The radiation oncologist faces a challenging task while treating paranasal sinus cancers because these tumors are anatomically located close to numerous vital normal tissues, including the brain, optic nerves, eyes, optic chiasm, brainstem, spinal cord, parotid glands, and lacrimal glands. High-dose radiotherapy, which is frequently given together with chemotherapy, may cause severe normal tissue harm.^[17]

As Maxillary Sinus Carcinoma (MSC) is a rare and serious condition and due to the variable treatment modalities, that are seeking to manage it, this systematic review is to assess the prevalence, types, and effectiveness of Chemoradiotherapy (CRT) and Proton Therapy (PBT) in the management of MSC.

Materials and Methods

This systematic review was conducted following accepted standards (Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA).

Study design 

This was a systematic Review. 

Study duration

From November to December 2022.

Study condition

The purpose of this systematic review is to assess the effectiveness of CRT and PBT in the management of MSC.

Search strategy

To locate the pertinent literature, a thorough search of five main databases, including PubMed, Web of Science, Science Direct, EBSCO, Scopus, Wiley, and Cochrane Library, was carried out. We limited our search to English and took into account each database's specific needs. The subsequent keywords were transformed into Mesh terms in PubMed and utilized to locate the relevant studies; "Maxillary sinus carcinoma," "MSC," "Maxillary sinus cancer," "Maxillary sinus tumor," "Maxillary sinus neoplasm," "Radiotherapy," "Chemotherapy," "Chemoradiotherapy," "Proton therapy," "Treatment," and "Management."  The necessary keywords were matched using the Boolean operators "OR" and "AND." The search results included full-text English-language publications, openly downloadable articles, and human trials.

Selection criteria

Inclusion criteria

According to the research's standards, the following criteria had to be met for the subjects to be included: male or female patients with MSC who underwent therapeutical trials, including RCT and BPT.

Exclusion criteria

All subsequent publications, ongoing investigations, and assessments of completed studies that did not focus on one of these subjects were excluded. Despite the rarity of this condition, we did not include case reports.

Data extraction

We used Rayyan (QCRI) to search for duplicates in the search strategy's output.^[18] The relevance of the titles and abstracts was determined by the researchers by reducing the combined search results based on a set of inclusion/exclusion criteria. The reviewers read every word of the papers that satisfied the requirements for inclusion. The writers addressed dispute-resolution techniques. Using a made-up data extraction form, the approved study was uploaded. The authors extracted data about the study titles, authors, study year, study designs, country, population type, participant number, mean age, gender, histological types, used therapy, and main outcomes.

Strategy for data synthesis

Summary tables compiled from the information gathered from the eligible studies were produced to provide a qualitative summary of the included study components and outcomes. The optimal way to use the data from the included study articles was selected after data extraction for the systematic review. Studies that met the full-text inclusion criteria but did not provide data on CRT or PBT used in MSC patients were excluded.

Risk of bias assessment

Using the ROBINS-I risk of bias assessment approach for non-randomized trials of therapies, the quality of the included studies was assessed.^[19] Confounding and participant selection for the study, classification of interventions, deviations from intended interventions, missing data, assessment of outcomes, and choice of the reported result were the seven issues that were examined.

Results and Discussion

Search results

A total of 395 study articles resulted from the systematic search, and then 90 duplicates were deleted. Title and abstract screening were conducted on 305 studies, and 226 studies were excluded. 79 reports were sought for retrieval, and only 9 articles were not retrieved. Finally, 70 studies were screened for full-text assessment; 42 were excluded for wrong study outcomes, 12 for unavailable data on therapeutical approaches for MSC, and 4 for the wrong population type. Twelve eligible study articles were included in this systematic review. A summary of the study selection process is presented in Figure 1.

Characteristics of the included studies

Table 1 includes the sociodemographic characteristics. A total of twelve studies with 468 MSC patients and 335 males were included. Ten studies were conducted in Japan,^[20-29] one in India,^[30] and one in South Korea.^[31] Their age ranged from 18 to 87 years. The most common histopathological types were SCC and adenoid cystic carcinoma.

Table 2 presents the characteristics of the included studies. More than half of the studies were retrospective.^{[24-26, 29-31]} We detected four studies that used PBT for MSC,^[20-23] two used intensity-modulated radiotherapy (IMRT),^{[30, 31]} and six studies used RCT^[24-29] for the management of MSC. The included studies reported that PBT was effective in managing MSC and its impact on anatomical changes. Narita et al. reported that the tumor shrank by about 3–4 weeks of PBT and the organs at risk (OARs) received a higher dosage as a result.^[21] Eight studies also reported that IMRT and CRT have high survival rates, good local control, and a low risk of recurrence.

