Unresectable Metastatic Colon Cancer Research Articles

Ultrasound-guided Phrenic Nerve Block for Intractable Hiccups in Patients with Metastatic Colon Cancer: A Case Report

Intractable hiccups can be a debilitating condition in cancer patients especially for those who have recently undergone thoracic or abdominal surgery and have tumor loads causing diaphragmatic irritation. The following case report details complete resolution of severe intractable hiccups due to an ultrasound guided phrenic nerve block in a patient with unresectable metastatic colon cancer. Ultrasound guided phrenic nerve block modification of the commonly performed interscalene brachial plexus may prove beneficial in relieving hiccups when medication therapy has failed or causes untoward side effects.

Prognostic Significance of MicroRNA-21 Expression in Patients with Unresectable Metastatic Colon Cancer.

MicroRNA (miR)-21 is overexpressed in most solid tumors and a high expression of miR-21 in tumor tissue is associated with a poor clinical outcome. The aim of this study was to clarify the association between the miR-21 expression in the tumor and the chemotherapeutic outcomes and survival for unresectable metastatic colon cancer (CC). Formalin-fixed, paraffin-embedded (FFPE) samples of primary tumor were obtained from 32 patients who underwent primary tumor resection and received palliative chemotherapy for unresectable metastatic CC. MiR-21 was extracted from the FFPE and the expression of miR-21 was evaluated using quantitative real time-polymerase chain reaction (RT-PCR). The expression of miR-21 was calculated with 2-ΔΔCT. A high miR-21 expression was associated with reduced progression-free survival (PFS) (p=0.0109) and tended to reduce overall survival (OS) (p=0.0675). miR-21 expression might be a useful prognostic marker for chemotherapeutic outcome and survival in patients with unresectable metastatic CC.

Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

Colon cancer with unresectable synchronous metastases: the AAAP scoring system for predicting the outcome after primary tumour resection.

The aim of this study was to develop a prognostic scoring system to predict the outcome of patients with unresectable metastatic colon cancer who received primary colon tumour resection. Patients with confirmed metastatic colon cancer treated at the Peking University Cancer Hospital between 2003 and 2012 were reviewed retrospectively. The correlation of clinicopathological factors with overall survival was analysed using the Kaplan-Meier method and the log-rank test. Independent prognostic factors were identified using a Cox proportional hazards regression model and were then combined to form a prognostic scoring system. A total of 110 eligible patients were included in the study. The median survival time was 10.4months and the 2-year overall survival (OS) rate was 21.8%. Age over 70years, an alkaline phosphatase (ALP) level over 160IU/l, ascites, a platelet/lymphocyte ratio (PLR) above 162 and no postoperative therapy were independently associated with a shorter OS in multivariate analysis. Age, ALP, ascites and PLR were subsequently combined to form the so-called AAAP scoring system. Patients were classified into high, medium and low risk groups according to the score obtained. There were significant differences in OS between each group (P<0.001). Age, ALP, ascites, PLR and postoperative therapy were independent prognostic factors for survival of patients with metastatic colonic cancer who underwent primary tumour resection. The AAAP scoring system may be a useful tool for surgical decision making.

Factors associated with the efficiency of maintenance therapy in patients with metastatic colorectal cancer

Objective : to evaluate tolerability and efficacy of maintenance treatment in the absence of progression after 16 weeks of first-line therapy in patients with unresectable metastatic colon cancer. Materials and methods . We have analyzed medical case histories of patients with metastatic colorectal cancer who underwent treatment in the department of clinical pharmacology and chemotherapy of N. N. Blokhin Russian Cancer Research Center from 2007 to 2015 years. Inclusion criteria were the following: 16–24 weeks of first-line chemotherapy with no signs of progression and the inability to perform metastasectomy. Progression-free survival was the main criterion for effectiveness in our study. Results. 160 (44.5 %) of 359 treated patients met the inclusion criteria. 102 (63.7 %) patients were followed up, while the other 58 (36.3 % – comparison group) patients underwent maintenance chemotherapy. Grade I–II toxic reactions and grade III complications associated with first-line chemotherapy were insignificantly more common in the group of patients left on maintenance chemotherapy: 72.4 % and 37.9 % versus 57.8 % and 24.5 % in the comparison group, p = 0.07 and p = 0.07 respectively. The frequency of grade I–II toxic reactions and grade III complications in the second-line treatment did not differ between treatment groups (p = 0.9 and p = 0.8). The median of progression-free survival in observation group and comparison group was 4, and 6 months (odds ratio (OR) 0.6; p = 0.009), and life expectancy – 23 and 31 months (OR 0.75; p = 0.1), respectively. Statistically significant differences between groups with respect to achieving the objective response and/or normalization of carcinoembryonic antigen level were revealed: median of progression-free survival was 13 (n = 26 of 57; 45.6 %) and 4 months (n = 31 of 57, 54.4 %), respectively (HR 0.38; p = 0.002), median of life expectancy – 34 months versus 26 months (OR 0.37; p = 0.3). Conclusions . Carrying out maintenance therapy is associated with increased incidence of grade III complications during the first-line treatment, but does not affect the tolerability of the second-line treatment. Supportive chemotherapy with fluoropyrimidines remains to be the most effective in patients with favorable prognostic factors such as normalization of carcinoembryonic antigen and/or achievement of the objective response on the background of first-line chemotherapy.

Does asymptomatic primary tumor need to be removed in unresectable metastatic colon cancer?

