The American Society for Radiation Oncology recently held their annual meeting. Dr. Matthew Katz, a radiation oncologist in Lowell, MA, provides us with his interpretation of several of the studies that were presented. For more information from Dr. Katz, follow him on Twitter: @subatomicdoc.
Radiation treatment for breast cancer is usually with 3-dimensional (3D) techniques, allowing accuracy but sometimes uneven doses that can lead to more skin injury. Intensity modulated radiation therapy (IMRT) is a sophisticated way to ‘sculpt’ radiation doses in important ways for prostate, head and neck cancers.
Jean-Phillippe Pignol et al. report 10-year results of a phase III randomized trial on using IMRT to lessen the toxicity of radiation.
Arm 1: 3-dimensional (3D) planned radiation
Arm 2: Intensity modulated radiation therapy planning (IMRT)
IMRT was already more homogeneous (evenly distributed) and has less short-term toxicity, but it is much more expensive. Is it worth it? Can it possibly have a worse outcome?
Key endpoint: Less long-term/chronic breast/chest wall pain.
Results: This update at 9.8 years from treatment for 241 patients had evaluated patient-reported quality of life, recurrence and survival data along with skin reaction, pain information. Some level of chronic pain was present in 29.6% with IMRT vs. 36.2% with 3D radiation. – not statistically any different. Younger age and pain during radiation predicted poor cosmetic outcomes and worse quality of life. Desquamation (skin peeling like bad sunburn) during radiation was linked to more fibrosis/scar tissue within the breast. IMRT didn’t help or hurt cancer control rates.
My interpretation: This trial failed to show a different in its primary endpoint, less chronic pain. Lessening skin reactions is important but that short-term help may not justify the much higher costs of IMRT. I find this particularly true as sophisticated 3D planning can approach what you get with IMRT. I’d say the value is on the mometasone cream and there are ways to treat some skin, breast problems from radiation with pentoxifylline that may further make IMRT not worth it.
Radiation Dose Schedule
Breast radiation in the U.S. historically took 5-6 .5 weeks depending upon the findings at surgery. Some studies outside the U.S. suggested shorter course treatments would work equally well.
MD Anderson conducted a phase III trial 287 evaluable breast cancer patients comparing shorter (hypofractionated) radiation to women ≥40 years having breast conserving surgery then radiation. Initial reports looked great for short term side effects with the hypofractionated treatment. This study by Swanick et al. looks at longer-term follow-up.
Arm 1: Conventional radiation 6-6.5 weeks, 60-64 Gy [radiation dose]
Arm 2: Hypofractionated radiation, 4-4.5 weeks, 52.56 – 55.06 Gy
Key endpoint: Cosmetic outcome and patient-reported quality of life 2+ years after radiation.
Results: Shorter course radiation was similar to conventional, longer treatment. As time passes, patients have less pain and improving functional outcomes.
My interpretation: Hypofractionated radiation is more convenient without any higher risk of long term complications compared to conventional radiation treatment schedules.
Radiation Dose – Need for a Boost in DCIS?
It is common for invasive breast cancer that women receiving whole breast radiation have a ‘boost’, some additional treatment to the surgery site in the breast after lumpectomy.
Ductal carcinoma in situ (DCIS) is non-invasive breast disease also treated with radiation after surgery. But it wasn’t clear whether there is any real need for a ‘boost’ in DCIS.
Led by Meena Moran, ten academic institutions pooled data to analyze results in 4,131 women with pure DCIS, comparing women with and without additional boost radiation.
Key endpoint: Tumor recurrence in the same breast, called ipsilateral breast tumor recurrence (IBTR).
Results: 35.6% of patients received a boost, usually patients with worse features (involved margins or necrosis, an aggressive feature). Despite these worse features, women receiving a boost had a slightly lower rate of IBTR at 15 years, 9.4% versus 12% without a boost. Looking only at patients with positive margins, the boost didn’t lower IBTR. For women with negative margins, multivariate analysis accounting for various factors found that a radiation boost was associated with a lower risk of recurrence.
My interpretation: A boost can’t make up for negative margins, so for some women a re-excision may be needed. The extra radiation dose does lower recurrence, but I suspect a more sophisticated tool for assessing risk may be helpful, like a nomogram. But it’s definitely worth discussion between women with DCIS and their doctors.
One of the most practical trials of the meeting was a double-blinded randomized trial of 124 women receiving postmastectomy radiation therapy (PMRT) by
Olm-Shipman et al. . This phase III trial evaluated optimal skin care with two creams twice daily starting day 1 of radiation, through treatment and for 2 weeks after RT complete
Arm 1: Eucerin (E)
Arm 2: Mometasone furoate 0.1% (MF)
Key endpoint: Moderately severe skin reaction with moist desquamation
Results: All patients had bolus (rubbery material put on top of the skin) for treatment. To account for differences in stratified by radiation type (3D vs IMRT), body mass index, reconstruction (yes/no). Cohorts otherwise similar in both arms. 89% of women were Stage III, 69% had reconstruction. The type of radiation was 6.5% electrons to chest only, 70.5% photon/electron, 23% IMRT. No description of field sizes, inclusion of internal mammary lymph nodes
Result: Moist desquamation 64.5% for E, 45% for MF. Grade 3 reactions 33% E vs 19%. Grade 3 reaction happened quicker with E (36 days) than with MF (46 days). All p<0.05.
My interpretation: If you are going to spend money on a cream for skin care to lessen radiation skin reactions, mometasone furoate is the only one with higher levels of evidence. This study confirms prior findings by NCCTG and from the UK. I will now be advising patients to use this cream and not spend money on other products.