Online first
Research paper
Published online: 2024-07-16
Clinical outcomes and prognostic factors of volumetric modulated arc therapy (VMAT) of esophageal cancer
Abstract
Background: The objective was to evaluate the efficacy and safety of radiotherapy and the prognostic factors in patients with esophageal cancer who received definitive radiotherapy, using volumetric modulated arc therapy (VMAT).
Materials and methods: Forty-seven patients who received definitive radiotherapy using VMAT between September 2017 and December 2020 were enrolled. Prescription doses were 60 Gy in 30 fractions to the PTV primary and 48 Gy in 30 fractions to the PTV subclinical. Overall survival (OS), progression free survival (PFS), and toxicity were analyzed, and univariate and multivariate analyses were used to investigate the prognostic factors.
Results: Median follow up time was 10 months. Most of the patients had an advanced disease stage (stage I, 12.8%; II, 8.5%; III, 27.7%; IV, 51.0%) patients (38.3%) had a T4 tumor. The median survival time was 14 months (range: 0–56 months). The 2-year OS and PFS were 31.3% and 20.4%, respectively. Acute adverse events (≥ Grade 3) were observed in 25 patients (53.2%), and the most frequent types were dysphagia, hematological toxicities including leukopenia, and febrile neutropenia in 14 (29.8%), 10 (21%), and 10 (21%) patients, respectively. Late adverse events (Grade 3 or higher) were observed in eight patients (17.0%), and the most frequent types were pneumonitis in four patients (8.5%), and Grade 5 in one patient (2.1%; esophageal fistula). In multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) > 3 (p = 0.026) was significantly associated with poor survival.
Conclusion: Definitive radiotherapy of 60Gy with VMAT is feasible and safe for patients with esophageal cancer. Pre-treatment NLR >3 was an independent prognostic factor for OS.
Keywords: esophageal cancervolumetric modulated arc therapyneutrophil-to-lymphocyte ratio
References
- Pennathur A, Gibson MK, Jobe BA, et al. Oesophageal carcinoma. Lancet. 2013; 381(9864): 400–412.
- Kato H, Sato A, Fukuda H, et al. A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708). Jpn J Clin Oncol. 2009; 39(10): 638–643.
- Li J, Shen Li, Liu F. Chemoradiotherapy for T1bN0M0 Esophageal Squamous Cell Carcinoma: A Practical Dilemma Delimited by Invasion Depth. Gastroenterology. 2022; 162(7): 2129–2130.
- Kato K, Muro K, Minashi K, et al. Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group (JCOG). Phase II study of chemoradiotherapy with 5-fluorouracil and cisplatin for Stage II-III esophageal squamous cell carcinoma: JCOG trial (JCOG 9906). Int J Radiat Oncol Biol Phys. 2011; 81(3): 684–690.
- Ishida K, Ando N, Yamamoto S, et al. Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516). Jpn J Clin Oncol. 2004; 34(10): 615–619.
- Shinoda M, Ando N, Kato K, et al. Japan Clinical Oncology Group. Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303). Cancer Sci. 2015; 106(4): 407–412.
- Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002; 20(5): 1167–1174.
- Xu D, Li G, Li H, et al. Comparison of IMRT versus 3D-CRT in the treatment of esophagus cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2017; 96(31): e7685.
- Münch S, Aichmeier S, Hapfelmeier A, et al. Comparison of dosimetric parameters and toxicity in esophageal cancer patients undergoing 3D conformal radiotherapy or VMAT. Strahlenther Onkol. 2016; 192(10): 722–729.
- Kumar G, Rawat S, Puri A, et al. Analysis of dose-volume parameters predicting radiation pneumonitis in patients with esophageal cancer treated with 3D-conformal radiation therapy or IMRT. Jpn J Radiol. 2012; 30(1): 18–24.
