rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/410-1893-2023-10-3-3NFPSPQrpmj-924Research ArticleОригинальные статьи. Онкология, лучевая терапияOriginal Articles. ОncologyВлияние курения на непосредственную эффективность индукционной химиотерапии при комбинированном лечении ВПЧ-ассоциированного орофарингеального ракаThe effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of HPV-associated oropharyngeal cancerhttps://orcid.org/0000-0003-3532-6476ГолубевП. В.GolubevP. V.

 

Голубев Павел Вячеславович – аспирант Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Российская Федерация

ORCID: https://orcid.org/0000-0003-3532-6476, SPIN: 9592-7730, AuthorID: 1053065, Scopus Author ID: 57223386922

 

Pavel V. Golubev – Postgraduate student, P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0003-3532-6476, SPIN: 9592-7730, AuthorID: 1053065, Scopus Author ID: 57223386922

golubev194@gmail.comhttps://orcid.org/0000-0003-4879-2687БолотинаЛ. В.BolotinaL. V.

 

Болотина Лариса Владимировна – д.м.н., доцент РАН, заведующая отделением химиотерапии Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Российская Федерация

ORCID: https://orcid.org/0000-0003-4879-2687, SPIN: 2787-5414, AuthorID: 594953, Scopus Author ID: 50960914200

 

Larisa V. Bolotina – Dr. Sci. (Medicine), Associate Professor of the Russian Academy of Sciences, Chair of the Department of Chemotherapy, P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0003-4879-2687, SPIN: 2787-5414, AuthorID: 594953, Scopus Author ID: 50960914200

lbolotina@yandex.ruhttps://orcid.org/0000-0002-9181-7811ГеворковА. Р.GevorkovA. R.

 

Геворков Артем Рубенович – к.м.н., доцент, старший научный сотрудник отделения лучевой терапии с модификацией Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Российская Федерация

ORCID: https://orcid.org/0000-0002-9181-7811, SPIN: 4561-1466, AuthorID: 702141, Scopus Author ID: 57207641315

 

Artem R. Gevorkov – Cand. Sci. (Medicine), Associate Professor, Senior Researcher, Department of Radiation Therapy with Modification, P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0002-9181-7811, SPIN: 4561-1466, AuthorID: 702141, Scopus Author ID: 57207641315

torsurg@mail.ruhttps://orcid.org/0000-0002-3371-7548ДешкинаТ. И.DeshkinaT. I.

 

Дешкина Татьяна Игоревна – к.м.н., старший научный сотрудник отделения химиотерапии Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Российская Федерация

ORCID: https://orcid.org/0000-0002-3371-7548, SPIN: 5950-5474, AuthorID: 878173, Scopus Author ID: 57218694102

 

Tatiana I. Deshkina – Cand. Sci. (Medicine), Senior Researcher, Chemotherapy Department, P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0002-3371-7548, SPIN: 5950-5474, AuthorID: 878173, Scopus Author ID: 57218694102

rew9@yandex.ruМосковский научно-исследовательский онкологический институт им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияP. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian FederationRussian Federation2023210820231033242Copyright © Голубев П.В., Болотина Л.В., Геворков А.Р., Дешкина Т.И., 20232023Голубев П.В., Болотина Л.В., Геворков А.Р., Дешкина Т.И.Golubev P.V., Bolotina L.V., Gevorkov A.R., Deshkina T.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/924Цель исследования

Цель исследования. Оценить влияние курения на непосредственную эффективность (достижение объективного ответа) индукционной химиотерапии (ИХТ) у пациентов, получающих комбинированное лечение по поводу местно-распространенного плоскоклеточного рака ротоглотки, ассоциированного с вирусом папилломы человека.

