Manuel J. Koppe

Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies.

Objective:To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). Summary Background Data:Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC. Methods:The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC. Results:The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment. Conclusions:Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.

Antibody-guided radiation therapy of cancer.

SummaryRadioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens has evolved from an appealing concept to one of the standard treatment options for patients with non-Hodgkins lymphoma (NHL). Inefficient localization of radiolabeled MAbs to nonhematological cancers due to various tumor-related factors, however, has refrained RIT from outgrowing the experimental stage in solid tumors. Still, small volume or minimal residual disease has been recognized as a potentially suitable target for radiolabeled antibodies. Several strategies are being explored aimed at improving the targeting of radiolabeled MAbs to solid tumors thus improving their therapeutic efficacy. In this review, a historical overview of the application of RIT is given and various aspects of the application of radiolabeled MAbs as anti-cancer agents are discussed. Finally, the clinical results of RIT of NHL, colorectal cancer, ovarian cancer, breast cancer, and renal cell cancer are reviewed.

Experimental radioimmunotherapy of small peritoneal metastases of colorectal origin

Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor‐associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti‐CEA MoAb MN‐14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose‐escalation study was carried out to determine the maximal dose of radioiodinated MN‐14 to be used in radioimmunotherapy. The biodistribution of radioiodinated MN‐14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of 131I‐labeled MN‐14 (62.5–500 μCi) was assessed and compared to that of unlabeled MN‐14 or 500 μCi of 131I‐labeled irrelevant control antibody. At protein doses higher than 25 μg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN‐14) and 52 days (131I‐labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of 131I‐labeled MN‐14 was 42 days (62.5 μCi), 49 days (125 μCi), 63 days (250 μCi) and 101 days (500 μCi), respectively (p < 0.0001 compared to unlabeled MN‐14). The present study shows that the anti‐CEA‐antibody MN‐14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal radioimmunotherapy using 131I‐labeled MN‐14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.

Recent insights into the pathophysiology of omental metastases

Although, useful in inflammatory conditions, the greater omentum represents an important site of metastasis in peritoneal carcinomatosis and is therefore frequently removed as a staging or therapeutic tool. Apart from the milky spots, omental adipose stem cells, and adipocytes have recently been identified to play a role in the preferential homing of tumor cells to the omentum. The extent of omentectomy and whether a routine omentectomy should be done are still known unknowns. J. Surg. Oncol. 2014 110:670–675.