|Ahead of print
The efficacy of function-preservation in treating paranasal sinus and nasal cavity neoplasms
Xiaoli Deng1, Zhaoyi Lu2, Xiaomin Wang2, Junjie Zhang2, Shixian Liu2, Mingjie Zhang2, Jie Meng2, Deshang Chen2, Shiyin Ma2, Hui Li2
1 Key laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, Shihezi University, Shihezi, Xin jiang, People's Republic of China
2 Department of Otolaryngology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People's Republic of China
|Date of Submission||23-Sep-2019|
|Date of Decision||23-Sep-2019|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||21-Jun-2021|
Department of Otolaryngology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui
People's Republic of China
Source of Support: None, Conflict of Interest: None
Background: Craniofacial resection (CFR) has been regarded as the gold standard for paranasal sinus and nasal cavity (PNSNC) neoplasms. The improvement of surgical procedures has been ongoing in recent years. We analyzed the clinical curative effects of the function-preservation therapy that was mainly using nasal endoscopic surgery along with appropriate radiotherapy and chemotherapy as applicable.
Methods: We performed a retrospective analysis of factors that influence the survival time of the 28 patients with PNSNC neoplasms who underwent nasal endoscopic surgery. All patients with tumor lesions underwent a complete resection in en bloc or piecemeal resection. Five cases did not undergo radiotherapy or chemotherapy; the remaining 23 patients had multimodality therapy.
Results: The median follow-up time was 41.5 (range = 14–97) months. The overall 3-year survival rate was 78.57% for T3 cancer and 50% for those with T4. T classification (P = 0.031) and multimodality therapy (P = 0.038) were independent prognostic factors for postoperative 3-year survival rate of patients with PNSNC neoplasms.
Conclusion: Function-preservation therapy based on the minimally invasive endoscopic resection (MIER) with appropriate adjuvant therapy not only prolonged the overall survival time but also provided an opportunity to preserve organ function at the same time, which helped to improve the patients' quality of life.
Keywords: Function-preservation therapy, nasal endoscope, neoplasms, paranasal sinus and nasal cavity (PNSNC)
Function-preservation therapy based on the minimally invasive endoscopic resection not only prolonged the overall survival time but also improved the living quality of patients with paranasal sinus and nasal cavity neoplasms.
|How to cite this URL:|
Deng X, Lu Z, Wang X, Zhang J, Liu S, Zhang M, Meng J, Chen D, Ma S, Li H. The efficacy of function-preservation in treating paranasal sinus and nasal cavity neoplasms. Indian J Cancer [Epub ahead of print] [cited 2021 Jul 27]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=318902
Xiaoli Deng and Zhaoyi Lu have contributed equally to this work.
| » Introduction|| |
The paranasal sinus and nasal cavity (PNSNC) neoplasms only account for about 1% of malignancies in humans and 3% of those malignancies affect the head and neck, which occur most frequently in the nasal cavity (44%) and maxillary sinus (36%). The most common pathological classification is the squamous cell carcinoma. Early clinical symptoms of the tumor are atypical and easily misdiagnosed as nasal sinus inflammatory disease. So, most patients delayed their optimal treatment time window, and the diagnosis of advanced PNSNC cancers can be a significant challenge. Craniofacial resection (CFR) has been regarded as the gold standard for PNSNC malignancies since 1963. The improvement of surgical procedures has been ongoing over this time, and endoscopic surgery is also developing synchronously in China. Over the past 20 years, our surgeons had gradually mastered the opening of traditional craniofacial, maxillary total and subtotal resection, lateral nasal rhinotomy, endoscopic-assisted Caldwell-Luc operations, and the nasal endoscopic intranasal approach. Moving from the earliest minimally invasive treatment that only resected the tumor to the current preservation functions performed is considerable progress. In this paper, the clinical data of 28 patients with PNSNC neoplasms were retrospectively analyzed, and the curative effect of the treatment they received was preliminarily investigated.
| » Methods|| |
Patients and settings
Twenty-eight patients with PNSNC neoplasms were diagnosed by the otorhinolaryngology department in our hospital between October 2012 and October 2016. Among the patients, 19 were male, and 9 were female. The median age was 59 years, ranging from 16 to 75 years. The tumor's primary site was mainly in the nasal cavity or ethmoid sinus (n = 12), and maxillary sinus (n = 16). All patients underwent biopsies before their operation, combined with an endoscopic diagnosis and imaging examination to determine the tumor's pathological type and origin. All patients had integrated clinical data collected before and after their operation.