Пациенты и методы

Пациенты и методы. В исследование, проведенное с 2021 по 2023 гг. на базах Московского научно-исследовательского онкологического института им. П. А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России и ГБУЗ «Городская клиническая онкологическая больница № 1» Департамента здравоохранения г. Москвы включено 68 больных (51 мужчина и 17 женщин) с местно-распространенным плоскоклеточным раком ротоглотки, ассоциированным с вирусом папилломы человека. Больные были разделены на 2 равные группы, полностью сопоставимые по основным характеристикам (стаж курения, стадия, гистологический тип и степень дифференцировки опухоли). На первом этапе пациенты 1-й (основная) группы получили деэскалированную индукционную химиотерапию: три 21-дневных курса по схеме ТР (доцетаксел в дозе 75 мг/м2 + цисплатин 75 мг/м2); пациенты 2-й (контрольная) группы – стандартную схему (доцетаксел 75мг/м2 + цисплатин 75 мг/м2 + 5-фторурацил 1000 мг/м2). Пациенты обеих групп получали профилактически гранулоцитарный колониестимулирующий фактор. На втором этапе проводили стандартную химиолучевую терапию на фоне лекарственной радиомодификации карбоплатином. Корреляционный анализ проводили, вычисляя коэффициент Спирмена с поправкой Бонферрони. Различия считали достоверными при p < 0,05.

Результаты

Результаты. При оценке объективного ответа на лечение выявлено, что контроль над болезнью достигнут у 33 (97 %) больных из 1-й группы и у всех 34 (100 %) пациентов из 2-й. Полный ответ отмечен у 3 (8,8 %) больных из 1-й группы и у 4 (11,8 %) из 2-й; частичный регресс – у 22 (64,7 %) и у 24 (70,6 %); стабилизация опухолевого процесса – у 8 (23,5 %) и у 6 (17,6 %) соответственно. Дальнейший анализ показал, что между курением и дифференцированным уровнем ответа (первичный очаг, измененные лимфатические узлы) нет ни прямой, ни обратной корреляционной связи; все пациенты (курящие и никогда не курившие) одинаково эффективно отвечают на первый этап комбинированного лечения, независимо от схемы ИХТ.

Заключение

Заключение. В нашей работе не получено статистически значимого влияния курения на непосредственную эффективность ИХТ при комбинированном лечении местно-распространенного ВПЧ-ассоциированного плоскоклеточного рака ротоглотки независимо от схемы индукции. Однако необходим более длительный период наблюдения для оценки влияния курения на отдаленные онкологические результаты.

Purpose

Purpose. Evaluation of the effect of smoking on the immediate effectiveness (achievement of objective response – OR) of induction chemotherapy in patients receiving combined treatment for locally advanced HPV-positive squamous cell carcinoma of the oropharynx.

Patients and methods

Patients and methods. Sixty-eight patients (51 men and 17 women) with locally advanced squamous cell cancer of the oropharynx associated with papillomavirus were included in the study, which was carried out from 2021 to 2023 at the P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre, Ministry of Health of the Russian Federation, Moscow, Russian Federation and the Municipal Clinical Oncological Hospital № 1 of the Department of Health of Moscow. The patients were divided into 2 equal groups, fully comparable in terms of the main characteristics (smoking history, stage, histological type, and degree of tumour differentiation). At the first stage, patients of the 1st (main) group received de-escalated induction chemotherapy: three 21-day courses according to the TR scheme (docetaxel in the dose of 75 mg/m2 + cisplatin 75 mg/m2); patients of the 2nd (control) group were treated with standard scheme (docetaxel 75 mg/m2 + cisplatin 75 mg/m2 + 5-fluorouracil 1000 mg/m2). Patients in both groups received prophylactic granulocyte colony-stimulating factor. At the second stage, standard chemoradiotherapy was carried out against the background of drug radiomodification with carboplatin. Correlation analysis was performed by calculating the Spearman coefficient with Bonferroni correction. Differences were considered reliable at p < 0.05.

