Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

Haddock, Michael G.; Miller, Robert C.; Pembérton, John H.; Dozois, Eric J.; Alberts, Steven R.; Gunderson, Leonard L.

doi:10.1016/j.ijrobp.2009.10.046

Cited by 119 publications

(100 citation statements)

References 54 publications

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“…Based on the early findings reported by Shaw et al, which described a significant association between increased IORT dose and neuropathy rate [20], the IORT dose was limited to 10–12 Gy in our study protocol. Interestingly, Haddock et al described a significant reduction of neuropathy with intraoperative doses of less than 12.5 Gy in a recently updated series of rectal cancer treated with IORT [38], indicating that our dose constraint seemed reasonable.…”

Section: Discussionmentioning

confidence: 84%

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

et al. 2014

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BackgroundTo report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).MethodsBetween 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45–50 Gy to PTV and 50–56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10–12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6–31).ResultsMedian follow-up was 33 months (5–75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26–55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10–20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.ConclusionCombination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.Trial registrationNCT01566123.

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Section: Discussionmentioning

confidence: 84%

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

et al. 2014

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“…Results of multimodality therapy including IORT for locally advanced recurrent colorectal cancer were reported in a Mayo Clinic series of 607 patients in 2011 [19]. This series included 180 patients with recurrent colon cancer treated between 1981 and 2008.…”

Section: Introductionmentioning

confidence: 99%

Intraoperative radiation therapy for colon and rectal cancers: a clinical review

Haddock

2017

Radiat Oncol

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Although there have been significant advances in the adjuvant therapy of colorectal cancer, results for patients have historically been poor when complete resection is unlikely or not possible. Similarly, locally recurrent colorectal cancer patients often experience significant tumor related morbidity and disease control and long term survival have historically been poor with standard therapies. Intraoperative radiation therapy (IORT) has been proposed as a possible tool for dose escalation in patients with locally advanced colorectal cancer.For patients with locally advanced primary or recurrent colon cancer, the absence of prospective controlled trials limits the ability to draw definitive conclusions in completely resected patients. In subtotally resected patients, the available evidence is consistent with marked improvements in disease control and survival compared to historical controls. For patients with locally advanced primary or recurrent rectal cancer, a relatively large body of evidence suggests improved disease control and survival, especially in subtotally resected patients, with the addition of IORT to moderate dose external beam radiation (EBRT) and chemotherapy. The most important prognostic factor in nearly all series is the completeness of surgical resection. Many previously irradiated patients may be carefully re-treated with radiation and IORT in addition to chemotherapy resulting in long term survival in more than 25% of patients. Peripheral nerve is dose limiting for IORT and patients receiving 15 Gy or more are at higher risk.IORT is a useful tool when dose escalation beyond EBRT tolerance limits is required for acceptable local control in patients with locally advanced primary or recurrent colorectal cancer. Previously irradiated patients should not be excluded from treatment consideration.

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“…24 also, several studies have shown that complete surgical resections provide a significant survival advantage compared with incomplete resections. [11][12][13]15,17,19,21,[26][27][28][29][30][31][32] in the included studies, most recurrences were treated with chemoradiation instead of radiotherapy alone. in patients with PRC, chemoradiation results in better lC than radiotherapy alone, without a positive effect on os.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Locally Recurrent Rectal Carcinoma in Previously (Chemo)Irradiated Patients

Meij¹,

Rombouts²,

Rütten

et al. 2016

Diseases of the Colon &Amp; Rectum

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Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

Cited by 119 publications

References 54 publications

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

Clinical Phase I/II trial to Investigate Preoperative Dose-Escalated Intensity-Modulated Radiation Therapy (IMRT) and Intraoperative Radiation Therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis

Intraoperative radiation therapy for colon and rectal cancers: a clinical review

Treatment of Locally Recurrent Rectal Carcinoma in Previously (Chemo)Irradiated Patients

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