Patient-reported outcomes in older breast cancer survivors with and without prior chemotherapy treatment.

BACKGROUND: Little is known about long-term treatment-related symptoms in older breast cancer survivors. We characterized long-term patient-reported symptoms and examined factors associated with the presence and severity of symptoms, and symptom interference with daily activities. METHODS: Texas Cancer Registry (TCR) Medicare linkage data was used to identify breast cancer patients age 65 and older with local/regional stage disease diagnosed between 2012-2013. Symptom burden was assessed using breast-specific items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). Demographic and clinical data also were collected. Logistic regression models were used to assess the association between symptom burden and respondent sociodemographic and clinical characteristics. RESULTS: Of 4448 eligible patients, 1594 (response-rate 35.8%) completed questionnaires. Of these, 1245 eligible respondents were included in the analysis based on self-reported data. Median time from diagnosis to survey completion was 68 months (IQR: 62-73). Most frequently reported symptoms were fatigue/lack of energy (76.8%), aching muscles (72.1%) and aching joints (72.5%). Receipt of chemotherapy was associated with higher symptom burden. Patients treated with adjuvant chemotherapy had higher risk of numbness/tingling (OR: 3.16; 95% CI: 2.36-4.24), hair loss (OR: 2.72; 95% CI: 2.05-3.60), and fatigue/lack of energy (OR: 1.80; 95% CI: 1.29-2.52). Similarly, patients who received chemotherapy were more likely to report the majority of symptoms as moderate to severe and as interfering with daily activities. CONCLUSION: Receipt of chemotherapy is associated with significant symptom burden more than 5 years after breast cancer treatment. Long-term chemotherapy impact should be discussed with patients in a shared-decision making process and approaches to symptom management during survivorship care are needed.

Adherence to treatment guidelines and survival for older patients with stage II or III colon cancer in Texas from 2001 through 2011.

BACKGROUND: Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. METHODS: Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. RESULTS: The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. CONCLUSIONS: The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to improve guideline-concordant treatment adherence. Cancer 2018;124:679-87. © 2017 American Cancer Society.

An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

INTRODUCTION: Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. METHODS: The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. RESULTS: The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). CONCLUSIONS: This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

Individualized Treatment Sequencing Selection Contributes to Optimized Survival in Patients with Rectal Cancer and Synchronous Liver Metastases.

BACKGROUND: The optimal treatment sequence for patients with advanced rectal cancer and synchronous resectable liver metastases is controversial. We examined the outcomes associated with an individualized selection of classic, reversed, or combined approaches. METHODS: Between 1999 and 2014, 268 patients with rectal cancer and synchronous liver-only metastases underwent curative-intent multimodality therapy. Demographics and tumor and treatment details were reviewed. Survival outcomes were examined across treatment sequences and time periods (1999-2003, 2004-2008, and 2009-2014). RESULTS: Overall, 150 (56.0%) patients underwent primary tumor resection first ('classic' approach), 44 (16.4%) patients underwent simultaneous resection of the primary and liver metastases ('combined' approach), and 74 (27.6%) patients underwent liver resection first ('reversed' approach). Patients who underwent the reversed approach had more liver metastases (3 [2-5]) at presentation (vs. 1 [1-2.5] in the combined approach or 1 [1-3] in the classic approach; p < 0.001). Over time (from 1999 to 2003, to 2009 to 2014), both patients undergoing curative-intent treatment (62-122 patients) and the relative proportion of patients undergoing the reversed approach (6.4-37.7%) significantly increased. Despite higher disease burden, the 5-year overall survival (OS) was higher for patients treated in 2009-2014 versus those treated in 1999-2003 (76% vs. 45%; p < 0.002). Two hundred and ten patients (78%) were rendered free of disease; however, 58 were not due to disease progression or treatment complications, and their 5-year OS was poor at 6%. CONCLUSIONS: Individualized selection of treatment sequence based on the liver metastases and primary tumor disease burden allowed most patients to complete resection of all gross disease, and is associated with a 5-year OS rate approaching that for stage III rectal cancer in the most recent era.

Comparable long-term oncologic outcomes of laparoscopic versus open pancreaticoduodenectomy for adenocarcinoma: a propensity score weighting analysis.

