oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2022-21-1-20-28oncotomsk-2024Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESИнтраоперационная радиотерапия фотонной радиохирургической системой в лечении местнораспространенного рака прямой кишкиIntraoperative radiotherapy with a photonic radiosurgical system in the treatment of locally advanced rectal cancerhttps://orcid.org/0000-0002-5650-6591ПотеминС. Н.PoteminS. N.

Потемин Сергей Николаевич, кандидат медицинских наук, доцент, кафедра хирургии № 2

Author ID (Scopus): 57188746062

Россия, 350063, Краснодар, ул. Митрофана Седина, 4

Sergey N. Potemin, MD, PhD, Assistant Professor of the Department of Surgery № 2

Author ID (Scopus): 57188746062

4, Mitrofan Sedin St., 350063, Krasnodar, Russia

https://orcid.org/0000-0002-2725-3281УваровИ. Б.UvarovI. B.

Уваров Иван Борисович, доктор медицинских наук, доцент, профессор кафедры хирургии № 2; заведующий онкологическим отделением № 3

SPIN-код: 6871-1440. Researcher ID (WОS): A-4192-2014

Россия, 350063, Краснодар, ул. Митрофана Седина, 4

Россия, 350040, г. Краснодар, ул. Димитрова, 146

Ivan B. Uvarov, MD, DSc, Assistant Professor, Professor, Department of Surgery № 2; Head of the Oncology Department № 3

Researcher ID (WОS): A-4192-2014

4, Mitrofan Sedin St., 350063, Krasnodar, Russia

146, Dimitrova St., 350040, Krasnodar, Russia

uvarovivan@yandex.ruhttps://orcid.org/0000-0002-5257-4247ПотеминД. С.PoteminD. S.

Потемин Даниил Сергеевич, врач-онколог, хирург

Россия, 350063, г. Краснодар, ул. Кубанская набережная, 37/1, Россия

Daniil S. Potemin, MD, Oncologist, Surgeon

37/1, Kuban Embankment St., 350063, Krasnodar, Russia

ФГБОУ ВО «Кубанский государственный медицинский университет» Минздрава РоссииРоссияKuban State Medical UniversityRussian FederationФГБОУ ВО «Кубанский государственный медицинский университет» Минздрава России; ГБУЗ «Клинический онкологический диспансер № 1» Минздрава Краснодарского краяРоссияKuban State Medical University; Regional Oncological Center of KrasnodarRussian FederationООО клиника «Екатерининская»РоссияOOO clinic «Ekaterininskaya»Russian Federation2022030320222112028Copyright © Потемин С.Н., Уваров И.Б., Потемин Д.С., 20222022Потемин С.Н., Уваров И.Б., Потемин Д.С.Potemin S.N., Uvarov I.B., Potemin D.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2024

Цель исследования – оценка результатов применения интраоперационной радиотерапии (ИОРТ) фотонной радиохирургической системой у пациентов с местнораспространенным раком прямой кишки (мРПК).

Материал и методы

Материал и методы. Проведен ретроспективный анализ результатов лечения 172 пациентов с гистологически подтвержденным РПК II –III стадии (pT3–4 или pN+), которым выполнена хирургическая операция и ИОРТ (n=92) или неоадъювантная дистанционная лучевая терапия (ДЛТ), операция и ИОРТ (n=80). ИОРТ проводилась фотонной радиохирургической системой Intrabeam® (Carl Zeiss Meditec AG , Oberkochen, Германия) с использованием сферических аппликаторов диаметром 4,5 см или 5,0 см. Процедура проводилась непосредственно после хирургического удаления опухоли. Разовая доза составляла 10–20 Гр. Средний период наблюдения для группы ИОРТ составил 25 мес, для группы ДЛТ/ИОРТ – 22 мес (p=0,52).

