Minimally invasive techniques for management of early glottic cancer

This article reviews management of early laryngeal squamous cell carcinoma with respect to current standards of practice and recent advances in minimally invasive endoscopic surgery, specifically highlighting powered instrumentation as an alternative to transoral laser resection of early glottic lesions. Limitations of the current staging system, controversy regarding management of lesions involving the anterior commissure, and the role of radiation therapy versus surgical management are also discussed with reference to current outcomes literature.     

Radiotherapy of early glottic cancer

Patients (383) with stage Tis, Tla and Tlb NoMo glottic cancer are reviewed. Radiotherapy cured 93% of Tis patients and 86% of Tla and Tlb cases. Of all recurrences, 63% were cured. No patient with stage Tis died as a result of tumor and only 5% of stage Tla and Tlb died from tumor. Involvement of the anterior commissure or both vocal cords did not influence control rates by radiotherapy. Mobility of the vocal cord and size of radiotherapy field were significant factors influencing control by radiotherapy. Late recurrences and/or second primaries in the larynx following radiotherapy are rare. Second primaries in the respiratory tract (especially lung) are common and are as important a cause of death as laryngeal cancer in Tl cases. It is concluded that moderate dose radiotherapy with surgery for salvage is a highly effective method of management for early glottic cancer.     

早期声门型喉癌治疗方式的评价与选择

早期声门型喉癌（early glottic cancer，EGC）通常是指Tis-T2病变且无颈淋巴及远处转移者。放疗与手术治疗，包括开放性手术、支撑喉镜下激光手术（简称激光手术）和非激光手术等，均是EGC的有效治疗手段，并具有相近的治疗效果。由于尚缺少理想的前瞻性随机对照研究，还没有足够的证据表明哪种治疗方式对EGC具有更好的治疗效果，对其治疗方式的选择亦缺少统一的意见，现将国内外的主流意见总结如下。     

Surgical options in radiotherapy-failed early glottic cancer

After failure of curative radiotherapy (RT), surgery is the main therapeutic option to control recurrent laryngeal cancer. Recurrences after RT for T1–T2 tumours of the glottic larynx are often diagnosed at a more severe stage than the original disease and, thus, usually treated by radical approaches. Our aim is to investigate the feasibility of more conservative strategies for proper treatment of post-RT recurred glottic cancer. We collected and reviewed our files from 1990 to 2006, selecting 75 patients which matched the following inclusion criteria: (1) patient was originally diagnosed with early stage squamous cell carcinoma of the glottic larynx (stage I–II according to 2010 TNM), (2) patient was treated by RT with curative intent, (3) patient presented a recurrence of disease after RT which was surgically treated at our Institution. T stage at first diagnosis was T1a in 41 cases (55 %), T1b in 12 (16 %) and T2 in 22 (29 %). At clinical examination of RT-recurred lesions, we documented advanced lesions (rT3–rT4) in 29 out of 75 patients (39 %). Overall, an upstage was reported for 56 % RT-recurred cancers, while 37.3 % remained at the same stage than the original tumour and 6.7 % were downstaged. Twelve patients (16 %) underwent salvage partial laryngectomy (SPL), while 63 (84 %) received a salvage total laryngectomy (STL). Multivariate analysis showed that rTNM according to the AJCC-UICC of 2010 was the only prognostic factor for both disease-free survival (p = 0.042) and overall survival (p = 0.004). Considering the prognostic impact of rT and rN we documented a statistical significance only in terms of overall survival for both factors (p = 0.004 and p = 0.04, respectively). Although STL remains the most frequent treatment choice for failures after RT in laryngeal carcinomas, SPL represents a valid option for selected patients with limited recurrence and can deliver good oncologic and functional results if performed according to careful indications.     

