Volumetric Modulated Arc Therapy Improves Outcomes in Definitive Radiochemotherapy for Anal Cancer Whilst Reducing Acute Toxicities and Increasing Treatment Compliance.

Jacqueline Possiel,Lena-Christin Conradi,Stephan Samel,Stefan Rieken,Manuel Guhlich,Leif Hendrik Dröge,Hendrik Andreas Wolff,Markus Anton Schirmer,Martin Leu,Hanne Elisabeth Ammon,Michael Ghadimi,Michael Mügge

doi:10.3390/cancers13112533

Abstract

Simple SummaryIntensity-modulated radiotherapy (IMRT) is the standard of care in definitive chemoradiotherapy (CRT) for anal cancer. Only a limited number of studies have analyzed the clinical results with VMAT (volumetric modulated arc therapy, the advanced form of IMRT). We conducted a retrospective study on patients treated at our institution. We compared the outcomes of VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. VMAT reduced acute toxicities (i.e., primarily dermatitis and enteritis) to a great extent. Additionally, VMAT relevantly improved treatment compliance (i.e., less CRT interruptions/delays, shorter overall treatment time, and higher absolute 5-fluorouracil dose applied). Finally, we found improved cancer-specific survival and distant control in VMAT-treated patients. The present study underlines the great progress that has been achieved with IMRT/VMAT in the CRT of anal cancer. Our study is the first to demonstrate an improvement in treatment compliance and outcomes with VMAT. Future studies could address whether VMAT is advantageous when compared to conventional IMRT.Background: Intensity-modulated radiotherapy (IMRT) is the standard of care in chemoradiotherapy (CRT) for anal cancer. Until now, only a limited number of studies have analyzed the results with VMAT (volumetric modulated arc therapy). We conducted a retrospective study on patients treated at our institution. Patients and Methods: We included patients who received curative CRT for anal cancer. We compared VMAT-treated and 3DCRT (3D conformal radiotherapy)-treated patients. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. Results: A total of 149 patients (3DCRT: n = 87, VMAT: n = 62) were included. The median follow-up was longer in 3DCRT-treated patients (3DCRT: 61.3 months; VMAT: 39.1 months; p < 0.05). VMAT-treated patients had more G3 tumors (3DCRT: 12/87 (13.8%); VMAT: 18/62 (29.0%), p < 0.001). VMAT reduced acute toxicities ≥grade 3 (3DCRT: n = 48/87 (55.2%); VMAT: n = 11/62 (17.7%), p < 0.001). VMAT improved treatment compliance (less interruptions/delays) (3DCRT: 37/87, 42.5%; VMAT: 4/62, 6.5%; p < 0.001), provided a shorter median overall treatment time (3DCRT: 41 days; VMAT: 38 days; p = 0.02), and gave a higher median absolute 5-fluorouracil dose (3DCRT: 13,700 mg; VMAT: 14,400 mg; p = 0.001). Finally, we found improved CSS (p = 0.02; 3DCRT: 81.9% at 3 years; VMAT: 94.1% at 3 years) and DC (p = 0.01; 3DCRT: 89.4% at 3 years; VMAT: 100.0% at 3 years) with VMAT. Summary: Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer. Previous studies have indicated that organs at risk sparing might be more improved with the use of VMAT vs. with conventional IMRT. Future studies should address whether these advantages lead to a further reduction in CRT-associated morbidity.

Highlights

The incidence of anal cancer has constantly increased during the last few decades [1].Deshmukh et al reported a two-fold increase in the incidence of non-metastatic disease and a three-fold increase in the incidence of metastatic disease during the period 2001–2015 in the United States [2]
The present study underlines the great progress that has been achieved with Intensity-modulated radiotherapy (IMRT)/VMAT in the CRT of anal cancer
Only a limited number of small studies have analyzed the clinical results with VMAT [24,25,26,27,28]

Summary

Introduction

The incidence of anal cancer has constantly increased during the last few decades [1].Deshmukh et al reported a two-fold increase in the incidence of non-metastatic disease and a three-fold increase in the incidence of metastatic disease during the period 2001–2015 in the United States [2]. Definitive chemoradiotherapy (CRT) is the standard treatment for non-metastatic anal cancer [3]. Definitive CRT is associated with high rates of acute and hematologic toxicities [7]. As a consequence of CRT-related toxicities, treatment interruptions or delays are necessary for a relevant proportion of patients [4,10]. These events can negatively affect oncologic outcomes [4,10]. We analyzed toxicities (acute: CTCAE criteria; late: LENT/SOMA criteria), treatment compliance, overall survival, cancer-specific survival (CSS), distant control (DC), and locoregional control. Summary: Our study is the first to demonstrate improved treatment compliance and outcomes with VMAT for anal cancer.

Methods

Results

Discussion

Conclusion