PMID- 32337356
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 2378-8038 (Print)
IS  - 2378-8038 (Electronic)
IS  - 2378-8038 (Linking)
VI  - 5
IP  - 2
DP  - 2020 Apr
TI  - mTOR inhibitor use in head and neck squamous cell carcinoma: A meta-analysis on 
      survival, tumor response, and toxicity.
PG  - 243-255
LID - 10.1002/lio2.370 [doi]
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has been rising in 
      incidence primarily related to HPV-associated oropharyngeal cancers. Novel 
      molecular therapeutics are evolving with the mTOR pathway as a new target. 
      Previous studies have shown variable outcomes with relatively low toxicity. This 
      study reports the tumor response, survivability, and toxicity of mTOR inhibitors 
      (mTORi) in HNSCC. Despite expanding research on this pathway, there remains 
      controversy around mTORi use for treatment of HNSCC. MATERIALS AND METHODS: 
      Studies were included if: (a) Used mTORi alone or in combination with other 
      treatment modalities in HNSCC. (b) Site of cancer included were one of the 
      following: nasopharyngeal, oral cavity, oropharynx, hypopharynx or larynx. (c) 
      All stages of cancer and treatment stage (neoadjuvant, adjuvant, and palliative) 
      were included. The rate of adverse events (AEs), tumor response, progression free 
      survival, and overall survival were meta-analyzed. RESULTS: From 1299 
      publications only 11 studies met inclusion criteria with a combined 232 total 
      patients treated. Two studies used mTORi neoadjuvantly, five adjuvantly, and four 
      in palliative/unresectable/metastatic setting. Monotherapeutic mTORi resulted in 
      stabilization of disease (52.5%), but partial response was the most common 
      response when mTORi were combined with chemotherapy and/or radiation (CRT) 
      (48.1%). Survival rate was the highest in the mTORi combined with CRT. 
      Hyperglycemia of any grade was the most commonly reported toxicity while grade 3 
      or less AEs were the most common grade of toxicity. CONCLUSION: The use of mTORi 
      as monotherapy in HNSCC has thus far not yielded significant tumor response, 
      however, in combination with other agents, an improved partial tumor response is 
      evident that may or may not be associated with the addition of mTORi. Although 
      adverse events were common, grade 4/5 AEs were uncommon. Further prospective, 
      randomized clinical trials are necessary to confirm the direct roles of these 
      agents in HNSCC tumor response. LEVEL OF EVIDENCE: 2a.
CI  - (c) 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley 
      Periodicals, Inc. on behalf of The Triological Society.
FAU - Patel, Jaimin
AU  - Patel J
AUID- ORCID: 0000-0002-5679-0772
AD  - Head and Neck Tumor Center, Hollings Cancer Center, Department of 
      Otolaryngology-Head and Neck Surgery Medical University of South Carolina 
      Charleston South Carolina USA.
FAU - Nguyen, Shaun A
AU  - Nguyen SA
AUID- ORCID: 0000-0003-0664-4571
AD  - Head and Neck Tumor Center, Hollings Cancer Center, Department of 
      Otolaryngology-Head and Neck Surgery Medical University of South Carolina 
      Charleston South Carolina USA.
FAU - Ogretmen, Besim
AU  - Ogretmen B
AD  - Head and Neck Tumor Center, Hollings Cancer Center, Department of 
      Otolaryngology-Head and Neck Surgery Medical University of South Carolina 
      Charleston South Carolina USA.
FAU - Gutkind, Jorge S
AU  - Gutkind JS
AD  - Moores Cancer Center, Department of Pharmacology University of California San 
      Diego La Jolla California USA.
FAU - Nathan, Cherie-Ann
AU  - Nathan CA
AUID- ORCID: 0000-0001-7386-318X
AD  - Head and Neck Surgical Oncology, Feist-Weiller Cancer Cancer, Department of 
      Otolaryngology-Head and Neck Surgery Lousiana State University Health Center 
      Shreveport Louisiana USA.
FAU - Day, Terry
AU  - Day T
AD  - Head and Neck Tumor Center, Hollings Cancer Center, Department of 
      Otolaryngology-Head and Neck Surgery Medical University of South Carolina 
      Charleston South Carolina USA.
LA  - eng
GR  - R01 DE016572/DE/NIDCR NIH HHS/United States
GR  - R01 DE026870/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20200312
PL  - United States
TA  - Laryngoscope Investig Otolaryngol
JT  - Laryngoscope investigative otolaryngology
JID - 101684963
PMC - PMC7178455
OTO - NOTNLM
OT  - head and neck cancer
OT  - head and neck squamous cell carcinoma
OT  - mTOR inhibitors
OT  - oral cancer
OT  - oropharyngeal cancer
OT  - outcomes
COIS- The authors report no conflict of interest.
EDAT- 2020/04/28 06:00
MHDA- 2020/04/28 06:01
PMCR- 2020/03/12
CRDT- 2020/04/28 06:00
PHST- 2019/08/09 00:00 [received]
PHST- 2019/11/18 00:00 [revised]
PHST- 2020/02/17 00:00 [accepted]
PHST- 2020/04/28 06:00 [entrez]
PHST- 2020/04/28 06:00 [pubmed]
PHST- 2020/04/28 06:01 [medline]
PHST- 2020/03/12 00:00 [pmc-release]
AID - LIO2370 [pii]
AID - 10.1002/lio2.370 [doi]
PST - epublish
SO  - Laryngoscope Investig Otolaryngol. 2020 Mar 12;5(2):243-255. doi: 
      10.1002/lio2.370. eCollection 2020 Apr.