Big Blue Quest

The Role of Radiation in the Management of Rectal Cancer
The standard approach at Allegheny General Hospital in the treatment of locally advanced rectal carcinoma centers around a multidisciplinary approach, usually consisting of preoperative chemoradiotherapy followed by surgical resection. The treatment of rectal cancer will continue to evolve to improve survival and functional outcomes

A fun walk and run for Colon and Rectal Cancer awareness and research.

Article Sections
Introduction Etiology & Treatment Genetics & Family History Screening & Prevention	Radiologic Imaging Advancements Systemic Therapy Surgery Radiation

The Role of Radiation in the Management of Rectal Cancer - Continued (page 2 of 2)
By Stephen M. Karlovits, M.D., and Tom Colonias, M.D.
Department of Radiation Oncology

Neoadjuvant Chemoradiation
Neoadjuvant or preoperative therapy is an increasingly utilized option in the treatment of locally advanced rectal carcinoma. However, timing of radiation therapy (pre- or postoperative) is still debated in some circles. Historically, the inadequacy of clinical staging has encouraged the use of primary surgery with postoperative adjuvant therapy. Proponents of this approach argue that the principle advantage is knowledge of the actual tumor stage following resection. Disadvantages include a higher risk of acute and chronic radiation enteritis, as well as theoretically reduced radiation effectiveness secondary to tumor bed hypoxia. Preoperative adjuvant therapy has the potential advantage of tumor downstaging possibly improving resectability and expanding sphincter preservation options. There is also less likelihood of tumor seeding and less risk of radiation enteritis. The potential disadvantage of preoperative radiation is the possibility of overtreating some patients.

In Europe, several trials have used relatively moderate doses of preoperative RT in short courses and have shown a significant improvement in local control and survival compared to surgery alone. A Swedish randomized multicenter trial of 471 patients compared a radiotherapeutic dose of 25 Gray (Gy) preoperatively in 5 Gy fractions over 5-7 days followed by immediate surgery versus 60 Gy postoperatively in 2 Gy fractions over eight weeks with a two-week split course. The local recurrence rate was significantly better in the preoperative group (12 percent versus 21 percent; p=0.02).

Preoperative RT has been combined with systemic CT as a radiation sensitizer to improve local control, distant metastatic rate and overall survival. Memorial Sloan-Kettering Cancer Center combined RT to 50.4 Gy with 5-FU and leucovorin for stage T3 rectal cancers and reported a 22 percent pathologic complete response rate (pCR). The University of Kentucky experience with fixed rectal cancer treated with continuous infusion 5-FU and RT (55 Gy) showed only a 10 percent pCR, but 76 percent of patients were clinically downstaged and, despite initially fixed cancers, were able to undergo resection with negative surgical margins. Local recurrence of disease was observed in 16 percent (5 of 31) of patients with a three-year survival of 68 percent. Preoperative versus postoperative CRT was evaluated by two randomized studies, one from the NSABP (R-03) and the second an Intergroup study. However, neither study accrued an adequate number of patients, and no significant conclusions regarding these questions could be drawn. Preoperative combined modality therapy is now being used extensively, but the parameters of radiation dose and optimal chemotherapy remain to be defined.

The primary areas of local failure are in the tumor bed, perirectal lymph nodes and presacral region. The radiation treatment volume thus encompasses these regions in addition to the at-risk pelvic lymph nodes. A shrinking field technique is generally utilized with the entire pelvis receiving a dose of 45 Gy at 1.8 Gy per fraction. The boost volume includes the tumor bed with a margin and is treated to 50.4 to 55.8 Gy, with T4 fixed and/or distal rectal tumors receiving the highest dose.

A Multidisciplinary Approachas the Standard of Care
The standard approach at Allegheny General Hospital in the treatment of locally advanced rectal carcinoma centers around a multidisciplinary approach, usually consisting of preoperative CRT followed by surgical resection. Initial evaluation includes transrectal ultrasound combined with computed tomography in order to clinically stage each patient as accurately as possible. Preoperative magnetic resonance imaging is currently under study. Resources available through the Allegheny Cancer Center such as expert nutritional/dietary support and clinical trials through the Allegheny Protocol Department further promote comprehensive patient care.

Future Directions
The treatment of rectal cancer will continue to evolve to improve survival and functional outcomes. Intensity modulated radiation therapy (IMRT) is an emerging radiation technology that allows for increased radiation dose conformality that may allow for increased total doses to areas of disease without an increase in toxicity and thus effectively broadening the therapeutic ratio. With IMRT, dose escalation to the primary site is achieved without increased dose to normal critical structures resulting in potential improved local control and outcomes. The use of standardized surgical techniques such as total mesorectal excision and the use of newer chemotherapeutic agents may also promote better outcomes.

Conclusions
The treatment of rectal cancer continues to evolve toward goals of improved clinical outcomes of increased survival and improved quality of life. At the Allegheny Cancer Center, a multidisciplinary approach in the care of these patients has been the standard for years. The resources available through the Allegheny Cancer Center ensure comprehensive and empathic care of these patients. Emerging technologies such as IMRT should continue therapeutic advancement.