早期声门型喉癌的治疗进展

声门型喉癌占喉癌发病的70%,淋巴结转移少见。早期声门型喉癌常常引起声音嘶哑,就诊过程中,易于早期发现,在所有喉癌中预后最好。近10年来美国国家综合癌症网络(NCCN)指南中关于早期声门型喉癌的诊治经历20余次的更新,已逐步形成经口内镜下CO₂激光手术或单纯放疗为主的治疗模式。喉功能保留和嗓音质量是衡量治疗成功与否的关键因素,目前开放手术的应用越来越少,而首选CO₂激光手术还是单纯放射治疗方案的问题一直是悬而未决的。本文将分别介绍早期声门型喉癌的治疗进展及个性化治疗选择的关键要点,并总结影响肿瘤复发的预后因素及预测复发的生物学标志物,以期为指导早期声门型喉癌患者的治疗及随访提供临床参考。     

声门型喉癌早期病变不应切除杓状软骨

近年来，不断读到刊物上发表涉及肿瘤治疗措施不足或治疗过度的报告，这是临床医学发展中在所难免的，但我们应根据临床经验和治疗结果，及时调整手术适应证和治疗措施。喉癌的治疗，各级T及N病变的手术选择，已有一定成规。近来读到柳斌等”0报告（以下简称“柳文”），用喉垂直部分切除加杓状软骨切除来治疗声门型喉癌87例，其中T1、他病变61例，T3 26例。局部复发率T1为0，T2为7．4％（4／54）。直接法统计5年生存率T1-T3混合计算，为81％（51／63），拔管率98．9％。该文有70．1％（61／87）的早期病变，做杓状软骨切除，手术范围似乎过大，值得商榷。     

嗓音显微手术治疗早期声门癌的远期疗效观察

目的观察应用嗓音显微手术治疗早期声门癌的远期疗效.方法1989-1997年采用嗓音显微外科技术对44例声带早期癌（T1a）进行了手术治疗.声带早期癌按病变的侵袭深度分为：原位癌（5例）、低侵袭癌（33例）和侵袭癌（6例）.原位癌和低侵袭癌采用微瓣切除技术;对侵袭癌则采取激光切除声带,切缘经过微波或激光处理的方法.每例患者均进行术前、术中和术后录像,术后常规病理送检,并进行长期随访.随访最长时间为11年,最短时间5年.结果应用微瓣切除方法的38例原位癌和低侵袭癌中有6例在手术后随访的2～3年内发现局部复发,局部复发率为15.8%.6例复发患者再次行微瓣切除,其中1例在10年内经历3次微瓣切除手术.1例失随访后1年再次因肿瘤复发就诊,后改喉全切除手术.微瓣切除术病例失访4例,其余随访5年以上均存活,5年生存率为89.5%（失访以死亡计）.应用声带切除术的6例早期侵袭癌中2例于术后2个月发现肿瘤复发而行喉切除术,1例失随访后3年复发改喉全切除术,1例梭型细胞癌术后采用局部放射治疗.声带切除术局部复发率为4/6;3例在3年内死亡,1例3年后失访,2例存活5年以上.结论对病变局限的早期癌,嗓音显微手术不仅能有效地治愈疾病,同时能保护和维持正常的发声功能.对于病变局限在黏膜表面的声带早期癌,嗓音显微手术的微瓣技术不仅是有效的微创治疗措施,同时微瓣切除的病变标本经连续切片的病理诊断也成为了早期声带癌诊断及鉴别诊断的“金标准”.     

累及双侧喉腔的T2声门癌的手术治疗

目的探讨累及双侧喉腔的T2声门癌的手术方法和临床疗效.方法对22例累及双侧喉腔的T2声门癌患者行额侧喉部分切除术,以会厌、双蒂接力肌甲状软骨膜瓣、颈阔肌皮瓣、胸骨舌骨肌筋膜瓣、甲状软骨膜瓣、胸锁乳突肌骨膜瓣等修复组织缺损并重建喉功能.结果全组病例3年生存率为90.9%(20/22),5年生存率为88.9%(16/18).喉功能全恢复(吞咽保护、呼吸、发声)为90.9%(20/22),喉功能部分恢复(吞咽保护、发声)9.1%(2/22).结论额侧喉部分切除术是治疗累及双侧喉腔的T2声门癌的较好方法,肿瘤切除彻底,喉功能恢复良好.     

早期声门型喉癌的循证治疗方案

目的 通过1例早期声门型喉癌患者的治疗问题,检索当前最佳临床证据,针对患者具体情况为治疗提供依据.方法 在充分评估患者情况后,提出临床问题,检索Cochrane图书馆(2009年第1期)、美国国家指南交换中心NGC(2000-2009)、PubMed(1966-2009.12)、Embase(1980-2009.12)和CBM(1989-2009.12)数据库,收集相关证据,对所获证据进行评价,并结合医生的经验及患者的愿望制定治疗方案.结果 本文共纳入2篇临床指南,5篇RCT和1篇队列研究.证据结果表明,对于早期声门型喉癌的治疗,手术和放疗具有相似的5年生存率,目前缺少理想的前瞻性随机对照研究提供证据,还没有足够的证据表明哪种治疗方式具有更好的治疗效果,综合指南推荐、文献报道、临床经验及患者具体情况,对该例早期声带癌患者推荐方案为支撑喉镜下CO2激光手术,术后加行免疫治疗.结论 对于早期声门型喉癌治疗方式的选择缺少统一意见,需要遵循循证医学的原则,综合各方面因素考虑.     