BACKGROUND: To date, no study has reported long-term oncologic outcome for patients undergoing laparoscopic pancreaticoduodenectomy (LPD) compared to open surgery (OPD). The aim of this study is assess long-term oncologic outcomes for patients with adenocarcinoma undergoing LPD versus OPD using propensity score weighting modeling to minimize selection bias. PATIENTS AND METHODS: All patients undergoing PD at Institut Mutualiste Montsouris between January 2000 and April 2010 were included. Propensity scores were calculated using multivariate logistic regression, relating preoperative covariates to surgical approach. Logistic regression was performed, and Cox proportional hazards models for postoperative outcomes were constructed, with and without adjustment for propensity scores weights. RESULTS: Among 87 patients who underwent PD, 40 underwent LPD and 25 OPD for confirmed adenocarcinoma. Preoperative covariates across both groups were comparable. The median follow-up time was 34.5 months. During follow-up, metastasis was identified in 16 (40%) LPD and 7 (28%) OPD patients. After propensity score adjustment, the median overall survival (OS) was 35.5 versus 29.6 months, respectively. The 1-, 3-, and 5-year OS rates were 80.5, 49.2, 39.7% and 77.8, 46.4, 30% in the LP and OPD groups (P = 0.41, 0.42, 0.25), respectively. The median recurrence-free survival (RFS) was 21.5 versus 13.7 months (LPD vs. OPD), and the 1-, 3-, and 5-year RFS rates were 70.9, 33.3, 21.9% and 62.3, 37.9, 25.7% in the LP and OPD groups (P = 0.27, 0.37, 0.39), respectively. CONCLUSIONS: Due to the early adoption of LPD, this study is the first to report on long-term oncologic safety of LPD: LPD is non-inferior to OPD with respect to long-term outcomes for patients with adenocarcinoma.

Estimating regimen-specific costs of chemotherapy for breast cancer: Observational cohort study.

BACKGROUND: One goal for high-quality patient care is communicating treatment costs to patients, yet cost information can be elusive. This is especially relevant for breast cancer care, for which numerous guideline-concordant adjuvant chemotherapy regimens exist. The objective of the current study was to generate cost estimates for such regimens from payers' and patients' perspectives in a large, insured US population. METHODS: Adult women who had incident breast cancer diagnosed between 2008 and 2012 (from the MarketScan database), had no secondary malignancy within 1 year of diagnosis, and received chemotherapy within 3 months of diagnosis were included (n = 14,643). Total and out-of-pocket costs were calculated using all claims within 18 months of diagnosis and were normalized to 2013 US dollars. The extended estimating equations method was used to assess cost by regimen adjusting for demographic and clinical factors. RESULTS: Among patients who did and did not receive trastuzumab, the median insurance payments were $160,590 and $82,260, respectively, and the median out-of-pocket payments were $3381 and $2724, respectively. Among patients who did not receive trastuzumab, 25% paid more than $4712, and 10% of patients paid more than $7041. For patients who did receive trastuzumab, 25% paid more than $5604, and 10% paid more than $8384. Among patients who were covered by high-deductible health plans, the median out-of-pocket cost was $5158, 25% paid at least $8128, and 10% paid ≥ $11,344. CONCLUSIONS: The costs of breast cancer chemotherapy vary widely across regimens, and patients bear a substantial out-of-pocket burden. Cancer 2016;122:3447-3455. © 2016 American Cancer Society.

Increased Risk of Death for Patients on the Waitlist for Liver Transplant Residing at Greater Distance From Specialized Liver Transplant Centers in the United States.

BACKGROUND: We have previously shown that patients listed for orthotopic liver transplantation (OLT) in United Network for Organ Sharing Region 4 (Texas and Oklahoma) have higher waitlist mortality rates when residing more than 30 miles from specialized liver transplant centers (LTC). Considering that findings might only be exclusive for this region with its peculiarities in terms of having the highest land surface extensions, lowest population densities, and largest rural populations. We investigated the entire OLT patient population in the United States to assess if our previous regional findings are nationally validated and if a rural, micropolitan, or metropolitan residence location affects outcome of waitlisted OLT patients in the nation. METHODS: Patients waiting for OLT in the United States from 2002 to 2012 were stratified by distance from the patients' residence to LTC and by Rural Urban Commuting Area (RUCA) codes classification. Statistical analyses were performed to evaluate risk of mortality on the waitlist and the likelihood to receive an OLT using a Cox proportional hazards model and a generalized additive model with a logistic link. RESULTS: Survival time and probability of death while on the waitlist for OLT using distance to LTC showed significant increased risk with the distance (P = 0.001 and P < 0.0001, respectively). At the same time, using RUCA classification as the variable did not show significance (P = 0.14 and P = 0.73, respectively). CONCLUSIONS: Distance from an LTC is a risk factor of mortality on the waitlist for OLT, whereas RUCA classification is not a significant factor.

Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases.

