Intensity-modulated radiation therapy (IMRT) methods to plan and deliver radiation therapy are not uniform. (1-3) IMRT may use beams that remain on as the multileaf collimator (MLC) moves around the patient (dynamic MLC), or that are turned off during movement and turned on when the MLC reaches prespecified positions (“step and shoot” technique). A third alternative uses a very narrow single beam that moves spirally around the patient (tomotherapy). Each of these methods uses different computer algorithms to plan treatment and yields somewhat different dose distributions in and outside the target. Patient position can alter target shape and thus affect treatment plans. IMRT may be delivered with the patient in the prone or supine position. However, data are unavailable to compare clinical outcomes for patients treated in prone versus supine positions, and consensus is lacking. Respiratory motion of the internal organs during radiation treatments is another concern when using IMRT to treat lesions in those compartments. Treatment plans are usually based on one imaging scan, a static 3-dimensional computed tomography (CT) image. They partially compensate for day-to-day (inter-fraction) variability in patient set-up, and for (intrafraction) motion of the target and organs at risk, by expanding the target volume with uniform margins around the tumor (generally 0.5–1 cm for all positional uncertainty).
Current methods seek to reduce positional uncertainty for tumors and adjacent normal tissues by various techniques. Patient immobilization cradles and skin or bony markers are used to minimize day-to-day variability in patient positioning. An active breathing control device combined with moderately deep inspiration breath-holding techniques may be used to improve conformality and dose distributions during IMRT. Other techniques being studied with internal tumors include gate beam delivery to the patient’s respiratory movement or continuous monitor of tumor (by in-room imaging) or marker (internal or surface) positions to aim radiation more accurately at the target. The impact of these techniques on outcomes of IMRT for any cancer is unknown. However, it appears likely that respiratory motion alters the dose distributions actually delivered while treating patients from those predicted by plans based on static CT scans, or measured by dosimetry, using stationary (non-breathing) targets. In addition, many tumors have irregular edges that preclude drawing tight margins on CT scan slices when radiation oncologists contour the tumor volume. It is unknown whether omitting some tumor cells or including some normal cells in the resulting target affects outcomes of IMRT. Finally, tumor size may change over the course of treatment as tumors respond or progress, which has potential effects on radiation dose delivery and distribution. Whether outcomes might be improved by repeating scans and modifying treatment plans accordingly (termed adaptive radiation therapy) is unknown.
The Advanced Technology Consortium (ATC) has helped to develop general guidelines for protocols that incorporate IMRT as an option. These guidelines were communicated to all clinical trial groups by the National Cancer Institute (NCI) and clearly stated that respiratory motion could cause far more problems for IMRT than for traditional radiotherapy treatments (http://www3.cancer.gov/rrp/imrt.doc).
These considerations emphasize the need to compare clinical outcomes rather than treatment plan predictions to determine whether one radiotherapy method is superior to another.
Technology Assessments and Systematic Reviews
A systematic review published in 2008 summarized evidence on the use of IMRT for a number of cancers, including head and neck, prostate, gynecologic, breast, lung, and gastrointestinal. (4) The authors presented the review as an analysis of comparative clinical studies; in reality, they categorized several small case series using historical cohorts as controls as comparative studies for several tumor types. This method limits the value of the review in assessing the role of IMRT for the diseases addressed in this policy.
A literature search found no studies that compared health outcomes with IMRT versus those in patients treated concurrently with any other type of radiotherapy for tumors of the thorax (e.g., esophagus), upper abdomen (e.g., stomach, pancreas, bile duct, liver), or pelvis (e.g., rectal, anal, gynecologic). A few case series of IMRT were identified, including some with historical controls treated with non-IMRT methods.
As outlined in a recent review article, IMRT has been investigated for treatment of gastric cancer in several studies, but only one reported clinical outcomes. (1) In a small (n=7) case series, patients with stage III gastric cancer received postoperative chemoradiotherapy with 5-fluorouracil (5-FU) and leucovorin and IMRT delivered to a dose of 50.4 Gy in 1.8 Gy fractions. (5) Chemoradiotherapy with IMRT was well tolerated, with no acute gastrointestinal (GI) tract toxicities (nausea, diarrhea, esophagitis) greater than grade 2.