Результаты

Результаты. Течение послеоперационного периода при использовании ИОРТ не имело специфических особенностей, профиль токсичности был низкий в обеих группах с общей частотой осложнений 5,4 %. Не отмечено значимых различий между обеими группами в показателях 4-летней общей выживаемости (59,1 % в группе ИОРТ против 67,4 % в группе ДЛТ/ИОРТ, р=0,66), выживаемости без прогрессирования (53,6 против 55,1 %, p=0,51) и выживаемости без местного рецидива (59,4 против 65,4 %, p=0,70). При дополнительном анализе подгрупп с РПК II и III стадии не обнаружено значимых различий в общей выживаемости между группами ИОРТ и ДЛТ/ИОРТ (p=0,63 и p=0,98 соответственно). Значимых различий в местном и отдаленном прогрессировании между обеими группами у пациентов II стадии (р=0,5 и р=0,19 соответственно) и III стадии (р=0,23 и р=0,75 соответственно) также не получено.

Заключение

Заключение. ИОРТ при мРПК является безопасным методом, обеспечивающим достижение адекватного локального контроля, и может рассматриваться как эффективный метод лечения как в изолированном варианте, так и в интеграции в алгоритм мультимодального лечения в условиях специализированного онкологического учреждения.

Aim of the study

Aim of the study: to evaluate the results of using intraoperative radiotherapy (IO RT) in patients with locally advanced rectal cancer (RC).

Material and Methods

Material and Methods. A total of 172 patients with histologically confirmed stage II –III (pT3–4 or pN+) RC were included in this retrospective analysis; of those, 92 (53,5 %) were treated with IO RT alone and 80 (46,5 %) received both neoadjuvant EBRT and IO RT. The median follow-up was 25 months for the IO RT group and 22 months for the EBRT/IO RT group (p=0,52).

Results

Results. The incidence of toxicity was low in both groups with an overall complication rate of 5,4 %. There were no statistically significant differences between both groups in 4-year overall survival rates (59,1 % in the IO RT group versus 67,4 % in the EBRT / IO RT group, p=0,66), progression-free survival (53,6 versus 55,1 %, p=0,51) and local progression free survival (59,4 versus 65,4 %, p=0,70).

Conclusion

Conclusion. IO RT for locally advanced RC is a safe method that ensures adequate local control and can be considered as an effective treatment method both in an isolated version and in integration into a multimodal treatment algorithm in a specialized oncological clinics.

