Advanced Head and Neck Cancers

Defining the term un-resectable is difficult, as resectability has evolved over time due to advances in surgical techniques and reconstruction Criteria for unresectability is varied ranging from structural and anatomical aspects to functional and co-existing medical conditions.

Advanced Head and Neck cancers have a propensity to recur locally. Early detection of recurrence holds the key to a successful salvage when feasible. 18F-Fluorodeoxy D glucose Positron emission tomography computed tomography is an important diagnostic tool for the evaluation of pre-operative staging, tumour response assessment, post therapy follow up in Head and neck SCC (4). PET CT scan is effective in detecting the loco regional recurrence in head and neck tumours earlier when compared to physical examination and/or conventional imaging modality. In our series, PET-CT gave an accurate assesement of the recurrences/ residual disease. This helped us make timely decisions to successfully salvage these cases.

An integrated approach towards the management of cancer is of paramount importance. Multi- disciplinary clinic(MDC) is one such outlook to deliver the essential and effective treatment based on scientific evidence. Inputs during the MDC from various disciplines of healthcare personnel help in achieving the co- ordinated patient care. It’s a great portal for involving the patients and their kin in the decision making of treatment. Discussion of challenging cases, as in the case series provided an avenue to make rational decisions. The involvement of the family in the decision making could have long term impact on recovery and outcomes. NCCN guideline has suggested criteria to assess resectability in Head and Neck cancers, though not absolute. Involvement of the skull base, invasion or encasement of carotids, involvement of infratemporal fossa, direct extension of neck disease to external skin are considered technically inoperable and portend poor prognosis. All our cases were borderline operable tumours. As our surgical expertise improves, we set new boundaries. Operability in the authors view is a relative and dynamic term and keeps evolving.

Carotid space involvement is associated with poor survival rate and disease-free survival rate. Kennedy et.al. in a study reported the 5- year survival in carotid encased tumours as 7% and a dismal recurrence rate of 46% and a 68% rate of distant metastases. Hiranandani also reported similar outcomes and noted the operative mortality of 21.9 % with carotid resection. Treatment of cancer contiguous to the carotid artery becomes a challenge in recurrent or persistent disease secondary to fibrosis adjacent to carotid adventitia owing to previous radiation or surgical procedures. Similarly, previously untreated disease can present with various degrees of carotid artery encasement. In many of these cases, intraoperative assessment of the carotid adventitia can guide a surgeon to attempt a resection in a sub-adventitial plane (“curative peel”). Additional factor of weakened vessel walls pose a threat of carotid blow out in perioperative period. Despite this there does seem to be a survival advantage to pursuing curative treatment. In special situations, resection of primary tumours in-toto with carotid space extension, salvage surgery and benign vascular tumours- Carotid artery dissection, resection and re anastomosis is recommended. Aggressive surgical treatment options have shown better survival rate when compared to non-surgical treatment (12- 14). Studies have shown similar outcomes to resection anastomosis when a sub-adventitial peel was feasible. In our experience, the decision regarding unrespectability can only be made intraoperatively by direct assessment of the arterial anatomy, and we could peel off the disease from over the carotid artery without any added complications. The stenting in one of the cases provided additional support to the vessel wall.

For advanced tumours of oral cavity resection of tumour in continuity with underlying surrounding structures including muscles, submandibular, sublingual glands with/without bone as a single unit termed “compartmental resection” offers better oncological outcomes [15-19]. Compartmental resection addresses the worry of in-contiguous microscopic spread without disturbing the lymphatic pathway to the neck nodes (18). In our case, the residual tumour was addressed using the concepts of compartmental resection. These resections, result in greater functional morbidity and demands a good and experienced reconstructive team to optimise outcomes.

Labelling a tumour as unresectable based on broad consensus fails to identify and precisely treat the select favourable borderline case. This is against the principles of precision oncology and personalised medicine. Our experience over the years suggests that operability is a dynamic entity and keeps evolving and improving as the surgeon, technology and treatment modalities get better.

Precision Pearls

1. Tumour growth rate is widely used for prognostic purposes and assess therapeutic effects of different treatment modalities. When a tumour becomes larger, its growth rate decreases and change to nonexponential growth model (the Gompertzian model). These observations have been made by following the tumour for a long period with several volume measurements. However, in clinical studies, volume estimations of nontreated tumours are usually available only for short measurement time intervals where tumour growth is well explained by an exponential model.
2. Induction chemotherapy (IC) has a proven role in organ preservation and in reducing distant failure, however, its ability to prolong OS has not been demonstrated. The MACH-NC study showed that IC cisplatin/5-fluorouracil (PF) followed by local treatment was associated with a small but significant improvement in OS and in distant failures. In a recent, MACH-NC update, induction PF plus a taxane increased progression free survival (PFS) and OS versus PF.
3. Planned neck dissection was carried out in the past in patients with N2 and N3 neck disease irrespective of treatment response to concurrent chemoradiation. The procedure was usually performed weeks after completion of chemoradiation before the onset of fibrosis, thereby making the surgery technically easier.
4. The CPS is given by summing the number of PD-L1–stained cells (tumour cells, lymphocytes, macrophages) and dividing the result by the total number of viable tumour cells, multiplied by 100 .
5. Head and neck sarcomas being rare tumours (1% of all H&N tumours), pose a challenge in the management due to close proximity to vital structures. All except Rhabdomyosarcoma and Ewing’s sarcoma need surgery as the primary modality of treatment. The local recurrence rates for high-grade soft tissue sarcomas after surgical excision have been reported to be as high as 50%. The survival and incidence of the local recurrence, however, depends on the extent and adequacy of the excision. Local excision with wide margins are necessary to remove the microscopic pseudopodia else may lead to local recurrence. With advances in reconstructive techniques, including free tissue transfer, have made more aggressive surgical resection a reality. A multidisciplinary meeting is advised to help in the decision making of adjuvant radiotherapy and/or chemotherapy.
6. Traditional maximum tolerable dose, single-agent palliative chemotherapy in head and neck cancer has shown marginal improvement in survival. The effect of this treatment on quality of life (QOL) is an issue considering the side effects. Efforts of improving survival by use of combination chemotherapy have not been successful either. Combination chemotherapy regimens increase the toxicity. The addition cetuximab to the combination chemotherapy has shown improved survival, but this is not a cost effective option. Metronomic chemotherapy was developed as an option in such situations for improvement in efficacy in a cost effective manner. The efficacy of oral metronomic chemotherapy (OMCT) consisting of low-dose methotrexate (15 mg/m 2 weekly) and celecoxib, in terms of progression-free survival (PFS), QOL, and OS, was better than single-agent cisplatin and with a favorable toxicity profile.

OMCT has shown encouraging results, especially in the context of patients who are not able to take cetuximab- based therapy in the palliative setting. These results need to be improved with various innovative ways. OMCT, however, has limited activity in platinum refractory patients. The site and sub-site influence the outcomes to metronomic chemotherapy in head and neck cancer.