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. Author manuscript; available in PMC: 2025 Apr 10.
Published in final edited form as: Int J Radiat Oncol Biol Phys. 2023 May 6;117(3):652–663. doi: 10.1016/j.ijrobp.2023.04.035

Intensity-Modulated Radiation Therapy for Early-Stage Squamous Cell Carcinoma of the Glottic Larynx: A Systematic Review and Meta-Analysis

Niema B Razavian *, Ralph B D’Agostino Jr †, Rachel F Shenker ‡, Ryan T Hughes *
PMCID: PMC11984751  NIHMSID: NIHMS2071867  PMID: 37150263

Abstract

Purpose:

Early-stage squamous cell carcinoma of the glottic larynx is commonly treated with 2-dimensional or 3-dimensional conventional radiation therapy (CRT). Despite its use in other head and neck cancers, intensity-modulated radiation therapy (IMRT) remains controversial in this patient population.

Methods and Materials:

A systematic review was performed by querying 3 databases (Pubmed, Embase, Web of Science) for articles published between December 1, 2000 and September 2, 2022. Included studies reported outcomes in at least 10 patients treated with IMRT for early-stage glottic cancer. Data were extracted and reported following PRISMA standards. Pooled outcomes were estimated using random-effects models. Primary outcome was the rate of local failure (LF) following IMRT. Secondary outcomes included rates of regional failure (RF) following IMRT and rates of LF and RF following CRT.

Results:

A total of 15 studies (14 retrospective, 1 prospective) consisting of 2083 patients were identified. IMRT was used in 873 patients (64% T1, 28% T2). Multiple treatment (partial larynx, single vocal cord carotid sparing) and image-guided radiation therapy techniques were used. The pooled crude rate of LF was 7.6% (95% confidence inverval [CI], 3.6%–11.5%) and actuarial LF rates at 3 and 5 years were 6.3% (95% CI, 2.2%–10.3%) and 9.0% (95% CI, 4.4%–13.5%), respectively. The pooled crude rate of RF after IMRT was 1.5% (95% CI, 0.5%−2.5%). On metaregression analysis, increased rate of LF was significantly associated with T2 disease (P < .001) and grade 2 to 3 histology (P < .001). Treatment with CRT was reported in 738 patients (76% T1, 22% T2). Among the studies reporting outcomes of both modalities, there was no significant difference in LF (log odds ratio; P = .12) or RF (log odds ratio; P = .58) between IMRT or CRT.

Conclusions:

In patients with early-stage glottic cancer, retrospective data suggests local and regional control are similar for patients treated with IMRT and CRT. Additional prospective studies with uniform methods of volume delineation and image guidance are needed to confirm the efficacy of IMRT.

Introduction

Squamous cell carcinoma of the glottic larynx accounts for 60% of all larynx cancers.1 For patients with early-stage disease, there are multiple treatment options including surgery (eg, transoral laser microsurgery, cordectomy) and radiation therapy (RT). Classically, RT for early-stage glottic cancers is delivered using parallel opposed fields that encompass the glottis, carotid arteries, and portions of the neck nodal regions adjacent to the larynx via 2-dimensional or 3-dimensional conventional RT (CRT) planning. While this treatment is associated with high rates of local control—approximately 85% to 94% for T1 disease and 70% to 80% for T2 disease—RT to the bilateral neck is not without toxicity.2–8 In patients with head and neck cancers, irradiation of the bilateral neck is associated with increased risk of stroke and cerebrovascular events.9–17 A commonly used technique for head and neck cancer RT, intensity-modulated RT (IMRT), presents an alternative to CRT with more conformal dose distributions that may reduce dose to carotid arteries and potentially mitigates these risks. IMRT has been widely accepted as a standard of care in the radiotherapeutic management of head and neck cancer based on its ability to achieve target coverage while sparing normal tissues.18–20 While reports on the feasibility of IMRT for early glottic larynx cancers were published over 10 years ago, its use remains controversial.21–23 Given the rapid dose fall-off inherent with IMRT, the potential for geographic miss, and the limited dose to the immediately adjacent neck that would have otherwise been treated with CRT, there have been concerns for increased risk of local failure (LF) and regional failure (RF) after glottic IMRT.24

To better understand the efficacy of IMRT for early glottic larynx cancers, we performed a systematic review and meta-analysis. In particular, we focused on the LF and RF rates associated with this technique. We also examined clinical and pathologic factors associated with treatment outcomes as well as toxicity and salvage treatments.

Methods and Materials

A systematic literature review was performed and results were outlined following the PRISMA reporting standard.25 Review and analyses were designed prospectively and registered with PROSPERO (CRD42022367511). In total, 3 databases (Pubmed, Embase, and Web of Science) were queried using standardized search terms to identify publications that contained glottic larynx cancer and IMRT. Only peer-reviewed articles published between December 1, 2000 and September 2, 2022 were included for screening. After removing duplicate publications, titles and abstracts were screened by at least 2 reviewers. In the case of discordance, a third reviewer was added, and inclusion for full text review was determined by consensus opinion. Articles were included for analysis if they contained at least 10 patients treated with early-stage, node negative, glottic larynx cancer treated with IMRT. Case reports/series, systematic reviews, cancer database studies, studies in foreign languages, and those that did not have full text available were excluded. Furthermore, studies that only used CRT, included patients treated for recurrent disease, metastatic disease, reirradiation, or those that used stereotactic body RT were excluded. To reduce confounding, if 2 or more studies had overlapping patient populations, only the more recently published article was included for statistical analysis. A full list of search terms and exclusion criteria is enclosed in Appendix E1.

Following full text review, LF and RF rates were recorded. Patient, clinical, and treatment characteristics that were extracted included: radiation treatment modality, IMRT modality, IMRT planning and treatment delivery techniques, American Joint Committee on Cancer staging edition, tumor (T) stage, nodal (N) stage, use of elective nodal irradiation, use of chemotherapy, smoking history, anterior commissure involvement, and tumor grade. Additionally, treatment-related toxicity and salvage treatment modalities were recorded. Quality of studies included for statistical analysis was quantified using the methodological index for nonrandomized studies criteria.26

The primary outcome was the rate of LF following IMRT. Secondary outcomes included pooled RF rates following IMRT and LF and RF rates following CRT. Pooled rates of treatment failure were estimated using random effects models. Publication bias was evaluated using Egger’s regression test for funnel plot symmetry. Heterogeneity among the studies was assessed using Cochran’s Q-tests for heterogeneity. Sensitivity analyses to assess the effect of type of IMRT technique and use of daily cone beam CT (CBCT) imaging on treatment failure were performed. Differences between subgroups were examined using a metaregression model. Univariate metaregression analyses were performed to examine the relationship between treatment failure and T2 disease, smoking history, grade 2 to 3 histology, and median follow-up time. A multivariate metaregression model was constructed using the variables significantly associated with treatment failure. Differences in rates of treatment failure in patients receiving IMRT or CRT was assessed using a random effect meta-analysis comparing log odds ratios across studies. For this analysis, only studies that reported patients treated with IMRT or CRT were included. Aggregate toxicity and salvage treatment data were compiled using descriptive statistics. Statistical significance was defined as P < .05. All tests were performed using ‘metafor’ package (version 3.0–2) in Rstudio (Version 1.3.1073 2009–2020).27

