PTCOG Gastrointestinal Subcommittee Lower Gastrointestinal Tract Malignancies Consensus Statement

Abstract

Purpose: Radiotherapy delivery in the definitive management of lower gastrointestinal (LGI) tract malignancies is associated with substantial risk of acute and late gastrointestinal (GI), genitourinary, dermatologic, and hematologic toxicities. Advanced radiation therapy techniques such as proton beam therapy (PBT) offer optimal dosimetric sparing of critical organs at risk, achieving a more favorable therapeutic ratio compared with photon therapy.

Materials and methods: The international Particle Therapy Cooperative Group GI Subcommittee conducted a systematic literature review, from which consensus recommendations were developed on the application of PBT for LGI malignancies.

Results: Eleven recommendations on clinical indications for which PBT should be considered are presented with supporting literature, and each recommendation was assessed for level of evidence and strength of recommendation. Detailed technical guidelines pertaining to simulation, treatment planning and delivery, and image guidance are also provided.

Conclusion: PBT may be of significant value in select patients with LGI malignancies. Additional clinical data are needed to further elucidate the potential benefits of PBT for patients with anal cancer and rectal cancer.

Keywords: Anal cancer; Proton therapy; Quality of life; Rectal cancer; Toxicity.

Figure 1

41-year-old female with p16+, moderately-differentiated anal SCCa, cT2N1M1 (para-aortic LNs), who received definitive SIB-IMPT to 45 Gy(RBE)-50 Gy(RBE) in 25 fractions and concurrent capecitabine/mitomycin-C (MMC). Proton and VMAT axial (A,C) and sagittal (B,D) representative cross-sections. Dose threshold of 50% prescription dose (blue). Low-dose CTV (blue outline), high-dose CTV (pink), bowel (cyan).

Figure 2

49-year-old male with HIV and recurrent anal intraepithelial neoplasia (AIN) treated with local excisions followed by salvage definitive RT to 55.8 Gy(RBE). Twelve years later, he developed T3N1aM0 invasive anal SCCa. SIB-PBS-PBT to 42 Gy(RBE)-50.4 Gy(RBE) in 28 fractions with concurrent capecitabine/MMC was delivered. Proton and VMAT axial (A,C) and sagittal (B,D) representative cross-sections. The dose threshold of 50% prescription dose. Low-dose PTV (blue), prostate (salmon), bladder (yellow). (E-F) Significant tumor response from pre-treatment baseline (E) to end-of-treatment (F) after PBT.

Figure 3

46-year-old male with glomerulonephritis and kidney failure status-post renal transplant with keratinizing anal/distal rectal SCCa, well-differentiated, cT3N0M0. He received concurrent capecitabine/MMC and SIB-PBT to 58 Gy(RBE)-47 Gy(RBE) in 29 fractions. The mean transplanted kidney dose with PBT and comparative VMAT plan was 0.7 Gy and 29.6 Gy, respectively. Proton and VMAT axial (A,C) and sagittal (B,D) representative cross-sections. Dose threshold of 50% of the prescription dose (blue). Low-dose CTV (yellow), high-dose CTV (red-orange), pelvic transplanted kidney (protons=red; photons=cyan). Abbreviation: VMAT, volumetric modulated arc therapy.

Figure 4

31-year-old female with cT4bN2M0 mid-rectal adenocarcinoma status-post ovarian transposition. She received preoperative concurrent capecitabine and PBT for ovarian function preservation using SIB to 45.64 Gy(RBE)-50.4 Gy(RBE) in 28 fractions. Proton and VMAT axial (A,C; D,F) and sagittal (B,E) representative cross-sections. The dose threshold set at 50% of the prescription dose, A-D (blue). Low-dose CTV (blue), transposed left ovary (yellow, red arrows, E-F).