To the best of our knowledge, this is the first systematic review to emphasize the published literature on PBT and CRT as management modalities for patients with MSC. However, this systematic review is limited by the lack of quantitative assessments of survival rates and tumor control on using these therapeutic options. Our study is also limited by the lack of earlier longitudinal, cohort, and pooled analyses for the management of MSC.

We noted that most of the included studies (10 out of 12 studies) were conducted in Japan. This is documented in some cancer registries that in comparison to international statistics, the cancer of the nasal sinus has a comparatively high incidence in Japan. In Asia, MSC occurs more frequently than in Western nations.^{[32, 33]}

We also documented that the most common histopathological types of MSC were SCC and adenoid cystic carcinoma. This was consistent with the previous investigation.^[33] Malignancies of the nasal and paranasal cavities have a wider range of histological categories than those of the larynx and pharynx; however, squamous cell carcinoma is the most common kind. This is due to the ciliated pseudostratified columnar epithelium that makes up the mucosa of the nasal and paranasal canals, which evolves into squamous epithelium where cancer originates. Because squamous cell carcinoma responds to CRT reasonably well, multimodal therapy is used.^[34]

PBT was effective in managing MSC and its impact on the anatomical changes in this study. Narita et al. reported that the tumor shrank by about 3–4 weeks of PBT and the organs at risk (OARs) received a higher dosage as a result.^[21] Historically, oropharyngeal cancer has been successfully treated with IMRT, which has fewer side effects (such as xerostomia). To provide the highest possible standard of living, treatment-related toxicities must be further decreased as the percentage of young, HPV-positive patients rises. Proton therapy has the advantage of sparing contralateral oropharyngeal and nasopharyngeal tissue from radiation, whereas IMRT frequently causes unneeded radiation of healthy tissue because of the nature of the photon. Particularly following a transoral robotic surgery, proton treatment can be used to lessen incidental radiation administered outside of the target volume.^[35]

The use of proton radiation treatment for head and neck cancer appears to be promising at this time. Proton radiation therapy is becoming more popular, and as a result, more clinical studies and technological developments will shed light on its genuine usefulness as a therapeutic choice for the treatment of head and neck cancer. Additionally, stronger treatment plans and quality assurance systems will be created with the aid of automated proton plan adaption and advance in proton delivery to precisely deliver the radiation dosage to the required target volumes.^[36]

We also reported that IMRT and CRT have high survival rates, good local control, and a low risk of recurrence. With a 6.5% increase in survival at five years, concurrent CRT appears to be more effective than sequential methods. The outcomes of using radiotherapy and chemotherapy in order were poorer.^[37] The best time to administer CRT—preoperatively or postoperatively—remains up for debate. The effectiveness and safety of neoadjuvant CRT followed by radical surgery in treating oral squamous cell carcinoma have been demonstrated in numerous trials.^{[38, 39]}

Recent research by our team has shown that in patients with oral squamous cell carcinoma and stage N2 cervical lymph node involvement, neoadjuvant CRT is preferable to primary surgery, followed by adjuvant CRT.^[30] Preoperative CRT facilitates full resection, lowers the likelihood of perioperative tumor cell spread with implanted metastases, and provides the chance for tissue preservation and retained functional integrity. Due to better oxygenation of the tumor, the radiotherapeutic impact is enhanced in contrast to postoperative CRT.^[40] However, this method of treatment may be linked to a higher incidence of pre-and postoperative problems.

Conclusion

PBT is an effective therapeutic modality in managing MSC and offers a promising future in the treatment of head and neck cancer. Proton beam therapy's precise function will become clearer as it becomes more widely used and as clinical research's purview broadens. IMRT and CRT have high survival rates, good local control, and a low risk of recurrence. MSC was prevalent in Japan and SCC was the most common histopathological type of MSC.

Acknowledgments

Many thanks to Dr. Malik Azhar Hussain; Consultant of General Surgery, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia, for his continuous help, support, and encouragement to complete this work.

Conflict of interest

None.

Financial support

None.

Ethics statement

None.