- McFarlane MR, Hochstedler KA, Laucis AM, et al. Michigan Radiation Oncology Quality Consortium as part of the Blue Cross Blue Shield of Michigan and Blue Care Network of Michigan Value Partnerships Program. Predictors of Pneumonitis After Conventionally Fractionated Radiotherapy for Locally Advanced Lung Cancer. Int J Radiat Oncol Biol Phys. 2021; 111(5): 1176–1185.
- Wei X, Liu HH, Tucker SL, et al. Risk factors for pericardial effusion in inoperable esophageal cancer patients treated with definitive chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2008; 70(3): 707–714.
- Vošmik M, Hodek M, Buka D, et al. Cardiotoxicity of radiation therapy in esophageal cancer. Rep Pract Oncol Radiother. 2020; 25(3): 318–322.
- Liu HH, Wang X, Dong L, et al. Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004; 58(4): 1268–1279.
- Kato K, Ito Y, Nozaki I, et al. Japan Esophageal Oncology Group of the Japan Clinical Oncology Group. Parallel-Group Controlled Trial of Surgery Versus Chemoradiotherapy in Patients With Stage I Esophageal Squamous Cell Carcinoma. Gastroenterology. 2021; 161(6): 1878–1886.e2.
- Kato K, Nakajima TE, Ito Y, et al. Phase II study of concurrent chemoradiotherapy at the dose of 50.4 Gy with elective nodal irradiation for Stage II-III esophageal carcinoma. Jpn J Clin Oncol. 2013; 43(6): 608–615.
- Sasaki Y, Kato K. Chemoradiotherapy for esophageal squamous cell cancer. Jpn J Clin Oncol. 2016; 46(9): 805–810.
- Welsh JW, Seyedin SN, Allen PK, et al. Local Control and Toxicity of a Simultaneous Integrated Boost for Dose Escalation in Locally Advanced Esophageal Cancer: Interim Results from a Prospective Phase I/II Trial. J Thorac Oncol. 2017; 12(2): 375–382.
- Yokota T, Kato K, Hamamoto Y, et al. Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer. Br J Cancer. 2016; 115(11): 1328–1334.
- Terada M, Hara H, Daiko H, et al. Phase III study of tri-modality combination therapy with induction docetaxel plus cisplatin and 5-fluorouracil versus definitive chemoradiotherapy for locally advanced unresectable squamous-cell carcinoma of the thoracic esophagus (JCOG1510: TRIANgLE). Jpn J Clin Oncol. 2019; 49(11): 1055–1060.
- Network NC. Network NCC.. NCCN GuidelinesVersion 4.2022 Esophageal and Esophagogastric Junction Cancer. NCCN Clinical practice Guidelines in Oncology. September 7, 2022.
- Asakura H, Hashimoto T, Zenda S, et al. Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer. Radiother Oncol. 2010; 95(2): 240–244.
- Fan XW, Wang HB, Mao JF, et al. Sequential boost of intensity-modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study. Cancer Med. 2020; 9(8): 2812–2819.
- Li C, Ni W, Wang X, et al. A phase I/II radiation dose escalation trial using simultaneous integrated boost technique with elective nodal irradiation and concurrent chemotherapy for unresectable esophageal Cancer. Radiat Oncol. 2019; 14(1): 48.
- Hulshof MC, Geijsen ED, Rozema T, et al. Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study). J Clin Oncol. 2021; 39(25): 2816–2824.
- Tonison JJ, Fischer SG, Viehrig M, et al. Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review. Sci Rep. 2019; 9(1): 2255.
- Hayashi K, Fujiwara Y, Nomura M, et al. Predictive factors for pericardial effusion identified by heart dose-volume histogram analysis in oesophageal cancer patients treated with chemoradiotherapy. Br J Radiol. 2015; 88(1046): 20140168.
- Tamari K, Isohashi F, Akino Y, et al. Risk Factors for Pericardial Effusion in Patients with stage I Esophageal Cancer Treated with Chemoradiotherapy. Anticancer Res. 2014; 34: 7389–94.
