Irinotecan Drug-Eluting Beads in the Treatment of Chemo-Naive Unresectable Colorectal Liver Metastasis with Concomitant Systemic Fluorouracil and Oxaliplatin: Results of Pharmacokinetics and Phase I Trial

Purpose

The primary objective of this study is to evaluate the safety, tolerance, and pharmacokinetic profile of liver-directed therapy with drug-eluting beads irinotecan (DEBIRI) in combination with systemic modified FOLFOX in the treatment of unresectable liver metastases in chemotherapy-naive patients with colorectal cancer.

Design

DEBIRI, loaded with 100?mg irinotecan (100?C300???m beads), was administered via hepatic artery during the off week of FOLFOX therapy. Primary endpoints were safety, tolerance, systemic dose-limiting toxicities, and pharmacokinetics of systemic irinotecan and its active metabolite SN-38 at each infusion at 1-, 4-, and 24-h post-DEBIRI. Secondary endpoints were response rate and survival.

Results

The ten patients have undergone at least 12 cycles of FOLFOX in combination with at least two DEBIRI bead treatments during the patients?? off week. Pharmacokinetic data has demonstrated minimal detectable levels of irinotecan (18.6, 21, and 18.6?ng/ml) and SN-38 (1.06, 1.47, and 1.55?ng/ml) after the first, second, and third DEBIRI treatments, respectively. Currently, there has been only one severe device-related adverse event, a grade 3 hypertensive episode that required 1?day of observation in the hospital. The initial 9- and 12-month response rates have been 100?% (2 CR, 8 PR). Four (40?%) patients were successfully downstaged to resection and/or ablation with a median overall survival of 15.2?months.

Conclusion

Concomitant DEBIRI and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.     

The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM): a single-centered retrospective study

Purposes

The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases.

Methods

Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy.

Results

Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95 % CI 38.13–75.73] and 25.07 months [95 % CI 17.87–32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95 % CI 8.82–31.65] months in the resected group.

Conclusion

Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.     

Influence of Modern Systemic Therapies as Adjunct to Cytoreduction and Perioperative Intraperitoneal Chemotherapy for Patients With Colorectal Peritoneal Carcinomatosis: A Multicenter Study

Background

To evaluate the role of modern systemic therapies and its role as palliative or curative therapy for patients with colorectal peritoneal carcinomatosis with an emphasis on patient selection with the colorectal Peritoneal Surface Disease Severity Score (PSDSS).

Methods

From three specialized treatment centers, patients with colorectal peritoneal carcinomatosis were identified between December 1988 to December 2009 to receive best supportive care, standard, or modern systemic therapies. Intent was classified as palliative or curative (if treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy). Patients were stratified according to the PSDSS. Survival was estimated by the Kaplan–Meier method.

Results

Palliative and curative treatment achieved a median survival of 9 (95% confidence interval [95% CI] 5.9–12.8) and 38 (95% CI 30.2–45.2) months, respectively (P < 0.001). The type of chemotherapy in the palliative and curative group influenced outcome (P < 0.001, P = 0.011, respectively). In the palliative group, PSDSS I/II had a median survival of 24 (95% CI 15.6–32.6) and PSDSS III/IV had a median survival of 6 (95% CI 4.9–8.0) months (P < 0.001). In the curative group, PSDSS I/II had a median survival of 49 (95% CI 40.0–58.3) and PSDSS III/IV had a median survival of 31 (95% CI 20.4–40.9) months (P = 0.002).

Conclusions

Modern systemic therapies were associated with improved outcome in patients with colorectal peritoneal carcinomatosis treated systemically alone or with cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Preoperative evaluation with the PSDSS may improve patient selection and optimize outcomes.     

Trends in Treatment and Survival in Older Patients Presenting with Stage IV Colorectal Cancer

Introduction

Trends in the use of modern chemotherapeutic regimens, primary tumor resection, and the timing of chemotherapy and resection in older patients with stage IV colorectal cancer have not been evaluated.

Methods

We used Cancer Registry- and Medicare-linked data (2000–2009) to describe time trends in resection of the primary tumor and receipt of chemotherapy in patients ≥66 presenting with stage IV colorectal cancer (N?=?16,168).