Voice quality after radiation therapy for early glottic cancer

OBJECTIVE: To evaluate the voices of irradiated patients with early glottic carcinoma and to compare these with the voices of healthy volunteers. DESIGN: Case-control study. SETTING: University Department of Otorhinolaryngology and Cervicofacial Surgery, University of Ljubljana, Ljubljana, Slovenia. SUBJECTS AND METHODS: The voice samples (sustained vowel) of 50 patients (44 men and 6 women) who had been irradiated for T1 (43 subjects) or T2 (7 subjects) glottic squamous carcinoma at least 1 year prior to the study were analyzed with the Multi-Dimensional Voice Program (Kay Elemetrics Corp, Lincoln Park, NJ) and compared with those of a normal group of 50 age- and sex-matched volunteers. Average fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, and degree of voiceless elements were determined. In the irradiated group, videostroboscopy was performed. The patients assessed their voice fatigue. RESULTS: The irradiated subjects demonstrated significantly higher values for jitter, shimmer, and degree of voiceless elements than did the healthy volunteers. The values for noise-to-harmonic ratio were higher in the irradiated group, but the difference was not significant (P =.08). The values for fundamental frequency were almost equal in both groups. In most of the irradiated subjects, some irregularities of the vocal fold vibration were noticed. Many of these patients also reported voice fatigue. CONCLUSIONS: Radiation therapy for early glottic cancer results in poorer voice quality compared with normal age- and sex-matched speakers. In most of the irradiated patients, greater than normal effort in voice production was found based on patient assessment. This may result from stiffness of the vibratory source and inadequate compensatory maneuvers in phonation. We suggest that voice therapy during and after radiation therapy may result in better voice quality.     

Prognostic significance of EGF receptor expression in early glottic cancer

Objective: A positive relationship between epidermal growth factor receptor (EGFR) expression and radioresistance has been shown both in vitro and in vivo. In a group of 31 patients with early glottic cancer treated with definitive radiotherapy, the relationship of EGFR expression with patient and tumor related parameters were analyzed and the prognostic effect of EGFR expression on local control (LC) was assessed. Material and method: Between 1991 and 2001, 114 patients with early glottic (Tis-T2N0M0) squamous cell carcinoma were treated with radiotherapy at our institution. Among these, 31 patients whose pretreatment pathology specimens were available for immunohistochemical analysis formed the study population. Median age was 64 (46–77). Anterior commissure involvement was evident in 12 (38.7%) patients. Distribution according to T stage was as follows: Tis 6 (19.3%), T1 22 (71%), and T2 3 (9.7%). Histopathological grades of the 25 T1-2 tumors were 10/25 (40%) grade 1, 9/25 (36%) grade 2 and 6/25 (24%) grade 3. Our radiotherapy regimen was 66–70 Gy in 33–35 fractions over 6.5–7 weeks. The median follow-up period was 45 months (range, 5–116). Following immunohistochemical staining, quantitative immunohistochemistry (IHC) was performed by image analysis software and stained tumoral area percentage (STAP) was identified. The cut-off value was ≤5% versus >5%. The relationship of EGFR expression with patient (age) and tumor related (T stage, histopathological grade, and anterior commissure involvement) parameters was evaluated using chi-square test. Prognostic significance of EGFR expression, age, T stage, histopathological grade, and anterior commissure involvement on LC was assessed using log-rank test. Results: No difference was found in EGFR content distribution in relation to age, T stage, histopathological grade, and anterior commissure involvement. In the univariate analysis including age (≤60 versus >60), T stage (Tis and T1 versus T2), histopathological grade (grade 1 and 2 versus grade 3), anterior commissure involvement (present versus absent), and EGFR expression (high versus low), only T stage and EGFR expression were found to be significant prognostic factors affecting LC (P = 0.0006 and P = 0.03, respectively). Conclusion: The results of this series support that EGFR expression is an unfavorable prognostic factor in early glottic carcinomas. For this reason EGFR IHC may be considered for selecting patients for more aggressive therapies (radiotherapy with different fractionation schemes or surgery) or enrollment into trials targeting EGFR signaling pathways.     

