|Year : 2021 | Volume
| Issue : 1 | Page : 1-3
Progress in head-and-neck cancer: Promise versus reality
Tejpal Gupta1, Jai Prakash Agarwal2
1 Department of Radiation Oncology, ACTREC, Tata Memorial Centre, HBNI, Kharghar, Navi Mumbai, India
2 Department of Radiation Oncology, Tata Memorial Centre, HBNI, Parel, Mumbai, Maharashtra, India
|Date of Submission||25-Apr-2021|
|Date of Acceptance||25-Apr-2021|
|Date of Web Publication||29-Jun-2021|
Jai Prakash Agarwal
Professor, and Head, Department of Radiation Oncology, Tata Memorial Centre, HBNI, Parel, Mumbai
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta T, Agarwal JP. Progress in head-and-neck cancer: Promise versus reality. J Head Neck Physicians Surg 2021;9:1-3
The past two decades have witnessed major scientific advances, both technological and biological, that have bolstered our diagnostic and therapeutic armamentarium against head-and-neck cancer with the promise to significantly improve disease-related outcomes as well as health-related quality-of-life (QOL). However, it still needs to be ascertained both at a global level as well as national/local level whether such promise has been realized in clinical practice by the head-and-neck oncology community.
Head-and-neck cancer is not a single disease but comprises a heterogeneous group of cancers associated with similar risk factors that arise in the upper aerodigestive tract, but have distinct clinicodemographic profile, symptom burden, treatment, and outcomes. As per GLOBOCAN estimates, a total of 6,50,000 new cases of head-and-neck cancer were diagnosed in the year 2016, making it the 6th most common cause of cancer worldwide. Conventionally, alcohol and tobacco-induced carcinogenesis were implicated in the etiopathogenesis of vast majority of head-and-neck cancers., However, the landscape of head-and-neck cancer has changed substantially over time with human papillomavirus (HPV)-associated oropharyngeal squamous cell cancer emerging as a distinct new disease entity, with ever-increasing incidence, particularly in the developed world in parallel with gradual but consistent decline in tobacco-related cancer. This epidemiological shift is somehow not reflected in many developing countries including India, which continues to have much lower yet highly variable prevalence of HPV-associated head-and-neck cancer, with chewing-tobacco-related cancer being the predominant form. Widespread use of chewable tobacco transforms the epithelial lining of the oral mucosa (alveolo-buccal complex and tongue) making the oral cavity the most common site of primary within the head–and-neck region in India thereby providing unique challenges as well as opportunities.
Surgery had been one of the cornerstones of curative-intent therapy for head-and-neck cancer that has been practiced for over 100 years. There has been increasing attention to the preservation of form and function during surgical planning. Advances in microsurgery and plastic surgery with free flaps and composite tissue transfers provide the ability to our current generation of surgeons to reconstruct virtually any defect in the head-and-neck region. However, despite achieving acceptable cancer control and cure, poor functional and cosmetic outcomes attendant to such radical surgery have spurred and driven more conservative and function-sparing surgical approaches in recent times to preserve and maintain QOL. The classic example of such transformation from radical approach to conservative surgery is the transition from radical neck dissection to modified neck dissection/selective neck dissection and even sentinel lymph node biopsy in the management of the neck. The development of minmally invasive techniques has led transoral laser microsurgery, endoscopic/endonasal skull-base surgery, and transoral robotic surgery being established in well-defined indications leading to better functional and cosmetic outcomes without compromising cancer control.
In parallel, high-quality evidence, from prospective randomized controlled trials has firmly established combined modality treatment (radiotherapy and chemotherapy) as the current standard of care in the non-surgical management of locally advanced head-and-neck cancers. Definitive radiotherapy with concurrent cisplatin-based chemotherapy, or induction chemotherapy followed by definitive concurrent (chemo) radiotherapy, is the backbone of contemporary organ-preservation protocols designed to provide cure while maintaining organ form and function. Conventionally, head-and-neck irradiation comprised of conventional techniques either as parallel opposed portals with or without matched low anterior neck ﬁeld or wedge-pair technique based on two-dimensional ﬂuoroscopic imaging without major emphasis on shielding normal tissues resulting in considerable acute and late morbidity., Acute toxicity of irradiation can sometimes lead to interruption and even premature discontinuation of therapy with potential adverse impact on outcomes, while persistent salivary gland hypofunction can lead dryness of mouth, oral discomfort, and difﬁculty in speech and swallowing with negative impact upon health-related QOL. Over the years, technological advances in treatment planning and delivery have resulted in progressive conformation of radiation dose to the target tissues while sparing adjacent organs-at-risk. Intensity-modulated radiation therapy-an advanced form of high-precision conformal technique that uses nonuniform beam intensities through computer-controlled optimization to achieve the desired dose distribution is currently the most preferred technique in the curative-intent radiotherapeutic management of head-and-neck cancer. The advent of in-room imaging on modern linear accelerators allows daily volumetric verification and online correction of set-up errors ushering the era of image-guided radiation therapy that could potentially allow smaller margins leading to reduction in the volume of irradiation and resultant normal tissue toxicity. Adaptive re-planning and the use of functional imaging for guiding selective dose-escalation might further improve outcomes during high-precision radiotherapy of head-and-neck cancers., Proton beam therapy with its superior depth-dose characteristics can further improve the therapeutic index of irradiation, but is neither widely available nor affordable by majority of patients even in the developed world.
