Current Status of Organ Preservation in Carcinoma Larynx

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Abstract

Organ preservation in carcinoma larynx is a long debated topic. There are multiple organ preserving approaches in the management of carcinoma larynx depending on various factors. Radical radiotherapy (RT) and conservation laryngeal surgery have shown equivalent results in early laryngeal cancer. Concurrent chemoradiation (CTRT) is the standard treatment in stage III and IV laryngeal cancer with intact cartilage and functional larynx. Patients with cartilage destruction or dysfunctional larynx are not the candidates for organ preservation. This systematic review is aimed at discussing the evolution of different organ preserving approaches, their efficacy, impact on voice quality, their pitfalls and future directions.

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Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group.

Gregory Wolf, Susan Gross Fisher, Waun Hong … (1991)

We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation. Three hundred thirty-two patients were randomly assigned to receive either three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. The clinical tumor response was assessed after two cycles of chemotherapy, and patients with a response received a third cycle followed by definitive radiation therapy (6600 to 7600 cGy). Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. After two cycles of chemotherapy, the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent. After a median follow-up of 33 months, the estimated 2-year survival was 68 percent (95 percent confidence interval, 60 to 76 percent) for both treatment groups (P = 0.9846). Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease. These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients, without compromising overall survival.

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Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Arlene Forastiere, Qiang Zhang, Randal Weber … (2013)

To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

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Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial.

Robert I Haddad, Anne O’Neill, Guilherme Rabinowits … (2013)

The relative efficacy of the addition of induction chemotherapy to chemoradiotherapy compared with chemoradiotherapy alone for patients with head and neck cancer is unclear. The PARADIGM study is a multicentre open-label phase 3 study comparing the use of docetaxel, cisplatin, and fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin-based concurrent chemoradiotherapy alone in patients with locally advanced head and neck cancer. Adult patients with previously untreated, non-metastatic, newly diagnosed head and neck cancer were eligible. Patients were eligible if their tumour was either unresectable or of low surgical curability on the basis of advanced tumour stage (3 or 4) or regional-node stage (2 or 3, except T1N2), or if they were a candidate for organ preservation. Patients were randomly assigned (in a 1:1 ratio) to receive either induction chemotherapy with three cycles of TPF followed by concurrent chemoradiotherapy with either docetaxel or carboplatin or concurrent chemoradiotherapy alone with two cycles of bolus cisplatin. A computer-generated randomisation schedule using minimisation was prepared and the treatment assignment was done centrally at one of the study sites. Patients, study staff, and investigators were not masked to group assignment. Stratification factors were WHO performance status, primary disease site, and stage. The primary endpoint was overall survival. Analysis was by intention to treat. Patient accrual was terminated in December, 2008, because of slow enrolment. The trial is registered with ClinicalTrials.gov, number NCT00095875. Between Aug 24, 2004, and Dec 29, 2008, we enrolled 145 patients across 16 sites. After a median follow-up of 49 months (IQR 39-63), 41 patients had died-20 in the induction chemotherapy followed by chemoradiotherapy group and 21 in the chemoradiotherapy alone group. 3-year overall survival was 73% (95% CI 60-82) in the induction therapy followed by chemoradiotherapy group and 78% (66-86) in the chemoradiotherapy alone group (hazard ratio 1·09, 95% CI 0·59-2·03; p=0·77). More patients had febrile neutropenia in the induction chemotherapy followed by chemoradiotherapy group (16 patients) than in the chemoradiotherapy alone group (one patient). Although survival results were good in both groups there was no difference noted between those patients treated with induction chemotherapy followed by chemoradiotherapy and those who received chemoradiotherapy alone. We cannot rule out the possibility of a difference in survival going undetected due to early termination of the trial. Clinicians should still use their best judgment, based on the available data, in the decision of how to best treat patients. The addition of induction chemotherapy remains an appropriate approach for advanced disease with high risk for local or distant failure. Sanofi-Aventis. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): World J Oncol

Journal ID (iso-abbrev): World J Oncol

Journal ID (publisher-id): Elmer Press

Title: World Journal of Oncology

Publisher: Elmer Press

ISSN (Print): 1920-4531

ISSN (Electronic): 1920-454X

Publication date (Print): April 2018

Publication date (Electronic): 1 May 2018

Volume: 9

Issue: 2

Pages: 39-45

Affiliations

[a ]Divison of Radiation Oncology, Tata Medical Center, Kolkata, India

[b ]Division of Radiation Oncology, Regional Cancer Centre, Trivandrum, India

Author notes

[c ]Corresponding Author: Cessal Thommachan Kainickal, Division of Radiation Oncology, Regional Cancer Centre, Trivandrum, India. Email: drcessalthomas@ 123456gmail.com

Article

DOI: 10.14740/wjon1105w

PMC ID: 5942206

PubMed ID: 29760831

SO-VID: 09d516ab-8a57-47bb-ace1-1e68ad56ff5e

License:

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 10 April 2018

Date accepted : 20 April 2018

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