ИОРТдистанционная лучевая терапиярак прямой кишкиintraoperative radiotherapyexternal beam radiotherapyrectal cancerReferencesPetersen S.H., Harling H., Kirkeby L.T., Wille-Jørgensen P., Mocellin S. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. 2012; 2012(3). doi: 10.1002/14651858.CD004078.pub2.Petersen S.H., Harling H., Kirkeby L.T., Wille-Jørgensen P., Mocellin S. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. 2012; 2012(3). doi: 10.1002/14651858.CD004078.pub2.Rodriguez-Bigas M.A., Chang G.J., Skibber J.M. Multidisciplinary approach to recurrent/unresectable rectal cancer: how to prepare for the extent of resection. Surg Oncol Clin N Am. 2010; 19(4): 847–59. https://doi.org/10.1016/j.soc.2010.07.001.Rodriguez-Bigas M.A., Chang G.J., Skibber J.M. Multidisciplinary approach to recurrent/unresectable rectal cancer: how to prepare for the extent of resection. Surg Oncol Clin N Am. 2010; 19(4): 847–59. https://doi.org/10.1016/j.soc.2010.07.001.Wong R.K., Tandan V., De Silva S., Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev. 2007; 2. doi: 10.1002/14651858.CD002102.pub2.Wong R.K., Tandan V., De Silva S., Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev. 2007; 2. doi: 10.1002/14651858.CD002102.pub2.Афанасьев С.Г., Старцева Ж.А., Тарасова А.С., Усова А.В., Самцов Е.Н. Результаты комбинированного лечения рака прямой кишки с применением пролонгированной предоперационной химиолучевой терапии. Сибирский онкологический журнал. 2012; 6: 5–12.Afanasyev S.G., Startseva Zh.А., Tarasova А.S., Usova А.V., Samtsov Е.N. Results of combined modality treatment including preoperative plolonged chemotherary for rectal cancer. Siberian Journal of Oncology. 2012. 6: 5–12. (in Russian).Li Y., Wang J., Ma X., Tan L., Yan Y., Xue C., Hui B., Liu R., Ma H., Ren J. A review of Neoadjuvant Chemoradiotherapy for locally advanced rectal Cancer. Int J Biol Sci. 2016; 12(8): 1022–31. doi: 10.7150/ijbs.15438.Li Y., Wang J., Ma X., Tan L., Yan Y., Xue C., Hui B., Liu R., Ma H., Ren J. A review of Neoadjuvant Chemoradiotherapy for locally advanced rectal Cancer. Int J Biol Sci. 2016; 12(8): 1022–31. doi: 10.7150/ijbs.15438.Gunderson L.L. Rationale for and results of intraoperative radiation therapy. Cancer. 1994; 74(2): 537–41.Gunderson L.L. Rationale for and results of intraoperative radiation therapy. Cancer. 1994; 74(2): 537–41.Guo S., Reddy C.A., Kolar M., Woody N., Mahadevan A., Deibel F.C., Dietz D.W., Remzi F.H., Suh J.H. Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience. Radiat Oncol. 2012; 7: 110. doi: 10.1186/1748-717X-7-110.Guo S., Reddy C.A., Kolar M., Woody N., Mahadevan A., Deibel F.C., Dietz D.W., Remzi F.H., Suh J.H. Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience. Radiat Oncol. 2012; 7: 110. doi: 10.1186/1748-717X-7-110.Завьялов А А., Мусабаева Л.И., Лисин В.А., Чойнзонов Е.Л., Новиков В.А., Коломиец Л.А., Тузиков С.А., Афанасьев С.Г., Дубский С.В., Анисеня И.И., Тюкалов Ю.И., Миллер С.В., Добродеев А.Ю., Чивчиш Л.Н., Нечитайло М.Н., Жеравин А.А. Пятнадцатилетний опыт применения интраоперационной лучевой терапии. Сибирский онкологический журнал. 2004; 2–3: 75–84.Zavyalov A.A., Musabaeva L.I., Lisin V.A., Choinzonov E.L., Novikov V.A., Kolomiets L.A., Tuzikov S.A., Afanasiev S.G., Dubsky S. V., Anisenya I.I., Tyukalov Yu.I., Miller S.V., Dobrodeev A.Yu., Chivchish L.N., Nechitailo M.N., Zheravin A.A. Fifteen years of experience in the use of intraoperative radiation therapy. Siberian Journal of Oncology. 2004; 2–3: 75–84. (in Russian).Бердов Б.А., Скоропад В.Ю., Евдокимов Л.В., Титова Л.Н. Интраоперационная лучевая терапия в комбинированном лечении рака желудка и ободочной кишки. Онкохирургия. 2010; 2(3): 10–18.Berdov B.A., Skoropad V.Yu., Evdokimov L.V., Titova L.N. Intraoperative radiotherapy in multimodal treatment of gastric and colon cancer. Oncosurgery. 2010; 2(3): 10–18. (in Russian).Чойнзонов Е.Л., Мусабаева Л.