Simon Brown

Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer—striking discordance between national guidelines and treatment recommendations by US radiation oncologists

Background Management of rectal cancer with involved lateral pelvic lymph nodes (LPLNs) at the time of diagnosis-the stage we refer institutionally to as Stage 3.5-is controversial. The American Joint Committee on Cancers 7th edition classifies internal iliac lymph nodes (LNs) as regional (Stage III), but both external and common iliac LNs as metastatic (Stage IV). However, in many Asian countries all LPLNs are considered regional and patients are treated with curative intent, with literature supporting improved outcomes with LPLN dissection. Management patterns of these patients by US radiation oncologists (ROs) are unknown. Methods American ROs completed an anonymous institutional review board-approved online questionnaire regarding rectal cancer management. Results Among the 220 completed responses, 45% treat more than 10 patients annually and 39% work in academia. We found 10.5% and 34.2% recommend biopsy of clinically involved internal and common iliac LNs, respectively. The vast majority of responders-98.6% and 94.5%-treat involved internal and common iliac LNs with curative intent, respectively. Respondents recommend treatment intensification to involved internal iliac LNs by dissection of the nodal basin (88.2%) and radiation therapy (RT) boost (59.1%), and treatment intensification to involved common iliac LNs by LN dissection (76.4%) and RT boost (63.6%). Conclusions Our analysis reveals that the vast majority of US ROs approach patients with involved LPLNs, both regional (internal iliac) and metastatic (common iliac), with curative intent. They recommend treatment intensification with surgical resection and/or RT boost to involved nodes. Prospective clinical trials need to determine the appropriate management of patients with Stage 3.5 rectal cancer.

Preferential use of imaging modalities in staging newly diagnosed rectal cancer: A survey of US radiation oncologists

Background Accurate staging is crucial for management of patients with newly diagnosed rectal cancer. Endorectal ultrasound (EUS) has been the standard modality in the United States for decades, with magnetic resonance imaging (MRI) now preferred by national guidelines. Positron emission tomography (PET), conversely, is not recommended. The current utilization of imaging modalities by American radiation oncologists in staging newly diagnosed rectal cancer is unknown. Methods American radiation oncologists completed an anonymous institutional review board-approved online survey probing their imaging preferences for initial staging of rectal cancer patients. Results We received 220 responses from American radiation oncologists, with 39% in academic centers and with 45% seeing more than 10 rectal cancer patients per year. Most respondents utilize all three imaging modalities for rectal cancer staging-EUS, MRI and positron emission tomography/computed tomography (PET/CT). Fifty-two percent and 38% of respondents are high utilizers of EUS and MRI, respectively, defined as ordering these tests at least 75% of the time. Forty seven percent were high PET utilizers. The latter was associated with practice in a private setting (P=0.015) and being within 10 years from residency training completion (P<0.01). Conclusions Our analysis reveals a dramatic discordance among national guidelines and the practice patterns among American radiation oncologists. More rely on PET for initial staging of rectal cancer patients than on pelvic MRI. Further research needs to determine the most effective imaging work-up of patients with an initial diagnosis of rectal cancer.