Other inclusion criteria included having no surgery at an external hospital; the primary tumor site was confined to the PNSNC; the biopsy pathology was confirmed at our hospital, and patients followed the indications for nasal endoscopic surgery., There were 13 cases of squamous cell carcinoma (SCC), 2 cases of adenocarcinoma, 4 cases of adenoid cystic carcinoma (ACC), 1 case of olfactory neuroblastoma (ONB), 1 case of melanoma, 3 cases of rhabdomyosarcoma (RMS), 2 cases of teratoma, 1 case of chondrosarcoma, and 1 case of epithelial-myoepithelial carcinoma (EMC). According to the American Joint Committee on Cancer, the seventh edition of the TNM Staging System: 8 cases were stage II T2N0M0, 14 cases were stage III, 12 cases were T3N0M0, 2 cases were T3N1M0 (unilateral neck), and 6 cases were stage IV, T4N0M0. Among them, the staging criteria are independent in melanoma.
We used the multi-angle Karl Storz endoscope to explore the tumor range and ion stripping to confirm the location of the tumor pedicle. Under the premise of not destroying the whole tumor, the pedicle and surrounding parts were removed using the plasma isothermal method. It was then completely removed. When the nasal cavity did not have adequate operating space, the nasal cavity was removed by piecemeal resection. That is, the suction device was cold cut to ensure that the tumor tissue was immediately sucked away after the tumor tissue was cut off. After removing the primary tumor, the surrounding bone destruction was examined under an endoscope, and the damaged, loose bone was removed using a grinding drill combined with occlusal forceps until the white dense bone was exposed. The periosteum and exposed bone surface were treated with a bipolar electric knife or plasma knife. In five cases with poorly exposed surgery field, an intranasal endoscopic prelacrimal recess approach was used to altogether remove the mass to preserve organ function and avoid injury to the anterior wall of the maxillary sinus (occipital nerve) and nasolacrimal duct. This approach helped reduce severe complications, such as facial numbness, neuralgia, and epiphora after surgery. Two cases of lymph node metastasis also underwent selective neck cleaning. Eye, mouth, and nose function was preserved in all cases.
After confirming the patients' pathologic type, we referred to the guidelines of the National Comprehensive Cancer Network (Head and Neck Cancers, Version 1.2012) to determine the adjuvant therapeutic regimen. Three patients with RMS cases, who are sensitive to radiochemotherapy, received a VAC regime (vincristine, dactinomycin, and cyclophosphamide) and radiotherapy, and the residual tumors were removed by endoscopic sinus surgery. Patients with adenocarcinoma, ACC, EMC, ONB, and chondrosarcoma underwent postoperative radiotherapy. Patients with SCC were given concomitant radiochemotherapy (CCRT) after surgery. Postoperative patients with melanoma were treated with dacarbazine combined with cisplatin. Postoperative chemotherapy with cisplatin, etoposide, and ifosfamide was given in patients with teratoma. Postoperative radiotherapy was based on intensity-modulated radiation therapy (IMRT), the median total dose of 60 Gy in conventional fractionation (1.8–2 Gy). The regimen of cisplatin, 5-fluorouracil, methotrexate, and leucovorin as the primary concurrent chemotherapy was combined with radiotherapy. Patients with orbital invasion were given the induction chemotherapy, which included docetaxel, cisplatin, and fluorouracil.
Consent documents were obtained from all patients, and the medical ethics committee of The First Affiliated Hospital of Bengbu Medical College approved this study.
Analyses were completed with SPSS software version 23.0, survival rates were determined by Kaplan-Meier analysis, survival rate difference analysis was carried out by the Log-rank test, and the prognostic factors were analyzed by multivariate analysis. Results were considered significant when P values were less than 0.05.
| » Results|| |
All patients were followed-up for a median of 41.5 (range = 14–97) months. Six patients died, of which there were three cases of SCC patients (3/13, 23%), one case of melanoma patient (1/1, 100%), one case of ACC patient (1/4, 25%), and one case of RMS patient (1/3, 33%). The overall 3-year survival rate of all patients was 78.57%, in which the 3-year survival rates of T3 and T4 were 78.57% and 50%, respectively. During the follow-up, there were no obvious poor outcomes among the 15 patients with infiltration of orbital periosteum except for 5 cases of dacryocystitis and 2 cases of death (1 case of SCC and 1 case of RMS). The results of log-rank test showed that age (P = 0.0466), pathological type (P = 0.0003), T stage (P = 0.0196), and treatment modality (P = 0.0197) had a statistically significant effect on the overall survival rate [Figure 1].There was no significant difference in survival outcomes between patients of different sex and primary tumor origin (P > 0.05). Further multivariate analysis confirmed early T-staging (P = 0.031) and multimodality therapy (P = 0.038) were independent prognostic factors for improved survival [Table 1].