钬激光手术治疗早期声门型喉癌疗效分析

目的总结钬激光治疗早期声门型喉癌的疗效。方法对2004年2月～2009年3月应用钬激光手术治疗的36例声门型喉癌的疗效进行临床分析。结果 36例钬激光术后复发4例,局部复发率为11%（4/36）,颈部转移率为3%（1/36）,平均复发时间13.5个月;T1a复发率3.7%（1/27）,T1b复发率33.3%（3/9）,两组间差异有显著意义（P〈0.05）;36例患者因复发死亡2例,非相关疾病死亡2例,3年生存率89.7%（26/29）。结论钬激光治疗早期声门型喉癌疗效可靠、喉功能保全好、术后恢复快,是早期声门型喉癌的首选治疗方式之一。     

Consensus statement on management in the UK: Transoral laser assisted microsurgical resection of early glottic cancer

Background: Transoral laser assisted microsurgical resection of early glottic laryngeal cancer is a relatively new treatment modality that is practised in many centres across the UK. In the absence of the results from randomised clinical trials, clinicians may be guided by an expert panel consensus statement on transoral laser assisted microsurgical resection of early squamous cell cancer of the larynx. Objective: To provide consensus recommendations on the various aspects of transoral laser assisted microsurgical resection for early glottic cancer. Evaluation method: Nine centres across the UK were invited to describe current practice and outcomes for transoral laser assisted microsurgical resection of early glottic cancer. Four working groups were created to draw consensus on standard of care, surgical procedures, outcomes measures and training/certification. The feedback from these groups was integrated into the consensus statement. Conclusions: The consensus meeting confirmed the stablished and widespread use of transoral laser assisted microsurgical resection for early glottic cancer throughout the UK. The common experience gained allowed a full discussion of all aspects of the management with consensus achieved in key areas of standards of care, surgery, histopathologic reporting, outcomes assessment and training. This consensus statement will result in closer auditing of management and dissemination of results.     

Radiotherapy for early glottic cancer and salvage surgery after recurrence

Early glottic cancer can be effectively treated with radiation or surgery, but recurrence is a possibility when using any of the treatment modalities.AimTo assess the outcome of radiotherapy as initial treatment in the control of squamous cell carcinoma of vocal cord (T1) and the effectiveness of salvage surgery (endoscopic or open) after treatment failure.Materials and MethodsA retrospective study was based on the analysis of medical records from 43 patients with T1 squamous cell carcinoma of the glottis, radiotherapy as initial treatment and follow-up period of five years.ResultsThe rate of recurrence after radiotherapy was 30.2% of the cases, mean diagnosis interval was 29.5 months. As an option for salvage treatment, patients underwent open partial laryngectomy or endoscopic surgery with control rates of 77.7% and 25% respectively.ConclusionOur cases showed high rates of recurrence after radiotherapy and open partial laryngectomy was more effective for the salvage surgery.     

早期声门癌经口激光显微手术患者获较高语音基频

目的评估早期声门癌患者治疗后嗓音特征和生活质量的长期疗效。研究设计回顾性分析台湾一家医学中心的患者资料。方法42例声门癌患者接受放疗（radiation therapy,RT）或经口激光显微手术（transoral laser microsurgery,TLM）治疗12个月后评估其嗓音和生活质量。结果24例患者接受RT,18例患者接受TLM。两组患者无听力学和空气动力学差异,对于男性患者仅有发音基频的差异。在癌症治疗——头颈调查的功能性评估中,TLM治疗组比RT治疗组能更好地交流,但无嗓音质量和强度的差异。同样,这两组在嗓音障碍指数10（VHI-10）评估中也没有显著性差异。结论接受TLM治疗的男性患者比接受RT治疗组的男性患者。具有较高的发音基频。对于早期声门癌患者,无论是接受TLM治疗,还是接受RT治疗,嗓音相关的生活质量是相似的：但是接受TLM治疗患者具有更好的交流能力。     