BACKGROUND: In patients with bilateral colorectal liver metastases (CLM) not resectable in 1 operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy. STUDY DESIGN: The study included all 109 patients for whom 2-stage hepatectomy for CLM was planned during 2003 to 2014. The RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis. RESULTS: Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after the first stage were disease progression (n = 12), insufficient liver growth (n = 5), and complications after first stage or portal vein embolization (n = 3). More than 6 cycles of preoperative chemotherapy were associated with failure to proceed to the second stage (p = 0.009). Rates of major complications (26% vs 6%; p < 0.001) and 90-day mortality (7% vs 0%; p = 0.006) were higher after the second stage. The cumulative rate of major complications was 15% (n = 29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than 1 lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs 6%; p < 0.001) and 5-year overall survival rates (49% vs 0%; p < 0.001) were better after 2-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p = 0.044), more than 5 CLMs (p = 0.043), need for chemotherapy after first stage (p = 0.046), and RAS mutation (p < 0.001). CONCLUSIONS: The RAS mutation independently predicts the oncologic efficacy of 2-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy.

Eradication of Missing Liver Metastases After Fiducial Placement.

BACKGROUND: The risk of colorectal liver metastases (CLM) disappearing on cross-sectional imaging has increased with advances in preoperative chemotherapy, but <50 % of disappearing CLM demonstrate complete pathological response. OBJECTIVE: The aim of this study was to evaluate the role of fiducial marker placement before potentially curative treatment of CLM at risk of disappearing with chemotherapy. METHODS: All consecutive patients who underwent fiducial placement for tracking of CLM at a tertiary center were reviewed. RESULTS: Among 1377 patients undergoing CLM resection between 2005 and 2015, 35 patients underwent fiducial placement. Three patients were excluded due to disease progression. The study population comprised 32 patients who underwent fiducial placement in 41 CLM. Among the 41 marked CLM, 34 (83 %) were located >10 mm deep in the liver parenchyma, 25 (61 %) were in the right liver, and median size was 12 mm (range, 6-20 mm). No complication occurred after fiducial placement. After chemotherapy, 19 (46 %) of the 41 marked metastases disappeared on cross-sectional imaging. All fiducial-tracked CLM were treated with resection (n = 31) or ablation (n = 10). After median follow-up of 14 months (range, 0-64 months), no local recurrences were observed. CONCLUSION: Fiducial placement represents a safe procedure that facilitates accurate localization for resection or ablation of small CLM at risk of disappearing with chemotherapy.

Evidence of Absorptive Function in vivo in a Neo-Formed Bio-Artificial Intestinal Segment Using a Rodent Model.

A promising therapeutic approach for intestinal failure consists in elongating the intestine with a bio-engineered segment of neo-formed autologous intestine. Using an acellular biologic scaffold (ABS), we, and others, have previously developed an autologous bio-artificial intestinal segment (BIS) that is morphologically similar to normal bowel in rodents. This neo-formed BIS is constructed with the intervention of naïve stem cells that repopulate the scaffold in vivo, and over a period of time, are transformed in different cell populations typical of normal intestinal mucosa. However, no studies are available to demonstrate that such BIS possesses functional absorptive characteristics necessary to render this strategy a possible therapeutic application. The aim of this study was to demonstrate that the BIS generated has functional absorptive capacity. Twenty male August × Copenhagen-Irish (ACI) rats were used for the study. Two-centimeter sections of ABS were transplanted in the anti-mesenteric border of the small bowel. Animals were studied at 4, 8, and 12 weeks post-engraftment. Segments of intestine with preserved vascular supply and containing the BIS were isolated and compared to intestinal segments of same length in sham control animals (n = 10). D-Xylose solution was introduced in the lumen of the intestinal segments and after 2 h, urine and blood were collected to evaluate D-Xylose levels. Quantitative analysis was performed using ELISA. Morphologic, ultrastructural, and indirect functional absorption analyses were also performed. We observed neo-formed intestinal tissue with near-normal mucosa post-implantation as expected from our previously developed model. Functional characteristics such as morphologically normal enterocytes (and other cell types) with presence of brush borders and preserved microvilli by electron microscopy, preserved water, and ion transporters/channels (by aquaporin and cystic fibrosis transmembrane conductance regulator (CFTR)) were also observed. The capacity of BIS containing neo-formed mucosa to increase absorption of d-Xylose in the blood compared to normal intestine was also confirmed. With this study, we demonstrated for the first time that BIS obtained from ABS has functional characteristics of absorption confirming its potential for therapeutic interventions.

Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome.

