Head and Neck Squamous Cell Carcinoma (HNSCC) Clinical Trial
Official title:
A Clinical and Biological Umbrella Protocol for Smoker or Non-smoker Patients With Oral Potentially Malignant Lesions (OPML) or Head and Neck Squamous Cell Carcinoma (HNSCC) (IHNPACT UMBRELLA)
This is a multicenter minimal risk or burden prospective 3-cohort follow-up and monitoring
study that aims to collect clinical, socio-psychological, medico-economics data and
biospecimens for patients with oral potentially malignant lesions (OPML) or resectable head
and neck squamous cell carcinoma (HNSCC) :
- Cohort A: OPML patients.
- Cohort B (specific design): smokers (adults who have smoked at least 100 cigarettes in
their lifetime) motivated to quit - either current smokers (who currently smokes
cigarettes every day (daily) or some days (nondaily)) or former smokers (adults who have
smoked at least 100 cigarettes in their lifetime, but say they currently do not smoke)
who stops smoking within 3 months prior to the diagnosis - with a resectable HNSCC
requiring postoperative radiotherapy or chemoradiation.
- Cohort C: Patients with resectable HNSCC non-eligible to cohort B.
The primary objective of this study is the identification of biomarkers (predictive of
malignant transformation or second primary tumor) and new strategies for prevention and
therapy, mainly through extensive genomic, epigenomic and immune characterization of OPML and
HNSCC.
The long-term goal of this study is to reduce the incidence of HNSCC which may impact as well
other smoking-related cancers. It may be interesting to foster excellent translational
research towards the target of reducing the incidence of HNSCC by developing a global and
personalized approach for prevention and treatment of HNSCC. The only way to reach this goal
is to develop an ambitious program that coordinates the efforts of experts from various
fields (surgeons, medical oncologists and addictologists, scientists, sociologists and
economists) that will work together toward the same goal.
This study intends to gather a large scale clinical, sociological, psychological data
gathering combined to a unique set of biospecimens collected prospectively including oral
preneoplastic disease and resectable HNSCC. This represents a unique setting to develop
multidisciplinary studies including a translational research component (validation and
discovery of biomarkers, high throughput molecular studies to understand the dynamics of
molecular changes and identify new strategies for prevention), a sociopsychological component
and an addiction component that aim to increase the percentage of patients entering a process
of weaning, as well as a medico-economics component that intend to evaluate the impact of new
approaches that may emerge from our work.
In summary, this study proposes to prospectively collect clinical, sociopsychological,
medico-economics data and biospecimens in patients included in 3 different cohorts. Cohort A
will include patients with OPML, either from smokers/drinkers (S/D) or
non-smokers/non-drinkers (NS/ND), while cohort B and C will include patients with HNSCC
eligible to upfront surgical resection. Patients in cohort B will be included in an
interventional randomized clinical trial evaluating an intensive and sustained smoking
cessation program.
In patients with OPML, no standard workup and treatment plan is recommended. OPMLs biopsy is
important to identify patients with high grade dysplasia and in situ carcinoma who should
undergo surgical resection of the OMPLs if possible. Although LOH status in OPML biopsies or
buccal brushes has been evaluated in this population as a biomarker of risk to develop oral
cancer, it is not routinely performed. More studies are required to validate their value as a
biomarker of risk in a prospective setting and to identify the best set of biomarkers. In
smokers and/or excessive alcohol drinkers, it is critical to counsel and help patients quit
and it should be part of the standard of care. Unfortunately, this is not always the case.
Studies of chemopreventive agents have not resulted in the development of an intervention
that can be considered as standard of care.
Despite the accumulated knowledge, no comprehensive molecular characterization of OPML is
available. Identification of new targets for prevention and therapy, mainly with genomic,
epigenomic and immune characterization of OPML is critical. Cohort A will allow to
prospectively collect clinical information and biospecimens (biopsies, buccal brushes and
saliva). These unique resources will allow to confirm the value of LOH as a biomarker of risk
and develop standardized procedures for sample processing that can be transferred in the
routine setting, validate or identify other biomarkers and improve risk assessments beyond
LOH, to understand the spatial and temporal dynamics of molecular changes that may help
predicting oral cancer risk, identify relevant targets and suggest new chemoprevention
strategies including immunoprevention interventions. Furthermore, patients included in this
cohort will benefit from standardized care plans and state of the art smoking and alcohol
cessation programs according to current recommendations, and will be given the opportunity to
participate in future chemoprevention studies that may be embedded in the near future in the
umbrella protocol.
In patients with resectable HNSCC (cohorts B and C), smoking and alcohol cessation is one
important step in the management. They allow reducing treatment-related morbidity and
improving radiation and chemoradiation efficacy. It is tempting to believe that they may also
improve patients' quality of life as in the general population, and reduce the risk of second
primary tumor (SPT). Available data focusing on patients with HNSCC and smoking cessation is
scarce. Although the diagnosis and treatment of patients with HNSCC favors smoking cessation,
a significant proportion of former smokers are actively smoking during follow-up despite
having completed treatments associated with substantial morbidity. The literature review
shows that the range of patients that continue to smoke at one year is in the range of
21-41%. Of note, those smoking quit rates at one year are based on patient self-reporting
without biological confirmation in the majority of the cases, which clearly overestimates
quit rates. Smoking cessation programs currently available lead to disappointing results.
HNSCC patients with smoking addiction harbor the highest risk of SPTs. In this vulnerable
population, beyond early management of nicotine dependence, new strategies / innovative
interventional approaches are warranted. Preliminary results from a monocentric study
indicate that an active intervention in this challenging population may lead to encouraging
results in motivated patients. Furthermore, an intensive smoking cessation program
implemented during radiation therapy is feasible in this population of patients. In cohort B,
the efficacy of an intensive and sustained smoking cessation program in a randomized cohort
of these patients at highest risk with potentially curable HNSCC (cohort B) will be
evaluated, with the hypothesis that an intensive and sustained smoking cessation program led
by an addictologist or a tobacco treatment specialist (TTS) during radiation therapy may
improve the 6- and 12-month quite-rate compared with a minimal tobacco cessation
intervention. Among secondary objectives of this trial, medico-economics information will be
gathered to provide an initial assessment of the cost-effectiveness of the experimental
versus standard arms.
Cohort C will allow prospective collection of clinical information and biospecimens
(biopsies, buccal brushes and saliva) only. Patients will benefit from state of the art
smoking and alcohol cessation programs according to current recommendations.
Well-annotated cohorts of patients with HNSCC are scarce. Information and biospecimens
collected in cohorts B and C will provide unique resources to identify biomarkers of risk of
recurrence and SPT.
Having access to large scale information and to biospecimens in patients with preneoplastic
disease (cohort A) who may or may not develop smoking/alcohol related cancers, and with HNSCC
(cohorts B and C) who may develop disease recurrence or SPT, represent a unique opportunity
to understand the dynamics of molecular changes and their interaction with smoking cessation
and/or alcohol withdrawal.
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