Results

Results. When evaluating the objective response to treatment, it was revealed that disease control was achieved in 33 (97 %) patients from group 1 and in all 34 (100 %) patients from group 2. Complete response was observed in 3 (8.8 %) patients from group 1 and 4 (11.8 %) from group 2; partial regression in 22 (64.7 %) and 24 (70.6 %); stabilisation of the tumour process in 8 (23.5 %) and 6 (17.6 %) respectively. Further analysis showed that there was no direct or inverse correlation between smoking and differentiated level of response (primary lesion, altered lymph nodes); all patients (smokers and those who had never smoked) responded equally effectively to the first stage of combined treatment, regardless of the ICT regimen.

Conclusion

Conclusion. In our study, no statistically significant effect of smoking on the immediate effectiveness of induction chemotherapy in the combined treatment of locally advanced HPV-associated squamous cell carcinoma of the oropharynx regardless of the induction regimen was found. However, a longer follow-up period is needed to evaluate the effect of smoking on long-term oncological outcomes.

курениеиндукционная химиотерапиявирус папилломы человекаплоскоклеточный ракsmokinginduction chemotherapyhuman papillomavirussquamous cell cancerReferencesЗлокачественные новообразования в России в 2020 году (заболеваемость и смертность). Под ред. А. Д. Каприна, В. В. Старинского, А. О. Шахзадовой. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2021; 252 с. Доступно по: https://oncology-association.ru/wp-content/uploads/2021/11/zis-2020-elektronnaya-versiya.pdf. Дата обращения: 20.06.2023Malignant neoplasms in Russia in 2020 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Мoscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, 2021, 252 p. (In Russ.). Available at: https://oncology-association.ru/wp-content/uploads/2021/11/ zis-2020-elektronnaya-versiya.pdf. Accessed: 20.06.2023.Oropharynx. Globocan – 2020. Доступно по: https://gco.iarc.fr/today/data/factsheets/cancers/3-Oropharynx-fact-sheet.pdf.Oropharynx. Globocan – 2020. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/3-Oropharynx-fact-sheet.pdfЧойнзонов Е. Л., Подвязников С. О., Минкин А. У., Мудунов А. М., Азизян Р. И., Пустынский И. Н., и др. Клинические рекомендации. Диагностика и лечение рака ротоглотки. Сибирский онкологический журнал. 2016;15(1):83–87. https://doi.org/10.21294/1814-4861-2016-15-1-83-87Choinzonov EL, Podvyaznikov SO, Minkin AU, Mudunov AM, Azizyan RI, Pustynsky IN, et al. Diagnosis and treatment of oropharyngeal cancer. Clinical recommendations. Siberian Journal of Oncology. 2016;15(1):83–87. (In Russ.). https://doi.org/10.21294/1814-4861-2016-15-1-83-87Anantharaman D, Abedi-Ardekani B, Beachler DC, Gheit T, Olshan AF, Wisniewski K, et al. Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer. Int J Cancer. 2017;140(9):1968–1975. https://doi.org/10.1002/ijc.30608Anantharaman D, Abedi-Ardekani B, Beachler DC, Gheit T, Olshan AF, Wisniewski K, et al. Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer. Int J Cancer. 2017;140(9):1968–1975. https://doi.org/10.1002/ijc.30608Haeggblom L, Ramqvist T, Tommasino M, Dalianis T, Näsman A. Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. Papillomavirus Res. 2017 Dec;4:1–11. https://doi.org/10.1016/j.pvr.2017.05.002Haeggblom L, Ramqvist T, Tommasino M, Dalianis T, Näsman A. Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years. Papillomavirus Res. 2017 Dec;4:1–11. https://doi.org/10.1016/j.pvr.2017.05.002Charfi L, Jouffroy T, de Cremoux P, Le Peltier N, Thioux M, Fréneaux P, et al. Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome. Cancer Lett. 2008 Feb 18;260(1-2):72–78. https://doi.org/10.1016/j.canlet.2007.10.028Charfi L, Jouffroy T, de Cremoux P, Le Peltier N, Thioux M, Fréneaux P, et al. Two types of squamous cell carcinoma of the palatine tonsil characterized by distinct etiology, molecular features and outcome. Cancer Lett. 2008 Feb 18;260(1-2):72–78. https://doi.org/10.1016/j.canlet.2007.10.028Gelwan E, Malm IJ, Khararjian A, Fakhry C, Bishop JA, Westra WH. Nonuniform Distribution of High-risk Human Papillomavirus in Squamous Cell Carcinomas of the Oropharynx: Rethinking the Anatomic Boundaries of Oral and Oropharyngeal Carcinoma From an Oncologic HPV Perspective. Am J Surg Pathol. 2017 Dec;41(12):1722–1728. https://doi.org/10.1097/pas.0000000000000929Gelwan E, Malm IJ, Khararjian A, Fakhry C, Bishop JA, Westra WH. Nonuniform Distribution of High-risk Human Papillomavirus in Squamous Cell Carcinomas of the Oropharynx: Rethinking the Anatomic Boundaries of Oral and Oropharyngeal Carcinoma From an Oncologic HPV Perspective. Am J Surg Pathol. 2017 Dec;41(12):1722–1728. https://doi.org/10.1097/pas.0000000000000929Tulay P, Serakinci N. The role of human papillomaviruses in cancer progression. J Cancer Metasta Treat. 2016;2:201 213.Tulay P, Serakinci N. The role of human papillomaviruses in cancer progression. J Cancer Metasta Treat. 2016;2:201 213.Винокурова С. В., Катаргин А. Н. Вирус папилломы человека и заболевания верхних дыхательных путей: рак головы и шеи и респираторный папилломатоз. Голова и шея. 2023;11(1):62–73. DOI: 10.25792/HN.2023.11.1.62-73Vinokurova SV, Katargin AN. Human papillomavirus and upper respiratory diseases: head and neck cancer and respiratory papillomatosis. Head and neck. Russian Journal. 2023;11(1):62–73. (In Russ.). DOI: 10.25792/HN.2023.11.1.62-73Sastre-Garau X, Harlé A. Pathology of HPV-Associated Head and Neck Carcinomas: Recent Data and Perspectives for the Development of Specific Tumor Markers. Front Oncol. 2020 Nov 16;10:528957. https://doi.org/10.3389/fonc.2020.528957Sastre-Garau X, Harlé A. Pathology of HPV-Associated Head and Neck Carcinomas: Recent Data and Perspectives for the Development of Specific Tumor Markers. Front Oncol. 2020 Nov 16;10:528957. https://doi.org/10.3389/fonc.2020.528957Thompson LDR, Burchette R, Iganej S, Bhattasali O. Oropharyngeal Squamous Cell Carcinoma in 390 Patients: Analysis of Clinical and Histological Criteria Which Significantly Impact Outcome. Head Neck Pathol. 2020 Sep;14(3):666–688. https://doi.org/10.1007/s12105-019-01096-0Thompson LDR, Burchette R, Iganej S, Bhattasali O. Oropharyngeal Squamous Cell Carcinoma in 390 Patients: Analysis of Clinical and Histological Criteria Which Significantly Impact Outcome. Head Neck Pathol. 2020 Sep;14(3):666–688. https://doi.org/10.1007/s12105-019-01096-0Геворков А. Р., Бойко А. В., Поляков А. П., Болотина Л. В., и др. ВПЧ-отрицательный рак ротоглотки как отдельная прогностически неблагоприятная нозологическая форма, требующая новых подходов к лечению (клиническое наблюдение). Опухоли головы и шеи. 2019;9(2):71–80. https://doi.org/10.17650/2222-1468-2019-9-2-71-80Gevorkov AR, Boyko AV, Polyakov AP, Bolotina LV, Volchenko NN, Rebrikova IV, et al. HPV-negative oropharyngeal carcinoma as a separate prognostically unfavorable form of cancer, requiring new approaches to treatment (case report). Head and Neck Tumors (HNT). 