Patient and Clinician Reported Acute Toxicity During Preoperative Chemoradiation for Locally Advanced Rectal Cancer

Abstract

Preoperative pelvic radiation therapy (RT) with concurrent 5-Fluorouracil (FU)-based chemotherapy is the standard of care for patients with locally advanced rectal cancer. Pelvic RT is associated with significant acute toxicities that can adversely impact a patient’s quality of life. As opposed to 3D conformal RT (3DCRT), intensity modulated RT (IMRT) allows for more focal dose delivery, thus sparing normal tissues. We compared clinician reported acute toxicity profiles between patients treated with IMRT and 3DCRT and described patient reported outcomes (PROs) for IMRT patients. We retrospectively reviewed records of 335 consecutive rectal cancer patients treated with preoperative pelvic RT at our institution from 2007–2014. Clinical information, including weekly acute toxicity graded according to the CTCAE v3.0, was collected. Weekly PROs using a 7 or 14-item questionnaire based on the Bowel Problems Scale, and NCI PRO-CTCAE were also collected for 150 patients treated with IMRT from 2009–2014. Symptom frequency, severity and interference with daily activities were reported on a 5-point Likert-type scale between 1-“not at all” and 5-“very frequently” A clinically meaningful PRO score was defined as ≥3. Fisher exact test was used to test for statistical differences. The median age was 56 years (range, 22–93) and 202 (60%) patients were male. The majority of patients had clinical stage T3 (79%) and N+ (79%) disease. Of the 335 patients, 229 (68%) were treated with IMRT and 106 (32%) with 3DCRT. All patients received concurrent 5-FU-based chemotherapy with no significant difference in the median RT dose between the two cohorts. Significantly fewer patients experienced ≥grade 2 diarrhea in the IMRT group compared to the 3DCRT group (11% vs 22%, P = .02). While no grade 3 cystitis or proctitis occurred in either groups, fewer patients experienced grade 2 cystitis in the IMRT group (5% vs 12% 3DCRT, P = .02), and there was a trend towards decreased grade 2 proctitis in the IMRT group (19% vs 28% 3DCRT, P = .06). Of the 150 IMRT patients who completed PROs, a high proportion reported PRO scores ≥3 for diarrhea (65%) and urgency (73%). About half of the patients experienced rectal pain (53%) and tenesmus (49%), with fewer complaining of abdominal cramping (42%), rectal bleeding (34%) and loss of bowel control (30%). In this large cohort of patients undergoing preoperative chemoradiation for locally advanced rectal cancer, compared to the use of 3DCRT, the use of IMRT significantly reduced lower gastrointestinal and genitourinary toxicity during treatment as measured by clinicians. Patient reported outcomes show that lower gastrointestinal toxicity is experienced frequently amongst patients treated with IMRT. Further studies are needed to determine the best method to assess the impact of IMRT on treatment related toxicities.