Results

Characteristics of included studies

After removing duplicate citations, 2153 abstracts were screened, and 60 articles underwent full text review (Fig. 1). In total, 15 studies (n = 2083) were included for statistical analysis.28–42 Median study quality was 16 (Table E1), and no significant evidence of publication bias was identified (Fig. E1). Patient, clinical, and treatment characteristics are summarized in Tables 1 and 2. Included studies were published from 2014 to 2022. Most studies were retrospective (14 of 15 studies) and had median follow-up ranging from 18 months to 66 months. The majority of patients receiving IMRT (n = 873) had T1 disease: 31 (3.4%), 588 (64%), and 254 (28%) patients had Tis, T1, and and T2 disease, respectively. Forty-four patients (4.6%) did not have an exact T-stage specified. Smoking history, anterior commissure involvement, and tumor histologic grade were reported in 8, 8, and 7 studies, respectively. Partial larynx, single vocal cord, and carotid-sparing IMRT were used in 2, 3, and 6 studies, respectively, while 4 studies did not report IMRT technique. Image-guided RT (IGRT) with daily CBCT was reported in 6 studies, while the remaining studies either did not report image guidance technique, used kV imaging, or used nondaily CBCT. Among the 5 studies using partial or single vocal cord IMRT, daily imaging was matched to the thyroid cartilage (4 studies), laryngeal soft tissue (1 study), or bone (1 study). Intrafractional motion was most commonly managed by asking patients not to swallow (4 studies). Of the remaining 10 studies using carotid-sparing or other IMRT techniques, only 1 study described the IGRT surrogate that was used (laryngeal cartilage). Use of hypofractionation (>2 Gy/fraction) or accelerated fractionation (at least 6 fractions per week) was reported in 14 studies. Elective nodal radiation and use of chemotherapy (for bulky T2 disease) were separately reported in 2 studies.

Fig. 1.

Fig. 1.

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PRISMA flowchart. Abbreviations: IMRT = intensity-modulated radiation therapy; SBRT = stereotactic body radiation therapy.

Table 1.

Characteristics and outcomes of included studies

Author (citation) Country (year) Study type Study total Median FU (range) Median dose (range) Median Gy/Fx (range) ENI Chemo Smoking history AC involved Grade 2–3 IMRT total IMRT T-stage CRT total CRT T-stage Crude local failure (n, %) Crude regional failure (n, %) IMRT actuarial focal control IMRT actuarial overall survival
Janssen28 CHE (2014) RR 77 28 mo (4–99) N/A Gy (61.6–70) N/A (2–2.25) Y Y - CC N/A N/A N/A 39 T1: 44%
T2: 56%		 N/A N/A N/A N/A 3 y: 95% N/A
Zumsteg29 USA (2015) RR 330 43 mo (N/A) 66 Gy (N/A) 2.25 (N/A) N/A N/A 83% N/A N/A 48 Tis: 6%
T1: 67%
T2: 27%		 282 Tis: 5%
T1: 75%
T2: 20%		 IMRT: 5 (10%)
CRT: 31 (11%)		 IMRT: 2 (4.2%)
CRT: 4 (1.4%)		 3 y: 88% N/A
Berwouts30 BEL (2016) RR 121 46 mo (12–60) N/A Gy (63–67.5) 2.25 (N/A) N/A N/A 82% 18% N/A 40 T1: 68%
T2: 32%		 81 T1: 72%
T2: 28%		 IMRT: 6 (15%)
CRT: 20 (25%)		 IMRT: 3 (7.5%)
CRT: 6 (7.4%)		 5 y: 83% 5 y: 85%
Low31 CAN (2017) RR 105 55 mo (N/A) 61 Gy (N/A) 2.44 (N/A) N/A N/A N/A N/A N/A 11 T1: 100%
T2:0%		 41 T1: 100%
T2:0%		 N/A N/A N/A 5 y: 84%
Rock32 CAN (2017) RR 139 60 mo (9–126) N/A Gy (60–70) N/A (2–2.4) Y N/A N/A 68% 76% 139 T1: 0%
T2: 100%		 N/A N/A IMRT: 28 (20%) IMRT: 6 (4.3%) 3 y: 81%
5 y: 79%		 5-y hypo-bone: 64%
5-y hypo-larynx: 83%
5-y accel-larynx: 89%
Cetinayak33 TUR (2019) RR 299 72 mo (3–288) 66 Gy (50–70) 2 (1.8–3.12) N/A N/A N/A N/A N/A 44 T1: N/A%
T2: N/A%		 N/A N/A N/A N/A 5 y: 95% 5 y: 87%
Cho34 KOR (2019) RR 160 30 mo (31–42) 66 Gy (N/A) N/A (1.8–2) N/A N/A N/A 44% 26% 23 T1: 100%
T2: N/A%		 137 T1: 100%
T2: 0%		 IMRT: 1 (4.3%)
CRT: 13 (9.5%)		 IMRT: 0 (0%)
CRT: 3 (2.2%)		 3 y: 94% N/A
Chung35 KOR (2019) RR 34 41 mo (6–125) 67.5 Gy (65.2–67.5) 2.25 (1.8–2.3) N/A N/A 24% 8.8% 15% 34 T1: 100%
T2: 0%		 N/A N/A IMRT: (2.9%) N/A 5 y: 97% 5 y: 100%
Mohamed36 USA (2019) RR 215 39 mo (9–103) N/A Gy (63–70) N/A (2–2.25) N/A N/A 43% N/A 58% 62 T1: 100%
T2: 0%		 153 T1: 100%
T2: 0%		 IMRT: 2 (3.2%)
CRT: 12 (7.8%)		 IMRT: 0 (0%)
CRT: 3 (2%)		 3 y: 97%
5-y T1a: 95%
5-y T1b: 100%		 5-y T1a: 90%
5-y T1b: 100%
Al Feghali37 USA (2020) RR 113 66 mo (N/A) 70 Gy (68–79.2) 2 (N/A) N Y-CC N/A N/A N/A 28 T1: 0%
T2: 100%		 85 T1: 0%
T2: 100%		 N/A IMRT: 1 (3.6%)
CRT: 2 (2.3%)		 5 y: 81% 5 y: 81%
Chatterjee38 IND (2020) P 59 53 mo (53–60) 55 Gy (N/A) 2.75 (N/A) N/A N/A N/A N/A N/A 18 T1: 89%
T2: 11%		 N/A N/A IMRT: 4 (22%) IMRT: 1 (5.6%) 5 y: 75% N/A
Uzel39 TUR (2020) RR 18 18 mo (6–44) 58.08 Gy (57.6–58.08) 3.63 (3.63–3.84) N/A N/A N/A N/A N/A 18 T1: 100%
T2: 0%		 N/A N/A IMRT: 0 (0%) N/A N/A N/A
Kim40 KOR (2021) RR 101 58 mo (11–90) 63 Gy (63–67.5) 2.25 (N/A) N/A N/A N/A 42% N/A 101 T1: 70%
T2: 30%		 N/A N/A IMRT: 13 (13%) IMRT: 1 (1%) N/A 5 y: 97%
Bicakci41 TUR (2022) RR 201 31 mo (6–88) 66 Gy (63–70) 2.2 (2–2.5) N/A N/A N/A 23% 14% 201 Tis: 14%
T1: 76%
T2: 10%		 N/A N/A IMRT: 7 (3.5%) IMRT: 4 (2%) 3 y: 95%
5 y: 92%		 5 y: 85%
Trans42 NLD (2022) RR 111 41 mo (8–84) 58.08 Gy (N/A) 3.62 (N/A) N/A N/A N/A 40% N/A 111 T1: 97%
T2: 3%		 N/A N/A IMRT: 2 (1.8%) IMRT: 0 (0%) 3 y: 99%
5 yr: 97%		 5 y: 81%
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Abbreviations: BEL = Belgium; CAN = Canada; CHE = Switzerland; IND = India; KOR = South Korea; N = no; NLD =; P = prospective; RR = retrospective review; TUR = Turkey; USA = United States of America; Y = yes.