|Table 1: Multivariate analysis of factors influencing the survival in 28 patients with PNSNC neoplasms|
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|Figure 1: Kaplan–Meier survival curves for (a) sex, (b) age, (c) origin, (d) pathological type, (e) T stage, and (f) treatment modality SCC = squamous cell carcinoma, ACC = adenoid cystic carcinoma, EMC = epithelial-myoepithelial carcinoma, ONB = olfactory neuroblastoma, RMS = Rhabdomyosarcoma. Note: Log-rank test result is shown in the lower right corner of each graph.*P < 0.05, **P < 0.01, ***P < 0.001|
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| » Conclusion|| |
Feasibility of endoscopic sinus surgery
The anatomy of PNSNC is complex, and the malignant tumors that originate here often invade the skull base and orbit. Their particular anatomical structure means that even open resections are rarely achieved. In the past, the CFR was the standard operation of PNSNC neoplasms. As patients' demand for minimally invasive surgery continues to increase, endoscopy and imaging technology are also constantly upgraded, making it possible to carry out nasal endoscopic surgery. Minimally invasive endoscopic resection (MIER) has excellent application value as compared with traditional open surgery. MIER has many advantages: a more visible, full field of operation, a changeable visual angle, smaller trauma, shorter operation, less hospitalization time, low cost, and a more satisfactory curative effect.
Many teams and research centers have begun to explore endoscopic sinus surgery for treating PNSNC neoplasms. Professor McCutcheon first proved that the efficacy of block resection under CFR is similar to that of block resection, which partly dispels the surgeon's concerns about the principle of mass resection in tumor surgery. Arnold et al. reported 123 endoscopic cases compared with open surgery. The positive margin rate under endoscopic sinus surgery was slightly higher (68% versus 62%), but there was no significant difference (P = 0.636). However, the complications of endoscopic sinus surgery were 11%, which was significantly reduced compared with the traditional open surgery group (33%), which further promoted MIER's development. A meta-analysis (n = 952 patients) showed that patients' survival rate with complete nasal endoscopic resection did not decrease. Although the optimal sequence of surgery and adjuvant therapy is still controversial, we believe that the therapy based on functional retention of MIER is a feasible method for treating PNSNC neoplasms.
The most common type of pathology is SCC, in the advanced stages when diagnosed, and often invades the skull base and orbit. MIER supplement with appropriate CCRT has become the best choice to improve overall survival. Intestinal-type adenocarcinoma is common adenocarcinoma, of which biological behavior is inert and less sensitive to radiotherapy, with local recurrence potential, rare lymph nodes, and distant metastasis. ACC is a kind of rare tumor of salivary gland origin. In pathological classification, the solid type is so poorly differentiated, more aggressive, and possible formulating metastasis, which has the worst prognosis. With biological characteristics of slow growth, neurotropic aggressiveness, uncommon lymphatic metastasis, high recurrence, and metastasis rate, the therapy of surgery supplemented by postoperative radiotherapy is mainly adopted. EMC is a low-grade malignant bipolar salivary gland tumor with a high recurrence rate, which can be prevented by IMRT effectively. ONB is vulnerable to radiotherapy and less sensitive to chemotherapy, but terminal patients with high metastasis rate and poor prognosis can consider adjuvant chemotherapy. The symptoms of melanoma are insidious and complicated, with increased malignancy and metastasis rate and poor prognosis. It should advocate treating extensive surgical resection supplemented with individualized targeted and biological immunotherapy, whereas the dacarbazine combined with cisplatin may be used as palliative care. Early diagnosis and comprehensive treatment are the keys to improve the survival rate. Teratocarcinoma sarcoma (TCS) is a rare and highly malignant tumor only seen in the head and neck, containing histological features of malignant teratoma, carcinoma, and sarcoma. The tumor progression mainly manifests as a local recurrence. At present, the treatment of TCS is mostly surgical resection and postoperative chemotherapy concerning the major components of this heterogeneous tumor. Chondrosarcoma is a slow-growing, mainly locally infiltrating tumor and rarely metastasizing. Radiotherapy can be used as an adjuvant to prolong patients' survival duration with the highly aggressive chondrosarcoma phenotype. In RMS, the embryonal type is in the majority (50%-60%), prone to recurrence and metastasis. Patients with RMS were sensitive to radiotherapy and chemotherapy; for those with pre-existing renal abnormalities were recommended to receive mainly the VAC regimen. Preoperative induction therapy in RMS helps expose the safe tumor boundary, and then the residual tumor needs to be surgically removed.