2019;9(2):71–80. (In Russ.) https://doi.org/10.17650/2222-1468-2019-9-2-71-80Болотина Л. В., Дешкина Т. И., Корниецкая А. Л., Кравцов С. А., Устинова Т. В., Пайчадзе А. А., и др. Влияние результатов международных исследований на выбор лечебной тактики при нерезектабельных формах плоскоклеточного рака головы и шеи. Опухоли головы и шеи. 2020;10(2):10–21. https://doi.org/10.17650/2222-1468-2020-10-2-10-21Bolotina LV, Deshkina TI, Kornietskaya AL, Kravtsov SA, Ustinova TV, Paychadze AA, et al. Influence of the results of international studies on the choice of treatment tactics for unresectable forms of squamous cell carcinoma of the head and neck. Head and Neck Tumors (HNT). 2020;10(2):10–21. (In Russ.). https://doi.org/10.17650/2222-1468-2020-10-2-10-21Голубев П. В., Болотина Л. В., Геворков А. Р., Дешкина Т. И. Современный взгляд на возможность деэскалации объема лечения ВПЧ-ассоциированного плоскоклеточного рака ротоглотки. Онкология. Журнал им. П. А. Герцена. 2021;10(3):47–53. https://doi.org/10.17116/onkolog20211003147Golubev PV, Bolotina LV, Gevorkov AR, Deshkina TI. A current view on the possibility of treatment volume de-escalation in HPV-associated oropharyngeal squamous cell carcinoma. P.A. Herzen Journal of Oncology. 2021;10(3):47–53. (In Russ.). https://doi.org/10.17116/onkolog20211003147Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24–35. https://doi.org/10.1056/nejmoa0912217Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24–35. https://doi.org/10.1056/nejmoa0912217Nakano K, Seto A, Sasaki T, Shimbashi W, Fukushima H, Yonekawa H, et al. Predictive Factors for Completion of TPF Induction Chemotherapy in Patients With Locally Advanced Head and Neck Cancer. Anticancer Res. 2019 Aug;39(8):4337–4342. https://doi.org/10.21873/anticanres.13601Nakano K, Seto A, Sasaki T, Shimbashi W, Fukushima H, Yonekawa H, et al. Predictive Factors for Completion of TPF Induction Chemotherapy in Patients with Locally Advanced Head and Neck Cancer. Anticancer Res. 2019 Aug;39(8):4337–4342. https://doi.org/10.21873/anticanres.13601Gau M, Karabajakian A, Reverdy T, Neidhardt EM, Fayette J. Induction chemotherapy in head and neck cancers: Results and controversies. Oral Oncol. 2019 Aug;95:164–169. https://doi.org/10.1016/j.oraloncology.2019.06.015Gau M, Karabajakian A, Reverdy T, Neidhardt EM, Fayette J. Induction chemotherapy in head and neck cancers: Results and controversies. Oral Oncol. 2019 Aug;95:164–169. https://doi.org/10.1016/j.oraloncology.2019.06.015Saito Y, Ando M, Omura G, Yasuhara K, Yoshida M, Takahashi W, Yamasoba T. Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma. Laryngoscope Investig Otolaryngol. 2016 Mar 29;1(2):28–32. https://doi.org/10.1002/lio2.18Saito Y, Ando M, Omura G, Yasuhara K, Yoshida M, Takahashi W, Yamasoba T. Induction Chemotherapy for p16 Positive Oropharyngeal Squamous Cell Carcinoma. Laryngoscope Investig Otolaryngol. 