Saturday, September 23, 2023
This activity is intended for primary care clinicians, gynecologists, oncologists, radiation therapists, and other health professionals caring for women with cervical cancer in whom IMRT is being considered.
The goal of this activity is to describe indications, benefits and harms, and technical strategies for use of IMRT in women with cervical cancer.
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CME Released: 12/10/2010
Valid for credit through: 12/10/2011, 11:59 PM EST
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Radiation therapy plays an important role in both the definitive and adjuvant treatment of patients with cervical cancer. However, although radiation therapy is effective in controlling tumor growth, associated acute and chronic adverse effects are well known. Intensity-modulated radiation therapy (IMRT) is increasingly being used to treat cervical cancer and has the potential to improve the therapeutic ratio because of its ability to escalate dose to cancer targets while sparing adjacent healthy tissue. Multiple dosimetric studies were initially performed, establishing the conceptual feasibility of IMRT in patients with cervical cancer. Subsequent early reported series of patients treated with IMRT showed dosimetric and clinical benefits, with reduction in acute gastrointestinal and hematologic toxicity compared with historic controls, particularly in the posthysterectomy setting. Consensus is evolving regarding the use of IMRT in treating cervical cancer, particularly in the posthysterectomy setting, and for dose escalation to para-aortic nodes and bulky sidewall disease. Target delineation in the context of internal organ motion and tumor shrinkage during a course of fractionated external-beam radiotherapy remains an area of active investigation. IMRT in treating cervical cancer in the setting of an intact uterus remains in its nascent stage and should be used judiciously only within clinical trials. Although not a routine substitute for brachytherapy, it may be considered as a boost for highly selected patients who are not brachytherapy candidates. (JNCCN 2010;8:1425-1434)
In 2010, the American Cancer Society (ACS) has estimated that 12,200 cases of uterine cervical cancer will be diagnosed and 4210 deaths will occur from the disease in the United States.[1] Worldwide, the most recent yearly ACS estimate of cervical cancer cases was 555,094, with an associated 309,808 deaths.[2] Among women globally, cervical cancer is second only to breast cancer in incidence, and third after breast and lung cancers with regard to mortality.
For many of these women, radiation therapy plays an important role in both the definitive and adjuvant (i.e., posthysterectomy) treatment setting. Definitive pelvic radiotherapy with concurrent platinum-based chemotherapy and brachytherapy boost has been established as the standard of care in locally advanced disease. In 1999, the publication of 5 randomized trials[3-7] led to the February 1999 NCI recommendation to consider concurrent platinum-based chemoradiation as primary therapy for patients with locally advanced cervical cancer. In the setting of clinical early-stage disease after radical hysterectomy, adjuvant pelvic radiotherapy is recommended, depending on the extent of cervical stromal invasion, lymphovascular space invasion, and tumor size, although adjuvant chemoradiation is recommended in the setting of positive lymph nodes after radical hysterectomy, involved parametria, or positive surgical margins.
Although radiation therapy maintains an effective track record in controlling locoregional tumors, associated acute and chronic adverse effects are well-known. Nausea, vomiting, diarrhea, irritation of the urinary tract, and bone marrow suppression are common side effects experienced by patients undergoing pelvic radiotherapy. Furthermore, these side effects are enhanced with the administration of concurrent chemotherapy. In the acute setting of chemoradiation, low-grade genitourinary, gastrointestinal, and hematologic toxicity have been reported, with respective rates of 17.5%, 45.2%, and 53.3%. High-grade acute effects (3 or 4) are less common, but rates of 1.5% genitourinary, 8% gastrointestinal, and 27.6% hematologic toxicity have been noted.[8]
In the longer term, anatomic and physiologic alterations, such as obstruction and strictures, fistulization, pelvic insufficiency fracture, soft tissue fibrosis or necrosis, and lymphedema, are potential causes of severe morbidity. Although less well documented than acute toxicities, incidence of late grade 3 and 4 complications have ranged from 6% to 23.3% of patients.[8] Most clinical trials have historically underemphasized late low-grade (i.e., grade 1 and 2) effects, but with recent increased emphasis on long-term quality of life, experts have recognized that this low-grade late toxicity (e.g., anal leakage) can be prevalent.[9]
The external beam component of radiation therapy has evolved dramatically in the past 2 decades and is now capable of differentially targeting tumor and normal tissues in the pelvis. Traditional anteroposterior and "4 field box" radiation therapy plans based on bony landmarks have been shown to inadequately address intended targets in many cases,[10] leading to the widespread implementation of 3-dimensional conformal treatment planning, facilitated with modern cross-sectional imaging.
Intensity-modulated radiation therapy (IMRT) has potential to further improve the therapeutic ratio of external-beam radiotherapy. The improved conformality achievable with IMRT can potentially mitigate adverse effects and, in some clinical scenarios, allow dose to be escalated to target volumes to optimize tumor control. Traditionally, whole-pelvic doses are limited to 45 to 50 Gy, primarily as a result of small bowel tolerance. In this dose range, greater volumetric sparing of small bowel with IMRT will reduce the risk of acute and late toxicity. Conversely, IMRT may also permit selective boosting of gross disease sites to higher tumoricidal doses, without a corresponding increase in small bowel dose.
The use of IMRT has increased dramatically over the past decade. The percentage of practicing radiation oncologists using IMRT increased from 32% in 2002 to 73% in 2004.[11,12] In the upper pelvis, IMRT increases sparing of the small bowel (particularly in the posthysterectomy setting) and bone marrow of the iliac wings (Figure 1). In the low pelvis, IMRT better spares the bladder, rectum, and femoral heads (Figure 2). The authors have used IMRT in selected posthysterectomy pelvic irradiation cases, in dose escalation for grossly positive para-aortic lymph nodes, in patients unfit for brachytherapy, and in reirradiation cases.
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EnlargeUpper pelvis axial CT planning image for an intensity-modulated radiation therapy (IMRT) dose plan in a patient status post radical hysterectomy with a positive resected pelvic lymph node undergoing concurrent chemoradiation. Nodal planning volume and small bowel are outlined. The prescription 5040 cGy representing the 100% isodose as well as the 110%, 105%, 98%, 95%, 89%, 69%, and 50% isodose lines are shown.
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EnlargeLower pelvis axial CT planning image for an intensity-modulated radiation therapy (IMRT) dose plan in a patient status post radical hysterectomy with a positive resected pelvic lymph node undergoing concurrent chemoradiation. Planning target volume, rectum, vagina, and bladder are outlined. The prescription 5040 cGy representing the 100% isodose as well as the 110%, 105%, 98%, 95%, 89%, 69%, and 50% isodose lines are shown.