In a retrospective series with a historical control cohort, clinical results achieved with image-guided IMRT (n=24) were compared to results with CRT (n=24) in patients with primary adenocarcinoma of the biliary tract. (6) The majority of patients underwent postsurgical chemoradiotherapy with concurrent fluoropyrimidine-based regimens. IMRT treatment plans prescribed 46 to 56 Gy to the planning target volume (PTV) that includes the tumor and involved lymph nodes, in daily fractions of 1.8–2 Gy. CRT involved 3-D planning that delivered 46–50 Gy in 1.8–2 Gy daily fractions. Both groups received boost doses of 4–18 Gy as needed. The median estimated overall survival (OS) for all patients who completed treatment was 13.9 months (range: 9.0–17.6); the IMRT cohort had median OS of 17.6 months (range: 10.3–32.3), while the CRT cohort had a median OS of 9.0 months (range: 6.6–17.3). Acute GI toxicities were mild to moderate, with no significant differences between patient cohorts. These results suggest that moderate dose escalation via conformal radiotherapy is technically and clinically feasible for treatment of biliary tract adenocarcinoma. However, while this series represents the largest group of patients with this disease treated with IMRT, generalization of its results is limited by the small numbers of patients, use of retrospective chart-review data, nonrepresentative case spectrum (mostly advanced/metastatic disease), and comparison to a nonconcurrent control radiotherapy cohort.
Three reports of case series provide clinical results with IMRT for pancreatic carcinoma. The largest series involved a retrospective analysis of 41 patients who received image-guided IMRT alone, postsurgically (41%), or with a number of concurrent primarily fluoropyrimidine-based chemotherapy regimens (88%). (7) The prescribed radiation dose to the PTV ranged from 41.4–60.4 Gy in daily fractions of 1.8–2 Gy. For all patients diagnosed with adenocarcinoma (85%), 1- and 2-year actuarial OS were 38% and 25%, respectively; median OS in resected patients was 10.8 months (range: 6.2–55.1), as compared to 10.0 months (range: 3.4–28.0) in inoperable cases. Four patients (9.7%) were unable to complete radiotherapy as prescribed. Any upper GI acute toxicity (none grade 4) was reported in 29 (70%) patients, most commonly nausea, vomiting, and abdominal pain; any lower GI acute toxicity (less than 5% grade 4) was reported in 17 (42%) cases, primarily diarrhea.
In a second series of 25 patients with pancreatic and bile duct cancers (68% unresectable), 24 were treated with IMRT and concurrent 5-FU, 1 refused chemotherapy. (8) Resected patients received 45–50.4 Gy to the PTV, whereas unresectable patients received 50.4–59.4 Gy. For all cancers, the median OS was 13.4 months, with 1- and 2-year OS of 55% and 22%, respectively. One- and 2-year median OS were 83% and 50%, respectively, among resected cases, and 40% and 8%, respectively, among unresected cases. IMRT was well tolerated, with grade 2 or less acute upper GI toxicity in 80% of patients; grade 4 late liver toxicity was reported in 1 patient who survived more than 5 years.
A third retrospective series included 15 patients with pancreatic adenocarcinoma (7 resected, 8 unresectable) who underwent IMRT plus concurrent capecitabine. (9) Resected cases received 45–54 Gy to the gross tumor volume, unresected cases received 54–55 Gy to the gross tumor volume; all cases received 45 Gy to the draining lymph node basin. At a median follow-up of 8.5 months, no deaths were reported among the resected patients, compared to 2 deaths in the unresected cases, yielding a 1-year OS rate of 69% among the latter. No grade 4 toxicities were reported, with the vast majority of acute toxicities reported at grade 1 (nausea, vomiting, diarrhea, neutropenia, anemia).