Results

The mean age was 77.8?±?7.3 years; 53.8 % were women and 82.9 % were white. Primary cancer sites were colon in 83.4 % and rectum in 16.6 %. Resection of the primary tumor decreased from 64.6 to 57.1 % (P?<?0.0001) from 2001 to 2009. Systemic chemotherapy was given to 45.1 % of the patients. While the use of chemotherapy was stable over time (P?=?0.48), the use of modern regimens containing oxaliplatin or irinotecan increased from 40.9 to 75.4 % (P?<?0.0001). Bevacizumab use increased from 0.10 to 54.2 % (P?<?0.0001). Survival improved by 4 % per year even after controlling for treatment and tumor location (HR?=?0.96, 95 % CI 0.95–0.97).

Conclusions

Survival in older patients with stage IV disease is improving over time. Surgical resection is still performed in the majority of patients. Resection rates decreased while modern chemotherapy was rapidly adopted perhaps suggesting a shift in practice patterns.     

Outcomes in Patients with Obstructive Jaundice from Metastatic Colorectal Cancer and Implications for Management

Introduction

Patients with metastatic colorectal cancer can develop jaundice from intrahepatic or extrahepatic causes. Currently, there is little data on the underlying causes and overall survival after onset of jaundice. The purpose of this study was to characterize the causes of jaundice and determine outcomes.

Methods

Six hundred twenty-nine patients treated for metastatic colorectal cancer between 2004 and 2010 were retrospectively reviewed. Those developing jaundice were grouped as having intrahepatic or extrahepatic obstruction. Demographics, clinicopathologic, and outcome data were analyzed.

Results

Sixty-two patients with metastatic colorectal cancer developed jaundice. Intrahepatic biliary obstruction was most common, occurring in younger patients. Time from metastatic diagnosis to presentation of jaundice was similar between groups, as was the mean number of prior lines of chemotherapy. Biliary decompression was successful 41.7 % of the time and was attempted more commonly for extrahepatic causes. Median overall survival after onset of jaundice was 1.5 months and it was similar between groups, but improved to 9.6 months in patients who were able to receive further chemotherapy.

Conclusions

Jaundice due to metastatic colorectal cancer is an ominous finding, representing aggressive tumor biology or exhaustion of therapies. Biliary decompression is often difficult and should only be pursued when additional treatment options are available.     

Predictors for Early Recurrence After Hepatectomy for Initially Unresectable Colorectal Liver Metastasis

Background

Early recurrence correlates with poor survival following various cancer surgeries and puts considerable stress on patients both physically and mentally. This retrospective study investigated the predictive factors for early recurrence after surgical resection for initially unresectable colorectal liver metastasis to elucidate indications for conversion strategies.

Methods

We retrospectively studied 46 patients who underwent hepatectomy after chemotherapy for initially unresectable colorectal liver metastasis from 1997 to 2010.

Results

Recurrences occurred within 6 months after hepatectomy in 13 patients (37 %). The median survival time of 21.2 months and the 5-year survival rate of 0 % after hepatectomy in patients with recurrence within 6 months were significantly worse than those in patients with recurrence more than 6 months after hepatectomy. Recurrence in less than 6 months was significantly correlated with impossibility of anticancer therapy for recurrence after hepatectomy (p?=?0.01). Eight or more hepatic tumors after chemotherapy were the only predictor of recurrence within 6 months (p?=?0.01; odds ratio 9.6; 95 % confidence interval 1.5–60.6).

Conclusion

Recurrence within 6 months was significantly correlated with a poorer outcome following surgery for initially unresectable colorectal liver metastasis. Surgical indication for initially unresectable colorectal liver metastasis with eight or more hepatic tumors after chemotherapy should be considered carefully in the light of mental and physical status, co-morbidity, and alternative treatment plans.     

Discrete Improvement in Racial Disparity in Survival among Patients with Stage IV Colorectal Cancer: a 21-Year Population-Based Analysis

Purpose

Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent.

Patients and Methods

Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988–2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses.

Results

Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p?<?0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991–1.000) per year (p?=?0.03).

Conclusion

A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.     

Modular therapy approach in metastatic castration-refractory prostate cancer

Purpose

The present multi-center phase II study was designed to support the hypothesis that networking agents, which bind to ubiquitous accessible targets in metastatic castration-refractory prostate cancer (CRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating PSA response (primary endpoint).

