Definitive radiation therapy offers a high degree of locoregional control in large, locally advanced basal cell carcinomas (BCC), according to results from a recent multi-institutional research study published by Su et al in the International Journal of Radiation Oncology · Biology · Physics. One hundred and forty tumors were treated with definitive radiation that resulted in a 5-year rate of locoregional control of 78%. A high-risk subgroup of patients in whom locoregional recurrence was more common was also identified.
This research represents one of the largest contemporary studies demonstrating the efficacy of definitive radiation therapy for locally advanced BCC, said the study’s authors.
Background
BCC is usually one of the most curable cancer types.
“Most times, [BCC] tumors present really small,” said Shlomo Koyfman, MD, study co-author and a radiation oncologist at Cleveland Clinic Cancer Institute. “However, because [BCC] is slow growing, it can sneak up on people. There is a population of patients who come in with large basal cell tumors because they’ve delayed coming in due to anxiety about seeing a doctor or because they live far away. If BCC is found early, it’s usually resolved with surgery or surface radiation, but this becomes complicated when the disease is advanced.”
“Patients need to be part of the decision making in their therapy,” added Allison Vidimos, MD, study co-author and a dermatologist at Cleveland Clinic Cancer Institute. “Some patients may benefit from surgery but decline it because it's a major undertaking based on where the tumor is located. We're grateful that this paper shows that radiotherapy can also be a very viable and tolerable treatment option for those patients.”
Study Design
Since there has been little data about outcomes in locally advanced BCC, investigators conducted a retrospective study to determine the impact of definitive radiation therapy and to understand risk factors for recurrence. The study aimed to focus on cases that were unresectable or where surgery would have resulted in extensive disfigurement.
The researchers reviewed data from patients treated with definitive radiation therapy for locally advanced BCC at Cleveland Clinic Foundation, the University of Pennsylvania Health System, and Brigham and Women’s Hospital between 2005 and 2021. For this study, “locally advanced” was defined as tumors that were ≥ 4 cm, required extensive resection, deemed unresectable, or would have required upfront radiation therapy or systemic therapy prior to resection.
Initially, 680 cases were identified, 140 of which were treated with definitive radiation therapy (101 patients at initial diagnosis and 39 patients at disease recurrence). Most of the 140 patients (70.4%) were treated with an electron plan with varying dose fractionation regimens ranging from hypofractionated regimens (30–35 Gy in 5 fractions delivered over 2 weeks) as well as conventionally fractionated regimens (60–70Gy in 30–35 fractions delivered 5 days per week). Most patients (93.5%) were treated with at least 50 Gy. Median follow-up was 22.9 months (range = 1.5–207 months)
Study Outcomes
This study showed that definitive radiation therapy is a safe and effective treatment for patients with locally advanced disease. Five-year Kaplan Meier estimates of locoregional control exceeded 75%.
At the latest follow-up, 26 (18.6%) patients developed a recurrence. Twenty-two of the 26 (84.6%) recurrences were locoregional failures, and 4 (15.4%) of the recurrences were distant metastases. The median time to recurrence was 25.8 months. For the patients experiencing locoregional failures, 1 of the 22 (4.5%) developed nodal recurrence.
Median survival was 27.1 months (range = 0.2–49.4 months) in the 26 individuals who developed a recurrence following radiation. Seven patients (26.9%) died from BCC. Five-year BCC survival was 85% (95% confidence interval [CI] = 74.3%–97.3%), and was similar in patients treated with upfront definitive radiation therapy (82.7%; 95% CI = 67.8%–100%) compared to radiation therapy for a recurrence (86.7%; 95% CI = 72.4%-–100%, P = .73).
On subset analysis, patients who had at least one high-risk feature (eg, tumor size ≥ 4 cm, the presence of bone invasion, perineural invasion, immunocompromised status, or recurrent disease) had a significantly lower 5-year freedom from locoregional failure rate than those without any of these risk factors (68.5% vs 92.4%; P = .004).
The study authors concluded, “Definitive radiation therapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study.”
Advances in Radiation Therapy
Clinicians used to be hesitant to recommend radiation for these patients due to side effects such as skin tissue damage and damage to underlying organs.
“With the emergence of advanced techniques such as intensity-modulated radiation therapy and volumetric arc therapy, we can shape the radiation beams in a much more precise way, as opposed to earlier types of radiation where there was very heterogenous dose distribution,” said Dr. Koyfman. “We can now treat complex target areas like the scalp or large flank lesions while minimizing the dose to critical organs very close by. This has dramatically reduced side effects. Also, for larger lesions, slow and steady radiation over 6 weeks rather than higher dose regimens over a shorter period of time can allow improved normal tissue healing.”
Dr. Koyfman pointed out that radiation is not for everyone. This is not an option for younger patients with Gorlin syndrome or related genetic conditions; in those patients, providers may consider surgery, topical medications for lower-risk sites, as well as oral hedgehog inhibitors, which inhibit the gene involved with BCC.
Conclusions
“We have very effective therapies for this disease, from medications to radiation to surgery,” noted Dr. Koyfman. “Figuring out treatment sequencing is the trick.”
“If you have patients with larger basal cell tumors, engage them in a multidisciplinary discussion up front,” he continued. “Don’t just refer them to a surgeon or radiation oncologist. You need to bring together multiple specialists to work as a team at diagnosis to figure out which therapy or combination of therapies to use first. And then throughout the course of treatment, these specialists should follow patients along to optimize the type and timing of treatment for these complex tumors.”
Disclosure: For full disclosures of the study authors, visit redjournal.org.