Avoiding Topical Agents Before Daily Radiotherapy: Debunking Dogma

The clinical science of radiotherapy (RT) has evolved considerably since the early use of low-energy (150to 300-kV) orthovoltage x-rays, which deposit much of their energy at the skin surface. Indeed, the skin “erythema dose” was the primary means of standardizing radiation doses given the limited tangible criteria for documenting radiation effects at the time.1 Contemporary RT uses high-energy photons that deposit their maximum dose several centimeters below the skin surface. Nevertheless, in 90% to 95% of cases, moderate to high doses of this megavoltage radiation can lead to acute radiation dermatitis, which begins as erythema during the first 2 weeks of treatment before progressing to dry desquamation, and, in some cases, on to moist desquamation.2 Management of these reactions varies; preventive and interventional strategies have included frequent washing with mild soap and using topical dressings and corticosteroidal and noncorticosteroidal topical agents. In the orthovoltage era, the 1920s through the 1950s, radiation oncologists often proscribed the use of topical agents or emollients immediately before daily RT sessions out of concern for increased toxic effects to the skin, purportedly arising from a bolus effect or from the x-rays interacting with metal salts in the topical agents that could raise the surface dose.3 A bolus is a tissue-equivalent material used to shift the maximum dose closer to the surface, reducing the dose deeper in the tissues. The bolus effect is helpful when desired but can be deleterious when unexpected. In this issue of JAMA Oncology, Baumann et al4 evaluate the validity of the popular recommendation to avoid applying topical agents before external-beam RT. Anonymous online surveys of patients and clinicians revealed that 83.4% of patients had been advised to avoid topical agents immediately before RT, and 54.1% were advised to wipe off any residual topicals before the RT session. These numbers correspond to the 91.4% of clinicians who advised patients to avoid applying topical agents immediately before RT, with 84.3% of respondents citing concern for the bolus effect; 93.3% of clinicians advised patients to avoid using metal-containing topical agents immediately before RT, citing both the bolus effect and electron scatter from metals. Next, Baumann and colleagues used dosimeters and a tissue-equivalent phantom to measure the dose from radiation beams of 4 energy levels (6-MV or 15-MV photons and 6-MeV or 9-MeV electrons) delivered at 5 beam angles (0°, 15°, 30°, 45°, and 60°), with or without a petroleum-based ointment (petrolatum, 41% [Aquaphor, Beiersdorf AG]) or silver sulfadiazine cream, 1%, at thicknesses of 1 to 2 mm vs 3 mm or greater. Doses were measured at the surface and at a depth of 2 cm. When either topical agent was applied at a thickness less than 2 mm, no difference in radiation dose was found at either depth when appositional (0°) photons or electrons were used, regardless of beam energy. However, a thicker layer of either topical agent (≥3 mm) led to a bolus effect at the surface for all appositional beams, with dose increases of 2% to 5% for electrons and, according to our calculations of data they provided, 15% to 35% for photons relative to controls. The only scenario in which 1 to 2 mm of topical agent led to an increased surface dose was when the beam angle was 60° (an increase of 7%), and that was true only for the silver sulfadiazine cream. The effects of nonappositional beam angles on surface RT dose when topical agents were applied thickly (≥3 mm) were not reported. The topical agent thicknesses were verified in several patient scenarios and even among patients with advanced dermatitis who were applying copious amounts of topicals; none had applied a topical agent thickness of greater than 2 mm. Therefore, the author’s definition of a “very thick” application (≥3 mm) seems to represent an atypical clinical scenario. In parallel studies using a C57BL/6 mouse model, use of the petroleum-based ointment did not affect the surface dose or the extent of DNA damage (phosphorylated histone [γ-H2AX] foci) or apoptosis (by terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] assay) during 24 hours after either a 2-Gy or 15-Gy dose regardless of ointment thickness. The silver sulfadiazine cream was not tested in this model. The authors’ conclusion was that thinly or moderately applied topical agents have a minimal effect on dose to the skin when applied immediately before RT. However, “moderately applied” (<2 mm) silver sulfadiazine cream was associated with an increase in surface dose only when the photon beam angle incidence was 60°, but no such increase was noted with the non–metal-containing petroleum-based ointment. Two mechanisms could account for this modest increase in surface dose: the oblique beam incidence, which is known to increase surface doses, especially with beam angles >50°,5 and increased scatter dose in the presence of silver. The concern that metalliccontaining topical agents would increase surface dose and enhance toxic effects to the skin is prevalent, especially among radiation oncologists who treat breast cancer. Use of deodorants containing aluminum during RT for breast cancer had been discouraged for this reason, until recent studies showed no link between deodorant use and toxic effects to the skin.6 Although the authors are to be commended for investigating an issue that affects many patients undergoing RT, theirs was not the first study to evaluate the association of topical agents with surface dose. In 1997, investigators at the Medical College of Georgia measured the association of 15 metallic and nonmetallic topical agents (deodorants, powders, and creams/lotions) Related article Debunking Advice to Avoid Topical Agents Before Radiotherapy Invited Commentary