Multimodal treatment (prolonged neoadjuvant chemoradiotherapy in accelerated hyperfractionating regimen followed by D2 gastrectomy) for locally advanced gastric cancer: feasibility and safety assessment

«Radiation and Risk», 2019, vol. 28, No. 3, pp.47-53

DOI: 10.21870/0131-3878-2019-28-3-47-53


Kudryavtsev D.D. – Researcher. Contacts: 4 Korolyov str, Obninsk, Kaluga region, 249036, Russia.
Tel.: +7(484) 399-32-66; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Skoropad V.Yu. – Head of Dep., MD.
Kaprin A.D.1 – General Director, Academician of RASб MD, Prof. NMRCR.
Ivanov S.A. – Director, MD, Prof.
Titova L.N. – Radiologist C. Sc., Med.
Gulidov I.A. – Head of Dep., MD, Prof. A. Tsyb MRRC.

A. Tsyb MRRC, Obninsk.
1 NMRRС Russian Ministry of Health, Moscow.


In this paper, we assess feasibility and safety of the novel therapeutic modality in the multimodal treatment of locally gastric cancer. The treatment program included perioperative neoadjuvant chemoradiotherapy in the accelerated hyperfractionation regimen: twice-daily fractions of 1 Gy+1.5 Gy with 5-6 hour interval between the fractions, total tumor dose – 45 Gy; concurrent delivery of capecitabine: 925 mg/m2, twice-daily, 12 hour interval between drug intakes; intravenous administration of oxaliplatin: 85 mg/m2, 3 week interval between the administrations. After 4-6 week interval followed by the perioperative treatment, the follow-up examination included X-ray imaging, CT scan, gastroscopy, tumor markers tests, was performed. If the disease progression was not confirmed, the patients underwent radical surgery, including extended and combined interventions. The treatment tolerability was satisfactory, the toxicity of side effects for most cases was not higher than grade 2. Successful treatment outcomes were in 87% of cases. The presented treatment with the use of perioperative neoadjuvant therapy made it possible to increase the frequency of radical (R0) gastrectomies and subtotal resections (89%). It did not adversely affect the course of the postoperative period. There were no deaths among postoperative patients. The results demonstrate the feasibility, safety and satisfactory tolerability of the combined treatment of gastric cancer. The efficiency of the treatment is close to that reported previously by other authors.

Key words
neoadjuvant chemoradiotherapy, hyperfractionation regimen, gastric cancer, combined treatment, multimodal treatment, immediate results, feasibility and safety, toxicity, surgical treat-ment, extended operations, postoperative complications.


1. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, vol. 136, no. 5, pp. 359-386.

2. Malignant neoplasms in Russia in 2015 (morbidity and mortality). Eds.: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow, Р. Hertsen MORI, 2018. 250 p. (In Russian).

3. Mahul B., Amin M.D., FCAP. American Joint Committee on cancer (AJCC) Cancer Staging Manual 8th Edition. New York, Springer, 2017. 213 p.

4. Sugisawa N., Tokunaga M., Makuuchi R., Miki Y., Tanizawa Y., Bando E., Kawamura T., Terashima M. A phase II study of an enhanced recovery after surgery protocol in gastric cancer surgery. Gastric Cancer, 2016, vol. 19, no. 3, pp. 961-967.

5. Chakravarty T., Crane C.H., Ajani J.A., Mansfield P.F., Briere T.M., Beddar A.S., Mok H., Reed V.K., Krishnan S., Delclos M.E., Das P. Intensity-modulated radiation therapy with concurrent chemotherapy as preoperative treatment for localized gastric adenocarcinoma. Int. J. Radiat. Oncol. Biol. Phys., 2012, vol. 83, no. 2, pp. 581-586.

6. Inoue T., Yachida S., Usuki H., Kimura T., Hagiike M., Okano K., Suzuki Y. Pilot feasibility study of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced gastric cancer featuring adjacent tissue invasion or JGCA bulky N2 lymph node metastases. Ann. Surg. Oncol., 2012, vol. 19, no. 9, pp. 2937-2945.

7. Lee D.J., Sohn T.S., Lim D.H., Ahn H.K., Park S.H., Lee J., Park J.O., Park Y.S., Lim H.Y., Choi D.I., Kim K.M., Choi M.G., Noh J.H., Bae J.M., Kim S., Min B.H., Kang W.K. Phase I study of neoadjuvant chemoradiotherapy with S-1 and oxaliplatin in patients with locally advanced gastric cancer. Cancer Chemother. Pharmacol., 2012, vol. 69, no. 5, pp. 1333-1338.

8. Trip A.K., Poppema B.J., van Berge Henegouwen M.I., Siemerink J.C., Beukema J.C., Verhejj J.T., Pluccer J.T., Richel D.J., Hulshof J.W., Cats A., Jansen E.P., Hospers G.A. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study. Radiother. Oncol., 2014, vol. 112, no. 2, pp. 284-288.

9. Li Z., Shan F., Wang Y., Li S., Jia Y., Zhang L., Yin D., Ji J. Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy: Safety and short-term oncologic results. Surg. Endosc., 2016, vol. 30, no. 10, pp. 4265-4271.

10. Badgwell B., Ajani J., Blum M., Ho L., Fournier K., Chiang Y.J., Matamoros A., Das P., Mansfield P. Post-operative morbidity and mortality rates are not increased for patients with gastric and gastroesophageal cancer who undergo preoperative chemoradiation therapy. Ann. Surg. Oncol., 2016, vol. 23, no. 1, pp. 156-162.

11. Hu J.B., Sun X.N., Gu B.X., Wang Q., Hu W.X. Effect of intensity modulated radiotherapy combined with s-1-based chemotherapy in locally advanced gastric cancer patients. Oncol. Res. Treat., 2014, vol. 37, no. 1-2, pp. 11-16.

12. Oppedijk V., van der Gaast A., van Lanschot J.J., van Hagen P., van Os R., van Rij C.M., van der Sangen M.J., Beukema J.C., Rütten H., Spruit P.H., Reinders J.G., Richel D.J., van Berge Henegouwen M.I., Hulshof M.C. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J. Clin. Oncol., 2014, vol. 32, no. 5, pp. 385-391.

13. Schulz C., Kullmann F., Kunzmann V., Fuchs M., Geissler M., Vehling-Kaiser U., Stauder H., Wein A., Al-Batran S.E., Kubin T., Schäfer C., Stintzing S., Giessen C., Modest D.P., Ridwelski K., Heinemann V. NeoFLOT: Multicenter phase II study of perioperative chemotherapy in resectable adenocarcinoma of the gastroesophageal junction or gastric adenocarcinoma-Very good response predominantly in patients with intestinal type tumors. Int. J. Cancer, 2015, vol. 137, no. 3, pp. 678-685.

14. Leong T., Smithers B.M., Haustermans K., Michael M., Gebski V., Miller D., Zalcberg J., Boussioutas A., Findlay M., O'Connell R.L., Verghis J., Willis D., Kron T., Crain M., Murray W.K., Lordick F., Swallow C., Darling G., Simes J., Wong R. TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG. Ann. Surg. Oncol., 2017, vol. 24, no 8, pp. 2252-2258.

15. Kaprin А.D., Galkin V.N., ZHavoronkov L.P., Ivanov V.K. Ivanov S.А., Romanko Yu.S. Synthesis of basic and applied research is the basis of obtaining high-quality findings and translating them into clinical practice. Radiatsiya i risk – Radiation and Risk, 2017, vol. 26, no. 2, pp. 26-40. (In Russian).

Full-text article (in Russian)