Abbreviations: AC = anterior commissure; CC = concurrent chemotherapy; chemo = chemotherapy; CRT = conventional radiation therapy; ENI = elective nodal irradiation; FU = follow-up; fx = fraction; IMRT = intensity-modulated radiation therapy; N/A = not available; N = no; P = prospective; RR = retrospective review; Y = yes.

Table 2.

Intensity modulated radiation treatment (IMRT) details of included studies

Author (citation) IMRT technique Delivery method Beam arrangement IGRT details Bolus aize and indication GTV contour CTV contour PTV contour Dosimetry parameters
Janssen28 PL SW, VMAT 4–5 coplanar beams Daily kV; routine CBCT; instruct patients not to swallow 0.5 cm – (1) <0.5 cm GTV-skin, (2) AC involved Gross disease GTV + 10–15 mm PTV1: CTV + 2–3 mm (for T1–2, PTV1 will include up to 2/3 of larynx volume);
PTV2: small region CrCa to PTV1;
PTV3: elective neck		 PTV1: D95% = 95%, D98% < 110%; avoid hotspots in Ar
Zumsteg29 CS N/A 4 anterior coplanar beams N/A N/A –AC involved N/A Gross disease + entire larynx (AC, PC, Ar, top of TC to bottom of CrC) CTV + 10 mm PTV: D95% = 100%, Dmax = 105%, Mean CA = 52 Gy
Berwouts30 N/A SS 6 coplanar beams Daily CBCT No bolus Involved VC, C G, SubG, part of SupraG (including FVC and ArC) and ≥2 cm Cr-Ca; for T1-Cr/A boarder: thyroid notch at level of arytenoid superior process, Ca/A boarder: middle of CrC; for T2, similar to T1 but included P edge of CrC CTV + 3 mm PTV: D95% ≥ 95%, D5% ≤ 107%
Low31 N/A N/A N/A N/A N/A N/A N/A N/A N/A
Rock32 PL N/A 4–5 beams Daily CBCT; align to laryngeal soft tissue or bone 0.5 cm – (1) minimal soft tissue, (2) AC involved Gross disease CTV1: GTV + 5-mm isotropic (trimmed at cartilage)
CTV2: 0.5 cm + PTV1		 PTV 1–2: CTV1–2 + 10 mm (CrCa) + 5 mm (LR, AP) PTV: D95% ≥ 95%
Cetinayak33 CS VMAT 2 arcs N/A N/A Gross disease TVC, Ven, FVC, Ar, SubG region, and AF (only for T2) PTV1: GTV + 5–10 mm CC, 10 mm LR, 3–5 mm AP;
PTV2: CTV + 5–10 mm (CrCa), 10 mm (LR), 3–5 mm (AP)		 N/A
Cho34 N/A Tomo, SS Tomo: FW, 2.5; MF, 2.468; Pi, 0.287;
IMRT: 6 beams VMAT: 1–2 arcs		 Daily CBCT N/A N/A CTV1: Gross disease, ipsilateral TVC, AC;
CTV2: True + FVC, SubG, part of SupraG
Margins: CrCa = thyroid notch to CrC, AP = TC to ArC, LR = TC		 PTV1–2: CTV1–2 + 3 mm PTV1–2: D95% > 95%, Dmax < 110%
Chung35 SVC Tomo, VMAT N/A MV, CBCT; instruct patients not to swallow; align to thyroid cartilage N/A Gross disease GTV + 0.3 cm CTV + 3–5 mm (AP, LR), 10 mm (CrCa) PTV: D99% > 95%
Mohamed36 CS SS, VMAT IMRT: 5–7 beams
VMAT: 2 arcs		 Daily kV; align to laryngeal cartilage Unspecified, N/A N/A Entire TC, CrC with ≤5 mm anteriorly N/A N/A
Al Feghali37 CS N/A N/A N/A N/A N/A Entire larynx (including suprahyoid epiglottis) N/A N/A
Chatterjee38 CS Tomo FW, 1; MF, 2; Pi, 0.4 N/A 0.5 cm, AC involved N/A Entire TC, paraglottic and preglottic tissue, minor larynx cartilages; CrCa extent: TC - CrC CTV + 5 mm isotropic (shaved 3 mm from skin) N/A
Uzel39 SVC VMAT N/A Daily CBCT; instruct patients not to swallow; align to thyroid cartilage N/A N/A Entire involved TVC + 3–5 mm margin if visible tumor extends to one end of cord CTV + 3 mm isotropic PTV: D100% > 95%, D2% > 107%
Kim40 N/A Tomo N/A N/A N/A N/A Bilateral VC + FVC, AC, PC, Ar, AF, SubG region CTV + 5 mm (LR, CrCa, A), 3 mm (P) PTV: D100% > 95%; CA: V35 < 50%, Dmean < 35 Gy
Bicakci41 CS VMAT IMRT: 3–9 beams
VMAT: 2–4 arcs		 Daily/QOD kV-kV or CBCT N/A Tumor or whole VC Entire larynx including FVC + TVC, ArC, SubG, AC, PC, ventricular band, superior hyoid, inferior CrC CTV + 3–5 mm N/A
Trans42 SVC N/A 5–9 beams Daily CBCT; instruct patients not to swallow; align to thyroid cartilage N/A N/A Entire involved VC CTV + 3 mm (LR, AP), 5 mm (CrCa) N/A
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Abbreviations: A = anterior; AC = anterior commissure; AF = aryepiglottic folds; Ar = arytenoid; ArC = arytenoid cartilage; CA = carotid artery; CBCT = cone beam computed tomography; CrC = cricoid cartilage; CrCa = craniocaudal; CS = carotid sparing; CTV = clinical target volume; Dmax = maximum dose; Dmean = mean dose; FVC = false vocal cord; FW = field width; G = glottic; GTV = gross tumor volume; IGRT = image-guided radiation therapy; LR = left right; N/A = not available; P = posterior; PC = posterior commissure; Pi = pitch; PL = partial larynx; PTV = planning target volume; QOD = every other day; SS = step and shoot; subG = subglottic; SupraG = supraglottic; SVC = single vocal cord; SW = sliding window; TC = thyroid cartilage; tomo = tomotherapy; TVC = true vocal cord; VC = vocal cord; VMAT = volumetric modulated arc therapy.

