma (HCC), and their needs along the patient journey. Methods: A group of patient charities (7) and medical centres (>15) in 13 countries conducted the ‘HCC Patient Voices’ survey. The questionnaire was approved by scientific advisory boards and an independent ethics review board. It contains 32 closed- and open-ended questions on demographics, diagnosis, and treatments, including side effects, quality of life (QoL), treatment access and most-recent treatment, and was available at www.hcc-voices.com in 8 languages from November 2016 through April 2017. Results: We analysed preliminary results for 190 returned surveys (70% from male, 30% from female patients), with a median age of 62 (range, 23-88 years). Time since diagnosis was <1 year (32%), 1–3 years (35%), 4–6 years (15%) or > 6 years (18%). Hepatologists or Gastroenterologists diagnosed most (68%) patients. Just over a quarter of patients received a liver transplant (26%), and 65% were treated with surgery and/or ablation as primary therapy. Later lines of therapy included transarterial chemoembolisation (TACE, 40%), oral chemotherapy (sorafenib, 14%) and selective internal radiation therapy (SIRT, 11%). Two-fifths (41%) of respondents reported using supplementary health insurance during their treatment, but for more than three-quarters (76%) insurance did not cover all treatment options. Three-quarters (74%) said that their treatment was determined based on what was covered by their insurance plan. Only 32% of respondents felt that their information needs were fully met. Medical specialists and nurses were considered the most valuable source of HCC information, more than patient charities and websites. Medical websites also proved valuable for 47% of respondents, whilst 51% said friends and family were a ‘good’ or ‘excellent’ source of information. Initial analysis indicates patients who required additional treatments after surgery, transplant or ablation were more likely to experience side effects and diminished QoL. Although the percentages of those last treated with TACE (11%), SIRT (4%) or oral chemotherapy with sorafenib (6%) were relatively small, useful generalisations about the comparative effects of each can still be made. Those treated systemically with sorafenib were less likely to report improvement in their energy levels, ease of daily activities and QoL than those treated last with SIRT or TACE. Respondents said TACE and SIRT were associated with shorter-lasting, moderate-to-significant abdominal pain (30% and 38%, respectively), fatigue (40% and 38%) and appetite loss (25% and 0%). However, those treated with sorafenib reported experiencing side effects that were more frequent and more persistent, including fatigue (83%), abdominal pain (42%), appetite loss (58%), nausea (50%), diarrhoea (41%) and skin disorders (25%). Conclusion: The vast majority of patients with HCC feel inadequately informed about their disease. A greater proportion of patients who received palliative oral systemic chemotherapy report a negative impact on their QoL, and more frequent and long-lasting side effects than those treated with liver-directed SIRT or TACE. For patients with incurable HCC, better treatment strategies are needed to maintain QoL. This survey was made possible by educational grants from Sirtex.

Oncological outcomes in a cohort of patients with biliary tract carcinoma in a Mexican reference center.

e15618 Background: In Mexico there is scarce information about oncological outcomes of biliary tract carcinomas (BTC). Methods: we retrospectively reviewed medical records from 150 patients with histologically confirmed BTC (excluding gallbladder cancer) treated in our institution from January 2005 to December 2015.Clinical and pathological information was recorded. Survival was estimated by Kaplan Meir method and compared by Log rank test. Results: we found 63.3% women and 36.7% men, with a median age of 62 years (23 - 88). Tumor localization was intrahepatic in 34.7%, hilar in 43.3% and distal in 22%. Clinical stage was advanced in 71%, regional in 13% and local in 16%. Diagnostic delay was 3.7 months (0.37 - 32.9). For patients with localized disease (which included local and regional disease, n=43), a potentially curative surgery was attempted in 64% (n=27), achieving a R0 resection in 59% (n=16) of cases. There was a 3.9 months (0.83-29.63) treatment initiation delay. There were 7 surgical deaths. For advanced disease (n=107), treatment initiation delay was 4.2 months (0.5 - 34.5), 59% (n=63) of patients did not received oncological active treatment, and 26% (n=28) of patients received a systemic palliative chemotherapy, more frequently gemcitabine (n=20). At progression just eleven patients received a second chemotherapy line. In localized disease resected patients by univariate analysis high levels of CA 19.9 (p=0.04) and CEA (0.03) were associated with decreased survival. For patients with advanced disease prognostic factors included poorly differentiated histology (p=0.04), high bilirrubin level (p=0.04), low albumin level (p=0.001), abscense of chemotherapy (p=0.000) and high CEA levels (p=0.03). Conclusions: Survival is poor in this Mexican cohort of patients with BTC possibly related to diagnostic and therapeutic delay and advanced disease at presentation. [Table: see text]