The data provided by these 3 series of IMRT for pancreatic cancer suggest that this technology may be safely used with concurrent chemotherapy in patients with resected or unresectable disease, producing mild to moderate toxicities primarily of the GI tract. However, given the limitations inherent in retrospective analyses, heterogeneity in terms of disease and use of concurrent therapies, small patient numbers, and a lack of direct comparative data, it is not possible to draw conclusions about the relative clinical efficacy or toxicities of IMRT versus any other radiotherapy method.
A series of reports from a single institution provided data on clinical outcomes achieved with IMRT in women with gynecologic malignancies. Patients from an initial series (10) were included in a subsequent report that comprised 40 patients who underwent IMRT to treat cancers of the cervix, endometrium, and other sites (3 patients). (11) Patients in this series underwent postsurgical IMRT (70%), with (58%) or without (42%) cisplatin chemotherapy, with a majority (60%) also undergoing postradiotherapy intracavitary brachytherapy (ICB). IMRT was prescribed to the PTV at a dose of 45 Gy, delivered in 1.8 Gy daily fractions; ICB delivered an additional 30–40 Gy to cervical cancer patients and 20–25 Gy to those with endometrial cancer. A well-matched nonconcurrent cohort of patients who underwent 4-field CRT (45 Gy to the PTV, 1.8 Gy daily fractions) using 3D planning and received cisplatin chemotherapy was used to compare acute GI and genitourinary (GU) toxicities between radiotherapy modalities. No grade 3 acute GI or GU toxicities were reported in IMRT or CRT recipients. Grade 2 GI toxicity was noted in 60% of the IMRT cohort versus 91% of the CRT group (p=0.002). No significant differences were noted in the incidence of grade 2 GU toxicity in IMRT recipients (10%) compared to the CRT cohort (20%). Three other reports from the same group provide data on acute hematologic toxicity (12), chronic GI toxicities (13), and acute GI toxicities (14)among patients who underwent IMRT with or without chemotherapy. It is unclear whether or not the patients in these reports are those from the initial studies or are new patients.
All of these studies uniformly suggest that the use of IMRT is associated with a low incidence of severe toxicities, although mild-to-moderate adverse effects were reported. However, no tumor control or survival data are available for comparison to CRT. Furthermore, generalization of these findings to current practice is limited by the small numbers of cases involved, the lack of concurrent controls, patient and treatment heterogeneities, and the relatively distant (1994-2002) timeframe during which they were accrued.
Two subsequent studies examined the use of post-hysterectomy radiotherapy in women with high-risk cervical cancer. In the first study, 68 patients were treated with adjuvant pelvic radiotherapy, high dose-rate ICB, and concurrent chemotherapy. (15) The initial 35 cases received 4-field box CRT delivered to the whole pelvis; a subsequent 33 patients underwent IMRT. All patients received 50.4 Gy of radiation in 28 fractions and 6 Gy of high dose-rate vaginal cuff ICB in 3 insertions; cisplatin was administered concurrently to all patients. All patients completed the planned course of treatment. At median follow-up of 34.6 months (range: 12–52 months) in CRT recipients and 14 months (range: 6–25 months) in IMRT recipients, the 1-year locoregional control rate was 94% for CRT and 93% for IMRT. Grades 1 to 2 acute GI toxicities were noted in 36% and 80% of IMRT and CRT recipients, respectively (p=0.00012), while acute grade 1 to 2 GU toxicities occurred in 30% versus 60%, respectively (p=0.022). There was no significant difference between IMRT and CRT in the incidence of acute hematologic toxicities. Overall, the IMRT patients had lower rates of chronic GI (p=0.002) toxicities than the CRT patients.
A subsequent report from the same group included the initial 33 patients in that experience with an additional 21 cases. (16) At a median follow-up of 20 months, this study showed a 3-year disease-free survival rate of 78% and an OS rate of 98% in IMRT recipients. While promising, the findings from these studies require confirmation in a true randomized trial to rigorously compare the relative clinical outcomes achieved with IMRT and CRT in this disease setting.
