Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort

Chin, Olivia; Yu, Eugene; O’Sullivan, Brian; Su, Jie; Tellier, Anais; Siu, Lillian L.; Waldron, John; Kim, John; Hope, Andrew; Cho, John; Giuliani, Meredith; Ringash, Jolie; Spreafico, Anna; Bratman, Scott V.; Hosni, Ali; Hahn, Ezra; Xu, Wei

doi:10.1016/j.radonc.2021.10.018

Cited by 26 publications

(13 citation statements)

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“…The eligibility criteria included histologically confirmed stage II and T3N0 NPC (by the 7th edition TNM) without adverse features (all lymph node[s] <3 cm, no level IV/VB lymph nodes, no extranodal extension, and Epstein-Barr virus DNA<4000 copies/mL); age between 18 and 65 years; Karnofsky performance scale score of at least 70; leukocyte count greater than 4 × 10 9 /L, neutrophil count greater than 2 × 10 9 /L, hemoglobin greater than 120 g/L, and a platelet count greater than 100 × 10 9 /L; and adequate hepatic and kidney function.…”

Section: Methodsmentioning

confidence: 99%

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

Tang

Guo

Zhang

et al. 2022

JAMA

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IMPORTANCE Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).OBJECTIVE To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.INTERVENTIONS Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m 2 every 3 weeks for 3 cycles [n = 169]). MAIN OUTCOMES AND MEASURESThe primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference Ն10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). RESULTS Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR,. Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, −1.4%; 1-sided 95% CI, −7.4% to ϱ; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, −29% [95% CI, −39% to −20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.CONCLUSIONS AND RELEVANCE Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.

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Section: Methodsmentioning

confidence: 99%

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

Tang

Guo

Zhang

et al. 2022

JAMA

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“…However, these two studies are small-sample retrospective studies, and the value of tumor volume and lymph node size needs to be further studied. Studies demonstrated that extranodal extension played an important role in predicting distant metastasis in stage II NPC patients with N1 category (56)(57)(58). Patients with high-grade extranodal extension (including coalescent nodes and metastatic node infiltrating into adjacent structures) had a significantly higher risk of distant metastasis and death than those without (including metastatic nodes infiltrating into surrounding fat and without extranodal extension) and were suggested to be classified as cN3.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma

Chen

Liang

et al. 2022

Front. Oncol.

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PurposeThe role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT).MethodsWe searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3–4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy.ResultsNine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44–0.82), LRFS (HR = 0.62, 95% CI 0.50–0.78), and PFS (HR = 0.65, 95% CI 0.54–0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46–1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62–1.15), LRFS (HR = 0.85, 95% CI 0.54–1.34), DMFS (HR = 0.96, 95% CI 0.60–1.54), and PFS (HR = 0.96, 95% CI 0.66–1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37–2.96), LRFS (HR = 0.70, 95% CI 0.34–1.45), DMFS (HR = 1.03, 95% CI 0.53–2.00), and PFS (HR = 1.04, 95% CI 0.58–1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3–4 leukopenia (RR = 4.00, 95% CI 2.29–6.97), mucositis (RR = 1.43, 95% CI 1.16–1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63–29.12). No significant differences of grade 3–4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85–13.94) was found between the two groups.ConclusionFor unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.

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“…rENE assessment included presence or absence of rENE, rENE pattern, and level of certainty of rENE declaration. The grade of rENE, reflecting the extent of rENE, was also recorded according to the categories described previously by Huang et al 9 and others 12–14 (Figure 1): Grade 1 rENE: Tumor invasion through the nodal capsule of an individual LN with unambiguous ill‐defined nodal border(s), but confined to perinodal fat. Grade 2 rENE: Tumor invasion through two or more inseparable adjoining nodes exhibiting unambiguous effacement of any component of their internodal plane(s) (implying replacement by tumor, that is, extranodal extension), which invariably produces a lobulated appearing nodal mass. Grade 3 rENE: Tumor invading beyond perinodal fat to overtly invade or encase adjacent structures, for example, skin, muscle, neurovascular structures, and so on. …”

Section: Methodsmentioning

confidence: 99%

Section: Rene Assessment Processmentioning

confidence: 99%

Augmenting inter‐rater concordance of radiologic extranodal extension in HPV‐positive oropharyngeal carcinoma: A multicenter study

Hoebers

O’Sullivan

et al. 2022

Head & Neck

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Objectives To assess intra‐ and inter‐institutional concordance and identify methods to increase precision in radiologic extranodal extension (rENE) ascertainment in HPV+ oropharyngeal carcinoma. Methods Six radiologists, blinded to clinical outcomes, from three centers assessed rENE in two phases: Phase‐I (20 cases) utilized each individual's a priori appreciation of the literature. Phase‐II (30 additional cases) was performed after deliberating experience and consolidating operating definitions. Intra‐ and inter‐institutional Kappa were calculated at >50% and >75% certainty levels, respectively. Results The Phase‐I intra‐institutional kappa was 0.76, 0.32, and 0.44 at >50% certainty and improved to 0.89, 0.61, and 0.66 at >75% certainty. Inter‐institutional Fleiss' kappa also improved with higher certainty (from 0.40 to 0.57, p = 0.039). The Phase‐II inter‐rater kappa was significantly higher than Phase‐I at the same certainty level (both p < 0.001). Conclusion A learning curve exists for rENE assessment. Strategies to augment reliability include high certainty for declaration, consolidated operating definitions, and sharing experience among radiologists.

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Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort

Cited by 26 publications

References 24 publications

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma

Augmenting inter‐rater concordance of radiologic extranodal extension in HPV‐positive oropharyngeal carcinoma: A multicenter study

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