Proton Reirradiation of Recurrent Rectal Cancer: Dosimetric Comparison, Toxicities, and Preliminary Outcomes

Abstract

Purpose: Locally advanced rectal adenocarcinoma is effectively treated with chemoradiation and surgery; however, 10 to 25% of patients locally recur within or near a previously irradiated field. Proton radiation therapy (PRT) is ideally suited to the problem of reirradiation for locally recurrent rectal cancer (LRRC). Patients and Methods: Seven patients with LRRC in or near prior radiation fields were enrolled on this prospective study from March 2010 to February 2011. All patients underwent positron emission tomography (PET)/computed tomography (CT) simulation and were stratified by low volume (clinical target volume,250 cm 3 , n¼4) or high volume (.250 cm 3 , n¼3). Primary endpoints were feasibility and acute toxicity (within 90 days from PRT initiation). Dosimetry was compared using the Wilcoxon signed-rank test. Tumor response was defined according to PERCIST criteria. Results: Median follow-up was 14 months (4.9-22.6). Median dose of prior RT was 5040 cGy. Mean PRT dose was 6120 cGy (RBE) (range, 4500-6480 cGy). The total dose sum of prior radiation therapy treatment and PRT was 109.8 Gy (RBE) (range, 95.4-151.2). One patient had surgery prior to and 1 after PRT. Six patients received concurrent 5-fluorouracil-based chemotherapy. Bowel volume receiving 10 and 20 Gy, and the dose to 200 and 150 cm 3 of bowel were significantly reduced. There were 3 acute grade 3 and 3 late grade 4 toxicities. Four patients were alive at time of follow-up. Six had a metabolic complete response, of whom 2 subsequently locally recurred. One had initial progressive disease. Of 6 symptomatic patients, 3 had complete pain resolution and 3 partial.Conclusions: This preliminary report indicates that PRT for LRRC provides dosimetric improvements over intensity-modulated radiation therapy, particularly to the bowel. The modest rates of acute and late toxicity as well as the preliminary outcomes of high tumor and symptom control rates are promising.

Proton beam reirradiation for locally recurrent pancreatic adenocarcinoma

“…Two patients were treated with definitive chemoradiation to unresectable disease as their initial therapy. Nine patients received adjuvant Gemcitabine following their initial treatment course for a median number of 4 months [2][3][4][5][6]. The median time from the prior radiation treatment course to local recurrence was 17.7 months .…”

“…One patient was treated with Gemcitabine/Abraxane and one patient was treated with FOLFIRINOX and then switched to Gemcitabine for continued progression. The median number of months of systemic treatment for local recurrence was 4 months [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] prior to PRT. The median number of months of observation from the time of recurrence to start of PRT for patients who did not receive chemotherapy for local recurrence was 1.7 months (1.2-10).…”

“…Eight patients developed metastatic disease in the liver and lungs with an indolent course and median survival of 8 months (0.5-27.8) from the diagnosis of metastatic disease. Only six patients were treated with chemotherapy following PRT for disease progression and the median chemotherapy-free interval in these patients was 7 months [4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”

“…The characteristic Bragg Peak of the proton beam, with its sharp fall off, confers the ability to retreat the tumor with essentially no exit dose potentially sparing normal tissues. We have previously reported on reirradiation with proton radiotherapy (PRT) in recurrent rectal cancer and showed that it was superior in sparing bowel from radiation compared to intensity modulated radiation therapy (IMRT) with modest toxicity and complete metabolic responses in the majority of patients (4). Similarly, a locally recurrent esophageal cohort treated with proton reirradiation reported modest toxicities (maximum radiation attributed acute non-hematologic toxicity was grade 2), median overall survival (OS) of 14 months from the start of PRT, and excellent symptom palliation (5).…”

Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review

“…A report from the University of Pennsylvania prospectively evaluated seven patients with recurrent rectal cancer after prior chemoradiotherapy and surgery (53). The median dose of prior RT was 50.4 Gy, and the mean PBT dose was 61.2 CGE.…”