Two case series describe results achieved with IMRT in patients with squamous cell carcinoma of the anal canal. The first is a single-institution series that included 17 patients with stage I/II cancer who underwent IMRT alone (n=3) or concurrent with 5-FU alone (n=1) or 5-FU with mitomycin C (MMC, n=13). (17) Patients generally received 45 Gy to the PTV at 1.8 Gy per fraction, followed by a 9 Gy boost to the gross tumor volume. Thirteen of 17 (76%) patients completed treatment as planned. None experienced acute or late grade 3 or above nonhematologic (GI or GU) toxicity. Grade 4 acute hematologic toxicity (leukopenia, neutropenia, thrombocytopenia) was reported in 5 of 13 (38%) patients who received concurrent chemoradiotherapy. At a median follow-up of 20.3 months, the 2-year OS rate was 91%.
A second multicenter series included a cohort of 53 consecutive patients who received concurrent chemotherapy and IMRT. (18) Forty-eight (91%) received 5-FU plus MMC, the rest received other regimens not including MMC. Radiation was delivered at 45 Gy to the PTV. Thirty-one (58%) patients completed therapy as planned, with breaks in the others because of grade 4 hematologic toxicities (40% of patients), painful moist desquamation, or severe GI toxicities. At the18-month follow-up, the local tumor control rate was 83.9% (range: 69.9–91.6%), with an OS rate of 93.4% (range: 80.6–97.8%). Univariate analyses did not reveal any factors significantly associated with tumor control or survival rates, whereas a multivariate analysis showed patients with stage IIIB disease experienced a significantly lower colostomy-free survival (hazard ratio 4.18; 95% CI: 1.062–16.417; p=0.041).
The authors of these series suggest that their tumor control, survival, and toxicity results are similar to those achieved in earlier trials with concurrent chemoradiotherapy using non-IMRT methods.
The efficacy and safety of two different adjuvant chemoradiotherapy regimens using 3D-CRT (n=27) or IMRT (n=33) were evaluated in two consecutive cohorts of patients who underwent primarily D2 resection for gastric cancer. (19) The cohorts in this study were generally well-matched, with American Joint Committee on Cancer (AJCC) advanced stage (II-IV) disease. The majority (n=26, 96%) of those who received 3D-CRT were treated with 5-fluorouracil plus folinic acid (5FU/FA); the other patient received oxaliplatin plus capecitabine (XELOX). In the 3D-CRT cohort, 13 (50%) patients completed the 5FU/FA regimen, 13 halted early because of acute toxicity or progression, and received a median 60% of planned cycles. Patients in the IMRT cohort received XELOX (n=23, 70%) or 5FU/FA (n=10, 30%). Five of 10 (50%) patients completed all planned 5FU/FA cycles, the other 5 received only a median 60% of cycles because of acute toxicity. Thirteen (56%) treated with XELOX completed all planned cycles; the other 10 received a median of 70% planned cycles because of toxicity. Radiation was delivered to a total prescribed dose of 45 Gy/1.8 Gy/fraction in 21 (81%) of the 3D-CRT cohort patients; 5 received less than 45 Gy because of intolerance to treatment. Thirty (91%) patients in the IMRT cohort received the planned 45 Gy dosage; 2 (6%) were unable to tolerate the full course, and 1 case planned for 50.4 Gy was halted at 47 Gy. The median overall survival (OS) was 18 months in the 3D-CRT cohort, and more than 70 months in the IMRT cohort (p=0.0492). The actuarial 2-year OS rates were 67% in the IMRT cohort and 37% in the 3D-CRT group (p not reported). Acute renal toxicity based on creatinine levels was generally lower in the IMRT cohort compared to the 3D-CRT group, with a significant difference observed at 6 weeks (p=0.0210). In the 3D-CRT group, LENT-SOMA grade 2 renal toxicity was observed in 2 patients (8%) whereas no grade 2 toxicity was reported in the IMRT group.