Method

Patients with metastatic CRPC received low-dose chemotherapy with capecitabine 1 g twice daily plus dexamethasone 1 mg daily for 14 days every 3 weeks, COX-2 blockade with rofecoxib 25 mg (or etoricoxib 60 mg) daily combined with pioglitazone 60 mg daily until disease progression.

Results

Thirty-six consecutive patients with metastatic CRPC were enrolled, of whom n = 18 (50%) had been extensively pretreated with radio- or radionuclid therapy and n = 16 (44%) with chemotherapies; n = 8 patients (22%) were medically none-fit, having an ECOG-score of 0–2. Nine of 15 patients with PSA response >50% showed objective response. Median time to PSA response was 2.4 months (range 1.0–7.3 months). Two of 9 patients responding with PSA < 4 ng/ml showed complete resolution of skeletal lesions after 9 and 16 months; 13 patients had a stable course of disease, and 5 patients experienced progressive disease. Median progression-free survival (PFS) was 4.0 months (2.8–5.1 months) and median overall survival (OS) 14.4 months (10.7–17.2 months). Toxicities according to WHO grade II were noticed in 9 patients.

Conclusions

This new combined modular therapy approach is able to induce major responses including resolution of skeletal lesions in patients with CRPC. Furthermore, the study may clinically support the above-mentioned hypothesis.     

Conversion to Complete Resection and/or Ablation Using Hepatic Artery Infusional Chemotherapy in Patients with Unresectable Liver Metastases from Colorectal Cancer: A Decade of Experience at a Single Institution

Background

When feasible, surgical treatment of colorectal liver metastases (CRLM) is the treatment of choice. Regional hepatic artery infusional (HAI) chemotherapy effectively treats CRLM. The combination of HAI and systemic chemotherapy may downsize tumors and allow for complete resection and/or ablation (R/A). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on conversion to complete R/A.

Methods

All patients with unresectable CRLM treated with HAI and systemic chemotherapy from 2000 to 2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Survival was compared using a landmark analysis to account for bias.

Results

A total of 373 patients were included; 93 patients (25 %) subsequently underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16 % during 2000–2003 to 30 % during 2004–2009. Factors associated with conversion on multivariate analysis were more recent treatment (2004–2009), no prior chemotherapy, clinical risk score <3, treatment on clinical protocol, and younger age. Median and predicted 5-year survival from the time of HAI pump placement was 59 months and 47 %, respectively, in the patients who converted to complete R/A, compared with 16 months and 6 %, respectively in those who did not (p < 0.001).

Conclusions

Despite extensive disease, 25 % of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Combination HAI and systemic chemotherapy is an effective strategy to convert patients to complete resection with an associated excellent long-term survival.     

Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer

Purpose

We evaluated the need for primary tumor resection in patients with colorectal cancer (CRC) and synchronous unresectable metastases who underwent chemotherapy, and identified the associations between the primary tumor characteristics and risk of intestinal obstruction or perforation.

Methods

We retrospectively analyzed the survival and complication rates of patients with synchronous metastatic CRC treated between April 2005 and December 2011.

Results

Of 131 patients, 68 underwent primary tumor resection before chemotherapy, and 63 were treated without resection before chemotherapy. The overall survival (OS) did not significantly differ between the two groups (log-rank P = 0.53). In the resection group, 12 patients (17.6 %) developed postoperative complications. In the non-resection group, 16 patients (25.4 %) required surgical intervention owing to obstruction or perforation during their treatment. Surgical intervention did not affect the OS. A circumferential tumor was a risk factor for obstruction or perforation of the colorectum in non-resected patients (odds ratio = 11.163; P = 0.006).

Conclusion

Resection of primary tumors before chemotherapy is unnecessary in selected patients with synchronous metastatic colorectal cancer. A circumferential tumor is a risk factor for obstruction or perforation during chemotherapy in cases without primary tumor resection.     

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Background

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population.

Methods

Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m²) or mitomycin C (35 mg/m²). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis.

Results

Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019).

Conclusions

Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.     

Cytoreduction and HIPEC in The Netherlands: Nationwide Long-term Outcome Following the Dutch Protocol

Purpose

This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol.

Methods

In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival.

Results

Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III–V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0–166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36–46 months). Median progression-free survival was 15 months (95 % CI 13–17 months) for CRC patients and 53 months (95 % CI 40–66 months) for PMP patients. Overall median survival was 33 (95 % CI 28–38 months) months for CRC patients and 130 months (95 % CI 98–162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients.

