Elisa Sperti

Asymptomatic Colorectal Cancer with Un-Resectable Liver Metastases: Immediate Colorectal Resection or Up-Front Systemic Chemotherapy?

BackgroundAbout 20% of patients with colorectal cancer have synchronous un-resectable liver metastases. Resection of colorectal cancer in patients with moderate-severe symptoms is mandatory before starting chemotherapy. Surgical treatment of asymptomatic colorectal cancers is still a matter of discussion.MethodsFrom January 2000 to December 2004, we prospectively collected data on 35 consecutive patients who were treated straightaway by chemotherapy without primary tumor resection. All patients underwent FOLFOX6 as first-line chemotherapy. The aim of the study was to evaluate the rate of surgical complications related to un-resected colorectal tumor.ResultsThe mean interval between diagnosis and start of chemotherapy was 23.1 days (95% CI: 17.3–28.8). Fifteen of the 35 patients (42.9%) were down-staged to surgery; the mean interval between chemotherapy start and colon-rectum cancer resection was 6.5 months (95% CI: 5.5–7.5). None of them developed complications related to the primary tumor during chemotherapy. Of the other 20 patients who did not undergo any curative surgery, 16 received a second line chemotherapy and 10 a third line: six patients are alive and without intestinal symptoms (mean follow up 22.5 months, 95% CI: 11.2–33.9). Only one patient (2.8%) developed clinical signs of intestinal occlusion 5.6 months from the start of chemotherapy and required urgent colostomy.ConclusionsThe rate of complications related to the non-resected colorectal tumor is very low using oxaliplatin as first line chemotherapy. Non-operative management of asymptomatic colorectal cancers with un-resectable liver metastases is a safe approach.

Induction Gemcitabine and Oxaliplatin Therapy Followed by a Twice-Weekly Infusion of Gemcitabine and Concurrent External-Beam Radiation for Neoadjuvant Treatment of Locally Advanced Pancreatic Cancer A Single Institutional Experience

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol.

Safety and activity of docetaxel and trastuzumab in HER2 overexpressing metastatic breast cancer: a pilot phase II study.

We conducted a pilot phase II trial of trastuzumab administered concurrently with docetaxel in women with HER2-overexpressing advanced breast cancer. Twenty-five women with HER2-positive (3+ by immunohistochemistry = 16, 2+ = 9) metastatic breast cancer received docetaxel (75 mg/m2 every 3 weeks for 6 cycles) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter). Twenty-three patients (92%) had visceral metastatic involvement. Twenty-three patients had received prior chemotherapy as part of adjuvant (18), metastatic (2), and both (3) treatment. The number of cycles administered was 121 (median 6, range 1–6). Symptomatic cardiotoxicity (GIII) occurred in one patient. The most common grade GIII/IV toxicity was neutropenia (80% of the cycles), although febrile neutropenia did not occur. No other GIII/IV toxicities were observed. Response rate was 70% (1 complete response and 15 partial responses) in 23 evaluable patients. The combination of docetaxel and trastuzumab is well tolerated and has clinically meaningful antitumor activity.

The Role of Lung Metastasis Resection in Improving Outcome of Colorectal Cancer Patients: Results From a Large Retrospective Study

BACKGROUND The role of surgery for lung metastases (LM) secondary to colorectal cancer (CRC) remains controversial. The bulk of evidence is derived from single surgical series, hampering any definitive conclusions. The aim of this study was to compare the outcomes of CRC patients with LM submitted to surgery with those who were not. PATIENTS AND METHODS Data from 409 patients with LM as the first evidence of advanced disease were extracted from a database of 1,411 patients. Patients were divided into three groups: G1, comprised of 155 patients with pulmonary and extrapulmonary metastases; G2, comprised of 104 patients with LM only and no surgery; G3, comprised of 50 patients with LM only and submitted to surgery. RESULTS No difference in response rates emerged between G1 and G2. Median progression-free survival (PFS) times were: 10.3 months, 10.5 months, and 26.2 months for G1, G2, and G3, respectively. No difference in PFS times was observed between G1 and G2, whereas there was a statistically significant difference between G2 and G3. Median overall survival times were 24.2 months, 31.5 months, and 72.4 months, respectively. Survival times were longer in resected patients: 17 survived >5 years and three survived >10 years. In patients with LM only and no surgery, four survived for 5 years and none survived >10 years. CONCLUSIONS Even though patients with resectable LM are more likely to be those with a better outcome, our study provides evidence suggesting an active role of surgery in improving survival outcomes in this patient subset.

