The purpose of this phase II trial was to determine the efficacy and safety of the XELOX (capecitabine/oxaliplatin) regimen as firstline therapy in the elderly patients with metastatic colorectal cancer (MCRC). A total of 50 patients with MCRC aged X70 years received oxaliplatin 130 mg m À2 on day 1 followed by oral capecitabine 1000 mg m À2 twice daily on days 1 -14 every 3 weeks. Patients with creatinine clearance 30 -50 ml min À1 received a reduced dose of capecitabine (750 mg m À2 twice daily). By intentto-treat analysis, the overall response rate was 36% (95% CI, 28 -49%), with three (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months (95% CI, 3.9 -7.8 months) and 13.2 months (95% CI, 7.6 -16.9 months), respectively. Capecitabine was well tolerated: grade 3/4 adverse events were observed in 14 (28%) patients: 11 (22%) diarrhoea, eight (16%) asthenia, seven (14%) nausea/vomiting, three (6%) neutropenia, three (6%) thrombocytopenia, and two (4%) hand -foot syndrome. There was one treatment-related death from diarrhoea and sepsis. In conclusion, XELOX is well tolerated in elderly patients, with respectable efficacy and a meaningful clinical benefit response. Given its ease of administration compared with combinations of oxaliplatin with 5-FU/LV, it represents a good therapeutic option in the elderly.

The epithelial appendiceal neoplasms are uncommon and are usually detected as an unexpected surgical finding. The general surgeon should be aware of the diversity of its clinical manifestations and biological behaviors along with the significance of the surgical treatment on the progression of the illness and the prognosis of the patients. The operative findings and, especially, tumor histology, determine the type of surgery. Intestinal histologic subtype behaves and should be treated similarly to the right colon neoplasms; while mucinous tumors, often discordant between histology and its aggressiveness, can be treated with a simple appendectomy or require complex oncological surgeries. Mucinous tumors are often associated with the presence of mucin or tumor implants in the abdominal cavity, being the clinical syndrome known as pseudomyxoma peritonei (PMP). PMP tends to present an indolent but deadly evolution and requires a multimodal approach as a single treatment with curative potential: complete cytoreductive surgery plus hyperthermic Intra-peritoneal chemotherapy (CCRS + HIPEC) now considered the standard of care in this pathology. The general surgeon should be aware of the governing principles of the treatment of appendiceal neoplasms with or without peritoneal dissemination, know the therapeutic frontiers in every situation (avoiding unnecessary or counterproductive surgeries) and sending early these patients to specialised centres in the radical management of malignant diseases of the peritoneum in the conditions and with the necessary information to facilitate a possible radical treatment.

Peritoneal carcinomatosis (PC) is a common form of tumour metastasis stemming from gastrointestinal and colorectal cancers. For a long time, PC has been considered a terminal clinical condition treated only with palliative systemic chemotherapy and associated with very limited results. During the last decade, the treatment of advanced colorectal disease has greatly improved with the emergence of new chemotherapy drugs and biological agents. However, the median survival rates still do not surpass 24 months, even though most of these studies correspond to groups of patients with metastatic disease to the liver and/or lung. The approach and development of cytoreductive radical surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) are based on performing radical surgery of the entire visible tumour within the abdomen/peritoneum, followed immediately by HIPEC, which acts upon microscopic tumour that remains present after surgery and which is responsible for the persistence or relapse of peritoneal disease. Peritonectomy procedures are demanding surgical techniques that permit elimination of the tumour present in the peritoneal lining and any other organs and/or structures that are infiltrated. The synergistic effect of hyperthermia and chemotherapy has been well documented. Hyperthermia increases the cytotoxicity of some cytostatic agents and increases the penetration of certain drugs into the neoplastic cells. The prognosis for patients with PC who undergo combined treatment correlates with the volume of PC (tumour burden) measured as the Peritoneal Cancer Index (PCI) and the ability to perform a CRS, to completely eliminate the gross tumour. At least one phase III study and an important number of phase II studies have shown that CRS + HIPEC provides important survival benefits for patients with PC of colorectal origin. The combination of CRS + HIPEC is indicated for patients with good general health, a low PCI, absence of extra-abdominal metastasis and who can, technically, undergo CRS. The early identification of this group of patients, rapid referral to centres specialised in CRS + HIPEC, together with the correct application of this treatment, are key in achieving the best results.

Purpose: Chemotherapy plus anti-EGFR is standard first-line therapy in RAS wt metastatic colorectal cancer (mCRC) but biomarkers of early response are clinically needed. We aimed to define the utility of ctDNA to assess early response in mCRC patients receiving first-line anti-EGFR therapy. Experimental Design: Prospective multicentric study of tissue RAS wt mCRC patients treated with first-line chemotherapy plus cetuximab undergoing sequential liquid biopsies. Baseline and early (C3) ctDNA were analyzed by NGS. Trunk mutations were assessed as surrogate marker of total tumor burden. RAS/BRAF/MEK/EGFR-ECD were considered mutations of resistance. ctDNA results were correlated with clinical outcome. Results: 100 patients were included. ctDNA was detected in 72% of patients baseline and 32% at C3. Decrease in ctDNA trunk mutations correlated with progression-free survival (PFS) (HR= 0.23 P=0.001). RAS/BRAF were the only resistant mutations detected at C3. An increase in the relative fraction of RAS/BRAF at C3 was followed by an expansion of the RAS clone until PD, and was associated with shorter PFS (HR= 10.5, P<0.001). The best predictor of response was combined analysis of trunk and resistant mutations at C3. Accordingly, patients with “early molecular response” (decrease in trunk and decrease in resistant mutations) had better response (77.5% vs. 25%, P=0.008) and longer PFS (HR=0.18, P<0.001) compared to patients with “early molecular progression” (increase in trunk and/or increase in resistant mutations). Conclusions: ctDNA detects early molecular response and predicts benefit to chemotherapy plus cetuximab. A comprehensive NGS-based approach is recommended to integrate information on total disease burden and resistant mutations.