Conclusions

The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.     

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Background

Approximately 20 % of patients diagnosed with colorectal cancer will have distant metastases at first presentation (stage IV disease). The effect of removing the primary tumor on survival for patients with stage IV disease with unresectable metastases remains unclear. To address this a meta-analysis of all studies comparing primary tumor resection with chemotherapy alone in cases of stage IV colorectal cancer with unresectable metastases was performed.

Methods

A comprehensive search for published studies examining the effect of primary tumor resection in the setting of colorectal cancer with unresectable metastases was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data.

Results

There were 21 studies including a total of 44,226 patients that met the inclusion criteria. Resection of the primary tumor in patients with unresectable metastases compared with chemotherapy alone was associated with a lower mortality risk (OR 0.28; 95 % CI 0.165–0.474; P < 0.001), translating into a difference in mean survival of 6.4 months in favor of resection (95 % CI 5.025–7.858, P < 0.001). Patients who underwent resection of the primary tumor were more likely to have liver metastasis only (OR 1.551; 95 % CI 1.247–1.929; P < 0.001), were less likely to have ≥2 metastasis (OR 0.653; 95 % CI 0.508–0.839; P = 0.001), and were less likely to have rectal cancer (OR 0.495; 95 % CI 0.390–0.629; P < 0.001). There was significant cross-study heterogeneity.

Conclusions

Resection of the primary tumor may confer a survival advantage in stage IV colorectal cancer with unresectable metastases but significant selection bias exists in current studies. Randomized controlled trials are essential to validate these findings.     

Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan

Purposes

This retrospective study evaluated the treatment outcomes and clinical relevance of the KRAS mutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy.

Methods

The subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, the KRAS mutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened for KRAS mutations using direct sequencing.

Results

A detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3–4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively; P = 0.03). A KRAS mutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively; P = 0.018).

Conclusions

The present results indicated the clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.     

Bevacizumab Doubles the Early Postoperative Complication Rate after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis of Colorectal Origin

Background

Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.

Methods

From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.

Results

The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6–10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05–4.95) (p = 0.04).

Conclusions

Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.     

Potential value of sonazoid-enhanced intraoperative laparoscopic ultrasonography for liver assessment during laparoscopy-assisted colectomy

Purpose

Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colorectal cancer. However, conventional palpation of the liver and adequate observation of the abdominal cavity are not achievable during LAC. The aim of this study was to assess the clinical value of using Sonazoid (contrast enhanced)-intraoperative laparoscopic ultrasonography (S-IOLUS) in patients with primary colorectal cancer.

Methods

From May 2005 to August 2008, 454 patients underwent 339 LACs and 115 open colectomies for colorectal cancer. One hundred forty-eight patients with clinical stage II or III colorectal cancer, as determined by preoperative imaging, who were undergoing LACs were prospectively enrolled.

Results

Although IOLUS did not detect any lesions, small hypoechoic lesions were detected by the S-IOLUS (n = 71) in the Kupffer-phase view of two patients (2.8 %). None of the 71 patients who underwent S-IOLUS showed liver metastases within 6 months after LAC. In the conventional IOLUS group (n = 77), metastatic lesions were identified in two patients (2.6 %). The new liver metastases in these two patients were detected within 6 months after LAC.

Conclusions

S-IOLUS of the liver during colorectal cancer surgery is useful for staging and as a diagnostic modality. It can identify lesions that are undetectable by preoperative imaging, and may be considered for routine use during LAC.     

A Retrospective Review of 126 High-Grade Neuroendocrine Carcinomas of the Colon and Rectum

Background

High-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum are rare, constituting less than 1 % of colorectal cancers. The purpose of this study was to identify the natural history and oncologic outcomes of this disease, describe the use of surgery, and determine the clinical and pathological factors associated with outcomes.

Methods

Following Institutional Review Board approval, patients with HGNEC were identified from our institutional database. Patient charts and pathology reports were analyzed retrospectively for clinical and pathological factors.