И., Лисин В.А., Тюкалов Ю.И., Новиков В.А. Новая технология интраоперационной лучевой терапии в сочетании с дистанционной гамма-терапией при комбинированном лечении онкологических больных. Онкохирургия. 2010; 2(3): 26–36.Choynzonov E.L., Musabaeva L.I., Lisin V.A., Tyukalov Yu.I., Novikov V.A. Novel technique of intraoperative electron radiation therapy with external radiation therapy for combined modality treatment in cancer patients. Oncosurgery. 2010; 2(3): 26–36. (in Russian).Alberda W.J., Verhoef C., Nuyttens J.J., Rothbarth J., van Meerten E., de Wilt J.H., Burger J.W. Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor. Ann Surg Oncol. 2014; 21(2): 520–6. doi: 10.1245/s10434-013-3306-x.Alberda W.J., Verhoef C., Nuyttens J.J., Rothbarth J., van Meerten E., de Wilt J.H., Burger J.W. Outcome in patients with resectable locally recurrent rectal cancer after total mesorectal excision with and without previous neoadjuvant radiotherapy for the primary rectal tumor. Ann Surg Oncol. 2014; 21(2): 520–6. doi: 10.1245/s10434-013-3306-x.Alberda W.J., Verhoef C., Nuyttens J.J., van Meerten E., Rothbarth J., de Wilt J.H., Burger J.W. Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2014; 88(5): 1032–40. doi: 10.1016/j.ijrobp.2014.01.014.Alberda W.J., Verhoef C., Nuyttens J.J., van Meerten E., Rothbarth J., de Wilt J.H., Burger J.W. Intraoperative radiation therapy reduces local recurrence rates in patients with microscopically involved circumferential resection margins after resection of locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2014; 88(5): 1032–40. doi: 10.1016/j.ijrobp.2014.01.014.Haddock M.G. Intraoperative radiation therapy for colon and rectal cancers: a clinical review. Radiat Oncol. 2017; 12(1): 11. doi: 10.1186/s13014-016-0752-1.Haddock M.G. Intraoperative radiation therapy for colon and rectal cancers: a clinical review. Radiat Oncol. 2017; 12(1): 11. doi: 10.1186/s13014-016-0752-1.Schild S.E., Gunderson L.L., Haddock M.G., Wong W.W., Nelson H. The treatment of locally advanced colon cancer. Int J Radiat Oncol Biol Phys. 1997; 37(1): 51–8.Schild S.E., Gunderson L.L., Haddock M.G., Wong W.W., Nelson H. The treatment of locally advanced colon cancer. Int J Radiat Oncol Biol Phys. 1997; 37(1): 51–8.Debenham B.J., Hu K.S., Harrison L.B. Present status and future directions of intraoperative radiotherapy. Lancet Oncol. 2013; 14(11). doi: 10.1016/S1470-2045(13)70270-5.Debenham B.J., Hu K.S., Harrison L.B. Present status and future directions of intraoperative radiotherapy. Lancet Oncol. 2013; 14(11). doi: 10.1016/S1470-2045(13)70270-5.Roeder F., Krempien R. Intraoperative radiation therapy (IORT) in soft-tissue sarcoma. Radiat Oncol. 2017; 12(1): 20. doi: 10.1186/s13014-016-0751-2.Roeder F., Krempien R. Intraoperative radiation therapy (IORT) in soft-tissue sarcoma. Radiat Oncol. 2017; 12(1): 20. doi: 10.1186/s13014-016-0751-2.Weil R.J., Mavinkurve G.G., Chao S.T., Vogelbaum M.A., Suh J.H., Kolar M., Toms S.A. Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. J Neurosurg. 2015; 122(4): 825–32. doi: 10.3171/2014.11.JNS1449.Weil R.J., Mavinkurve G.G., Chao S.T., Vogelbaum M.A., Suh J.H., Kolar M., Toms S.A. Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. J Neurosurg. 2015; 122(4): 825–32. doi: 10.3171/2014.11.JNS1449.Veronesi U., Orecchia R., Maisonneuve P., Viale G., Rotmensz N., Sangalli C., Luini A., Veronesi P., Galimberti V., Zurrida S., Leonardi M.C., Lazzari R., Cattani F., Gentilini O., Intra M., Caldarella P., Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013; 14(13): 1269–77. doi: 10.1016/S1470-2045(13)70497-2.Veronesi U., Orecchia R., Maisonneuve P., Viale G., Rotmensz N., Sangalli C., Luini A., Veronesi P., Galimberti V., Zurrida S., Leonardi M.C., Lazzari R., Cattani F., Gentilini O., Intra M., Caldarella P., Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013; 14(13): 1269–77. doi: 10.1016/S1470-2045(13)70497-2.Pilar A., Gupta M., Ghosh Laskar S., Laskar S. Intraoperative radiotherapy: review of techniques and results. Ecancermedicalscience. 