The authors of this study assert that adjuvant IMRT with XELOX is more efficacious and associated with less renal toxicity than 3D-CRT with 5FU/FA in patients with advanced gastric cancer. However, the nonconcurrent cohorts study design precludes direct comparison of outcomes data and conclusions about the relative efficacy of these radiotherapy modalities in this setting.
Two single arm studies reported outcomes with IMRT in patients with hepatobiliary cancers. The first study involved 42 patients with advanced (33% AJCC stage IIIC, 67% stage IV) hepatocellular carcinoma (HCC) with multiple extrahepatic metastases. (20) Among the 42 cases, 33 (79%) had intrahepatic HCC with extrahepatic metastases, 9 (21%) had only extrahepatic lesions. The extrahepatic locations of HCC metastatic lesions included lung (n=19), lymph node and adrenal (n=20), other soft tissues (n=6), and bone (n=5). Helical tomotherapy was performed simultaneously for all lesions in each patient, with a total radiation dose of 50 and 40 Gy to 95% of the GTV and PTV in 10 fractions divided over 2 weeks. All received capecitabine during the course of IMRT as a radiosensitizer. After completion of tomotherapy, additional transarterial or systemic chemotherapy was administered to patients eligible for it according to tumor location. Among 31 patients who underwent hepatic IMRT, a mean of 3 courses (range: 1-6) transarterial chemolipiodolization was performed in 23. Among 9 patients with extrahepatic lesions only, 3 received an additional 3-7 cycles of systemic chemotherapy consisting of epirubicin, cisplatin, and 5FU. Median follow-up was 9.4 months (range: 1.9–25.3 months). Tumor response was reported separately for each organ treated with IMRT. The overall objective tumor response rate was 45% for intrahepatic HCC, 68% for pulmonary lesions, 60% for lymph node and adrenal cases, and 67% for soft-tissue metastases. Three cases of local tumor progression occurred within the target radiation area, including 2 intrahepatic HCC and 1 abdominal lymph node metastasis. Median OS was 12.3 months, with 15% OS at 24 months. The most common acute adverse events were mild anorexia and constitutional symptoms that occurred 1-2 weeks after start of IMRT, regressed spontaneously or subsided with symptomatic care, and did not interfere with the scheduled delivery of IMRT. However, it is not possible to discern the impact of IMRT on adverse events because almost all occurred in patients who received chemotherapy following IMRT. However, most patients were reported to have tolerated therapy well, with no treatment-related mortality.
A second retrospective single-arm study involved 20 patients with primary, unresectable HCC who were treated with IMRT and concurrent capecitabine. (21) Patients had AJCC grade T1 (n = 7) and T3 (n = 13) HCC. IMRT was prescribed to a minimum tumor dose of 50 Gy in 20 fractions over 4 weeks, with the optimization goal of delivering the prescription dose to 95% of the PTV. Capecitabine was administered as radiosensitizer on the days of IMRT delivery. Eleven (55%) patients underwent at least 1 transarterial chemoembolization (range: 1-3 procedures) before radiotherapy planning. Eighteen of 20 (90%) patients completed the full course of IMRT, 2 died before follow-up imaging was obtained. The mean survival of 18 patients who completed IMRT was 9.6 months after its conclusion. Disease progression occurred in-field in 3 patients, 2 failed elsewhere in the liver. Four patients (25%) required hospitalization during therapy, due to encephalopathy (n=1), gastric ulcer (n=1), acute hepatitis (n=1), and sepsis (n=1). Four required a break from chemotherapy because of peripheral neuropathy (n=2), acute hepatitis (n=1), and sepsis (n=1). Grade 1 acute abdominal pain was observed in 15%, 30% reported grade 1 nausea, 5% experienced grade 2 nausea. No acute or late toxicity greater than grade 2 was reported.
The evidence from these studies is insufficient to draw conclusions as to the efficacy and safety of IMRT for treatment of HCC. No other studies were identified in the 2010 literature update that evaluated this technique in other hepatobiliary cancers.