Protocolo de manejo de la carcinomatosis peritoneal

ConceptPeritoneal carcinomatosis (CP) includes all tumor spread affecting the peritoneal serosa and surrounding anatomical structures. Clinical manifestationsUsually it manifests very differently and has a bad prognosis. TreatmentThe usual treatment is palliative systemic chemotherapy with or without surgery. The multidisciplinary treatment with radical surgery, intraperitoneal chemotherapy and hyperthermia, in some cases, increased survival and has been one of the last advances in the treatment of metastatic cancer.

Clinical features and tumor mutational profile of younger versus older patients with cholangiocarcinoma (CCA).

240 Background: As seen in lung cancer, young patients with cancer can have different risk factors, presentation, and tumor genotype than older patients with the same disease. The clinical and molecular features of young patients with CCA have yet to be well characterized. Methods: Retrospective chart review was performed on patients with intrahepatic (ICC) or extrahepatic cholangiocarcinoma (ECC) across 5 institutions. Data on demographics, risk factors, treatments, pathology, and overall survival (OS) were collected. Tumor genotyping results from MGH SNaPShot and Foundation Medicine were analyzed. Log-rank tests and Kaplan-Meier survival curves were used for statistical analysis. Results: Of 567 patients analyzed, 134 (23.6%) were &lt; 50 years old (yo) and 455 (80.2%) had ICC. When assessed for risk factors, younger patients ( &lt; 50yo) were more likely to have primary sclerosing cholangitis (PSC) (p &lt; 0.001) and less likely to have diabetes (p = 0.05), compared to older patients ( ≥ 50yo). Surgical resection rates were similar in younger vs older patients (41.9 vs 42.6%, p = 0.890), but younger patients had larger tumors (median size 7.1 vs 5.3cm p = 0.012). Younger patients were also more likely to receive palliative systemic chemotherapy (p &lt; 0.001) and more lines of therapy (median, 2 vs 1 line, p &lt; 0.001). Frequency of treatment with liver directed therapy did not differ between the two groups. Molecular testing was performed on 222/567 (39.1%) patients of which 84/134 (62.7%) were younger patients and 138/433 (31.9%) were older patients. FGFR aberrations were more common in younger patients versus older patients (17.6 vs. 5.7%, p = 0.002). Targeted therapy was given to 15/84 (17.9%) younger and 28/138 (20.3%) older patients based on results of mutational profiling. Finally, no significant difference was seen in OS between younger and older patients (22.9 vs 22.7 months, p = 0.89). Conclusions: Younger patients with CCA may have different risk factors, tumor biology, and tolerance of systemic therapy compared to older patients. Further study is needed as referral patterns to tertiary care centers and motivation of younger patients to seek tertiary care may impact these results.