Outcomes post IMRT

Among the 15 studies included for analysis, reported outcomes included crude LF, crude RF, actuarial LF at 3 and 5 years, and actuarial overall survival at 5 years. From 795 patients treated with IMRT, the pooled rate of crude LF was 7.6% (95% confidence interval (CI), 3.6%–11.5%; Fig. 2A). When examined by IMRT technique, the LF rate was lower in studies using carotid-sparing (4.1%; 95% CI, 1.9%–6.2%) or single-vocal cord techniques (2.0%; 95% CI, 0.0%–4.2%) than in studies using other/unknown techniques (13.2%; 95% CI, 6.6%–19.9%; P < .001; Fig. E2). Crude LF was similar for studies using daily CBCT for imaging guidance (7.3%; 95% CI, 1.2%–13.4%) and studies using other/unknown image guidance methods (7.8%; 95% CI, 2.6%–13.0%; Fig. E3).

Fig. 2.

Fig. 2.

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Forest plot and pooled estimates of crude local and regional failure in patients treated with (A, B) intensity-modulated radiation therapy (IMRT) and (C, D) conventional radiation therapy (CRT). Abbreviation: CI = confidence interval; RE = random effects.

Among 10 studies (n = 771) that reported nodal failures, the pooled RF rate was low: 1.5% (95% CI, 0.5%–2.5%; Fig. 2B). When compared by IMRT technique, the crude RF rate was similar in studies using carotid-sparing techniques (1.8%; 95% CI, 0.4%–3.1%) and studies using other/unknown techniques (1.7%; 95% CI, 0.0%–3.5%; P = .65; Fig. E4). The RF rates were also comparable by image guidance method: daily CBCT and other/unknown methods had pooled crude failure rates of 2.1% (95% CI, 0.2%–3.9%) and 1.3% (95% CI, 0.0%–2.6%), respectively (Fig. E5).

Actuarial LF and overall survival associated with IMRT were reported in 9 (n = 677) and 10 studies (n = 771), respectively. The pooled rate of actuarial LF was 6.3% (95% CI, 2.2%–10.3%) at 3 years and 9.0% (95% CI, 4.4%–13.5%) at 5 years post IMRT (Fig. E6). Overall survival at 5 years was high: 87.6% (95% CI, 82.8%–92.4%; Fig. E7).

Clinical characteristics associated with treatment failure post IMRT

To better understand factors associated with treatment failures post IMRT, metaregression analyses were performed. Separate models for each factor of interest were examined using metaregression models, and the test for beta coefficient (β) corresponding to each factor was examined (Table E2). On univariate analysis, T2 disease (β = 0.19; P < .001), grade 2 to 3 histology (β = 0.18; P < .001), and median follow-up time (β = 0.004; P < .001) were significantly associated with higher LF rates (Fig. 3A–C). T2 disease (β = 0.0004; P = .021) was significantly associated with higher RF rates (Fig. 3D). When the study by Rock et al was removed, the association with T2 disease remained significant (β = 0.36; P = .003), and the association with grade was lost (β = 0.0; P = .992). History of smoking and anterior commissure involvement were not associated with LF or RF (Table E2). Among the 5 studies reporting T2 disease, grade 2 to 3 histology, and median follow-up time, multivariate metaregression modeling revealed that only T2 disease was significantly associated with LF (β = 0.15; P = .015; Table E3).

Fig. 3.

Fig. 3.

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Metaregression analyses demonstrating an association between local failure (A) after intensity-modulated radiation therapy and T2 disease, (B) grade 2 to 3 histology, and (C) median follow-up time. (D) The association of T2 disease and regional failure after intensity modulated radiation therapy is also presented. Degree of correlation (β) and significance (P value) are displayed.

Toxicity and salvage treatment reported with IMRT

Toxicities associated with IMRT that were reported in at least 2 studies included feeding tube use, dysphagia, dermatitis, laryngeal edema, laryngeal necrosis, hoarseness, and carotid/cerebrovascular events (Table 3). The most commonly reported toxicities post IMRT were acute dysphagia, acute dermatitis, and late hoarseness; these were most frequently reported as grade 1 in severity (57%, 35%, and 14%, respectively). Carotid and cerebrovascular events post IMRT were reported in 2 of 130 patients (1.5%) from 3 studies. Using random effects models, the pooled rates of late (6 months or longer) feed tube use (n = 402), late grade 3 or more laryngeal edema (n = 397), and any late grade 3 or more toxicity (n = 330) were 0.4% (95% CI, 0.0%–1.0%), 1.8% (95% CI, 0.4%–3.1%), and 2.2% (95% CI, 0.0%–5.1%), respectively (Fig. E8).

Table 3.

Summary of intensity modulate radiation therapy toxicities reported in at least 2 studies

Toxicity # Studies (citations) Total # at risk Total # with toxicity (%) Grade 1 (%) Grade 2 (%) Grade 3+ (%)
Feeding tube (during treatment) 228,31 179 5 (2.8) N/A N/A N/A
Feeding tube (6 mo after treatment) 332,36,41 402 1 (0.2) N/A N/A N/A
Any acute grade 3+ 239,42 129 0 (0) N/A N/A 0
Any late grade 3+ 428,32,33,42 330 18 (5.5) N/A N/A 18 (5.5)
Late laryngeal edema 428,32,39,41 397 11 (2.8) 4 (1.0) 0 (0) 7 (1.8)
Laryngeal necrosis 232,42 247 6 (2.4) N/A N/A 6 (2.4)
Acute dysphagia 230,39 58 39 (67.2) 33 (56.9) 6 (10.3) 0 (0)
Acute dermatitis 430,33,34,39 115 53 (46.1) 40 (34.8) 10 (8.7) 3 (2.6)
Cerebrovascular event 330,36,37 130 2 (1.5) N/A N/A N/A
Late hoarseness 230,42 143 28 (19.6) 20 (14) 5 (3.5) 3 (2.1)
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Abbreviation: N/A = not available.

