Larynx Preservation Strategy Research Articles

Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer.

During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n=59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n=47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n=33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5-year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9%, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p=0.030). According to our results, the oncological outcomes of three different platinum-based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment.

Racial disparities in laryngeal cancer treatment and outcome: A population-based analysis of 24,069 patients.

To determine the impact of race on laryngeal preservation strategies and overall survival (OS) for laryngeal squamous cell carcinoma (SCC). Retrospective, national cancer database analysis. Data were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 20.0 (Armonk, NY: IBM Corp.) for data analyses. A total of 24,069 patients with laryngeal SCC were identified. Of these, 18,166 (75.5%) patients were white, 3,475 (14.4%) were black, 1,608 (6.7%) were Hispanic, and 820 (3.4%) were Asian. Compared with other races, black patients were more likely to be diagnosed at a younger age (P < 0.001), undergo lymph node dissection (P < 0.001), have nodal metastasis (P < 0.001), be with advanced stage disease (P < 0.001), and be unmarried (P < 0.001). Black patients with T1 to T2 and T3 disease were more likely to undergo total laryngectomy as compared with white patients (T1-2: 8.2% vs. 4.3%; P < 0.001; T3: 28.4% vs. 24.3%; P = 0.023). For patients with T4 disease, however, rates of primary radiotherapy among black patients were higher (40.5% vs. 35.7%; P = 0.015). The 5-year OS for white, black, Hispanic, and Asian patients were 60.6%, 52.7%, 59.5% and 65.7% (P < 0.001). This significant 5-year OS difference by race persisted regardless of age, gender, year of diagnosis, primary treatment, nodal status, or tumor grade. On multivariate analysis, race remained an independent prognostic factor for OS. Race is an independent prognostic factor for OS. Further studies are warranted to evaluate causes for racial disparities and discrepancies in OS and laryngeal preservation strategies.

10th Biennial Cancer Meeting in Monaco: innovations in head and neck cancer

Of significance in 2011 was the introduction of IMRT following the publication of the results from the Parsport clinical trials, results from combining cetuximabwith chemoradiotherapy using cisplatin, and laryngeal preservation strategies. TPF was used, however, the optimum combination with radiotherapy treatment (versus radiotherapy alone) is yet to be defined. Induction is more andmore favourable for the advanced stages of cancer. Supportive care is also being considered on an increasing basis (MACC7). Despite a better prognosis and response to treatments, de-escalation strategies for human papillomavirus associated head and neck cancers are yet to achieve a satisfactory level of results. Rare forms of cancer are high on the agenda, with one of the aims of REFCOR being to identify the different sub-types of such cancers. In the absence of standardisation, the National Cancer Institute (NCI) and DATECAN initiatives provide some order to the clinical objectives, and recent publications highlight the importance of considering competing risks, such as co-morbidity, in defining specific clinical objectives for head and neck cancers.

Multimodaler Larynxerhalt

This article presents the current data and discussion on multimodal laryngeal preservation strategies in advanced laryngeal/hypopharyngeal carcinoma. Principally a distinction is made between simultaneous and induction chemoradiation protocols. In terms of late toxicity and related functional limitations, induction protocols are far superior to simultaneous platinum-based chemoradiation. Currently, the individual response to the first cycle of (short) induction chemotherapy appears to be the most reliable clinical marker for making treatment decisions, and this is under clinical investigation. No standard multimodal therapeutic alternative to laryngectomy exists; therefore, at this time multimodal strategies should only be carried out within the framework of clinical trials.

Evidence‐based review of treatment options for patients with glottic cancer

Evidence-based medicine integrates the best available data in decision making, with the goal of minimizing physicians' and patients' subjectivity. In 2006, the American Society of Clinical Oncology edited clinical practice guidelines for the use of larynx preservation strategies. The objective of this review was to evaluate the current levels of evidence for glottic squamous cell carcinoma. Current guidelines for early stage glottic cancer are based on low-level evidence. Conservation surgery (open or transoral) and radiation therapy are all valid options for T1 and selected T2 lesions. For advanced lesions, surgery and combined chemotherapy and radiation are options. High-level evidence favors combined chemotherapy and radiation therapy or altered fractionation radiation therapy as nonsurgical strategies for organ preservation, compared with radiation therapy alone. The optimal combination of chemotherapy, targeted therapy, and radiation therapy remains to be demonstrated, however, and for high-volume tumors, total laryngectomy may still be warranted.