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 µm; medium 150-300 µm; small, <150 µm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.

Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases.

BACKGROUND: The optimal duration, safety, and benefit of preoperative chemotherapy in patients with colorectal liver metastases (CLM) are unclear. We evaluated the association between the duration of preoperative chemotherapy with 5-fluorouracil (5-FU), leucovorin, oxaliplatin (FOLFOX) ± bevacizumab, pathologic response, and hepatotoxicity after hepatic resection for CLM. METHODS: A total of 219 patients underwent hepatic resection following FOLFOX with or without bevacizumab and were divided into 2 groups according to the chemotherapy duration: 1-8 cycles (short duration [SD]; N = 157) and ≥9 cycles (long duration [LD]; N = 62). The frequency of complete or major pathologic response, sinusoidal injury, and major postoperative morbidity were compared. RESULTS: Treatment consisting of ≥9 cycles was not associated with an increase in complete or major pathologic response (SD vs. LD, 57% vs. 55%; P = .74). The incidence of sinusoidal injury was higher in the LD group (26% vs. 42%; P = .017). The incidence of liver insufficiency was higher in the LD group (4% vs. 11%; P = .035). Sinusoidal injury did not predict postoperative liver insufficiency; multivariate analysis revealed ≥9 cycles was the only independent predictor of postoperative liver insufficiency (P = .031; odds ratio = 3.90). Chemotherapy including bevacizumab was associated with a significantly higher frequency of complete or major response in both SD and LD groups. CONCLUSIONS: Extended preoperative chemotherapy increases the risk of hepatotoxicity in CLM without improving the pathologic response. The type of chemotherapy (FOLFOX with bevacizumab) has more impact on pathologic response than the duration of chemotherapy.

Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry.

OBJECTIVE(S): This study aimed to determine the effect of preoperative liver volumetry on postoperative outcomes after extended right hepatectomy. Primary end point was to evaluate whether future liver remnant (FLR)/standardized liver volume ratio (sFLR) >20% is sufficient for a safe hepatic resection. Secondary end point was to assess whether preoperative portal vein embolization (PVE) is associated with improved outcome in patients with initial sFLR ≤ 20%. BACKGROUND DATA: An sFLR >20% of the total liver volume has been proposed as sufficient for safe hepatic resection, but this concept has not been validated in a large series. In addition, recent reports suggest preoperative PVE is indicated for sFLR <30%. METHODS: The impact of sFLR and PVE on short-term outcomes (postoperative complications, liver insufficiency, and 90-day mortality) was analyzed in 301 consecutive patients after extended right hepatectomy. Liver volumetry accounted for partial resection of segment IV. Liver insufficiency was defined as peak postoperative serum bilirubin >7 mg/dL. Predictors of liver insufficiency were identified by multivariate logistic regression. RESULTS: Postoperative liver insufficiency occurred in 45 patients (15%) and accounted for 61% of deaths. Among 290 patients who underwent liver volumetry, sFLR was <20% in 38 patients, 20.1% to 30% in 144, and ≥ 30% in 108. Rates of postoperative liver insufficiency and death from liver failure were similar between patients with sFLR 20.1% to 30% and sFLR ≥ 30% but higher in patients with sFLR ≤ 20% (P 0.05). Postoperative outcomes were similar between patients with increase in sFLR from ≤ 20% to >20% after PVE and patients with initial sFLR >20%. Multivariate analysis revealed that body mass index >25 kg/m2, intraoperative blood transfusion, and sFLR ≤ 20% (odds ratio = 3.18; 95% CI, 1.34-7.54) independently predicted postoperative liver insufficiency. CONCLUSIONS: Systematic measurement of FLR volume is important to select patients for PVE and extended right hepatectomy. A sFLR >20% is sufficient for safe hepatic resection and sFLR 20.1% to 30% is not an indication for preoperative PVE.

Major hepatic resection for hepatocellular carcinoma with or without portal vein embolization: Perioperative outcome and survival.