Salvage therapies after IMRT are summarized in Table E4. Of the 67 patients in which salvage therapy was reported after LF and/or RF, total laryngectomy was the most common salvage treatment (72%). Other salvage therapies included partial laryngectomy (15%), neck dissection (20%), cordectomy (6%), and chemotherapy (1.5%).

Treatment outcomes post CRT

In addition to IMRT, 5 studies (n = 738) reported treatment failure outcomes in patients treated with CRT. Similar to IMRT, the majority of patients receiving CRT had T1 disease: 13 (2%), 557 (76%), 166 (22%) patients had Tis, T1, and T2 disease, respectively. Post CRT, the pooled crude LF and RF rates were 12.2% (95% CI, 6.1%–18.3%) and 1.9% (95% CI, 0.9%–2.9%), respectively (Fig. 2C, D). On metaregression analysis, median follow-up time was not significantly associated with higher LF (P = .29) or RF (P = .86) rates post CRT (Table E2). Among the studies that reported outcomes for patients treated with IMRT or CRT, there was no significant difference (P = .12) in the LF rate between the 2 modalities (log odds ratio −0.48; 95% CI, −1.09%–0.14%; Fig. E9). Similarly, there was no significant difference (P = .58) in the RF rate between the 2 modalities (log odds ratio, 0.25; 95% CI, −0.66%–1.16%; Fig. E10). Finally, toxicity was reported in 4 studies that included patients treated with CRT (Table E5). Only acute dermatitis and cerebrovascular events were reported in more than 1 study (2 studies each). Toxicities associated with CRT included late feeding tube use (2.6%), late laryngitis (0.7%), acute dermatitis (grade 1, 50%; grade 2, 13%; grade 3+, 15%), cerebrovascular events (2.1%), and aspiration (6.5%).

Discussion

For most head and neck cancers, IMRT has become the primary treatment technique due to its improved toxicity profile.43–46 In early-stage cancers of the glottis, however, use of IMRT is controversial. Early dosimetric studies demonstrated that IMRT is associated with reduced doses to the carotid arteries compared with CRT.8,22,23 These reduced doses would, in theory, mitigate acute side effects of treatment, as well as the increased risk of stroke and cerebrovascular events associated with neck treatment for head and neck cancer.9–17 Despite this purported benefit, studies of the National Cancer Database and Surveillance, Epidemiology, and End Results database found that in 2015 to 2016, approximately 22% to 40% patients received IMRT.47,48 There are several possible reasons why IMRT in this patient population remains controversial. First, published literature on IMRT for early glottic cancers is limited to small institutional series. Large prospective trials are lacking, and there is no randomized controlled evidence evaluating differences between IMRT and CRT. Additionally, while national database studies did not demonstrate an overall survival difference between IMRT and CRT, 1 study found that IMRT was associated with reduced cancer-specific survival at 2 years, particularly in patients with T1 disease.47,48 Finally, perhaps the most significant concern with the use of IMRT is the risk of increased LF and RF rates due to highly conformal treatment, intrafractional laryngeal motion, heterogeneous methods for target delineation, variable provider experience/education, and minimal elective neck coverage.24,49

Given the concerns about IMRT, we performed a systematic review and meta-analysis to better understand outcomes associated with this irradiation technique. In terms of local control, we found that the crude LF rate was 7.6%, while the LF rate at 3 and 5 years post IMRT was 6.3% and 9%, respectively. Additionally, IMRT was associated with a pooled crude nodal failure rate of 1.5%. These findings are consistent with prior institutional and pooled analyses of patients treated with CRT.3,5–8,50–58 For example, a report of 735 patients from Princess Margaret Hospital found that CRT was associated with a 5-year local relapse-free rate of 81.7% and a crude RF rate of 3.0%.6 Similarly, the University of Florida reported 5-year local control rates of 94%, 93%, 80%, and 70% for T1a, T1b, T2a, and T2b disease, respectively, and a neck failure rate of 4%.8 Prior meta-analyses of CRT have reported 3-year local control rates of 89.3% and 86.2% for T1a and T1b disease, respectively, and a 5-year local control rate of 75.8% for T2 disease.57,58

Several studies in our analysis reported a separate population of patients treated with CRT. Both IMRT and CRT groups had similar proportions of patients with T2 disease (approximately 20%−30%). Pooled analyses of outcomes post CRT revealed crude LF and RF rates of 12.2% and 1.9%, respectively, which is in line with the previously described studies. When the 2 treatment techniques were compared directly, there was no significant difference in LF or RF rates between IMRT and CRT. While these findings suggest that early-stage glottic cancer may have similar cancer control outcomes regardless of the radiation modality employed, they must be interpreted with caution: only a subset of studies (5) were used for this analysis. These studies were retrospective and employed different IMRT (most commonly carotid-sparing IMRT) and IGRT techniques, heterogeneous methods for treatment volume delineation, and different planning objectives. Moreover, the effect of dose and fraction could not be evaluated. Thus, while direct comparison between CRT and IMRT afforded by this meta-analysis is not without limitations, our aforementioned pooled outcomes data demonstrate that IMRT for early glottis larynx cancers is associated with low LF and RF rates, which are in line with historic outcomes of CRT.

We also examined clinical and treatment factors associated with LF and RF post IMRT. T2 disease and histologic grade have been associated with treatment failure post CRT.3,6,8 Similarly, we found that studies that contained a greater proportion of patients with these factors reported higher rates of LF and/or RF. In terms of IMRT treatment technique, LF rates were higher among the studies that used partial larynx, or did not describe, IMRT treatment technique. This, in part, is because these studies had a greater proportion of patients with T2 disease (55%) compared with studies using carotid-sparing (11% T2 disease) or single vocal cord (2% T2 disease) techniques. Studies using single vocal cord IMRT predominantly treated patients with T1a disease.35,39,42 Additionally, the increased failure rates in studies where treatment techniques were not described highlight the importance of consensus contouring guidelines. As outlined in Table 2, there is variability in target definition, even within the same IMRT treatment technique. The use of a consensus definition for target delineation, similar to the one proposed by Gujral and colleagues, may help improve provider confidence with using IMRT as well as minimize risk of geographic miss.59

In addition to the type of IMRT, another variable that could potentially affect outcomes are IGRT techniques and motion management methods. This point is highlighted by Rock et al, who found that daily imaging alignment to bone, compared with laryngeal soft tissue, was associated with worse 3- and 5-year local control.32 Outside of the type of IGRT used (eg, CBCT, kV imaging), only 5 studies mentioned daily imaging surrogates (thyroid cartilage, laryngeal cartilage, laryngeal soft tissue, and bone)—and 4 studies described methods to manage intrafractional motion (asking patients not to swallow). Of the 5 studies that provided this information, 4 studies used partial or single vocal cord IMRT techniques, while 1 study used carotid-sparing IMRT. The fact that this information was provided in studies using smaller treatment volumes highlights the importance of IGRT when reducing RT fields. While type of daily imaging, alignment surrogate, and intrafractional motion management can affect disease control with IMRT, this information was too heterogeneously reported in the included studies to conduct sensitivity analyses. Future work on developing consensus target volumes for early glottis cancers should also provide recommendations on acceptable IGRT techniques.