1. Takes RP, Ferlito A, Silver CE, Rinaldo A, Medina JE, Robbins KT, et al. The controversy in the management of the N0 neck for squamous cell carcinoma of the maxillary sinus. Eur Arch Oto-Rhino-Laryngol. 2014;271(5):899-904.
2. Turner JH, Reh DD. Incidence and survival in patients with sinonasal cancer: a historical analysis of population‐based data. Head Neck. 2012;34(6):877-85.
3. Bhattacharyya N. Cancer of the nasal cavity: Survival and factors influencing prognosis. Arch Otolaryngol–Head Neck Surg. 2002;128(9):1079-83.
4. Dulguerov P, Jacobsen MS, Allal AS, Lehmann W, Calcaterra T. Nasal and paranasal sinus carcinoma: Are we making progress? A series of 220 patients and a systematic review. Cancer: Interdiscip Int J Am Cancer Soc. 2001;92(12):3012-29.
5. Khademi B, Moradi A, Hoseini S, Mohammadianpanah M. Malignant neoplasms of the sinonasal tract: Report of 71 patients and literature review and analysis. Oral Maxillofac Surg. 2009;13(4):191-9.
6. Bhattacharyya N. Factors affecting survival in maxillary sinus cancer. J Oral Maxillofac Surg. 2003;61(9):1016-21.
7. Camp S, Van Gerven L, Poorten VV, Nuyts S, Hermans R, Hauben E, et al. Long‐term follow‐up of 123 patients with adenocarcinoma of the sinonasal tract treated with endoscopic resection and postoperative radiation therapy. Head Neck. 2016;38(2):294-300.
8. Tiwari R, Hardillo JA, Mehta D, Slotman B, Tobi H, Croonenburg E, et al. Squamous cell carcinoma of the maxillary sinus. Head Neck: J Sci Spec Head Neck. 2000;22(2):164-9.
9. Myers LL, Nussenbaum B, Bradford CR, Teknos TN, Esclamado RM, Wolf GT. Paranasal sinus malignancies: An 18‐year single institution experience. Laryngoscope. 2002;112(11):1964-9.
10. Carrillo JF, Güemes A, Ramirez-Ortega MC, Onate-Ocana LF. Prognostic factors in maxillary sinus and nasal cavity carcinoma. Eur J Surg Oncol (EJSO). 2005;31(10):1206-12.
11. Carrau RL, Myers EM, Johnson JT. Paranasal sinus carcinoma--diagnosis, treatment, and prognosis. Oncology (Williston Park, NY). 1992;6(1):43-50.
12. Al-Mamgani A, van Rooij P, Mehilal R, Tans L, Levendag PC. Combined-modality treatment improved outcome in sinonasal undifferentiated carcinoma: Single-institutional experience of 21 patients and review of the literature. Eur Arch Oto-Rhino-Laryngol. 2013;270(1):293-9.
13. Suárez C, Rodrigo JP, Rinaldo A, Langendijk JA, Shaha AR, Ferlito A. Current treatment options for recurrent nasopharyngeal cancer. Eur arch oto-rhino-laryngol. 2010;267(12):1811-24.
14. Guntinas-Lichius O, Kreppel MP, Stuetzer H, Semrau R, Eckel HE, Mueller RP. Single modality and multimodality treatment of nasal and paranasal sinuses cancer: A single institution experience of 229 patients. Eur J Surg Oncol (EJSO). 2007;33(2):222-8.
15. Kang JH, Cho SH, Kim JP, Kang KM, Cho KS, Kim W, et al. Treatment outcomes between concurrent chemoradiotherapy and combination of surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus cancer: A multi-institutional retrospective analysis. J Oral Maxillofac Surg. 2012;70(7):1717-23.
16. Leeman JE, Romesser PB, Zhou Y, McBride S, Riaz N, Sherman E, et al. Proton therapy for head and neck cancer: expanding the therapeutic window. Lancet Oncol. 2017;18(5):e254-65.
17. Chera BS, Malyapa R, Louis D, Mendenhall WM, Li Z, Lanza DC, et al. Proton therapy for maxillary sinus carcinoma. Am J Clin Oncol. 2009;32(3):296-303.
18. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:1-0.
19. Jüni P, Loke Y, Pigott T, Ramsay C, Regidor D, Rothstein H, et al. Risk of bias in non-randomized studies of interventions (ROBINS-I): Detailed guidance. Br Med J. 2016;355:i4919.
20. Sugiyama S, Katsui K, Tominaga Y, Waki T, Katayama N, Matsuzaki H, et al. Dose distribution of intensity-modulated proton therapy with and without a multi-leaf collimator for the treatment of maxillary sinus cancer: a comparative effectiveness study. Radiat Oncol. 2019;14(1):1-0.
21. Narita Y, Kato T, Ono T, Oyama S, Yamazaki Y, Ouchi H, et al. Trend analysis of the dosimetric impact of anatomical changes during proton therapy for maxillary sinus carcinoma. J Appl Clin Med Phys. 2021;22(9):298-306.
