CHAPTER 7: Gastrointestinal Cancers

AC is a rare cancer with an estimated 8200 new cases diagnosed in 2017; however, there has been a recent increase in the incidence. Some 86%–97% of ACs are associated with human papillomavirus (HPV) infection; HPV-16 and HPV-18 are the high-risk forms associated with AC. Other risk factors associated with AC include history of receptive anal intercourse, immunosuppression after solid-organ transplantation or HIV infection, or other autoimmune disorders.¹

Most patients with AC will present with non-metastatic disease, which is treated with combined modality with chemotherapy and radiation. Metastatic AC represents around 10%–20% of cases, which are treated with systemic chemotherapy.¹

A 48-year-old woman undergoes evaluation by her primary care physician for rectal bleeding. Digital rectal examination revealed a 2-cm mobile mass 2 cm from the anal verge. She undergoes biopsy of the mobile mass, and results are consistent with squamous cell carcinoma of the anus. HIV test is negative, and PET scan is negative for any distant metastasis. MRI of the pelvis demonstrates sub-centimeter inguinal lymph nodes but no other pathologically enlarged lymph nodes. What are her treatment options?

Clinical trials has investigated the role of radiation therapy (RT) alone versus combined modality with chemoradiation.^2-4

The landmark UKCCCR^** Anal Cancer Trial demonstrated chemoradiation as the standard treatment for AC, compared with RT alone, with lower local failure rates and improvements in recurrence-free survival.²

The RTOG/ECOG^# conducted a subsequent trial comparing 5-fluorouracil (5FU)/radiation therapy with 5FU-mitomycin-RT and found improved colostomy-free survival and disease-free survival with the 5FU-mitomycin arm, which then became the standard of care.^2,3

One phase 2 study has evaluated capecitabine, which has been used interchangeably with 5FU in colorectal trials, along with mitomycin C. Results showed a tolerable side effect profile and comparable efficacy, with 77% with complete clinical response and 16% partial response.⁴

In an HIV-positive patient presenting with AC as their HIV/AIDS-defining illness and a CD4 count >200, consider a chemotherapy regimen similar to 5FU and mitomycin as for an HIV-negative patient.^5,6

1. National Comprehensive Cancer Network guidelines for anal carcinoma. Version 2.2017. Available at: www.nccn.org.

2. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996;14(9):2527-39.

3. Northover J, Glynne-Jones R, Sebag-Montefiore D, et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer 2010;102(7):1123-8.

4. Glynne-Jones R, Meadows H, Wan S, et al. EXTRA—a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys ...