Users Online: 117
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 3  |  Issue : 3  |  Page : 147-150

Organ preservation strategies: Review of literature and their applicability in developing nations


Department of Head Neck Surgery, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Date of Web Publication15-Jul-2014

Correspondence Address:
Anil D'Cruz
Department of Head Neck Surgery, Tata Memorial Hospital, Parel, Mumbai, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-330X.136764

Rights and Permissions
  Abstract 

There has been a change in practice in locally advanced laryngopharyngeal cancers toward non-surgical treatment modalities. Although, there have been landmark trials pertinent to organ preservation, their applicability in developing nations is a topic of much debate. The organ preservation concept was based on the findings of pivotal trials by the Veterans Affairs, European Organization for Research and Treatment of Cancer group and Radiation Therapy Oncology Group. Subsequently numerous studies have been designed to evaluate intensification of treatment as well as study toxicity and tolerability. This review critically analyses current evidence for larynx preservation, experience from various centers on organ preservation strategies as well as applicability of these protocols to developing nations.

Keywords: Chemoradiotherapy, clinical protocols, developing countries


How to cite this article:
Dandekar M, D'Cruz A. Organ preservation strategies: Review of literature and their applicability in developing nations. South Asian J Cancer 2014;3:147-50

How to cite this URL:
Dandekar M, D'Cruz A. Organ preservation strategies: Review of literature and their applicability in developing nations. South Asian J Cancer [serial online] 2014 [cited 2019 Dec 16];3:147-50. Available from: http://journal.sajc.org/text.asp?2014/3/3/147/136764


  Introduction Top


In the past three decades locally advanced laryngopharyngeal cancer management has undergone a paradigm shift from surgical dominance to non-surgical organ preservation strategies. Randomized controlled trials on larynx preservation approaches have contributed to this change in practice. Larynx preservation was possible without compromising survival against the time tested surgical approach of laryngectomy with adjuvant radiotherapy (RT). However, applicability of these trials out of a protocol setting was a cause of concern more so in the developing nations. Therefore, individual centers adopted these protocols some of them with certain modifications to increase their applicability. However, there remains a paucity of robust data from the developing world on non-surgical organ preservation strategies. This review aims at analyzing available literature and put forth current evidence as well as discuss applicability of these strategies especially in the developing countries.


  Current Evidence Top


Inception of organ preservation strategies took seed in the early 80s with initial trials demonstrating the potential of chemotherapy to cause tumor regression as well as predict response to RT. [1] Since, then chemotherapy is used in conjunction with RT as an approach to organ preservation in various combinations (neoadjuvant, concurrent and alternating).

The Veterans Affairs (VA) Laryngeal Cancer Study group was pivotal in establishing the role of non-surgical methods of treatment for advanced laryngeal cancers. [2] In this study, patients were randomized to the experimental arm of induction chemotherapy followed by RT in those with partial response against the standard of care i.e. surgery followed by adjuvant RT. This approach was able to achieve larynx preservation in 64% maintaining similar overall survival in both arms. This study set the stage for further larynx preservation studies and established induction chemotherapy as standard of care.

A study with similar design but predominantly focused on locally advanced hypopharyngeal cancers was conducted by the European Organization for Research and Treatment of Cancer (EORTC). [3] The results of this trial, like the VA results strongly established the role of induction chemotherapy in hypopharyngeal cancers as well. With similar overall survival, larynx preservation was achieved in 48%. The group essentially concluded that larynx preservation protocol was a feasible option in hypopharyngeal cancers in the form of induction chemotherapy and RT. The authors however noted that the response was more favorable for T2 disease when compared to T3 and T4 disease. The 10 year update suggests similar overall survival in both the arms and survival with a functional larynx in 8.7%. [4]

Such was the popularity of larynx preservation approaches that a study conducted by Groupe d'Etude des Tumeurs de la TeΓ te et du Cou (GETTEC), Head and Neck Tumor Study Group had to be prematurely abandoned due to a strong patient preference for organ preservation over surgical resection. [5] Although, the findings were not adequately powered, the study demonstrated significantly poorer survival in the induction chemotherapy arm than those who underwent primary surgery (2 year survival 84% in the surgery group vs. 69% in the chemotherapy group).

In the 1990s, Forastiere et al. conducted a three armed study comparing induction chemotherapy, concurrent chemoradiotherapy (CRT) and RT alone in patients with locally advanced glottic and supraglottic cancers. [6] With comparable overall survival in the three arms, larynx preservation was best with concurrent CRT (2 year larynx preservation rate of 88%, 75% and 70% in the concurrent CRT, induction chemotherapy and RT alone arm). In addition, locoregional control was significantly better with concurrent CRT. This was further corroborated by the meta-analysis of chemotherapy in head neck cancer (MACH-NC) which demonstrated an absolute benefit of chemotherapy administered concomitantly. [7]

Similarly, Prades et al. compared induction chemotherapy versus concurrent CRT in hypopharyngeal cancers. [8] The induction chemotherapy regimen comprised of two drugs as in the EORTC trial. Amongst 71 patients with advanced pyriform sinus cancer, larynx preservation was superior for concurrent CRT group (2 year larynx preservation 92%) compared with induction chemotherapy (68%). However, there was no survival benefit with concurrent CRT.

A 10 year update of the Radiation Therapy Oncology Group (RTOG) 9111 trial gave some insight into the long-term effect of these approaches. [9] RT alone was significantly inferior to both the chemotherapy arms. With regards to toxicity, deaths unrelated to cancer or treatment were significantly higher in the concomitant chemotherapy arm (30.8% vs. 20.8% in the induction arm vs. 16.9% in RT alone arm). It could be attributed to late toxicity related to swallowing dysfunction along with silent aspiration. [10] Long-term interpretation of speech and swallowing showed acceptable results although available data was limited.

Thus while locoregional control and larynx preservation was significantly improved by concomitant use of chemotherapy with RT, the tolerance of such intensive regimens was a cause of concern. Since RT alone was proven to be inferior in treating such cancers, the search for alternative treatment strategies started.

Bonner et al. in their randomized trial of Cetuximab with RT vs RT alone in head neck cancers (nearly 40% were laryngopharynx), demonstrated significant improvement in locoregional control (24.4 months vs. 14.9 months in Cetuximab with RT and RT alone respectively) as well as overall survival (49 months vs. 29.3 months) in those patients who received targeted therapy with RT. [11] Although, these results were best seen in the subset of oropharyngeal cancers, there was a positive trend even in laryngopharynx. However, the targeted chemotherapy approach has never been compared head on to concurrent CRT, which still remains the standard of care. This approach would seem logical however in elderly patients, those with compromised renal functions and patients with poor performance status in whom CRT is not tolerated. In an attempt to avoid the toxicities associated with chemotherapy, other approaches using altered fractionation have also been studied. Accelerated RT (6 days) is found to have better locoregional control when compared to conventional 5 day RT (70% vs. 60% 5 year locoregional control respectively). This was demonstrated by the Danish Head and Neck Cancer Group (DAHANCA) six and seven trial where more than 90% of patients were glottic, supraglottic or pharyngeal cancers. [12] More than 97% patients completed the intended treatment. Although, toxicity was higher in the 6 day RT arm, it was found to be transient.

Simultaneously, researchers explored alternate schedules incorporating aggressive induction chemotherapy in an attempt to improve preservation and survival results. Induction chemotherapy regimens became more intensive from the use of single agent chemotherapy (Platinum based) in the 1970s to doublet chemotherapy (addition of 5-fluorouracil) in the 1980s to three drug (addition of taxanes) in 1990s. (Taxotere) TAX 324 study had determined the benefit of three drug versus two drug chemotherapy as induction chemotherapy regimen for overall survival. [13] At about the same time, Groupe d'Oncologie Radiothιrapie Tκte Et Cou (GORTEC) 2000-01 trial compared three drug (Docetaxel, Cisplatin, 5-fluorouracil) versus two drug (Cisplatin, 5 fluorouracil) in laryngeal and hypopharyngeal cancers for larynx preservation. [14] Among 220 patients, 3 year larynx preservation rate was 73% in the Taxane, platinum, fluorouracil group compared to 63% in the platinum, fluorouracil arm.

While three drug chemotherapy did demonstrate superiority over doublet chemotherapy, concerns were raised about tolerance to CRT following three drug induction chemotherapy. These were addressed by the trial conducted by the GETTEC and GORTEC group, TREMPLIN trial (RT with cisplatin vs. RT with cetuximab after induction chemotherapy for larynx preservation). [15] It attempted to evaluate the feasibility of sequential chemotherapy i.e. induction chemotherapy followed by concurrent CRT versus induction chemotherapy followed by bioradiotherapy. Although larynx preservation and control rates were equal in both the arms, compliance was higher in the bioradiotherapy arm albeit high toxicity in both arms (nephrotoxicity in concurrent CRT and skin toxicity in targeted therapy arm). However, no conclusive proof exists on the role of sequential induction chemotherapy followed by concurrent chemotherapy.


  Critical Analysis of Literature Top


Non-surgical organ preservation was established following the VA and EORTC trial. Amongst non-surgical approaches to advanced laryngopharyngeal cancers, CRT has become the standard of care in view of its head on comparison with induction chemotherapy regimens. However, it may be kept in mind that long-term results of the RTOG 9111 study show a trend toward induction chemotherapy although not statistically significant. Furthermore, benefit of sequential three drugs over two drug induction chemotherapy remains to be compared with concurrent CRT.

A common critique for organ preservation trials remains the primary endpoint which in all the studies was larynx preservation. These trials would be inadequately powered to compare survival in the comparative arms. To add to that, the definition of larynx preservation is not standard across all the studies. Consequent to this, a consensus panel laid down recommendations on the trial design for future studies on larynx preservation. [16] The panel recommended the endpoint to be a combination of survival along with a functional larynx. Observations by Chen and Halpern, Hoffman et al. of trend toward decreasing survival in laryngeal cancers must be kept in mind particularly due to increased popularity of non-surgical approaches to such advanced cancers. [17],[18]


  Outcomes of Organ Preservation in Individual Centers Top


Preferences for organ preservation strategies are diverse with North America and Australia preferring the concomitant CRT regimen while European centers preferring the induction chemotherapy approach. [10] Various authors have shared their individual center experiences, which are tabulated [Table 1]. Trends are by and large comparable to evidence from randomized controlled trials.
Table 1: Experience of individual centers on organ preservation strategies

Click here to view



  Experience of Surgical Salvage after Organ Preservation Top


Major wound complications more than 60% have been reported in salvage surgeries after larynx preservation strategies. [24] Salvage laryngectomy reports from the RTOG 9111 study suggest major complications in more than 50% cases. Pharyngocutaneous fistulas were maximum for those who received concurrent CRT. [25]


  Experience from Developing Nations Top


Differences exist in several aspects, which preclude universal applicability of the larynx preservation strategies [26],[27] viz:

  1. Preponderance of advanced cancers in the form of bulky disease and large nodal burden (Stage IV). Larynx preservation studies had limited number of such patients. The tumor characteristics of patients in RTOG 9111 showed that 42-47% patients were T2 or T3 without cord fixation in all 3 arms. Less than 10% of patients had T4 disease in stark contrast to those presenting in developing nations
  2. Poor performance status partially contributed by the preponderance of hypopharyngeal cancers resulting in dysphagia
  3. Hypopharyngeal cancers, which are traditionally known to be poor performers form the major subsite along with marginal zone cancer (supraglottis with hypopharynx). [28],[29] This is in contrast to the areas from where these trials originated where the major burden is that of glottic and supraglottic cancers
  4. Limited availability of infrastructure and expertise to administer and monitor such intensive regimens.


Treatment modifications have been adopted to cater to such a patient profile as well as logistic limitations

  1. Weekly low dose chemotherapy (Cisplatin 30 mg/m 2 ) was found to be a more feasible option with acceptable toxicity and lesser treatment interruptions (<15%). This regimen showed similar control rates when compared to routinely practiced 3 weekly high dose chemotherapy. [30] The feasibility of this regimen is based on the evidence that a cumulative therapeutic dose of chemotherapy (>200 mg/m 2 ) is essential for therapeutic benefit. [31]
  2. Six day RT which was proven to give better locoregional control when compared to 5 day RT as a regimen was applicable in developing nations as was tested by the randomized controlled trial by the International Atomic Energy Agency (IAEA) ACC trial. [32] The control rates were found to be significantly higher and this strategy was found to be logistically feasible.
  3. Neoadjuvant chemotherapy to determine responders and feasibility to organ preservation particularly in patients with bulky disease, N3 nodes or exolaryngeal disease without cartilage erosion. As many as 73% patients could be further considered for organ preservation as was determined by an analysis of neoadjuvant chemotherapy on hypopharyngeal cancers. [33] This approach helps in determining RT responders since both chemo and RT response follow a similar mechanism of deoxyribonucleic acid strand breakage. This could behave as a surrogate marker avoiding potential salvage surgery related complications. This was demonstrated by the VA study in which amongst all those patients who underwent surgery on the induction chemotherapy arm, 50% underwent surgery (30 patients) prior to RT while 50% (29 patients) underwent surgery after RT.


A large cohort of advanced hypopharyngeal cancers (more than 500 patients) treated with non-surgical approach was retrospectively reviewed. [34] There were varied treatment strategies adopted depending on the time period of presentation which influenced a change in treatment policy from RT alone to neoadjuvant to concurrent, weekly CRT in most recent cases. The 3 year locoregional control achieved was 47.1% comparable to published literature.

In a survey conducted among patients in a Tertiary Cancer Center from India, it was found that global quality-of-life was similar between those who underwent organ preservation strategies versus those with total laryngectomy except xerostomia affecting those on non-surgical treatment and voice related problems affecting those with total laryngectomy. [35] It must also be kept in mind that patients would rather prefer intact function after laryngectomy with deglutition without aspiration as well as good quality prosthetic voice as opposed to a functionless, frozen larynx. [36] Thus, total laryngectomy may still be considered a viable option with optimum prosthetic voice rehabilitation in such moderately advanced cancers.

Future trends

Determining molecular biomarkers as predictors for response to non-surgical treatment modalities has been attempted. The role of epidermal growth factor receptor, E-catherin and b-catenin Tp53 mutation has been explored. [37] Although, no conclusive evidence exists, protein profiling using tissue microarrays and immunohistochemistry could be exploited. [38] However, these approaches are investigational as of date.


  Conclusion Top


Organ preservation protocols appear to be promising and are here to stay. Current evidence shows CRT to be standard of care. Feasible modifications have been adopted for improving applicability of these strategies like weekly concurrent chemotherapy with RT and altered fractionation RT. Future studies for organ preservation strategies should be designed with survival as the end point.

 
  References Top

1.Ensley JF, Jacobs JR, Weaver A, Kinzie J, Crissman J, Kish JA, et al. Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer 1984;54:811-4.  Back to cited text no. 1
[PUBMED]    
2.Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991;324:1685-90.  Back to cited text no. 2
[PUBMED]    
3.Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: Preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88:890-9.  Back to cited text no. 3
    
4.Lefebvre JL, Andry G, Chevalier D, Luboinski B, Collette L, Traissac L, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol 2012;23:2708-14.  Back to cited text no. 4
    
5.Richard JM, Sancho-Garnier H, Pessey JJ, Luboinski B, Lefebvre JL, Dehesdin D, et al. Randomized trial of induction chemotherapy in larynx carcinoma. Oral Oncol 1998;34:224-8.  Back to cited text no. 5
    
6.Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-8.  Back to cited text no. 6
    
7.Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.  Back to cited text no. 7
    
8.Prades JM, Lallemant B, Garrel R, Reyt E, Righini C, Schmitt T, et al. Randomized phase III trial comparing induction chemotherapy followed by radiotherapy to concomitant chemoradiotherapy for laryngeal preservation in T3M0 pyriform sinus carcinoma. Acta Otolaryngol 2010;130:150-5.  Back to cited text no. 8
    
9.Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, et al. 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. J Clin Oncol 2013;31:845-52.  Back to cited text no. 9
    
10.Corry J, Peters L, Kleid S, Rischin D. Larynx preservation for patients with locally advanced laryngeal cancer. J Clin Oncol 2013;31:840-4.  Back to cited text no. 10
    
11.Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.  Back to cited text no. 11
    
12.Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 2003;362:933-40.  Back to cited text no. 12
    
13.Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705-15.  Back to cited text no. 13
    
14.Calais G, Pointreau Y, Alfonsi M, Sire C, Tuchais C, Tortochaux J, et al. Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000-01. J Clin Oncol 2006;24:5506.  Back to cited text no. 14
    
15.Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: The TREMPLIN randomized phase II study. J Clin Oncol 2013;31:853-9.  Back to cited text no. 15
    
16.Lefebvre JL, Ang KK, Larynx Preservation Consensus Panel. Larynx preservation clinical trial design: Key issues and recommendations - A consensus panel summary. Head Neck 2009;31:429-41.  Back to cited text no. 16
    
17.Chen AY, Halpern M. Factors predictive of survival in advanced laryngeal cancer. Arch Otolaryngol Head Neck Surg 2007;133:1270-6.  Back to cited text no. 17
    
18.Hoffman HT, Porter K, Karnell LH, Cooper JS, Weber RS, Langer CJ, et al. Laryngeal cancer in the United States: Changes in demographics, patterns of care, and survival. Laryngoscope 2006;116:1-13.  Back to cited text no. 18
    
19.Taguchi T, Nishimura G, Takahashi M, Komatsu M, Sano D, Sakuma N, et al. Treatment results and prognostic factors for advanced squamous cell carcinoma of the larynx treated with concurrent chemoradiotherapy. Cancer Chemother Pharmacol 2013;72:837-43.  Back to cited text no. 19
[PUBMED]    
20.Kogashiwa Y, Yamauchi K, Nagafuji H, Matsuda T, Tsubosaka T, Tsutsumi T, et al. Concurrent chemoradiotherapy for organ function preservation in advanced patients with hypopharyngeal and laryngeal cancer. Oncol Rep 2009;22:1163-7.  Back to cited text no. 20
    
21.Nishimura G, Tsukuda M, Horiuchi C, Satake K, Yoshida T, Nagao J, et al. Concurrent chemoradiotherapy for T4 patients with hypopharyngeal and laryngeal squamous cell carcinomas. Auris Nasus Larynx 2007;34:499-504.  Back to cited text no. 21
    
22.Rades D, Schroeder U, Bajrovic A, Schild SE. Radiochemotherapy versus surgery plus radio (chemo) therapy for stage T3/T4 larynx and hypopharynx cancer-Results of a matched-pair analysis. Eur J Cancer 2011;47:2729-34.  Back to cited text no. 22
    
23.Lambert L, Fortin B, Soulières D, Guertin L, Coulombe G, Charpentier D, et al. Organ preservation with concurrent chemoradiation for advanced laryngeal cancer: Are we succeeding? Int J Radiat Oncol Biol Phys 2010;76:398-402.  Back to cited text no. 23
    
24.Sassler AM, Esclamado RM, Wolf GT. Surgery after organ preservation therapy. Analysis of wound complications. Arch Otolaryngol Head Neck Surg 1995;121:162-5.  Back to cited text no. 24
    
25.Weber RS, Berkey BA, Forastiere A, Cooper J, Maor M, Goepfert H, et al. Outcome of salvage total laryngectomy following organ preservation therapy: The Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg 2003;129:44-9.  Back to cited text no. 25
    
26.Sanabria A, Domenge C, D′cruz A, Kowalski LP. Organ preservation protocols in developing countries. Curr Opin Otolaryngol Head Neck Surg 2010;18:83-8.  Back to cited text no. 26
    
27.Trivedi NP, Kekatpure VD, Trivedi NN, Kuriakose MA, Shetkar G, Manjula BV. Feasibility of organ-preservation strategies in head and neck cancer in developing countries. Indian J Cancer 2012;49:15-20.  Back to cited text no. 27
[PUBMED]  Medknow Journal  
28.Kulkarni MR. Head and neck cancer burden in India. Int J Head Neck Surg 2013;4:29-35.  Back to cited text no. 28
    
29.Popescu CR, Bertesteanu SV, Mirea D, Grigore R, lonescu D, Popescu B. The epidemiology of hypopharynx and cervical esophagus cancer. J Med Life 2010;3:396-401.  Back to cited text no. 29
    
30.Gupta T, Agarwal JP, Ghosh-Laskar S, Parikh PM, D′Cruz AK, Dinshaw KA. Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: A single-institution experience. Head Neck Oncol 2009;1:17.  Back to cited text no. 30
    
31.Brizel DM, Esclamado R. Concurrent chemoradiotherapy for locally advanced, nonmetastatic, squamous carcinoma of the head and neck: Consensus, controversy, and conundrum. J Clin Oncol 2006;24:2612-7.  Back to cited text no. 31
    
32.Overgaard J, Mohanti BK, Begum N, Ali R, Agarwal JP, Kuddu M, et al. Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): A randomised, multicentre trial. Lancet Oncol 2010;11:553-60.  Back to cited text no. 32
    
33.Joshi P, Patil V, Joshi A, Norohna V, Chaturvedi P, Chaukar D, et al. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma. Indian J Cancer 2013;50:25-30.  Back to cited text no. 33
[PUBMED]  Medknow Journal  
34.Gupta T, Chopra S, Agarwal JP, Laskar SG, D′cruz AK, Shrivastava SK, et al. Squamous cell carcinoma of the hypopharynx: Single-institution outcome analysis of a large cohort of patients treated with primary non-surgical approaches. Acta Oncol 2009;48:541-48.  Back to cited text no. 34
    
35.Trivedi NP, Swaminathan DK, Thankappan K, Chatni S, Kuriakose MA, Iyer S. Comparison of quality of life in advanced laryngeal cancer patients after concurrent chemoradiotherapy vs total laryngectomy. Otolaryngol Head Neck Surg 2008;139:702-7.  Back to cited text no. 35
    
36.Takes RP, Strojan P, Silver CE, Bradley PJ, Haigentz M Jr, Wolf GT, et al. Current trends in initial management of hypopharyngeal cancer: The declining use of open surgery. Head Neck 2012;34:270-81.  Back to cited text no. 36
    
37.Denaro N, Russi EG, Lefebvre JL, Merlano MC. A systematic review of current and emerging approaches in the field of larynx preservation. Radiother Oncol 2013 doi: 10.1016/j.radonc. 2013.08.016. [Epub ahead of print]  Back to cited text no. 37
    
38.Holgersson G, Ekman S, Reizenstein J, Bergqvist M, Pontén F, Uhlén M, et al. Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy. Cancer Genomics Proteomics 2010;7:1-7.  Back to cited text no. 38
    



 
 
    Tables

  [Table 1]


This article has been cited by
1 The interobserver agreement in the detection of recurrent HNSCC using MRI including diffusion weighted MRI
Boris Peltenburg,Juliette P. Driessen,Marielle E.P. Philippens,Frank A. Pameijer,Jonas Castelijns,Jan Willem Dankbaar,Bart Dorgelo,Charlotte A.H. Lange,Frederick J.A. Meijer,Walter M. Palm,Stefan D. Roosendaal,Stefan C.A. Steens,Berit M. Verbist,Inge Stegeman,Luuk M. Janssen,Remco de Bree,Chris H.J. Terhaard
European Journal of Radiology. 2018; 105: 134
[Pubmed] | [DOI]
2 Trans-oral miniature X-ray radiation delivery system with endoscopic optical feedback
Axel Boese,Fredrick Johnson,Till Ebert,Ali Mahmoud-Pashazadeh,Christoph Arens,Michael Friebe
International Journal of Computer Assisted Radiology and Surgery. 2017;
[Pubmed] | [DOI]
3 Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma
DIDIER DEQUANTER,MAUREEN VAN DE VELDE,ISABELLE BAR,VINCENT NUYENS,ALEXANDRE ROUSSEAU,NATHALIE NAGY,LUC VANHAMME,MICHEL VANHAEVERBEEK,DANY BROHÉE,PAUL DELRÉE,KARIM BOUDJELTIA,PHILIPPE LOTHAIRE,PIERRICK UZUREAU
Oncology Letters. 2016; 11(6): 3660
[Pubmed] | [DOI]
4 Response to docetaxel and cisplatin induction chemotherapy of locally advanced head and neck squamous cell carcinoma: a multicenter, non-comparative, open-label interventional pilot study
V Noronha,C Goswami,S Patil,A Joshi,V M Patil,V Murthy,S Arya,S Juvekar,S Goud,K Prabhash
The Journal of Laryngology & Otology. 2016; 130(9): 833
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Current Evidence
Critical Analysi...
Outcomes of Orga...
Experience of Su...
Experience from ...
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed2215    
    Printed37    
    Emailed1    
    PDF Downloaded723    
    Comments [Add]    
    Cited by others 4    

Recommend this journal