We adopt IMRT to ensure that the local lesions can receive adequate fractionated doses. Simultaneously, the healthy tissues and organs can be protected to the maximum extent, provide the curative effect, and reduce the adverse effects of conventional radiotherapy. The impact of induction chemotherapy on organ retention has been reported, which is not only beneficial to the exposure of the intraoperative safety boundary and complete resection of the tumor but also provides an opportunity for the preservation of eye, mouth and nose functions. Safi et al. pointed out that CCRT to protect organs for terminal patients with SCC of maxillary sinus had a similar survival rate compared with traditional open surgery combined with radiochemotherapy. For terminal cancer patients, CCRT can improve the local control rate while killing micrometastases and inhibiting distant metastases, thereby ensuring the overall survival rate and organ function preservation. In summary, choosing an appropriate adjuvant therapeutic regimen for different pathological types is particularly crucial for patients' functional retention and long-term survival.
The importance of early diagnosis
As early diagnosis is critical, unilateral symptoms of rhinosinusitis, and patients with nosebleeds along with a headache or facial numbness should be carefully examined to prevent a misdiagnosis. Nasopharyngeal carcinoma and oropharynx cancer will often invade the PNSNC after the T3 stage, and we need to distinguish between other potential diagnoses carefully. The formulation of the treatment plan should be discussed and agreed with the imaging, pathology, ophthalmology, stomatology, radiotherapy, oncology, and neurosurgery departments to achieve proper, individualized treatments and to ensure that the curative effect is achieved.
Matthew et al. studied 114 patients with malignant tumors of the nasal cavity and sinus who underwent surgery, radiotherapy, and systemic chemotherapy. They showed that the high T stage was associated with poor prognosis (P = 0.02), which matched the conclusions (P = 0.0196) in our study.
Complications and clinical follow-up
Among the 28 patients reviewed in this paper, there were 16 (57.14%) cases of nasal dryness, 5 (17.86%) cases of dacryocystitis, 3 (10.71%) cases of epistaxis, and 1 (3.57%) case of maxillary osteomyelitis. So far, there has been no cerebrospinal fluid (CSF) leakage caused by surgery. CSF leakage was one of the most challenging complications of endoscopic nasal surgery in its earlier years. The incidence of premature CSF leakage is between 20% and 30%. The Thorp team used a nasal septal mucosal flap with the vascular pedicle to repair the skull base to reduce the occurrence of CSF leakage.
The first follow-up was checked by contrast-enhanced MRI (magnetic resonance imaging) and nasal endoscopy, one week after surgery. Periodic follow-up at 1, 3, and 8 weeks after the operation should be undertaken to ensure proper healing of the skin flap and no residual vesicles or early recurrence in the nasal cavity.
The five-year survival rate of PNSNC did not significantly improve (40%–50%), despite the development of therapy. Most high T-staging patients had no lymph node metastasis, and only about 5% had distant metastasis. The local recurrence is the leading cause of treatment failure; even though surgery is still the primary treatment for complete resection of lesions, multimodality therapy helped further improve the prognosis of patients with the relapsing PNSNC tumor.
In conclusion, function-preservation therapy based on the MIER with appropriate adjuvant therapy not only prolonged the overall survival time but also provide an opportunity to preserve organ function at the same time, which helped to improve patients' quality of life. We have reasons to believe that in the new era of artificial intelligence, with the continuous upgrading of high-throughput sequencing technology, new drug development, and surgical instruments, multimodal therapy as the central theme will bring patients a better prognosis and living quality.
The authors gratefully acknowledge the time and energy contributed by the participants.
Financial support and sponsorship
This study was funded by the Science and Technology Development Fund Project of the First Affiliated Hospital of Bengbu Medical College (BYKF1790).
Conflicts of interest
There are no conflicts of interest.
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