2017; 11: 750. doi: 10.3332/ecancer.2017.750.Pilar A., Gupta M., Ghosh Laskar S., Laskar S. Intraoperative radiotherapy: review of techniques and results. Ecancermedicalscience. 2017; 11: 750. doi: 10.3332/ecancer.2017.750.Ferenschild F.T., Vermaas M., Nuyttens J.J., Graveland W.J., Marinelli A.W., van der Sijp J.R., Wiggers T., Verhoef C., Eggermont A., de Wilt J. Value of intraoperative radiotherapy in locally advanced rectal cancer. Dis Colon Rectum. 2006; 49(9): 1257–65. doi: 10.1007/s10350-006-0651-x.Ferenschild F.T., Vermaas M., Nuyttens J.J., Graveland W.J., Marinelli A.W., van der Sijp J.R., Wiggers T., Verhoef C., Eggermont A., de Wilt J. Value of intraoperative radiotherapy in locally advanced rectal cancer. Dis Colon Rectum. 2006; 49(9): 1257–65. doi: 10.1007/s10350-006-0651-x.Valentini V., Coco C., Rizzo G., Manno A., Crucitti A., Mattana C., Ratto C., Verbo A., Vecchio F.M., Barbaro B., Gambacorta M.A., Montoro C., Barba M.C., Sofo L., Papa V., Menghi R., D’Ugo D.M., Doglietto G. Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: a prospective evaluation of a single institutional experience. Surgery. 2009; 145(5):486–94. doi: 10.1016/j.surg.2009.01.007.Valentini V., Coco C., Rizzo G., Manno A., Crucitti A., Mattana C., Ratto C., Verbo A., Vecchio F.M., Barbaro B., Gambacorta M.A., Montoro C., Barba M.C., Sofo L., Papa V., Menghi R., D’Ugo D.M., Doglietto G. Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: a prospective evaluation of a single institutional experience. Surgery. 2009; 145(5):486–94. doi: 10.1016/j.surg.2009.01.007.Ratto C., Valentini V., Morganti A.G., Barbaro B., Coco C., Sofo L., Balducci M., Gentile P.C., Pacelli F., Doglietto G.B., Picciocchi A., Cellini N. Combined-modality therapy in locally advanced primary rectal cancer. Dis Colon Rectum. 2003; 46(1): 59–67. doi: 10.1007/s10350-004-6497-1.Ratto C., Valentini V., Morganti A.G., Barbaro B., Coco C., Sofo L., Balducci M., Gentile P.C., Pacelli F., Doglietto G.B., Picciocchi A., Cellini N. Combined-modality therapy in locally advanced primary rectal cancer. Dis Colon Rectum. 2003; 46(1): 59–67. doi: 10.1007/s10350-004-6497-1.Mirnezami R., Chang G.J., Das P., Chandrakumaran K., Tekkis P., Darzi A., Mirnezami A.H. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol. 2013; 22(1): 22–35. doi: 10.1016/j.suronc.2012.11.001.Mirnezami R., Chang G.J., Das P., Chandrakumaran K., Tekkis P., Darzi A., Mirnezami A.H. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol. 2013; 22(1): 22–35. doi: 10.1016/j.suronc.2012.11.001.Dubois J.B., Bussieres E.,. Richaud P., Rouanet P., Becouarn Y., Mathoulin-Pélissier S., Saint-Aubert B., Ychou M. Intra-operative radiotherapy of rectal cancer: results of the French multi-institutional randomized study. Radiother Oncol. 2011; 98(3): 298–303. doi: 10.1016/j.radonc.2011.01.017.Dubois J.B., Bussieres E.,. Richaud P., Rouanet P., Becouarn Y., Mathoulin-Pélissier S., Saint-Aubert B., Ychou M. Intra-operative radiotherapy of rectal cancer: results of the French multi-institutional randomized study. Radiother Oncol. 2011; 98(3): 298–303. doi: 10.1016/j.radonc.2011.01.017.Kusters M., Valentini V., Calvo F.A., Krempien R., Nieuwenhuijzen G.A., Martijn H., Doglietto G.B., del Valle E., Roeder F., Buchler M.W., van de Velde C.J.H., Rutten H.J.T. Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases. Ann Oncol. 2010; 21(6): 1279–84. doi: 10.1093/annonc/mdp501.Kusters M., Valentini V., Calvo F.A., Krempien R., Nieuwenhuijzen G.A., Martijn H., Doglietto G.B., del Valle E., Roeder F., Buchler M.W., van de Velde C.J.H., Rutten H.J.T. Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases. Ann Oncol. 