Surgery for Laryngopharyngeal SCC in the Era of Organ Preservation

Over the past decades, randomized clinical trials have assessed and validated the concept of larynx preservation. This new concept has obviously modified the treatment algorithm for laryngopharyngeal squamous cell carcinoma. However surgery for larynx and hypopharynx cancer remains indicated in many cases. Initial partial surgery is indicated for early diseases. This surgery may be performed endoscopically or openly. The results are excellent in terms of local control and function. Transoral robotic surgery is under evaluation. Initial radical surgery is indicated for advanced diseases in case of very infiltrative tumor, in case of cartilage destruction or when tolerance and/or compliance to chemotherapy-based approached is questionable. Larynx preservation is to be discussed between these two situations. In randomized trials evaluating the different larynx preservation strategies, a substantial number of larynxes could be preserved without compromising disease control or survival. The best approach in terms of quality of function preservation, overall acute and late toxicity, disease control and survival is still a matter of clinical research. It must be stressed that salvage surgery is a definite part of these larynx preservation protocols in order to maintain the ultimate disease control. This discussion underscored the need of a multidisciplinary decision making and the need of a coordinated clinical research.

Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy

Determining which patients benefit from larynx preservation strategies remains problematic. We reviewed our experience using multiagent concurrent chemoradiotherapy to identify clinical predictors for success. Cisplatin and fluorouracil were given during weeks 1 and 4 of radiation to 115 patients with locoregionally advanced larynx or hypopharynx squamous cell cancer without cartilage invasion or laryngeal destruction. Laryngectomy was reserved for local failure. The 5-year Kaplan-Meier projected overall survival was 58%, survival with larynx preservation 52%, local control without surgery 82%, local control (including surgical salvage) 94%, and survival with functional larynx 49%. Local control without surgery was superior in patients with T1-2 versus T3-4 tumors (97% vs 77%, p = .032). No other clinical parameters proved predictive of local control. Larynx preservation was successful in all subsets of appropriately selected patients. Although local failure was more likely in patients with T3-4 tumors, it was infrequent and surgical salvage was effective.

Does Induction Chemotherapy Still Have a Role in Larynx Preservation Strategies? The Experience of Institut Catala d'Oncologia in Stage III Larynx Carcinoma

Radiotherapy with concurrent cisplatin is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of induction chemotherapy in larynx-preservation therapies remains unknown. Hyperfractionation radiotherapy might improve disease-free survival. From August 1993 to August 2004, 71 patients with T3N0-1 larynx tumors and eligible for total laryngectomy received induction chemotherapy with three cycles of cisplatin plus fluorouracil. Clinical tumor response was assessed by indirect laryngoscopy and computed tomography scan. Patients with complete response received hyperfractionation radiotherapy, whereas those without complete response were proposed for total laryngectomy. A total of 71 consecutive patients were included. Thirty-three patients achieved complete response to induction chemotherapy (46.5%), four of them presented a tumor relapse, and all underwent salvage surgery. Seventy-six percent of surviving patients preserved a functional larynx. Despite not achieving complete response, 15 patients refused total laryngectomy and received hyperfractionation radiotherapy. Seven patients presented a tumor relapse and salvage surgery was performed in three of them. Fifty percent of surviving patients preserved a functional larynx. Twenty-two patients without complete response underwent total laryngectomy; three of them presented a tumor relapse but none could be rescued. With a median follow up of 68 months, 5 five-year overall survival, 5-year disease-free survival, and 5-year larynx function preservation survival rates were 68% (confidence interval [CI], 57-80), 75% (CI, 64-87), and 42% (CI, 29-54), respectively. No differences in overall survival were observed between groups. Five-year disease-free survival of patients without complete response who received hyperfractionation radiotherapy was significantly lower than that of the other two groups (P < .02). Ten patients with larynx preservation and no tumor relapse had chronic toxicity that caused the loss of larynx function: seven patients required permanent tracheotomy, two died from pneumonia, and one patient died as a result of a laryngeal necrosis. Patients with complete response to induction chemotherapy in laryngeal carcinoma have a high probability of cure after hyperfractionation radiotherapy. However, hyperfractionation radiotherapy induces a high degree of toxicity that reduces the laryngeal function preservation rate and may jeopardize overall survival.

