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Advanced Colorectal Adenomas and Cancer Risk
Colorectal adenoma characteristics are an important determinant of the risk for colorectal cancer (CRC). A prospective cohort study included approximately 16,000 participants of a randomized trial who underwent colonoscopy for abnormal flexible sigmoidoscopy findings. At a median follow-up of approximately 13 years, individuals with advanced adenomas (≥10 mm or with villous components or high-grade dysplasia) on that baseline colonoscopy had a higher risk of CRC and CRC death compared with those without adenomas (relative risks 2.7 and 2.6, respectively). Although there was no significant difference in CRC risk between individuals with non-advanced adenomas and those without adenomas, the study may have been underpowered. This study lends further support to existing recommendations that patients with advanced colorectal adenomas have close follow-up for CRC surveillance.
Adjuvant Chemotherapy for Rectal Cancer With a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy
There is a paucity of direct evidence to support benefit for adjuvant chemotherapy following neoadjuvant chemoradiotherapy for locally advanced rectal cancer, and particularly, whether there is benefit for those with no residual tumor in the surgical specimen. Two separate observational cohort studies using data from the National Cancer Database concluded that adjuvant chemotherapy was associated with improved all-cause survival (relative risk reduction of 50 to 76 percent) in those with a complete pathologic response following neoadjuvant chemoradiotherapy and surgery. However, the magnitude of the survival benefit identified in this relatively favorable population of patients was inexplicably high and likely represents an overestimation of treatment effects based upon unassessed factors that could have influenced both the decision to offer postresection chemotherapy and all-cause survival. We do not base our decision whether or not to pursue postoperative chemotherapy on pathologic response following neoadjuvant chemotherapy and radiation.
Trastuzumab and Chemotherapy for Advanced or Recurrent Serous Endometrial Carcinoma
Standard treatment for women with advanced or recurrent serous endometrial cancer is chemotherapy, although novel strategies are under investigation for those whose tumors overexpress human epidermal growth factor receptor 2 (HER2). In a randomized phase II trial enrolling 61 such women, the addition of the anti-HER2 antibody trastuzumab to chemotherapy, compared with chemotherapy alone, improved median progression-free survival (12.6 versus 8.0 months), with no increase in toxicities. Given these data, some UpToDate contributors assess HER2 expression in advanced or recurrent endometrial serous carcinomas, for possible incorporation of trastuzumab with chemotherapy, although this remains an off-label indication for trastuzumab.
Trials Incorporating Cetuximab Plus Radiation Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck
While epidermal growth factor receptor (EGFR) is highly overexpressed in head and neck squamous cell carcinoma (SCC), the role of the EGFR inhibitor cetuximab in locally advanced disease, particularly as a radiosensitizer, is under investigation. For example, in one randomized trial, the strategy of chemotherapy followed by concurrent cetuximab/radiotherapy demonstrated similar survival outcomes and lower rates of distant metastases compared with concurrent chemoradiotherapy, but with greater toxicity and treatment-related mortality. In a second trial, concurrent cetuximab/radiotherapy was evaluated with or without concurrent carboplatin and 5FU. While disease outcomes were improved with the addition of chemotherapy, rates of severe mucositis, feeding tube insertion, and hospitalization were higher. Importantly, as all patients in this trial received cetuximab, its contribution to both the efficacy and toxicities observed is unknown. Given available evidence, concurrent platinum-based chemoradiotherapy remains our preferred approach for most locally advanced SCC of the head and neck. We reserve cetuximab for patients with a good performance status who are not candidates for platinum-based regimens due to a specific contraindication (eg, nephrotoxicity, ototoxicity, or neuropathy).
Checkpoint Inhibitor Immunotherapy in Older Adults
The use of checkpoint inhibitor immunotherapy has been a major advance in the treatment of a wide range of malignancies. Clinical trials demonstrating the benefits and side effects of this approach have been conducted in relatively young and fit patients. A meta-analysis of 5,458 patients in nine randomized trials that compared nivolumab, pembrolizumab, or atezolizumab versus chemotherapy or targeted therapy in solid tumors found that checkpoint inhibitor immunotherapy appeared to have similar efficacy and toxicity in those ≥65 years versus those <65 years of age. Chronologic age alone should not preclude the use of these agents.
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