In terms of nodal control, the RF rate was similar between carotid-sparing and other IMRT techniques.6,8 This is expected given that early-stage glottic cancers have a low RF rate, and that elective nodal irradiation was not standardly performed in studies using IMRT (Table 1).6,8,60 Other treatment factors, such as fractionation, could not examined due to lack of outcomes data.

In addition to tumor control, we also evaluated survival outcomes associated with IMRT. We found that the pooled overall survival was high: 87.6% at 5 years. This is in line with prior surgical and radiation series that report 5-year overall survival rates ranging from 63% to 92%.3,5,7,61–65 In part, this high survival rate is due to the fact that many failures post IMRT were salvageable: of the 69 local and 18 RFs, salvage treatments (most commonly total laryngectomy and nodal dissection) were reported in 67 patients (77%). Unfortunately, other survival outcomes of interest were reported heterogeneously and could not be pooled for statistical analysis. For example, disease specific survival at 5 years post IMRT was reported in only 2 studies (both 100%).31,33 Similarly, ultimate local control at 5 years was reported in only 2 studies (99%−100%).30,42

Toxicity after IMRT is another relevant clinical outcome. For other head and neck cancers, prior comparisons between CRT and IMRT demonstrated that IMRT is associated with reduced xerostomia, fibrosis, and feeding tube use.43–46 The benefits of IMRT seen in patients with locally advanced disease may not be directly applicable to patients treated with limited volumes for early-stage disease. In this analysis, toxicities reported from IMRT appeared favorable: acute symptoms, such as dysphagia and dermatitis, were predominantly low-grade, while the pooled rates of late feeding tube use and laryngeal edema were low. In terms of CRT, toxicities were reported in 4 studies: acute dermatitis and late feeding tube use were more frequent post CRT than post IMRT; however, these could not be compared statistically. Cerebrovascular events are another adverse event of interest in early-stage glottic tumors.8,22,23 In our analysis, this toxicity was examined in only 15% and 32% of patients receiving IMRT and CRT, respectively. While rates of cerebrovascular events in both groups were low, these findings should be interpreted with caution: these studies were retrospective and not specifically designed to capture or compare cerebrovascular outcomes, which typically requires longer-term follow-up and consideration of baseline comorbidities. This is highlighted by the fact that the rates of cerebrovascular events reported here are lower than other institutional and national database cohorts (3.4%–34%).9–11,17 Additional studies are needed to better evaluate carotid artery stenosis and cerebrovascular outcomes associated with IMRT to the glottic larynx.

Overall, our study had several strengths. First, to our knowledge, this is the only pooled analysis of outcomes from IMRT for early glottic larynx cancer. The patient population is heterogeneous, and multiple IMRT treatment techniques are represented. Additionally, this analysis was designed prospectively, used appropriate statistics, and can be used to power future randomized studies. This study does, however, have some limitations. Because it is a study level meta-analysis and not a patient level analysis, detailed comparisons between subgroups were not possible, and some outcomes (eg, ultimate local control) were too heterogeneously reported for pooled statistical analysis. We could not control for differences in techniques, volume delimitation, and IGRT approaches. Moreover, metaregression analyses are hypotheses generating and require additional validation. Finally, certain risk factors of clinical and prognostic significance (eg, radiation dose, fractionation) were not addressed due to limited available data.

Ultimately, these data further inform the risk-benefit analysis radiation oncologists must make when selecting between radiation treatment modalities. By limiting the radiation target, IMRT has the potential to improve treatment toxicity and patient reported outcomes and does not appear to sacrifice tumor control. While a prospective, randomized trial is needed to best assess differences between CRT and IMRT, our findings allow for more comprehensive decision making for patients with early-stage glottic cancer.

Conclusion

For patients with early-stage squamous cell carcinoma of the glottic larynx, IMRT is associated with high rates of local and regional control. While the toxicity profile associated with this treatment modality appears to be favorable, additional studies are needed to assess the effect of IMRT on radiation-induced cerebrovascular disease. This study provides the strongest level of evidence to date to support the efficacy of IMRT in early-stage glottic larynx cancer.

Supplementary Material

Supplementary Tables
Supplementary Appendix
Supplementary Figures

Footnotes

Disclosures: none.

Data generated and analyzed during for this study are included in the published article and supplementary files. Additional data may be available upon written request to the corresponding author.

Supplementary material associated with this article can be found in the online version at doi:10.1016/j.ijrobp.2023.04.035.