2016 Mar 29;1(2):28–32. https://doi.org/10.1002/lio2.18Bhattasali O, Han J, Thompson LDR, Buchschacher GL Jr, Abdalla IA, Iganej S. Induction chemotherapy followed by concurrent chemoradiation versus concurrent chemoradiation alone in the definitive management of p16-positive oropharyngeal squamous cell carcinoma with low-neck or N3 disease. Oral Oncol. 2018 Mar;78:151–155. https://doi.org/10.1016/j.oraloncology.2018.01.031Bhattasali O, Han J, Thompson LDR, Buchschacher GL Jr, Abdalla IA, Iganej S. Induction chemotherapy followed by concurrent chemoradiation versus concurrent chemoradiation alone in the definitive management of p16-positive oropharyngeal squamous cell carcinoma with low-neck or N3 disease. Oral Oncol. 2018 Mar;78:151–155. https://doi.org/10.1016/j.oraloncology.2018.01.031Tam M, Hu K. Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. Semin Radiat Oncol. 2019 Apr;29(2):126–136. https://doi.org/10.1016/j.semradonc.2018.11.011Tam M, Hu K. Regional Radiation Therapy for Oropharyngeal Cancer in the HPV Era. Semin Radiat Oncol. 2019 Apr;29(2):126–136. https://doi.org/10.1016/j.semradonc.2018.11.011Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB, Cruz Hernandez JJ, et al.; Meta-Analysis of Chemotherapy in Head and Neck Cancer, Induction Project, Collaborative Group. Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013 Aug 10;31(23):2854–2860. https://doi.org/10.1200/jco.2012.47.7802Blanchard P, Bourhis J, Lacas B, Posner MR, Vermorken JB, Cruz Hernandez JJ, et al.; Meta-Analysis of Chemotherapy in Head and Neck Cancer, Induction Project, Collaborative Group. Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013 Aug 10;31(23):2854–2860. https://doi.org/10.1200/jco.2012.47.7802Janoray G, Pointreau Y, Garaud P, Chapet S, Alfonsi M, Sire C, Jadaud E, Calais G. Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation. J Natl Cancer Inst. 2015 Dec 16;108(4):djv368. https://doi.org/10.1093/jnci/djv368Janoray G, Pointreau Y, Garaud P, Chapet S, Alfonsi M, Sire C, Jadaud E, Calais G. Long-term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation. J Natl Cancer Inst. 2015 Dec 16;108(4):djv368. https://doi.org/10.1093/jnci/djv368Okano S, Enokida T, Onoe T, Ota Y, Motegi A, Zenda S, et al. Induction TPF chemotherapy followed by CRT with fractionated administration of cisplatin in patients with unresectable locally advanced head and neck cancer. Int J Clin Oncol. 2019 Jul;24(7):789–797. https://doi.org/10.1007/s10147-019-01418-wOkano S, Enokida T, Onoe T, Ota Y, Motegi A, Zenda S, et al. Induction TPF chemotherapy followed by CRT with fractionated administration of cisplatin in patients with unresectable locally advanced head and neck cancer. Int J Clin Oncol. 2019 Jul;24(7):789–797. https://doi.org/10.1007/s10147-019-01418-wPatel RR, Ludmir EB, Augustyn A, Zaorsky NG, Lehrer EJ, Ryali R, et al. De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Oral Oncol. 2020 Apr;103:104608. https://doi.org/10.1016/j.oraloncology.2020.104608Patel RR, Ludmir EB, Augustyn A, Zaorsky NG, Lehrer EJ, Ryali R, et al. De-intensification of therapy in human papillomavirus associated oropharyngeal cancer: A systematic review of prospective trials. Oral Oncol. 2020 Apr;103:104608. https://doi.org/10.1016/j.oraloncology.2020.104608Misiukiewicz K, Gupta V, Miles BA, Bakst R, Genden E, Selkridge I, et al. Standard of care vs reduced-dose chemoradiation aſter induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial. Oral Oncol. 