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Can Patients With Low-Risk Nasopharyngeal Cancer Be Treated Safely With Radiotherapy Alone?


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Intensity-modulated radiation therapy (IMRT) alone may be considered an effective treatment option for “low-risk” T1–2N1 and T3N0 nasopharyngeal carcinoma, according to trial data presented by Jun Ma, MD, MS, Professor of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, at the 2022 ASCO Annual Meeting.1 These findings also were published in JAMA.2

In the IMRT era, the benefit of concurrent chemoradiotherapy to treat low- and intermediate-risk nasopharyngeal cancers remains controversial. This trial investigated whether concurrent chemotherapy can be omitted safely for patients with low-risk nasopharyngeal carcinoma treated with IMRT.

According to Dr. Ma, results from the primary analysis of this multicenter, randomized phase III noninferiority trial showed that the low-risk nasopharyngeal carcinoma subgroup could be safely treated with IMRT alone instead of concurrent chemoradiotherapy.

Jun Ma, MD, MS

Jun Ma, MD, MS

“Patients with stage II and T3N0 nasopharyngeal carcinoma who have small lymph nodes (< 3 cm), no radiologic extranodal extension, and lower EBV DNA viral load are at a low risk for recurrence,” he reported. “In this group of patients, IMRT alone provides noninferior survival and disease control compared with concurrent chemoradiotherapy, reduces toxicities, and improves quality of life.”

Concurrent chemoradiotherapy with or without induction or adjuvant chemotherapy has been considered the standard treatment modality for stage II nasopharyngeal carcinoma. However, supportive evidence related to the role of concurrent chemoradiotherapy was based on a single randomized trial using two-dimensional conventional radiotherapy.3

“Although the addition of concurrent chemotherapy to two-dimensional radiotherapy did provide a significant survival benefit, patients who received concurrent chemoradiotherapy also experienced increased severe acute toxicities,” Dr. Ma reported. “Moreover, it increased the risk of treatment-related deaths, which could decrease the therapeutic gain.”4,5

High-level evidence regarding the role of chemotherapy for this population in the IMRT era is lacking. Data have shown that for patients with stage II or T3N0 disease, the addition of concurrent chemotherapy to IMRT did not provide a significant survival benefit.

Study Details

To provide the high-level evidence necessary for future clinical care, Dr. Ma and his colleagues conducted this trial in a population of “low-risk” patients without any of the following known adverse features: any cervical lymph node diameter ≥ 3 cm, level IV or level Vb lymph node(s), presence of radiologic extranodal extension, or Epstein-Barr virus (EBV) DNA ≥ 4,000 copies/mL.

“Our hypothesis is that, compared with concurrent chemoradiotherapy, IMRT alone provides noninferior 3-year failure-free survival with a lower toxicity profile in this low-risk population,” he said.

Patients with low-risk nasopharyngeal cancer, defined as stage II/T3N0M0 without adverse features (all nodes < 3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA < 4,000 copies/mL) were randomly assigned 1:1 to receive IMRT alone or IMRT plus concurrent cisplatin. Patients were stratified by treatment center (the trial was conducted at five hospitals in China) and T-N subset.

The study’s primary endpoint was failure-free survival (defined as locoregional/distant relapse and/or death from any cause). Secondary endpoints included overall survival, distant metastasis–free survival, locoregional relapse–free survival, toxicity profile, and quality of life.

A total of 341 adults were enrolled between November 11, 2015, and August 4, 2020; patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (n = 169). Median follow-up was 46 months. In the group given concurrent chemoradiotherapy, 60.4% of patients received three cycles of concurrent chemotherapy, and 97.0% received at least two cycles. Almost 90% received at least 200 mg/m2 of cisplatin.

“The primary endpoint analysis showed that the IMRT-alone group had noninferior 3-year failure-free survival compared with the concurrent-chemoradiotherapy group,” Dr. Ma reported.

The 3-year failure-free survival rates were 90.5% and 91.9% in the IMRT-alone and concurrent-chemoradiotherapy groups, respectively. Subgroup analyses revealed similar rates of failure-free survival across all patient subgroups, including tumor type, node category, and disease stage.

Regarding secondary endpoints, the 3-year overall survival rate was about the same in the two groups: 98.2% with IMRT alone and 98.6% with concurrent chemoradiotherapy. Distant metastasis–free survival and locoregional relapse–free survival were also similar in the two study arms.

KEY POINTS

  • Compared with concurrent chemoradiotherapy, radiotherapy alone provides comparable disease control and survival with less toxicity in patients with low-risk nasopharyngeal carcinoma.
  • Patients who received intensity-modulated radiation therapy (IMRT) alone reported significantly fewer grade 3 or 4 adverse events compared with those given concurrent chemoradiotherapy.
  • IMRT alone may be considered a valid treatment option to be included in future treatment guidelines for patients with low-risk stage II and T3N0 nasopharyngeal carcinoma.

Toxicity and Quality of Life

"During the entire treatment course, there was a significantly lower incidence of reported grade 3 or 4 adverse events in the IMRT-alone group (17% with IMRT alone vs 46% with concurrent chemoradiotherapy),” Dr. Ma noted.

In comparing quality-of-life scores, the investigators found that patients given IMRT alone had significantly better general quality-of-life scores and a lower symptom burden across multiple domains. Of the 15 quality-of-life items measured, 8 reached clinical significance, which was defined as more than a 10-point difference between the treatment groups. These eight domains included global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.

“This trial presented high-level evidence supporting IMRT alone as a valid option to be included in future treatment guidelines for patients with low-risk stage II and T3N0 nasopharyngeal carcinoma,” concluded Dr. Ma.

DISCLOSURE: Dr. Ma reported no conflicts of interest.

REFERENCES

1. Ma J, Tang LL, Guo R, et al: Radiotherapy alone versus concurrent chemoradiotherapy in intermediate risk nasopharyngeal carcinoma. 2022 ASCO Annual Meeting. Abstract 6000. 

2. Tang LL, Guo R, Zhang N, et al: Effect of radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy on survival without disease relapse in patients with low-risk nasopharyngeal carcinoma. JAMA 328:728-736, 2022.

3. Chen QY, Wen YF, Guo L, et al: Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: Phase III randomized trial. J Natl Cancer Inst 103:1761-1770, 2011.

4. Lee AW, Lau WH, Tung SY, et al: Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma. J Clin Oncol 23:6966-6975, 2005.

5. Zhang AM, Fan Y, Wang XX, et al: Increased treatment-related mortality with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy. Radiother Oncol 104:279-285, 2012.

 


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