- Takeuchi Y, Murakami Y, Kameoka T, et al. Analysis of cardiac toxicity after definitive chemoradiotherapy for esophageal cancer using a biological dose-volume histogram. J Radiat Res. 2020; 61(2): 298–306.
- Ishikura S, Nihei K, Ohtsu A, et al. Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus. J Clin Oncol. 2003; 21(14): 2697–2702.
- Byard RW. Causes of sudden death related to oesophageal carcinoma. Med Sci Law. 2021; 61(1): 69–72.
- Kumekawa Y, Kaneko K, Ito H, et al. Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma. J Gastroenterol. 2006; 41(5): 425–432.
- Morota M, Gomi K, Kozuka T, et al. Late toxicity after definitive concurrent chemoradiotherapy for thoracic esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2009; 75(1): 122–128.
- Boggs DH, Hanna A, Burrows W, et al. Primary Gross Tumor Volume is an Important Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Trimodality Therapy. J Gastrointest Cancer. 2015; 46(2): 131–137.
- Haefner MF, Lang K, Krug D, et al. Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy. J Radiat Res. 2015; 56(4): 742–749.
- Yamashita H, Takenaka R, Okuma K, et al. Prognostic factors in patients after definitive chemoradiation using involved-field radiotherapy for esophageal cancer in a phase II study. Thorac Cancer. 2016; 7(5): 564–569.
- Teoh AYB, Chiu PWY, Yeung WK, et al. Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial. Ann Oncol. 2013; 24(1): 165–171.
- Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140(6): 883–899.
- Guthrie GJK, Charles KA, Roxburgh CSD, et al. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013; 88(1): 218–230.
- Miyata H, Yamasaki M, Kurokawa Y, et al. Prognostic value of an inflammation-based score in patients undergoing pre-operative chemotherapy followed by surgery for esophageal cancer. Exp Ther Med. 2011; 2(5): 879–885.
- Sato H, Tsubosa Y, Kawano T. Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg. 2012; 36(3): 617–622.
- Endo M, Yoshino K, Kawano T, et al. Clinicopathologic analysis of lymph node metastasis in surgically resected superficial cancer of the thoracic esophagus. Dis Esophagus. 2000; 13(2): 125–129.
- Akutsu Y, Kato K, Igaki H, et al. The Prevalence of Overall and Initial Lymph Node Metastases in Clinical T1N0 Thoracic Esophageal Cancer: From the Results of JCOG0502, a Prospective Multicenter Study. Ann Surg. 2016; 264(6): 1009–1015.
- Onozawa M, Nihei K, Ishikura S, et al. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus. Radiother Oncol. 2009; 92(2): 266–269.
- Liu R, Zhang X, Zhang Q, et al. Adjuvant Radiotherapy of Involved Field versus Elective Lymph Node in Patients with Operable Esophageal Squamous Cell Cancer: A Single Institution Prospective Randomized Controlled Study. J Cancer. 2021; 12(11): 3180–3189.
- Yu WW, Zhu ZF, Fu XL, et al. Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma: early results of a phase II study. Strahlenther Onkol. 2014; 190(11): 979–986.
- Uchinami Y, Myojin M, Takahashi H, et al. Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa. Radiat Oncol. 2016; 11: 84.
- Yamashita H, Takenaka R, Omori M, et al. Involved-field radiotherapy (IFRT) versus elective nodal irradiation (ENI) in combination with concurrent chemotherapy for 239 esophageal cancers: a single institutional retrospective study. Radiat Oncol. 2015; 10: 171.
- Zhang WZ, Zhai TT, Lu JY, et al. Volumetric modulated arc therapy vs. c-IMRT for the treatment of upper thoracic esophageal cancer. PLoS One. 2015; 10(3): e0121385.
- Yang H, Feng C, Cai BN, et al. Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma. Dis Esophagus. 2017; 30(2): 1–8.