22. Nakamura T, Azami Y, Ono T, Yamaguchi H, Hayashi Y, Suzuki M, et al. Preliminary results of proton beam therapy combined with weekly cisplatin intra-arterial infusion via a superficial temporal artery for treatment of maxillary sinus carcinoma. Japan J Clin Oncol. 2016;46(1):46-50.
23. Narita Y, Kato T, Ono T, Oyama S, Komori S, Arai K, et al. Effect of anatomical change on dose distribution during radiotherapy for maxillary sinus carcinoma: Passive scattering proton therapy versus volumetric-modulated arc therapy. Br J Radiol. 2019;92(1093):20180273.
24. Heianna J, Makino W, Hirakawa H, Yamashita Y, Tomita H, Murayama S. Therapeutic efficacy of intra-arterial docetaxel and nedaplatin infusion concomitant with radiotherapy for T4 maxillary sinus squamous cell carcinoma. Int J Oral Maxillofac Surg. 2022;51(9):1123-30.
25. Nishino H, Miyata M, Morita M, Ishikawa K, Kanazawa T, Ichimura K. Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy for maxillary sinus carcinoma. Cancer: Interdiscip Int J Am Cancer Soc. 2000;89(9):1925-32.
26. Konishi K, Kamiya M, Ishiba R, Komatsu T, Asao T, Ikenohira T, et al. Impact of total radiation dose on the treatment outcomes in radiotherapy and concomitant superselective intra-arterial high dose cisplatin for locally advanced maxillary sinus cancer. Int J Radiat Oncol Biol Phys. 2020;108(3):e830-1.
27. Makino T, Tachibana T, Kariya S, Matsui Y, Matsuzaki H, Fujimoto S, et al. Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer. Auris Nasus Larynx. 2020;47(5):881-6.
28. Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Suzuki F, et al. Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. Br J Cancer. 2013;109(12):2980-6.
29. Yoshimura RI, Shibuya H, Ogura I, Miura M, Amagasa T, Enomoto S, et al. Trimodal combination therapy for maxillary sinus carcinoma. Int J Radiat Oncol Biol Phys. 2002;53(3):656-63.
30. Nandwana U, Verma M, Soni TP, Jakhotia N, Patni N, Gupta AK, et al. Survival impact of postoperative adjuvant radiotherapy for treatment of advanced stage maxillary sinus cancer patients. J Clin Diagn Res. 2018;12(2).
31. Suh YG, Lee CG, Kim H, Choi EC, Kim SH, Kim CH, et al. Treatment outcomes of intensity‐modulated radiotherapy versus 3D conformal radiotherapy for patients with maxillary sinus cancer in the postoperative setting. Head Neck. 2016;38(S1):E207-13.
32. Muir CS, Nectoux J. Descriptive epidemiology of malignant neoplasms of the nose, nasal cavities, middle ear, and accessory sinuses. Clin Otolaryngol Allied Sci. 1980;5(3):195-211.
33. Hohchi N, Wakasugi T, Takenaga F, Takeuchi S, Ohkubo JI, Koizumi H, et al. Maxillary sinus squamous cell carcinoma: A clinical study. Int J Pract Otolaryngol. 2018;1(01):e10-5.
34. OGAWA T. A clinicopathological study of adenocarcinomas of the nasal cavity and paranasal sinuses. Nippon Jibiinkoka Gakkai Kaiho. 1989;92(3):317-33.
35. Kim JK, Leeman JE, Riaz N, McBride S, Tsai CJ, Lee NY. Proton therapy for head and neck cancer. Curr Treat Options Oncol. 2018;19(6):1-4.
36. Kurz C, Nijhuis R, Reiner M, Ganswindt U, Thieke C, Belka C, et al. Feasibility of automated proton therapy plan adaptation for head and neck tumors using cone beam CT images. Radiat Oncol. 2016;11(1):1-9.
37. Pignon JP, Bourhis J, Domenge CO, Designé LL, Mach-NC Collaborative Group. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Lancet. 2000;355(9208):949-55.
38. Eich HT, Löschcke M, Scheer M, Kocher M, Bongartz R, Wacker S, et al. Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Strahlenther Onkol. 2008;184(1):23-9.
39. Klug C, Berzaczy D, Voracek M, Nell C, Ploder O, Millesi W, et al. Preoperative radiochemotherapy in the treatment of advanced oral cancer: outcome of 276 patients. J Cranio-Maxillofa Surg. 2009;37(6):344-7.
40. Bernier J. Current state-of-the-art for concurrent chemoradiation. InSeminars in radiation oncology 2009 Jan 1 (Vol. 19, No. 1, pp. 3-10). WB Saunders.