For resectable gastric cancer, perioperative chemotherapy or adjuvant chemoradiation with chemotherapy are standards of care. The decision making for adjuvant therapeutic management can depend on the stage of the cancer, lymph node positivity, and extent of surgical resection.
Charles R. Thomas, Jr, MD
The management of rectal cancer in patients with metastatic disease at presentation is highly variable. Although chemoradiation is standard for patients with stage II/III rectal cancer, its role in the metastatic setting is controversial.
Primary surgery with an abdominoperineal resection (APR) was historically the standard of care for localized anal squamous cell carcinoma. APR achieved 40%-70% survival rates at five years, with local failures from 27%-47%.[1,2] With modern technology and radiation dose escalation, external beam radiation therapy (EBRT) studies have improved complete response rates, decreased morbidity, and improved sphincter preservation rates. Nigro et al added 5-fluorouracil (5FU) and mitomycin C (MMC) to concurrent EBRT [3,4] and impressive complete response rates inspired other groups to investigate the role of chemotherapy as a component of sphincter-preserving therapy. The European Organization for Research and Treatment of Cancer (EORTC) and United Kingdom Coordinating Committee on Cancer Research (UKCCCR) studies reported improved local control and colostomy-free survival when chemotherapy (5FU/MMC) was administered in conjunction with radiation.[5,6] The five-year survival rate for patients receiving standard chemoradiation approaches 70%; however, 20%-40% experience grade 3-4 toxicity, and administration with MMC causes profound hematologic toxicity.
Dr. Abbas and colleagues delineate the current status of chemoradiation for anal carcinoma. Their thorough and thoughtful review serves as an excellent summation of the current therapeutic approach of the past few years.
In this issue of ONCOLOGY, Drs. Patel, Puthillath, Yang, and Fakih discuss the evolution of adjuvant therapy for locally advanced rectal cancer from postoperative to preoperative radiation and provide a fairly comprehensive review of the data on adjuvant/neoadjuvant chemoradiation for rectal cancer. The authors then attempt to critically evaluate the use of combination chemotherapy regimens in the neoadjuvant setting, asking the question, “Is more better?”
Squamous cell anal cancer remains an uncommon entity; however,
the incidence appears to be increasing in at-risk populations, especially
those infected with human papillomavirus (HPV) and human immunodeficiency
virus (HIV). Given the ability to cure this cancer using synchronous
chemoradiotherapy, management practices of this disease are
critical. This article considers treatment strategies for HIV-positive patients
with anal cancer, including the impact on chemoradiation-induced
toxicities and the role of highly active antiretroviral therapy in the treatment
of this patient population. The standard treatment has been
fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents
plus radiation. Consideration to modifying the standard treatment regime
is based on the fact that patients with HIV tend to experience greater
toxicity, especially when CD4 counts are below 200; these patients also
require longer treatment breaks. Additional changes to the chemotherapy
dosing, such as giving 5-FU continuously and decreasing mitomycin dose,
are evaluated and considered in relation to radiation field sizes in an effort
to reduce toxicity, maintain local tumor control, and limit need for
colostomy. The opportunity for decreasing the radiation field size and
using intensity-modulated radiation therapy (IMRT) is also considered,
particularly in light of the fact that IMRT provides dose-sparing while
maximizing target volume dose to involved areas. The impact of the immune
system in patients with HIV and squamous cell carcinoma of the
anus and the associated response to therapy remains unknown. Continued
studies and phase III trials will be needed to test new treatment strategies
in HIV-infected patients with squamous cell cancer of the anus to
determine which treatment protocols provide the greatest benefits.