The development of newer systemic therapies including chemotherapy, targeted therapy, and immunotherapy continues to advance the field of head-and-neck oncology beyond methotrexate, 5-fluorouracil, and platinum compounds. The use of taxanes (paclitaxel and docetaxel) is now firmly established in the neoadjuvant/induction chemotherapy setting and is being tested with irradiation in the concurrent setting for locoregionally advanced head-and-neck cancer. Epidermal growth factor receptor (EGFR) plays a crucial role in cellular growth and proliferation and is markedly overexpressed in tumor cells compared to normal cells making it an attractive therapeutic target. The addition of cetuximab an EGFR-targeting monoclonal antibody to radiation was demonstrated to result in significant improvement in outcomes compared to radiation alone in patients considered ineligible for high-dose cisplatin-based concurrent chemoradiotherapy. The next generation of EGFR and other tyrosine kinase inhibitors are currently being tested in several solid cancers including head-and-neck cancers. Recently, immune checkpoint inhibitors targeting the programmed death (PD)-1 (nivolumab, pembrolizumab), PD-ligand 1 (avelumab), and cytotoxic T-lymphocyte associated (CTLA)-4 (ipilimumab) have shown promise both in the palliative setting for recurrent/metastatic head and neck cancers as well as curative-intent setting for newly-diagnosed patients. Despite the use of modern conformal techniques, chemo-radiotherapy has substantial treatment-related morbidity, prompting de-escalation and de-intensification of treatment in patients with low-risk and/or favorable-biology disease such as HPV-associated oropharyngeal cancer with expected long-term survival. An unplanned post hoc subgroup analysis of the Bonner trial confirmed the survival benefit of adding cetuximab in HPV-positive oropharyngeal cancer, suggesting that cetuximab-based bioradiotherapy could be a potential strategy for treatment de-intensification in this favorable biology disease. However, the substitution of cisplatin with cetuximab was associated with clearly inferior locoregional control and overall survival, rendering such treatment untenable even for such low-risk disease. Advances in allied disciplines such as imaging (radiology and nuclear medicine), pathology (histopathology and molecular diagnostics), dental sciences (oro-dental care and prosthetics), rehabilitative services (speech, swallowing, physiotherapy, and occupational therapy), supportive care (including medical care, nursing care, social services, and patient support groups) and access to information (online and internet-based resources) have kept pace with advances in therapy leading to an integrated and multi-disciplinary team approach for optimizing outcomes in head-and-neck cancer.
It is axiomatic to state that 'prevention is better than cure'. A substantial proportion of head-and-neck cancers can be prevented by simple lifestyle changes such as cessation of alcohol and tobacco, avoidance of prolonged sun exposure, and nonindulgence in sexually promiscuous behavior. Progress in medicine is driven by coordinated global research in epidemiology, etiopathogenesis, biology, diagnostics, therapeutics, and survivorship in any discipline including head-and-neck oncology. Studies conducted through the International Head and Neck Cancer Epidemiology Consortium provide better understanding of the causes and mechanistic aspects of head-and-neck cancer that can translate into cancer prevention programs as well as identify relevant therapeutic targets for treatment. With the increasing incidence of head-and-neck cancer, particularly in developing countries, capacity building is imperative to create a competent and trained workforce to tackle the growing menace of head-and-neck cancer. The International Federation of Head and Neck Oncologic Societies (IFHNOS)-a global organization established through co-operation of various national and regional professional associations-provides a common platform for specialists in the field of head-and-neck cancer to interact in professional matters of common interest and coordinates a global educational fellowship program in head-and-neck oncology. The Foundation for Head and Neck Oncology-a multi-specialty national society for head-and-neck cancer in India-is a constituent member of the IFHNOS and aspires to oversee the standards of care, education, and research in head and neck oncology in the country. Finally, true progress in head-and-neck cancers can be assessed through quality performance indicators and patient satisfaction surveys designed and developed for a particular healthcare setting as proxy measures for delivery of quality of care.
This material has never been published and is not currently under evaluation in any other peer reviewed publication.
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