American Society of Clinical Oncology Clinical Practice Guideline for the Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer

To develop a clinical practice guideline for treatment of laryngeal cancer with the intent of preserving the larynx (either the organ itself or its function). This guideline is intended for use by oncologists in the care of patients outside of clinical trials. A multidisciplinary Expert Panel determined the clinical management questions to be addressed and reviewed the literature available through November 2005, with emphasis given to randomized controlled trials of site-specific disease. Survival, rate of larynx preservation, and toxicities were the principal outcomes assessed. The guideline underwent internal review and approval by the Panel, as well as external review by additional experts, members of the American Society of Clinical Oncology (ASCO) Health Services Committee, and the ASCO Board of Directors. Evidence supports the use of larynx-preservation approaches for appropriately selected patients without a compromise in survival; however, no larynx-preservation approach offers a survival advantage compared with total laryngectomy and adjuvant therapy with rehabilitation as indicated. All patients with T1 or T2 laryngeal cancer, with rare exception, should be treated initially with intent to preserve the larynx. For most patients with T3 or T4 disease without tumor invasion through cartilage into soft tissues, a larynx-preservation approach is an appropriate, standard treatment option, and concurrent chemoradiotherapy therapy is the most widely applicable approach. To ensure an optimum outcome, special expertise and a multidisciplinary team are necessary, and the team should fully discuss with the patient the advantages and disadvantages of larynx-preservation options compared with treatments that include total laryngectomy.

Induction Redux: Once More With Taxanes

For more than two decades, induction chemotherapy has been an attractive treatment strategy in patients with locoregionally advanced squamous cell head and neck cancer. In previously untreated patients, overall response rates of 70% to 90% and complete response rates of 30% to 50% have been reproducibly reported after combination chemotherapy with regimens such as fluorouracil plus cisplatin. These responses were gratifying to both patients and their physicians and promised the benefit of decreased morbidity and increased survival after definitive locoregional management. When phase III clinical trials of this approach were completed, however, the results proved disappointing. With rare exception, these studies were unable to demonstrate either a survival benefit or an improvement in locoregional control with induction chemotherapy before definitive management. Despite the impressive clinical responses seen with induction chemotherapy, interest in this treatment strategy subsequently waned. Concurrent chemotherapy and radiation therapy schedules have proven far more successful. Multiple studies of both single-agent chemotherapy and combination chemotherapy administered with concomitant definitive radiation have been conducted, and clear survival and locoregional control benefits have been demonstrated. Radiation with concurrent single-agent cisplatin has been established as a standard of care in the management of patients with unresectable head and neck cancers, patients with nasopharyngeal cancers, and postoperative patients with poor prognostic features and as a larynx preservation strategy. These conclusions have been confirmed and strengthened by the large Meta-Analysis of Chemotherapy on Head and Neck Cancer, which reported an 8% overall survival benefit (P .0001) from concurrent chemoradiotherapy regimens. However, this same meta-analysis was unable to demonstrate an overall survival advantage after neoadjuvant treatment, although when only those induction trials using a platinum and fluorouracil combination were examined, a marginally favorable benefit was noted (P .05). Despite this limited survival benefit from sequential treatment schedules, systemic chemotherapy has had an impact on the incidence of distant metastases. Both in the induction and adjuvant settings, the fluorouracil plus cisplatin combination has significantly decreased the likelihood of distant metastatic failure. That this did not result in improved overall survival likely reflects the limited importance of distant metastases in a disease usually marked by locoregional failure. As chemoradiotherapy schedules have become more intensive, this historical pattern of disease failure seems to have been altered. Recent single-institution phase II trials of aggressive chemoradiotherapeutic protocols, using multiagent chemotherapy and altered-fractionation radiation, have reported locoregional control rates in excess of 90% and the emergence of distant metastases as the most frequent cause of treatment failure. These data have rekindled interest in the potential use of induction chemotherapy in conjunction with definitive concurrent treatment in an effort to further improve survival by decreasing distant metastases. Along with this renewed interest in induction chemotherapy have been continued attempts to improve on the well-tested fluorouracil plus cisplatin combination. The taxanes have been identified as agents with considerable biologic activity in head and neck cancer, although for recurrent or metastatic head and neck cancer, the two-drug combination of paclitaxel and cisplatin has proven no more efficacious than conventional fluorouracil and cisplatin. More promising have been the phase II trials in previously untreated patients, which have explored threedrug combinations of cisplatin, fluorouracil, and a taxane. Response rates of 88% to 93%, with complete response rates as high as 59%, have been reported from these trials. Thus, the question of the most effective JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005

Concomitant boost radiochemotherapy to peserve larynx function in advanced laryngeal and hypopharyngeal cancer: role of the positron emission tomography (PET) to detect locoregional failure

Purpose: Early detection of locoregional failure is important in larynx preservation strategies to enable a salvage laryngectomy in a favourable time frame. CT and biopsy is complicated by mucositis, edema and fibrosis. In this prospective pilot study, the role of 18F-fluorodeoxyglucose (FDG)-PET to detect locoregional failure was evaluated.