No studies of IMRT in pancreatic cancer were identified in the 2010 literature update.
A small case series involved 10 patients who underwent IMRT with intracavitary brachytherapy boost for locally advanced (FIGO stage IIB and IIIB) cervical cancer. (22) During radiotherapy, all patients received cisplatin. Whole pelvic IMRT was administered to a dose of 50.4 Gy in 28 fractions, and intracavitary brachytherapy was delivered to a dose of 30 Gy in 6 fractions. The mean OS was 25 months (range: 3-27 months), with actuarial OS of 67%. Acute toxicities included 1 patient with grade 3 diarrhea, 1 with grade 3 thrombocytopenia, and 3 with grade 3 leukopenia. One case of subacute grade 3 thrombocytopenia was noted. These data are insufficient to draw conclusions about the efficacy or safety of IMRT in cervical cancer.
Three case series reports were identified in the 2010 update. One was a gastrointestinal toxicity study in 45 patients who received concurrent chemotherapy and IMRT for anal cancer. (23) Chemo-radiotherapy is becoming the standard treatment for anal cancer, in part due to preservation of sphincter function. Patients had T1 (n=1), T2 (n=24), T3 (n=16), and T4 (n=2) tumors; N stages included Nx (n=1), N0 (n=31), N1 (n=8), N2 (n=3), and N3 (n=2). Concurrent chemotherapy primarily comprised 5FU plus mitomycin C (MMC). IMRT was administered to a dose of 45 Gy in 1.8 Gy fractions, with areas of gross disease subsequently boosted with 9–14.4 Gy. Acute genitourinary toxicity was grade 0 in 25 (56%) cases, grade 1 in 10 (22%) patients, grade 2 in 5 (11%) patients, with no grade 3 or 4 toxicities reported; 5 (11%) patients had no genitourinary tract toxicities reported. Grades 3-4 leukopenia was reported in 26 (56%) cases, neutropenia in 14 (31%), and anemia in 4 (9%). Acute GI toxicity included grade 0 in 2 (4%) patients, grade 1 in 11 (24%), grade 2A in 25 (56%), grade 2B in 4 (95), grade 3 in 3 (7%) and no grade 4 toxicities. Univariate analysis of data from these patients suggests a statistical correlation between the volume of bowel that received 30 Gy or more of radiation and the risk for clinically significant (grade 2 or higher) GI toxicities.
The second report was a retrospective analysis of toxicity and disease outcomes associated with IMRT in 47 patients with anal cancer. (24) Thirty-one patients had squamous cell carcinoma (SCC). Patients had AJCC stage I (n=6, 13%), stage II (n=16, 36%), stage III (n=14, 31%), stage IV (n=6, 13%), or recurrent disease (n=3, 7%). IMRT was prescribed to a dose of at least 54 Gy to areas of gross disease at 1.8 Gy per fraction. Forty patients (89%) received concurrent chemotherapy with a variety of agents including MMC, 5FU, capecitabine, oxaliplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, and ifosfamide in various combinations. The 2-year actuarial OS for all patients was 85%. Eight patients (18%) required treatment breaks. Toxicities included grade 4 leukopenia (7%) and thrombocytopenia (2%); grade 3 leukopenia (18%) and anemia (4%); and, grade 2 skin (93%). These rates were much lower than previous trials of chemoradiation, where grade 3 to 4 skin toxicity was noted in about 50% of patients and grade 3 to 4 GI toxicity noted in about 35%. In addition, the rate of treatment breaks was lower than in many studies; and some studies of chemoradiation include a break from radiation therapy. Some investigators believe that treatment breaks reduce the efficacy of this combined approach. .
The third report in this update was a small (n=6) case series of IMRT and concurrent infusional 5FU plus cisplatin in patients in patients with anal cancer with para-aortic nodal involvement. (25) IMRT was delivered to a median dose of 57.5 Gy to the CTV, with nodal areas of involvement treated to a median dose of 55 Gy. Five of 6 completed the entire prescribed course of IMRT. The 3-year actuarial OS rate was 63%. Four patients developed grade 3 acute toxicities that included nausea and vomiting, diarrhea, dehydration, small bowel obstruction, neutropenia, anemia, and leukopenia. Five of 6 had grade 2 skin toxicity.