References

  • 1.American Cancer Society. Cancer facts & figures. 2022. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed October 11, 2022.
  • 2.Mendenhall WM, Werning JW, Hinerman RW, Amdur RJ, Villaret DB. Management of T1−T2 glottic carcinomas. Cancer 2004;100:1786–1792. [DOI] [PubMed] [Google Scholar]
  • 3.Mendenhall WM, Amdur RJ, Morris CG, Hinerman RW. T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 2001;19:4029–4036. [DOI] [PubMed] [Google Scholar]
  • 4.Wang C-C. Radiation therapy for head and neck neoplasms. Hoboken, NJ: Wiley; 1990. [Google Scholar]
  • 5.Le QT, Fu KK, Kroll S, et al. Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma. Int J Radiat Oncol Biol Phys 1997;39:115–126. [DOI] [PubMed] [Google Scholar]
  • 6.Warde P, O’Sullivan B, Bristow RG, et al. T1/T2 glottic cancer managed by external beam radiotherapy: The influence of pretreatment hemoglobin on local control. Int J Radiat Oncol Biol Phys 1998;41:347–353. [DOI] [PubMed] [Google Scholar]
  • 7.Garden AS, Forster K, Wong PF, Morrison WH, Schechter NR, Ang KK. Results of radiotherapy for T2N0 glottic carcinoma: Does the “2” stand for twice-daily treatment? Int J Radiat Oncol Biol Phys 2003;55:322–328. [DOI] [PubMed] [Google Scholar]
  • 8.Chera BS, Amdur RJ, Morris CG, Kirwan JM, Mendenhall WM. T1N0 to T2N0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy. Int J Radiat Oncol Biol Phys 2010;78:461–466. [DOI] [PubMed] [Google Scholar]
  • 9.Dorresteijn LD, Kappelle AC, Boogerd W, et al. Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 2002;20:282–288. [DOI] [PubMed] [Google Scholar]
  • 10.Smith GL, Smith BD, Buchholz TA, et al. Cerebrovascular disease risk in older head and neck cancer patients after radiotherapy. J Clin Oncol 2008;26 5119–1125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Brown PD, Foote RL, McLaughlin MP, et al. A historical prospective cohort study of carotid artery stenosis after radiotherapy for head and neck malignancies. Int J Radiat Oncol Biol Phys 2005;63:1361–1367. [DOI] [PubMed] [Google Scholar]
  • 12.Greco A, Gallo A, De Virgilio A, et al. Carotid stenosis after adjuvant cervical radiotherapy in patients with head and neck cancers: A prospective controlled study. Clin Otolaryngol 2012;37 376–281. [DOI] [PubMed] [Google Scholar]
  • 13.Dorth JA, Patel PR, Broadwater G, Brizel DM. Incidence and risk factors of significant carotid artery stenosis in asymptomatic survivors of head and neck cancer after radiotherapy. Head Neck 2014;36:215–219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Martin JD, Buckley AR, Graeb D, Walman B, Salvian A, Hay JH. Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation. Int J Radiat Oncol Biol Phys 2005;63:1197–1205. [DOI] [PubMed] [Google Scholar]
  • 15.Cheng SW, Ting AC, Ho P, Wu LL. Accelerated progression of carotid stenosis in patients with previous external neck irradiation. J Vasc Surg 2004;39:409–415. [DOI] [PubMed] [Google Scholar]
  • 16.Plummer C, Henderson RD, O’Sullivan JD, Read SJ. Ischemic stroke and transient ischemic attack after head and neck radiotherapy: A review. Stroke 2011;42:2410–2418. [DOI] [PubMed] [Google Scholar]
  • 17.Haynes JC, Machtay M, Weber RS, Weinstein GS, Chalian AA, Rosenthal DI. Relative risk of stroke in head and neck carcinoma patients treated with external cervical irradiation. Laryngoscope 2002;112:1883–1887. [DOI] [PubMed] [Google Scholar]
  • 18.Nutting CM, Morden JP, Harrington KJ, et al. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): A phase 3 multicentre randomised controlled trial. Lancet Oncol 2011;12:127–136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Eisbruch A, Harris J, Garden AS, et al. Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00–22). Int J Radiat Oncol Biol Phys 2010;76:1333–1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: Radiation therapy oncology group phase II trial 0225. J Clin Oncol 2009;27:3684–3690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Chera BS, Amdur RJ, Morris CG, Mendenhall WM. Carotid-sparing intensity-modulated radiotherapy for early-stage squamous cell carcinoma of the true vocal cord. Int J Radiat Oncol Biol Phys 2010;77:1380–1385. [DOI] [PubMed] [Google Scholar]
  • 22.Rosenthal DI, Fuller CD, Barker JL Jr, et al. Simple carotid-sparing intensity-modulated radiotherapy technique and preliminary experience for T1–2 glottic cancer. Int J Radiat Oncol Biol Phys 2010;77:455–461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Choi HS, Jeong BK, Jeong H, et al. Carotid sparing intensity modulated radiotherapy on early glottic cancer: Preliminary study. Radiat Oncol J 2016;34:26–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Feigenberg SJ, Lango M, Nicolaou N, Ridge JA. Intensity-modulated radiotherapy for early larynx cancer: Is there a role? Int J Radiat Oncol Biol Phys 2007;68:2–3. [DOI] [PubMed] [Google Scholar]
  • 25.Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews. Br Med J 2021;372:n160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (MINORS): Development and validation of a new instrument. ANZ J Surg 2003;73:712–716. [DOI] [PubMed] [Google Scholar]
  • 27.Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/. [Google Scholar]
  • 28.Janssen S, Glanzmann C, Huber G, Studer G. Risk-adapted partial larynx and/or carotid artery sparing modulated radiation therapy of glottic cancer. Radiat Oncol 2014;9:136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Zumsteg ZS, Riaz N, Jaffery S, et al. Carotid sparing intensity-modulated radiation therapy achieves comparable locoregional control to conventional radiotherapy in T1–2N0 laryngeal carcinoma. Oral Oncol 2015;51:716–723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Berwouts D, Swimberghe M, Duprez F, et al. Intensity-modulated radiotherapy for early-stage glottic cancer. Head Neck 2016;38(supp 1): E179–E184. [DOI] [PubMed] [Google Scholar]
  • 31.Low TH, Yeh D, Zhang T, et al. Evaluating organ preservation outcome as treatment endpoint for T1aN0 glottic cancer. Laryngoscope 2017;127:1322–1327. [DOI] [PubMed] [Google Scholar]
  • 32.Rock K, Huang SH, Tiong A, et al. Partial laryngeal IMRT for T2N0 glottic cancer: Impact of image guidance and radiation therapy intensification. Int J Radiat Oncol Biol Phys 2018;102:941–949. [DOI] [PubMed] [Google Scholar]
  • 33.Cetinayak O, Dogan E, Kuru A, et al. Outcome of early-stage glottic laryngeal carcinoma patients treated with radical radiotherapy using different techniques. J Oncol 2019. 8640549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Cho IJ, Chung W-K, Lee JK, et al. Intensity-modulated radiotherapy for stage I glottic cancer: A short-term outcomes compared with three-dimensional conformal radiotherapy. Radiat Oncol J 2019;37:271–278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Chung SY, Lee CG. Feasibility of single vocal cord irradiation as a treatment strategy for T1a glottic cancer. Head Neck 2020;42:854–859. [DOI] [PubMed] [Google Scholar]