Intraperitoneal cisplatin and doxorubicin as maintenance chemotherapy for unresectable ovarian cancer: a case report

BackgroundPrimary advanced, unresectable ovarian cancer (OC) is treated with palliative systemic chemotherapy. Intraperitoneal chemotherapy may be an alternative local maintenance therapy.Case presentationA 75 year old woman with laparoscopically and histologically confirmed unresectable OC was treated with 13 cycles of intraperitoneal cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 over 2 years using laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC). Objective tumor response (tumor regression on histology, stable disease on repeated video-laparoscopy and peritoneal carcinomatosis index) was noted. No Common Terminology Criteria for Adverse Events (CTCAE) > grade 3 were observed. EORTC QLQ-C30 quality of life measurements were stable throughout the therapy.ConclusionsRepeated intraperitoneal chemotherapy with cisplatin and doxorubicin applied as PIPAC may be an effective maintenance treatment in women with primary advanced, unresectable OC.

Gastric peritoneal carcinomatosis - a retrospective review.

AIMTo characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care.METHODSWe performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre.RESULTSWe studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority (n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001).CONCLUSIONGastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run.

Diagnostics and treatment of cholangiocellular carcinoma

Cholangiocellular carcinoma (CCA) is the second most frequent primary liver carcinoma and is an aggressive tumor, which is mostly diagnosed in advanced stages. The overall survival is poor. Histpathological analysis of tumor biopsies or cytological analysis of biliary brushings can be used to confirm the diagnosis. A differentiation is made between distal, perihilar and intrahepatic CCA. The anatomical position determines the diagnostic and therapeutic strategy. Before diagnostic or therapeutic measures are undertaken it is essential to resolve biliary obstruction via endoscopic stenting or percutaneous biliary drainage. Depending on the tumor stage curative treatment options comprise radical surgical resection with hepaticojejunostomy or in selected cases liver transplantation. For intrahepatic or distal CCA liver transplantation is not indicated. In the palliative setting systemic chemotherapy with gemcitabine and cisplatin leads to a significant improvement in survival time.

982P - Metronomic oral cyclosphosphamide as 3rd line systemic treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma

There is no standard 3rd line or further systemic treatment for patients inoperable locoregionally advanced recurrent/metastatic nasopharyngeal carcinoma (NPC). Oral cyclophosphamide provides a convenient and cheap option for these heavily pretreated patients who have very limited choices of treatment options. We conducted a prospective single-arm open-label study of metronomic oral cyclophosphamide in this setting. Patients with locoregionally advanced recurrent inoperable (rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had good ECOG performance status (PS) (0-2) and had progressed after at least 2 lines of palliative systemic chemotherapy were eligible. They received open-label oral cyclophosphamide between 50mg to 150mg daily dose. Best objective response rate (ORR), disease control rate (DCR), biochemical response assessed by plasma EBV DNA, progression-free survival (PFS), overall survival (OS) and safety profiles were evaluated. Of 56 patients who received cyclophosphamide, 16 and 37 (66.1%) had ECOG performance status (PS) 1 and 2 respectively. 33, 13, 6, 3 and 1 patients received cyclophosphamide as 3rd, 4th, 5th, 6th and 7th line of therapy respectively. After a median follow-up of 8.95 months (range 0.76-58.51), the ORR was 8.9% and the DCR was 57.1% after cyclophosphamide. Biochemical response with 2 consecutive decline in plasma EBV DNA was seen in 10 (17.9%) patients. The median PFS and OS were 4.47 and 9.20 months. Those with PS 1 had a longer median PFS (5.49 months) compared to those with PS 2 (3.75 months, p = 0.011). Univariable (p = 0.021) and multivariable analysis (p = 0.010) revealed that ECOG PS 1 was the only significant prognostic factor of PFS. 16 (28.6%) patients developed 3G3 adverse events, including malaise (5.4%), haematological (8.9%), gastrointestinal (3.6%) and feverish (3.6%) and hemorrhagic (1.8%) events. The median cost of the whole drug treatment was 51.65 USD (1 USD = 7.8 HKD). Oral cyclophosphamide is an acceptable 3rd line or subsequent line systemic therapy for locoregionally advanced recurrent or metastatic NPC with acceptable toxicity and limited financial burden to patients.