Voice in early glottic cancer compared to benign voice pathology

The purpose of this study is to compare (Dutch) Voice Handicap Index (VHIvumc) scores from a selected group of patients with voice problems after treatment for early glottic cancer with patients with benign voice disorders and subjects from the normal population. The study included a group of 35 patients with voice problems after treatment for early glottic cancer and a group of 197 patients with benign voice disorders. Furthermore, VHI scores were collected from 123 subjects randomly chosen from the normal population. VHI reliability was high with high internal consistency and test–retest stability. VHI scores of glottic cancer patients were similar to those of patients with voice problems due to benign lesions. Both groups of patients were clearly deviant from the normal population. Within the normal population, 16% appeared to have not-normal voices. Based on ROC curves a cut-off score of 15 points was defined to identify patients with voice problems in daily life. A clinical relevant difference score of 10 points was defined to be used for individual patients and of 15 points to be used in study designs with groups. Patients with voice problems after treatment for early glottic cancer encounter the same amount of problems in daily life as the other voice-impaired patients. The VHI proved to be an adequate tool for baseline and effectiveness measurement of voice.     

Prognostic significance of the DNA ploidy of the early glottic cancer

The stage classification is most frequently used at the present in predicting the outcome of laryngeal carcinoma. Recently, DNA ploidy pattern as detected by DNA flow cytometry and cytofluorometry has been also shown to be predictive. In this study, DNA cytofluorometry was performed on formalin-fixed paraffin-embedded tissues from 18 patients with T1 and T2 glottic squamous cell carcinoma for whom long-term follow-up data were available. The DNA ploidy pattern was classified into three types, diploid, diploid + tetraploid and aneuploid according to the DNA content of Go/G1 cells and mitotic cells. In these 18 cases, 8 cases (44%) had diploid pattern, 3 cases (17%) had the diploid + tetraploid pattern and 7 cases (39%) had the aneuploid pattern. The ploidy pattern was significantly associated with the relapse-free rate, but did not correlate with the stage of the carcinoma and differentiation of the cancer cells. Distribution of the patients by histology, stage and therapy was almost equal among the diploid, diploid + tetraploid and aneuploid groups. All the patients were treated with irradiation (60Gy). In the group as a whole, no patient died of glottic carcinoma. Relapse-free survival rates for diploid, diploid + tetraploid and aneupoid were 88%, 33% and 29% respectively. This retrospective study of glottic cancer treated with radiation therapy suggests the possibility that the DNA ploidy pattern would significantly predict patient outcome and would be useful for selecting patients whose poor prognosis demands more aggressive therapy.     

Analysis of failure following transoral laser surgery for early glottic cancer

This study aimed at clarifying further the clinical behavior of early glottic cancer following transoral laser surgery and to determine, using retrospective analysis, whether the site of tumor involvement along the vocal fold has prognostic significance. The study included all patients treated with transoral laser surgery, for early glottic cancer (T1/T2N0M0) between May 1998 and January 2012 in a university affiliated tertiary care medical center. Data on demographics, site and extent of disease, treatment and outcome were collected and analyzed. Patients with insufficient data and/or follow-up of <2 years were excluded from the study. One-hundred and twenty-one patients were eligible for the study. Mean follow up time was 6.7 years (range 2–12 years). Overall recurrence rate following primary transoral laser surgery was 16.5 %. Histological grade was associated with higher recurrence rate (p = 0.008). Anterior commissure involvement was associated with reduced disease-free survival and tumors extending to the middle third of the true vocal fold were associated with lower recurrence rate. As per the results, anterior extension of glottic tumors is associated with higher recurrence rate compared to middle vocal fold extension, presumably due to earlier detection, better visualization and different biological behavior pattern of middle vocal fold tumors. Patients with higher grade tumors should be closely monitored for disease recurrence.     

Recurrences after endoscopic management of early (T1) glottic carcinoma

From 1976 to 1986, 106 patients with early glottic carcinoma were managed endoscopically at our institution. Twenty-four (23%) patients required re-treatment of the larynx for local recurrences or new primary lesions after initial endoscopic management. The probability of remaining free of local recurrence 3 years after primary surgery was estimated to be 0.87 and, after 5 years, it was 0.81. Of the 24 patients who required re-treatment of their larynx, 10 did so beyond 3 years, indicating a new second primary. In 1 patient who required re-treatment within 3 years, a new primary developed on the opposite cord. Therefore, true local recurrences developed in 13 patients (12.3%); 3 of these patients (2.8%) ultimately required laryngectomy and 3 are dead (2.8%) with disease.