Resection of liver metastases from colorectal mucinous adenocarcinoma: Is this a different disease? Results of a case-control study

Objectives:To compare outcomes following liver resection of colorectal metastases (CRLM) from mucinous adenocarcinoma (Muc-CRLM) versus nonmucinous adenocarcinoma (non-Muc-CRLM). Background:Among colorectal adenocarcinomas, 10%–15% are mucinous and have worse prognoses than nonmucinous ones. Outcomes of liver resection for Muc-CRLM remain unknown. Methods:Among 701 patients undergoing liver resection for CRLM between 1998 and 2012, 102 (14.6%) had Muc-CRLM. Each was matched with a non-Muc-CRLM patient, based on tumor N status, disease-free interval (DFI) between primary tumor and metastases, CRLM number and diameter, extrahepatic disease, and preoperative chemotherapy. Results:Within the 2 groups, 69.6% of patients had N+ primary tumor, 72.5% had DFI of less than 12 months, 28.4% had 4 or more CRLM, and 22.5% had associated extrahepatic disease. 59.8% of patients received preoperative chemotherapy. Muc-CRLM patients had higher prevalences of right/transverse colon cancer (55.9% vs 29.4%; P < 0.0001) and K-ras mutation (67 patients tested, 61.8% vs 36.4%; P = 0.037), as well as lower response to preoperative chemotherapy (63.9% vs 85.2%; P = 0.006). Multivariate analysis showed Muc-CRLM to have lower rates of 5-year overall (33.2% vs 55.2%; P = 0.010) and disease-free survival (32.5% vs 49.3%; P = 0.037). Muc-CRLM recurrence was more often peritoneal (20.3% vs 6.5%; P = 0.024) and at multiple sites (47.5% vs 21.0%; P = 0.002), and had lower rates of re-resection (16.9% vs 43.5%; P = 0.002) and 3-year post-recurrence survival (11.7% vs 43.4%; P = 0.0003). Conclusions:Muc-CRLM patients strongly differed from non-Muc-CRLM patients, showing a lower chemotherapy response and higher K-ras mutation prevalence. Muc-CRLM appears to be a separate disease, which is associated with worse survival and aggressive rarely re-resectable recurrences.

Neoadjuvant oxaliplatin-based chemotherapy for liver metastases from colorectal cancer. An Italian survey.

Background Only 10% to 25% of patients with liver metastases from colorectal cancer are suitable for resection. Methods for increasing the resectability of liver metastases are based on specific surgical techniques and neoadjuvant chemotherapy. Methods We collected retrospective data on patients from various Italian hospitals from 1996 to 2002. Data from colorectal cancer patients with liver metastases treated with oxaliplatin-based neoadjuvant chemotherapy were considered. Analysis focused on patients and treatment description and on long-term survival. We considered 107 patients from 36 Italian hospitals. Results Of the 105 patients assessable for response, 8.4% achieved a complete response, 70.1% a partial response and 19.6% stable disease. Ninety-nine patients were treated with surgery for liver metastases. A radical resection was achieved in 79% of patients. Median survival time was 42 months. Thirteen patients experienced grade 3-4 hematologic toxicity, and 10 patients had grade 3-4 nonhematologic toxicity. Neurologic toxicity of grade >1 was observed in 21% of patients. Conclusions Neoadjuvant chemotherapy can be useful to increase the number of liver resections for metastatic colorectal cancer patients. Nevertheless, randomized trials are necessary to confirm this retrospective survey as well as the few single-institution experiences reported so far in the medical literature.

Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis

According to current ESMO - MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.