Input from Academic Medical Centers and Physician Specialty Societies
In response to requests, input was received from one physician specialty society (2 reviewers) and 3 academic medical centers while this policy was under review for May 2010. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. There was support for use of IMRT in a number of cancers discussed above. In general, this support was based on finding different radiation doses to various organs based on treatment planning studies.
Several Phase II or III clinical trials are recruiting patients to evaluate the use of IMRT in gynecologic, pancreatic, colorectal, and hepatobiliary tract cancer (http://clinicaltrials.gov/ct2/results?term=imrt&recr=Open&type=Intr&cond=cancer&phase=12&pg=1).
Guidelines and Position Statements
2010 National Comprehensive Cancer Network (NCCN) Guidelines
The 2010 NCCN Guidelines were reviewed in May 2010. The guidelines for anal carcinoma (http://www.nccn.org/professionals/physician_gls/PDF/anal.pdf, V.1.2010) state that IMRT “may be used in place of 3D conformal RT in the treatment of anal carcinoma,” They also mention that “IMRT studies (e.g., RTOG 0529) are now ongoing to further evaluate its benefit in the treatment of anal carcinoma” and that “Its use requires expertise and careful application to avoid reduction in local control probability.” The guidelines also indicate that IMRT remains investigational for gastric cancer (http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf, V.2.2010). In cervical cancer (http://www.nccn.org/professionals/physician_gls/PDF/cervical.pdf, V.1.2010), they mention that IMRT is “becoming more widely used” but issues with reproducibility, immobilization and definition of target “remain to be validated.” Although IMRT is mentioned as an option in the guidelines for pancreatic adenocarcinoma, they indicate a lack of consensus on radiotherapy dose and appropriate setting for use of IMRT in this disease (http://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf, V.1.2010). IMRT is not mentioned in the guidelines for hepatobiliary cancers (http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf, V.1.2010) and conformal or stereotactic radiotherapy is viewed as an option for patients with unresectable lesions but was changed from category 2A (uniform consensus) to category 2B (nonuniform consensus) in this update. Similarly, multiple conformal fields based on CT-treatment planning are mentioned as appropriate treatment for uterine endometrial cancer, but IMRT technology is not specified (http://www.nccn.org/professionals/physician_gls/PDF/uterine.pdf, V.1.2010). The guidelines for bladder cancer (http://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf, V.2.2010) make no mention of IMRT, but do list standard radiotherapy in combination with other treatments as a treatment option. NCCN does not currently have guidelines for vulvar cancer.
The body of evidence available to assess the role of IMRT in the treatment of cancers of the abdomen and pelvis generally comprises case series, both retrospective and prospective. No randomized trials have been reported that compared results with IMRT to any other CRT modality, nor do any of the case series include concurrently treated control patients. The available results are generally viewed as hypothesis-generating for the design and execution of comparative trials of IMRT versus CRT that evaluate tumor control and survival outcomes in the context of adverse events and safety. However, the comparative data on use of IMRT versus 3D CRT in chemoradiotherapy for anal cancer shows marked differences in rates of acute toxicity. Thus, use of IMRT in squamous cell cancer of the anus/anal canal may be considered medically necessary. Use in other cancers of the abdomen and pelvis is considered investigational.
While IMRT is considered a major advance in the delivery of radiotherapy, numerous potential pitfalls and hazards associated with this technology merit further examination. A recent review addresses these issues in the context of gynecologic cancers, and concludes that “IMRT gives an overstated impression of accuracy and precision of treatment delivery.” (3) The authors further assert that this has created a “tremendously false sense of security because the allure of precision from IMRT and inverse planning is at odds with the reality.” The review is written in the context of gynecologic cancers.