  • 36.Mohamed AS, Smith BD, Smith JB, et al. Outcomes of carotid-sparing IMRT for T1 glottic cancer: Comparison with conventional radiation. Laryngoscope 2020;130:146–153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Al Feghali KA, Youssef BY, Mohamed AS, et al. Outcomes after radiation therapy for T2N0/stage II glottic squamous cell carcinoma. Head Neck 2020;42:2791–2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Chatterjee S, Mallick I, Chakraborty S, et al. Helical radiotherapy in early laryngeal cancers could lead to excess local recurrence: Lessons from a phase II prospective study. Clin Oncol 2020;32:e67–e75. [DOI] [PubMed] [Google Scholar]
  • 39.Kocak Uzel E, Figen M, Uzel ÖE. Is single cord irradiation going to be a new standard for T1a glottic carcinoma? Front Oncol 2020;10:1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Kim D, Ki Y, Joo J, et al. Prognostic value of the maximum standardized uptake value for the locoregional control in early glottic cancer. Radiat Oncol J 2021;39:297–303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Bicakci BC, Mustafayev TZ, Cetinayak O, et al. Outcomes of carotid sparing intensity-modulated radiotherapy for early stage glottic cancer in 201 patients: Multicenter study of Turkish Radiation Oncology Society/TROD-01–007. Head Neck 2022;44:1825–1832. [DOI] [PubMed] [Google Scholar]
  • 42.Tans L, Al-Mamgani A, Kwa SL, et al. Single vocal cord irradiation for early-stage glottic cancer: Excellent local control and favorable toxicity profile. Oral Oncology 2022;127 105782. [DOI] [PubMed] [Google Scholar]
  • 43.Chao KC, Majhail N, Huang C-J, et al. Intensity-modulated radiation therapy reduces late salivary toxicity without compromising tumor control in patients with oropharyngeal carcinoma: A comparison with conventional techniques. Radiother Oncol 2001;61:275–280. [DOI] [PubMed] [Google Scholar]
  • 44.Gupta T, Sinha S, Ghosh-Laskar S, et al. Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: Long-term and mature outcomes of a prospective randomized trial. Radiat Oncol 2020;15:218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Lohia S, Rajapurkar M, Nguyen SA, Sharma AK, Gillespie MB, Day TA. A comparison of outcomes using intensity-modulated radiation therapy and 3-dimensional conformal radiation therapy in treatment of oropharyngeal cancer. J Am Med Assoc Otolaryngol HeadNeck Surg 2014;140:331–337. [DOI] [PubMed] [Google Scholar]
  • 46.Gupta T, Kannan S, Ghosh-Laskar S, Agarwal JP. Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma. Plos One 2018;13 e0200137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Amini A, Morgan R, Meyer E, et al. Outcomes between intensity-modulated radiation therapy versus 3D-conformal in early stage glottic cancer. Head Neck 2021;43:3393–3403. [DOI] [PubMed] [Google Scholar]
  • 48.Korpics MC, Turchan WT, Rooney MK, Koshy M, Spiotto MT. Patterns of care and outcomes of intensity-modulated radiotherapy and 3D conformal radiotherapy for early stage glottic cancer: A National Cancer Database analysis. Cancers 2019;11:1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.DePaoli B, Harper J, Albergotti WG, O’Rourke A, Chera BS. Regional recurrence after carotid sparing IMRT for early stage glottic cancer. Pract Radiat Oncol 2023;13:E95–E98. [DOI] [PubMed] [Google Scholar]
  • 50.Nomiya T, Nemoto K, Wada H, Takai Y, Yamada S. Long-term results of radiotherapy for T1a and T1bN0M0 glottic carcinoma. Laryngoscope 2008;118:1417–1421. [DOI] [PubMed] [Google Scholar]
  • 51.Groome PA, O’Sullivan B, Mackillop WJ, et al. Compromised local control due to treatment interruptions and late treatment breaks in early glottic cancer: Population-based outcomes study supporting need for intensified treatment schedules. Int J Radiat Oncol Biol Phys 2006;64:1002–1012. [DOI] [PubMed] [Google Scholar]
  • 52.Cellai E, Frata P, Magrini SM, et al. Radical radiotherapy for early glottic cancer: results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease. Int J Radiat Oncol Biol Phys 2005;63:1378–1386. [DOI] [PubMed] [Google Scholar]
  • 53.Frata P, Cellai E, Magrini SM, et al. Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. II. The case of T2N0 disease. Int J Radiat Oncol Biol Phys 2005;63:1387–1394. [DOI] [PubMed] [Google Scholar]
  • 54.Cho EI, Sasaki CT, Haffty BG. Prognostic significance of pretreatment hemoglobin for local control and overall survival in T1-T2N0 larynx cancer treated with external beam radiotherapy. Int J Radiat Oncol Biol Phys 2004;58:1135–1140. [DOI] [PubMed] [Google Scholar]
  • 55.Gowda RV, Henk JM, Mais KL, Sykes AJ, Swindell R, Slevin NJ. Three weeks radiotherapy for T1 glottic cancer: The Christie and Royal Marsden Hospital Experience. Radiother Oncol 2003;68:105–111. [DOI] [PubMed] [Google Scholar]
  • 56.Burke LS, Greven KM, McGuirt WT, Case D, Hoen HM, Raben M. Definitive radiotherapy for early glottic carcinoma: Prognostic factors and implications for treatment. Int J Radiat Oncol Biol Phys 1997;38:1001–1006. [DOI] [PubMed] [Google Scholar]
  • 57.O’Hara J, Markey A, Homer JJ. Transoral laser surgery versus radiotherapy for tumour stage 1a or 1b glottic squamous cell carcinoma: Aystematic review of local control outcomes. J Laryngol Otol 2013;127:732–738. [DOI] [PubMed] [Google Scholar]
  • 58.Warner L, Lee K, Homer JJ. Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: A systematic review of local control outcomes. Clin Otolaryngol 2017;42:629–636. [DOI] [PubMed] [Google Scholar]
  • 59.Gujral DM, Long M, Roe JWG, Harrington KJ, Nutting CM. Standardisation of target volume delineation for carotid-sparing intensity-modulated radiotherapy in early glottis cancer. Clin Oncol 2017;29:42–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Chung SY, Kim KH, Keum KC, et al. Radiotherapy versus cordectomy in the management of early glottic cancer. Cancer Res Treat 2018;50:156–163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Spector JG, Sessions DG, Chao KS, et al. Stage I (T1 N0 M0) squamous cell carcinoma of the laryngeal glottis: Therapeutic results and voice preservation. Head Neck 1999;21:707–717. [DOI] [PubMed] [Google Scholar]
  • 62.Steiner W. Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 1993;14:116–121. [DOI] [PubMed] [Google Scholar]
  • 63.Peretti G, Nicolai P, Redaelli De Zinis LO, et al. Endoscopic CO2 laser excision for tis, T1, and T2 glottic carcinomas: Cure rate and prognostic factors. Otolaryngol Head Neck Surg 2000;123:124–131. [DOI] [PubMed] [Google Scholar]
  • 64.Thomas JV, Olsen KD, Neel 3rd HB, DeSanto LW, Suman VJ. Early glottic carcinoma treated with open laryngeal procedures. Arch Otolaryngol Head Neck Surg 1994;120:264–268. [DOI] [PubMed] [Google Scholar]
  • 65.Spector JG, Sessions DG, Chao KS, Hanson JM, Simpson JR, Perez CA. Management of stage II (T2N0M0) glottic carcinoma by radiotherapy and conservation surgery. Head Neck 1999;21:116–123. [DOI] [PubMed] [Google Scholar]

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