Tracheal autotransplantation after extended hemilaryngectomy for advanced glottic cancer

The surgical treatment of a glottic cancer with fixation of the vocal fold (stage T3) usually consists of a total laryngectomy. Although total laryngectomy may be necessary to ensure adequate tumor margins, this mutilating operation is frequently done because preservation of the healthy laryngeal remnant will not sustain an adequate airway with normal voice production and swallowing. The challenge in the treatment of T3 glottic cancer is to preserve the larynx by reconstruction of the created defect after removal of the tumorally involved hemilarynx. Autotransplantation of the trachea has been shown to succeed in extended laryngeal reconstruction with maintenance of speech, swallowing, and respiration after removal of advanced glottic cancer. These findings will improve laryngeal preservation strategies in treating laryngeal cancer.

Progress in larynx-sparing surgery for glottic cancer through tracheal transplantation.

The current surgical treatment for unilateral, advanced glottic cancer is a total laryngectomy. Usually, the noninvolved hemilarynx needs resection because the resulting laryngeal defect cannot be reconstructed after adequate tumor resection. Experimental findings suggest that segments of autologous trachea may restore extended laryngeal defects. The authors used tracheal transplantation to save laryngeal function after the removal of advanced glottic cancer. In this case series review, 10 patients were treated during a 1.5-year period, with an average follow-up of 8 months. Evaluated factors included survival of the tracheal transplant and functional outcome with regard to the onset and quality of the airway, speech, and deglutition. The authors showed that segments of cervical trachea may restore extended laryngeal defects after initial revascularization by a radial forearm fascial flap. The fascial flap served as a vascular carrier for the transplanted trachea. Follow-up showed the stability of the reconstruction. Compared with a total laryngectomy, a striking improvement in patient comfort and function was noticed. Transplantation of the trachea is a technique that may save laryngeal function after the treatment of advanced-stage glottic cancer. These findings may improve laryngeal preservation strategies in treating laryngeal cancer.

LARYNX PRESERVATION IN HEAD AND NECK CANCERS: A Discussion of the National Comprehensive Cancer Network Practice Guidelines

The management of advanced cancers of the larynx and hypopharynx has become increasingly complex as different treatment modalities, including surgery, radiation, and chemotherapy, have been combined with the goal of improving local disease control and disease-specific survival. A union of 17 comprehensive cancer centers in the United States, the National Comprehensive Care Network (NCCN), was formed in 1995 to promote state-of-the-art cancer care. To achieve this goal, multidisciplinary panels of experts from member institutions have created disease-specific practice guidelines for the evaluation and treatment of cancer patients, including those with head and neck cancers. Although detailed analysis of surgical methods and radiation techniques are beyond the scope of this article, the evolving laryngeal preservation strategies for patients with advanced, resectable hypopharyngeal or laryngeal (including supraglottic and glottic) cancers are reviewed using relevant sections of the NCCN practice guidelines as a framework for discussion.

398 Chemotherapy (CT) with radiotherapy (RT): Larynx preservation strategy in cervical squamous cell carcinoma of the esophagus (CSCCE)

In order to evaluate a new strategy to increase long term survival avoiding laryngoesophagectomy (LE), from 5/1985 to 12/1993, 37 pts with CSCCE were treated with combined CT (CDDP 100 mg/sqm, day 1, FU 1000mg/m2 q, day 1–4 in 96 h infusion) every 4 week for 4–5 courses and RT (split course in 27 pts: 30 Gy days 1–19,20 Gy days 67–78; continuous in 10 pts: 60 Gy). LE was limited to pts with resectable residual disease at the end of the treatment program or local relapse after initial CR. Characteristics of pts were: median age 62 yrs, range 46–78, stage I: 4 pts, stage II: 13 pts, stage III: 20 pts (resectable 9/20). Response was documented in 33 of 34 evaluable pts (97%) with CR in 24 pts (71%). Three cases were not evaluable: fistula, toxic death and severe myelosuppression. As of January 1995, 13 pts are alive with a total 5 yrs survival of 32%. Relapses were observed in 21/34 responsive pts (local 14, distant 7). Salvage LE was performed in 6/14 local relapsed pts; 2 pts are alive at 41 and 15 mos.; two others progressed after 24 mos from LE; while the remaining pts deceased within 3 mos. All pts with stage I disease are alive and disease-free at 5 yrs, while no difference was detected between stage II (24%) and III (18%). Mortality due to toxicity of CT plus RT was 3% (1/37). In conclusion, combined CT plus RT provides at least the same expected long-term results as primary surgery but preserves the larynx in neatly one third of cases. Surgery could be advocated only in event of local relapse after failure of combined CT plus RT.