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Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

ABSTRACT: Purpose:Patients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial. Methods and materials:Patients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure. Results:A total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR. Conclusions:This subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

SUBMITTER: Sutera P

PROVIDER: S-EPMC6349603 | biostudies-literature | 2019 Jan-Mar

REPOSITORIES: biostudies-literature

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Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

Sutera Philip P Kalash Ronny R Clump David A DA D'Ambrosio David D Mihai Alina A Burton Steven A SA Heron Dwight E DE

Advances in radiation oncology 20180914 1

<h4>Purpose</h4>Patients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clini ...[more]

PMID: 30706011

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Project description:Background and purposeConsolidatory radiotherapy in form of stereotactic body radiation therapy (SBRT) with an ablative dose following induction chemotherapy is emerging as a promising treatment scheme for unresectable pancreatic cancer. Outcomes of given treatment at a single center for contiguous patients with unresectable pancreatic cancer were evaluated to build the optimal treatment strategy.Materials and methodsIn this retrospective study, a total of 50 patients with unresectable pancreatic cancer who underwent induction chemotherapy and ablative dose SBRT were included. SBRT dose was 40-50 Gy in five fractions. Two strategies were adopted to adhere to the organs at risk (OAR) dose constraints: simultaneous integrated protection (SIP) technique and magnetic resonance (MR)-guided adaptive technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated from the start date of SBRT.ResultsThe median follow-up period for survivors was 21.1 months (range, 6.2-61.0 months). Eleven (22.0%) patients underwent resection after SBRT, which were all R0 resection. In patients with non-metastatic disease, the median OS was 26.5 months (range, 4.1-61.0 months), and the 1- and 3-year LPFS were 90.0% (95% confidence interval [CI], 72.0-96.7%) and 57.4% (95% CI, 31.7-76.4%), respectively. Patients with oligometastatic disease had inferior survival outcomes, but there was no survival difference among responders to induction chemotherapy. In the multivariable analysis, tumor size ≤4 cm, non-metastatic status, and good response to induction chemotherapy were associated with improved LPFS. In dosimetric analysis, GTV Dmin ≥50.5 Gy was the strongest prognosticator against local progression. Grade ≥3 adverse events occurred in two (4.0%) patients with non-adaptive RT, but none in patients with MR-guided adaptive RT.ConclusionAblative dose SBRT following induction chemotherapy is an effective strategy for selected patients with unresectable pancreatic cancer. The SIP technique and MR-guided adaptive RT were attributed to minimizing the risk of adverse events. Further studies are needed to identify the best candidates for consolidatory SBRT in unresectable pancreatic cancer.

Project description:Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Project description:BackgroundTo investigate the effect of stereotactic body radiation therapy (SBRT) on pulmonary oligometastases and to analyze the clinical factors and dose parameters affecting local recurrence-free survival (LRFS) and overall survival (OS).MethodsThis study retrospectively enrolled a total of 84 patients (148 lesions) treated in our department from May 2015 to November 2018. Pulmonary oligometastases was defined as up to 5 metastatic lesions in the lung and with both the primary tumor and any extra-thoracic metastases being controlled. Patients receiving a BED10 (biological effective dose, α/β =10) of SBRT ≥75 Gy and a dose/fraction ≥4 Gy were enrolled. The patient group consisted of 52 men (61.9%) and 32 women (38.1%), with a median age 56 years (range, 29-80 years). Median tumor diameter was 1.71cm (range, 1.2-5.0 cm). The BED10 was 75-119 Gy in 4-15 fractions. Univariate and multivariate Cox regression analyses were performed on factors predicting the outcomes.ResultsAll patients completed the treatment as planned, and the median follow-up time was 20.3 months. The median OS for the entire group was 34.3 months, with an actuarial 1-, 2-, 3- and 5-year OS of 74.7%, 59.4%, 49.7%, and 36.8%, respectively. Among the 148 lesions in the whole group, 19 (12.8%) lesions had local recurrence (LR). The median LRFS time for all patients was 56.9 months. The LRFS rate was 93.6%, 83.5%, 81.4%, and 76.6% at 1, 2, 3, and 5 years, respectively. No patient developed acute grade 3 or 4 toxicity. On univariate analysis, age ≥63 years old, primary site of colorectal cancer, BED10 <85.2 Gy, pathological type of adenocarcinoma, planning target volume (PTV) min BED10 <76.6 Gy, and gross tumor volume (GTV) ≥8.8 cc, were significantly associated with poorer LRFS. Multivariate analysis showed that age ≥63 years old, primary site of colorectal cancer, and PTV min BED10 <76.6 Gy were significant risk factors affecting LRFS.ConclusionsSBRT is feasible for pulmonary oligometastasis with favorable local control and minimal toxicity. Multiple dose parameters, instead of a prescription dose only, in combination with clinical parameters, should be considered for optimal local control.

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Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

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Stereotactic Ablative Radiation Therapy for Unresectable Colorectal Oligometastases.

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