Clinical characteristics of young-age onset gastric cancer in Korea.

BackgroundGastric cancer is the fourth most common cancer worldwide and more frequently detected in Asian countries including Korea and Japan. The incidence of young-age gastric cancer (GC) is increasing worldwide, but clinical behavior of young-age GC patients is not well established. We retrospectively analyzed the clinical features and outcomes of GC diagnosed at young-age population.MethodsBetween Jan. 2009 to Jan. 2015, 163 patients diagnosed as early, advanced, recurrent, or metastatic GC at ages between 22 ~ 39 years were analyzed. Based on medical records, authors analyzed the clinicopathologic characteristics and survival outcomes including overall survival (OS), disease free survival (DFS), and progression free survival (PFS).ResultsOne-hundred and four patients (82.8 %) were diagnosed as GC at their thirties; especially 81 patients (31.2 %) patients were diagnosed over 35 years of age. The ratio of early GC and advanced GC were relatively similar (47.2 % vs. 52.8 %, respectively). Among stage II and III patients, 45 patients received 5-FU based adjuvant chemotherapy and recurrence rate was 48.9 %. Among patients diagnosed as recurrent or metastatic GC, recurrent GC patients showed relatively superior PFS and OS after cancer recurrence, compared to metastatic GC patients, but without statistical significance. Among metastatic GC patients, patients receiving palliative debulking surgery for ovary metastases showed superior PFS compared to patients who only received palliative systemic chemotherapy (P = 0.021, PFS 7.7 vs. 3.37 months, respectively).ConclusionsYoung age GC were commonly diagnosed at their thirties, without sexual predominance. The incidence of advanced GC in young age patients were higher compared to general patient population. Among recurrent GC patients, palliative debulking surgery might have role for superior survival outcomes. Considering relatively higher incidence for advanced GC, active surveillance for gastric cancer is warranted.

Rare Case of Malignant Melanoma of Lacrimal Sac

Presentation A 60 year old female presented to our clinic in July 2015 with complaints of left eye epiphora, and painless gradually increasing mass in the medial canthal area for 4 months. Probing revealed hard stop. At the time the mass was above the MCT and appeared separate from lacrimal sac. She was advised biopsy, but was lost to follow-up, only to present 6months later with a massive increase in the size of mass. There was no history of bloody discharge. On Examination, both eyes had senile cataract with BCVA of 6/24 in Right eye and absent light perception in left eye. A single, irregular, diffuse, firm mass was present in the medial canthal area of left eye, measuring approximately 2.5cmX2.5cm in size, with 3mm horizontal dystopia and blackish skin pigmentation. It involved the medial part of both upper and lower lid, lacrimal sac and canaliculi. It was non tender, immobile, with no surface ulcerations or pulsations. Excessive watering was present in the left eye, syringing could not be done since puncta were not visualized. There were no other swellings, no lymphadenopathy, and no history of significant weight loss. Hematological investigations were normal. Neuroimaging revealed a well-defined heterogenously enhancing solid lesion in the region of medial canthus of Left eye, about 2.3X2.8X1.7cm, involving the extraconal space, causing scalloping and widening of Left lacrimal fossa and NLD, and mild lateral displacement of the globe. Incisional biopsy showed tumor tissue composed of clusters of malignant cells-pleomorphic with high nuclear-cytoplasmic ratio, vesicular nuclei and prominent eosinophillic macronuclei. Foci of melanin pigment deposition were seen, leading to a diagnosis of malignant melanoma of the lacrimal sac. Metastatic work-up revealed lytic lesions in left frontal and right parietal skull bones and fibronodular opacities in upper and middle lobes of right lung, alongwith mediastinal lymphadenopathy. Hence the final staging was T4aN0M1c. No surgical treatment was planned and instead patient was referred for palliative systemic chemotherapy and radiotherapy. Discussion Malignant melanoma is a malignancy of the pigmentproducing melanocytes. It usually affects the skin and rarely