Every third colorectal cancer patient has inoperable metastatic disease upon diagnosis. And quite often the primary tumor is asymptomatic. The question stands for surgeon and medical oncologist, whether to proceed with upfront surgery or systemic chemotherapy. Considering the absence of prospective randomized clinical trials, we must discuss all potential benefits and drawbacks of both approaches, biological interactions between the primary tumor and metastases, risk of complications, associated with primary tumor during chemotherapy, relative efficacy of chemotherapy for primary tumor and metastatic nodes, we must perform a retrospective analysis of prognostic value of primary tumor resection. This review discusses all of the aforementioned questions.

Comparative effectiveness of primary tumor resection in metastatic colon cancer: An instrumental variable analysis.

674 Background: Although the safety of chemotherapy without primary tumor resection (PTR) has been established, questions remain regarding potential survival benefit with PTR. The purpose of this study was to compare mortality with and without PTR among patients with unresectable metastatic colon cancer using nationwide hospital based cancer registry data. Methods: An observational study was conducted of patients with stage 4 colon cancer identified from the National Cancer Data Base (2003-2005). Patients who underwent metastectomy were excluded. Patient, treatment, and hospital data were analyzed. Multivariate Cox regression stratified by receipt of chemotherapy was performed to compare survival with and without PTR. To account for treatment selection bias, Propensity Score Weighting (PSW) and Instrumental Variable (IV) analyses, using hospital-level PTR rate as the instrument, were performed. In order to account for the potential bias associated with early comorbidity or disease burden associated deaths (survivor treatment bias), 1 year landmark analysis was performed. Results: A total of 14,399 patients met inclusion criteria and 6,735 patients were eligible for landmark analysis. PTR was performed in 38.2% of the total cohort and 73.8% of those at landmark. Using multivariate Cox regression analysis, PTR was associated with a significant reduction in mortality (HR 0.39; 95% CI, 0.38-0.41). This effect persisted with PSW (HR 0.4; 95% CI, 0.38-0.43). However, IV analysis showed a much smaller effect, (RR 0.88; 95% CI, 0.83-0.93). While a smaller benefit was seen on landmark analysis using multivariate Cox regression (HR 0.6; 95% CI, 0.55-0.64) and PSW (HR 0.59; 95% CI, 0.54-0.64), IV analysis showed no improvement in survival with PTR (RR 0.97; 95% CI, 0.87-1.06). Stratification by chemotherapy did not alter the results. Conclusions: Among patients with stage IV colon cancer, PTR offered no survival benefit over systemic chemotherapy alone when the IV method was applied at the 1 year landmark. Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of PTR. Future study should focus on identifying patients most likely to benefit from PTR.

Primary mFOLFOX6 Plus Bevacizumab Without Resection of the Primary Tumor for Patients Presenting With Surgically Unresectable Metastatic Colon Cancer and an Intact Asymptomatic Colon Cancer: Definitive Analysis of NSABP Trial C-10

Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial. Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention. Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months). This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.

AVASTERB OUEST: A prospective cohort study of unresectable metastatic colon cancer treated successively by FOLFIRI bevacizumab and cetuximab irinotecan

e15103 Background: Bevacizumab and cetuximab regimen are approuved since 2005 in Europe for Metastatic Colorectal Cancer Patients (MCCP). Very few studies have reported data concerning the sequence (FOLFIRI BEVA and after failure CETUXIMAB- CAMPTO) in MCCP from the real world. Methods: Since 2003, in west of France, (Bretagne-Pays de Loire),a network called OMIT(Observatoire des Médicaments et Innovations Thérapeutiques) directed by Regional Health Agencies has been created. This structure gathered prospectively data from MCCP treated with targeted therapies. Since 2006, a cohort of MCCP treated successively by FOLFIRI BEVACIZUMAB (same protocol : same dose) as first line to progression or unacceptable toxicity and CETUXIMAB- CAMPTO after the first line failure was constitued (AVASTERB cohort). Criteria for initial unresectability of metastic lesions was based on investigator's evaluations during local comitee (surgeons and oncologists). In order to have a large follow up, the 35 first patients of the cohort were studied in this abstract.Age, sex, response rate to the different regimens,secondary metastatic lesion resection, time to progression to the different regimens, follow up and overall survival are the criterias studied. Results: Median age 60 years (49–83), Males : 60%, colon 71%,rectum: 17%, colorectal jonction :12%.Response rate(OR+SD)with Folfiri Bevacizumab : 45.7%. 17% of the patients underwent hepatic surgery with curative intent (all during Folfiri bevacizumab) Time to progression with Bevacizumab : 6 months. Fifty eight percent of the patients are still alive with a median follow up of 25 months (11–29)Median overall survival was not reached.The 12 months and 24 months overall survival rates are respectively 71.4% and 45.7% (date of point: 01/01/2009). Actualisation of the data will be provided during the meeting Conclusions: The results from this prospective unselected cohort of MCCP treated with the sequence FOLFIRI BEVA and after failure CETUX-CAMPTO from the real world show promising TTP, and overall survival. The study of the Kras mutation and others biomarkers could improve these results by personalization of the treatment. This part of our study is actually ongoing. No significant financial relationships to disclose.

Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil—leucovorin combination

We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination. The study population consisted of 41 patients with unresectable metastatic colon cancer, homogeneously, treated with bolus 5-FU and LV. Twenty-seven patients (66%) showed high levels of TS expression. The difference in the proportion of objective responses between patients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was statistically significant (P = 0.0001, chi-square test). p53 nuclear over-expression was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients with low TS expression. p53 status measured by immunohistochemistry does not seem to be useful to identify unresponsive patients with low TS expression.