BACKGROUND: Preoperative portal vein embolization (PVE) is performed to minimize perioperative risks of major hepatic resection for hepatocellular carcinoma (HCC), but its effects on tumor growth are ill defined. Perioperative outcome and survival after major hepatic resection for HCC, with and without PVE, were investigated. METHODS: Patients that underwent major hepatic resection (> or =3 segments) for HCC between January 1998 and May 2007 were analyzed retrospectively. Preoperative PVE was performed when the remnant liver volume was predicted to be insufficient. RESULTS: A total of 54 patients underwent major hepatic resection for HCC: 21 patients with PVE before resection (PVE group) and 33 patients without PVE (non-PVE group). PVE and non-PVE groups had similar rates of fibrosis or cirrhosis, hepatitis C virus, hepatitis B virus, American Joint Committee on Cancer stage, preoperative transarterial chemoembolization, overall postoperative complications, and positive margin (P = nonsignificant for all rates). There were no perioperative deaths in the PVE group and 6 (18%) deaths in the non-PVE group (P = .038). Median follow-up was 21 months. Excluding perioperative deaths, overall survival rates at 1, 3, and 5 years were 94%, 82%, and 72%, respectively, in the PVE group and 93%, 63%, and 54%, respectively, in the non-PVE group (P = .35). Similarly, disease-free survival (DFS) rates were not significantly different between the groups, with 1-, 3-, and 5-year DFS rates of 84%, 56%, and 56%, respectively, in the PVE group and 66%, 49%, and 49%, respectively, in the non-PVE group (P = .38). CONCLUSION: PVE before major hepatic resection for HCC is associated with improved perioperative outcome. Excluding perioperative mortality, overall survival and DFS rates were similar between patients with and without preoperative PVE.

Timing of multimodality therapy for resectable synchronous colorectal liver metastases: a retrospective multi-institutional analysis.

The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12-1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11-1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24-2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57-0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48-3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35-4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03-2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45-0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.

Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases.

PURPOSE: The primary goal of this study was to evaluate whether pathologic response to chemotherapy predicts patient survival after preoperative chemotherapy and resection of colorectal liver metastases (CLM). The secondary goal of the study was to identify the clinical predictors of pathologic response. PATIENTS AND METHODS: A retrospective review was performed of 305 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by resection of CLM. Pathologic response was systematically evaluated and reported as the mean of the percentage of cancer cells remaining within each tumor. Univariate and multivariate analyses were performed to identify the predictors of pathologic response and survival. RESULTS: Cumulative 5-year overall survival rates by pathologic response status were as follows: 75% complete response (no residual cancer cells), 56% major response (1% to 49% residual cancer cells), and 33% minor response (> or = 50% residual cancer cells; complete v major response, P = .037; major v minor response, P = .028). Multivariate analysis revealed that only surgical margin status (P = .050; hazard ratio [HR], 1.77) and pathologic response (major response: P = .034; HR, 4.80; minor response: P = .007; HR, 6.93) were independent predictors of survival. Multivariate analysis of the predictors of pathologic response revealed that carcinoembryonic antigen level < or = 5 ng/mL, tumor size < or = 3 cm, and chemotherapy with fluoropyrimidine plus oxaliplatin and bevacizumab were independent predictors of pathologic response. CONCLUSION: Pathologic response predicts survival after preoperative chemotherapy and resection of CLM. Degree of pathologic response represents a new outcome end point for prognosis after resection of CLM.

Chemotherapy with bevacizumab does not affect liver regeneration after portal vein embolization in the treatment of colorectal liver metastases.

BACKGROUND: Blockage of vascular endothelial growth factor (VEGF) in murine models has been shown to impair liver regeneration after partial hepatectomy. The aim of this study was to evaluate the effects of chemotherapy with or without bevacizumab (monoclonal antibody anti-VEGF) on liver regeneration after portal vein embolization (PVE) in the treatment of colorectal liver metastases and its possible effect on postoperative outcome after major liver resection. METHODS: Records of 65 consecutive patients treated with or without preoperative chemotherapy (with or without bevacizumab) and PVE for colorectal liver metastases from September 1995 to February 2007 were reviewed from a prospective database. Future liver remnant (FLR) volume, degree of FLR hypertrophy after PVE, morbidity, mortality, and survival were analyzed. RESULTS: Preoperative PVE was performed after chemotherapy in 43 patients and without chemotherapy in 22 patients. Among the 43 patients treated with chemotherapy, 26 received concurrent bevacizumab. After a median of 4 weeks after PVE, there was no difference in FLR volume increase among patients treated with or without chemotherapy. Similarly, there was no statistically significant difference in degree of FLR hypertrophy among patients treated without (mean, 10.1%) or with chemotherapy, with or without bevacizumab (8.8% and 6.8%) (P = .11). Forty-eight (74%) of 65 patients underwent extended right or right hepatectomy after PVE. No differences in morbidity and mortality were observed among patients treated with or without preoperative chemotherapy (with or without bevacizumab). CONCLUSION: Preoperative chemotherapy with bevacizumab does not impair liver regeneration after PVE. Liver resection can be performed safely in patients treated with bevacizumab before PVE.