Results

A total of 126 patients with a median follow-up of 9 months were identified. Median survival was 13.2 months, and 85 (67 %) patients had metastatic disease at diagnosis. Three-year overall survival (OS) was 5 and 18 % for patients with and without metastatic disease, respectively. Factors associated with improved OS on multivariable analysis were absence of metastatic disease and presence of an adenocarcinoma component within the tumor. In patients with metastatic disease, response to chemotherapy was the only factor associated with survival. In patients with localized disease, an adenocarcinoma component within the tumor was the only factor associated with survival. Resection of tumor was not associated with survival in either localized or metastatic disease.

Conclusion

High-grade colorectal NECs are extremely aggressive tumors with poor prognosis. Patients appear to have a marginally better prognosis if they present without metastatic disease, have an adenocarcinoma component within their tumor, or respond to chemotherapy. Surgery, particularly in the presence of metastatic disease, may not offer a survival benefit for the majority of patients.     

Association Between Palliative Resection of the Primary Tumor and Overall Survival in a Population-Based Cohort of Metastatic Colorectal Cancer Patients

Background

The impact of palliative resection of the primary tumor on outcomes in patients with metastatic colorectal cancer (mCRC) remains unclear. The primary objective of this study was to evaluate the association between palliative resection and overall survival (OS) in a population-based cohort of mCRC.

Methods

Patients diagnosed with mCRC between 2006 and 2008 and treated at the BC Cancer Agency were reviewed. Survival analysis was conducted using Kaplan–Meier methods. Cox proportional hazards regression models were fitted to evaluate the relationship between palliative resection and OS while controlling for potential confounders, such as age, gender, Eastern Cooperative Oncology Group status, carcinoembryonic antigen level, primary tumor location, metastatic site and number, and receipt of systemic therapy. To adjust for the heterogeneity and selection bias between the group that underwent palliative resection and the group that did not, a propensity score–matched analysis was also performed.

Results

A total of 517 patients were included. Among these cases, 378 (73 %) patients underwent palliative resection of their primary tumor, and 139 (27 %) patients did not. A total of 327 patients (63 %) were treated with palliative chemotherapy. Palliative resection was associated with a longer median OS (17.9 vs. 7.9 months) and more favorable unadjusted and adjusted hazard ratios (HRs) for death (HR 0.46, 95 % CI 0.37–0.56, p < 0.0001 and HR 0.56, 95 % CI 0.40–0.78, p = 0.0007, respectively) when compared with no resection. In a propensity score–matched analysis, prognosis was also more favorable in the resected group (p = 0.0017).

Conclusions

In this cohort of mCRC patients, palliative resection of the primary tumor was associated with improved OS.     

Benefit of Surgical Resection of the Primary Tumor in Patients Undergoing Chemotherapy for Stage IV Colorectal Cancer with Unresected Metastasis

Purpose

Resection of the primary tumor in patients with unresected metastatic colorectal cancer is controversial, and often performed only for palliation of symptoms. Our goal was to determine if resection of the primary tumor in this patient population is associated with improved survival.

Methods

This is a retrospective cohort study of the National Cancer Data Base from 2004 to 2012. The study population included all patients with synchronous metastatic colorectal adenocarcinoma who were treated with systemic chemotherapy. The study groups were patients who underwent definitive surgery for the primary tumor and those who did not. Patients were excluded if they had surgical intervention on the sites of metastasis or pathology other than adenocarcinoma. Primary outcome was overall survival.

Results

Of the 65,543 patients with unresected stage IV colorectal adenocarcinoma undergoing chemotherapy, 55% underwent surgical resection of the primary site. Patients who underwent surgical resection of the primary tumor had improved median survival compared to patients treated with chemotherapy alone (22 vs 13 months, p < .0001). The surgical survival benefit was present for patients who were treated with either multi-agent or single-agent chemotherapy (23 vs 14 months, p < 0.001; 19 vs 9 months, p < 0.001). Surgical resection of the primary tumor was also associated with improved survival when using multivariate analysis with propensity score matching (OR = 0.863; 95% CI [0.805–.924]; HR = 0.914; 95% CI [0.888–0.942]).

Conclusions

Our results show that in patients with synchronous unresected stage IV colorectal adenocarcinoma undergoing single- or multi-agent chemotherapy, after adjusting for confounding variables, definitive resection of the primary site was associated with improved overall survival. Large randomized controlled trials are needed to determine if there is a causal relationship between surgery and increased overall survival in this patient population.

     

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis

Purposes

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.

Methods

Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.

Results

A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).

Conclusion

Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.