Megan Greally

Comparing Clinical Characteristics and Outcomes of Young-onset and Late-onset Colorectal Cancer: An International Collaborative Study

Micro‐Abstract Colorectal cancer in young patients is often diagnosed late, at advanced stages. These patients have more resistant and aggressive disease, despite similar clinical treatment patterns compared with those with late‐onset disease. Background Compared with the general population, the incidence of young‐onset (YO) colorectal cancer (CRC) is increasing. However, a significant knowledge gap exists in the clinical characteristics, treatment patterns, and outcomes for these patients. Materials and Methods Six international tertiary cancer centers conducted a retrospective study. Patients with YO CRC (aged 18‐44 years) and LO CRC (aged > 44 years) diagnosed with histologically proven colorectal adenocarcinoma from June 2003 to June 2014 were enrolled. Patients were randomly chosen from each centers database, and the patient demographics and treatment information were collected. The data were then centralized, and the final analysis was performed at a single institution. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for progression‐free survival and mortality, and YO was compared with LO. Site‐specific HRs were pooled using a random‐effects meta‐analysis. Results Overall, 498 patients, including 224 with YO (129 men; mean age, 37 ± 5.5 years) and 274 with LO (167 men; mean age, 64.8 ± 9.5 years) CRC, were included. At the diagnosis, 137 patients (61.2%) and 122 patients (44.5%) with YO and LO CRC had metastatic disease, respectively. For both cohorts, the 3 most common presenting symptoms were pain, hematochezia, and weight loss. Surgery was performed in 141 YO (63.0%) and 219 LO (79.9%) patients. The longitudinal noncurative treatment patterns were similar, but more biologic therapy was used for these YO patients. The pooled progression‐free survival analysis results for first‐line noncurative treatment favored LO (HR, 1.96; 95% CI, 1.04‐3.68). The mortality analysis showed no significant differences between the 2 groups (YO: HR, 1.53; 95% CI, 0.91‐2.58). Conclusion Despite similar treatment patterns and survival outcomes, YO disease might be clinically more aggressive.

Neoadjuvant and Adjuvant Therapy

Recent years have seen advances in the management of esophageal cancer, which have led to clinically meaningful improvements in outcome. While surgical resection is the mainstay of treatment for locally advanced esophageal cancer, the addition of chemotherapy and/or radiotherapy are also recognized to be key components of the treatment paradigm. Definitive chemoradiation is standard-of-care for patients with unresectable esophageal cancer, and it is an option for patients with squamous cell carcinoma (SCC), with surgery reserved for patients with persistent/recurrent disease. This chapter focuses on established neoadjuvant and adjuvant therapy in the treatment of localized esophageal cancer. Evolving approaches and areas of clinical equipoise are also discussed.

Indolent Nodal Relapse of Colon Carcinoma with Associated Tumor Thrombus Invading the Superior Mesenteric Vein

Approximately 50–60% of patients with colorectal cancer develop metastatic disease, with the liver, lungs, and peritoneum being the commonest sites of occurrence. While there is data supporting the role of metastatectomy for liver disease, especially when occurring metachronously, evidence is limited for resection of extrahepatic disease. However, there is some evidence that judicious use of salvage surgery has a role in wellselected patients. This case highlights the extremely rare diagnosis of superior mesenteric vein (SMV) tumor thrombus related to metastatic nodal recurrence of colon cancer in a 54year-old male with a history of T3N2b colon cancer. We present the diagnostic and management issues associated with this complex case which demonstrated an unusual pattern of recurrence.

HER2: An emerging target in colorectal cancer

Despite advances in the treatment of metastatic colorectal cancer (CRC) the 5-year survival of patients with this disease remains low. A small proportion of CRCs overexpress the HER2 oncogene and the effective targeting of this pathway in other malignancies such as breast and gastric cancer has led to efforts to determine if it can also be exploited as a target in CRC. Activation of the HER2 pathway as a bypass signalling pathway has been identified as a mechanism of resistance for antiepidermal growth factor receptor antibody therapy in both the first line and salvage settings. It has also been shown that RAS and BRAF wild type metastatic CRC enriches for the presence of HER2 amplification. This knowledge, in addition to preclinical data providing a rationale for dual anti-HER2 targeted therapy has led to several clinical trials. To date, recently published and presented early phase data provide promising evidence suggesting anti-HER2 therapy may have a potentially beneficial role in the treatment of HER2-positive metastatic CRC. Namely, the HERACLES-A and MyPathway studies have shown benefit in a small number of patients with the use of combination trastuzumab-lapatinib and trastuzumab-pertuzumab, respectively. However, data from larger clinical trials are required before HER2-directed therapy is incorporated into standard treatment paradigms for CRC. This review presents an overview of epidermal growth factor receptor and HER2 pathways in CRC and discusses preclinical and clinical studies carried out in this field to date. There is potential that with continued evolution of data in this area, HER2 may become a validated therapeutic target and thus, anti-HER2 therapy may become an additional treatment option for a small population of patients with metastatic CRC.

Metabolic assessment by PET in the treatment of esophageal cancer

The use of [ 18 F]-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) imaging is emerging as an important tool in the treatment of esophageal cancer. Over a decade ago, the MUNICON investigators first incorporated metabolic assessment by PET into clinical trial design and evaluated the strategy of taking patients with locally advanced gastroesophageal junction (GEJ) adenocarcinomas, who had a suboptimal response to two weeks of induction chemotherapy with 5-fluorouracil (FU)/cisplatin directly to surgery (1).