2019 Aug;95:170–177. https://doi.org/10.1016/j.oraloncology.2019.06.021Misiukiewicz K, Gupta V, Miles BA, Bakst R, Genden E, Selkridge I, et al. Standard of care vs reduced-dose chemoradiation aſter induction chemotherapy in HPV+ oropharyngeal carcinoma patients: The Quarterback trial. Oral Oncol. 2019 Aug;95:170–177. https://doi.org/10.1016/j.oraloncology.2019.06.021Tsai CJ, McBride SM, Riaz N, Kang JJ, Spielsinger DJ, Waldenberg T, et al. Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus-Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy. JAMA Oncol. 2022 Mar 1;8(3):364–372. https://doi.org/10.1001/jamaoncol.2021.6416Tsai CJ, McBride SM, Riaz N, Kang JJ, Spielsinger DJ, Waldenberg T, et al. Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus-Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy. JAMA Oncol. 2022 Mar 1;8(3):364–372. https://doi.org/10.1001/jamaoncol.2021.6416Schaner PE, Chandra RA. Decreasing the Dose and Volume of Elective Nodal Radiotherapy in HPV-Associated Oropharyngeal Cancer: How Low Can We Go? JAMA Oncol. 2022 Mar 1;8(3):372–373. https://doi.org/10.1001/jamaoncol.2021.6411Schaner PE, Chandra RA. Decreasing the Dose and Volume of Elective Nodal Radiotherapy in HPV-Associated Oropharyngeal Cancer: How Low Can We Go? JAMA Oncol. 2022 Mar 1;8(3):372–373. https://doi.org/10.1001/jamaoncol.2021.6411Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, Portugal L, Brisson RJ, Dekker A, Kochanny S, Gooi Z, Lingen MW, Villaflor VM, Ginat DT, Haraf DJ, Vokes EE. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019 Feb 1;30(2):297–302. https://doi.org/10.1093/annonc/mdy522 Erratum in: Ann Oncol. 2019 Oct 1;30(10):1673Seiwert TY, Foster CC, Blair EA, Karrison TG, Agrawal N, Melotek JM, Portugal L, Brisson RJ, Dekker A, Kochanny S, Gooi Z, Lingen MW, Villaflor VM, Ginat DT, Haraf DJ, Vokes EE. OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer. Ann Oncol. 2019 Feb 1;30(2):297–302. https://doi.org/10.1093/annonc/mdy522 . Erratum in: Ann Oncol. 2019 Oct 1;30(10):1673Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, et al. Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 2010 Feb 15;16(4):1226–1235. https://doi.org/10.1158/1078-0432.ccr-09-2350Maxwell JH, Kumar B, Feng FY, Worden FP, Lee JS, Eisbruch A, et al. Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 2010 Feb 15;16(4):1226–1235. https://doi.org/10.1158/1078-0432.ccr-09-2350Lin BM, Wang H, D’Souza G, Zhang Z, Fakhry C, Joseph AW, Drake VE, Sanguineti G, Westra WH, Pai SI. Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer. 2013 Oct 1;119(19):3462–3471. https://doi.org/10.1002/cncr.28250Lin BM, Wang H, D’Souza G, Zhang Z, Fakhry C, Joseph AW, Drake VE, Sanguineti G, Westra WH, Pai SI. Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer. 2013 Oct 1;119(19):3462–3471. https://doi.org/10.1002/cncr.28250Lin BM, Wang H, D’Souza G, Zhang Z, Fakhry C, Joseph AW, Drake VE, Sanguineti G, Westra WH, Pai SI. Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer. 2013 Oct 1;119(19):3462–3471. https://doi.org/10.1002/cncr.28250Lin BM, Wang H, D’Souza G, Zhang Z, Fakhry C, Joseph AW, Drake VE, Sanguineti G, Westra WH, Pai SI. Long-term prognosis and risk factors among patients with HPV-associated oropharyngeal squamous cell carcinoma. Cancer. 2013 Oct 1;119(19):3462–3471. https://doi.org/10.1002/cncr.28250

The authors declare that there are no conflicts of interest present.