2010; 21(6): 1279–84. doi: 10.1093/annonc/mdp501.Masaki T., Takayama M., Matsuoka H., Abe N., Ueki H., Sugiyama M., Tonari A., Kusuda J., Mizumoto Sh., Atomi Yu. Intraoperative radiotherapy for oncological and function-preserving surgery in patients with advanced lower rectal cancer. Langenbecks Arch Surg. 2008; 173–80. doi: 10.1007/s00423-007-0260-8.Masaki T., Takayama M., Matsuoka H., Abe N., Ueki H., Sugiyama M., Tonari A., Kusuda J., Mizumoto Sh., Atomi Yu. Intraoperative radiotherapy for oncological and function-preserving surgery in patients with advanced lower rectal cancer. Langenbecks Arch Surg. 2008; 173–80. doi: 10.1007/s00423-007-0260-8.Martinez-Monge R., Nag S., Martin E.W. Three different intraoperative radiation modalities (electron beam, high-dose-rate brachytherapy, and iodine-125 brachytherapy) in the adjuvant treatment of patients with recurrent colorectal adenocarcinoma. Cancer. 1999; 86(2): 236–47.Martinez-Monge R., Nag S., Martin E.W. Three different intraoperative radiation modalities (electron beam, high-dose-rate brachytherapy, and iodine-125 brachytherapy) in the adjuvant treatment of patients with recurrent colorectal adenocarcinoma. Cancer. 1999; 86(2): 236–47.Vermaas M., Nuyttens J.J., Ferenschild F.T., Verhoef C., Eggermont A.M., de Wilt J.H. Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients. Radiother Oncol. 2008; 87(3): 357–60. doi: 10.1016/j.radonc.2008.02.021.Vermaas M., Nuyttens J.J., Ferenschild F.T., Verhoef C., Eggermont A.M., de Wilt J.H. Reirradiation, surgery and IORT for recurrent rectal cancer in previously irradiated patients. Radiother Oncol. 2008; 87(3): 357–60. doi: 10.1016/j.radonc.2008.02.021.Herskind C., Steil V., Kraus-Tiefenbacher U., Wenz F. Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy X rays for early-stage breast cancer. Radiat Res. 2005; 163(2): 208–15. doi: 10.1667/RR3292.Herskind C., Steil V., Kraus-Tiefenbacher U., Wenz F. Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy X rays for early-stage breast cancer. Radiat Res. 2005; 163(2): 208–15. doi: 10.1667/RR3292.Sauer R., Liersch T., Merkel S., Fietkau R., Hohenberger W., Hess C., Becker H., Raab H.R., Villanueva M.T., Witzigmann H., Wittekind C., Beissbarth T., Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012; 30(16): 1926–33. doi: 10.1200/JCO.2011.40.1836.Sauer R., Liersch T., Merkel S., Fietkau R., Hohenberger W., Hess C., Becker H., Raab H.R., Villanueva M.T., Witzigmann H., Wittekind C., Beissbarth T., Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012; 30(16): 1926–33. doi: 10.1200/JCO.2011.40.1836.Guillem J.G., Chessin D.B., Cohen A.M., Shia J., Mazumdar M., Enker W., Paty P.B., Weiser M.R., Klimstra D., Saltz L., Minsky B.D., Wong W.D. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005; 241(5): 829–36. doi: 10.1097/01.sla.0000161980.46459.96.Guillem J.G., Chessin D.B., Cohen A.M., Shia J., Mazumdar M., Enker W., Paty P.B., Weiser M.R., Klimstra D., Saltz L., Minsky B.D., Wong W.D. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005; 241(5): 829–36. doi: 10.1097/01.sla.0000161980.46459.96.Timonin S., Danilova I., Andreev E., Shkolnikov V.M. Recent Mortality Trend Reversal in Russia: Are Regions Following the Same Tempo? Eur J Popul. 2017; 33(5): 733–63. doi: 10.1007/s10680-017-9451-3.Timonin S., Danilova I., Andreev E., Shkolnikov V.M. Recent Mortality Trend Reversal in Russia: Are Regions Following the Same Tempo? Eur J Popul. 2017; 33(5): 733–63. doi: 10.1007/s10680-017-9451-3.Poppe F., Annuss R., Kuhn J. Regional life expectancy rankings: methodological artefacts in population updates. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2017; 60(12): 1422–8. doi: 10.1007/s00103-017-2648-0.Poppe F., Annuss R., Kuhn J. Regional life expectancy rankings: methodological artefacts in population updates. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2017; 60(12): 1422–8. doi: 10.1007/s00103-017-2648-0.

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