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Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

ABSTRACT: Chemotherapy and targeted therapies are effective palliative options for numerous unresectable or metastatic cancers. However, treatment resistance inevitably develops leading to mortality. In a subset of patients, systemic therapy appears to control the majority of tumors leaving 5 or less to progress, a phenomenon described as oligoprogression. Reasoning that the majority of lesions remain responsive to ongoing systemic chemotherapy, we hypothesized that local treatment of the progressing lesions would confer a benefit. The present study describes the cases of 5 patients whose metastatic disease was largely controlled by chemotherapy. The oligoprogressive lesions (≤5) were treated with stereotactic body radiotherapy (SBRT), justifying continued use of an effective systemic regimen. A total of 5 patients with metastatic disease on chemotherapy, with ≤5 progressing lesions amenable to SBRT, were treated with ablative intent. Primary tumor site and histology were as follows: 2 with metastatic colon adenocarcinoma, 2 with metastatic rectal adenocarcinoma and 1 with metastatic pancreatic adenocarcinoma. Imaging was performed prior to SBRT and every 3 months after SBRT. In total, 4 out of the 5 patients achieved disease control for >7 months with SBRT, without changing chemotherapy regimen. The median time to chemotherapy change was 9 months, with a median follow-up time of 9 months. The patient who failed to respond developed progressive disease outside of the SBRT field at 3 months. In conclusion, the addition of SBRT to chemotherapy is an option for the overall systemic control of oligoprogressive disease.

SUBMITTER: Wray J

PROVIDER: S-EPMC5403710 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

Wray Justin J Hawamdeh Rana Fawzi RF Hasija Nalini N Dagan Roi R Yeung Anamaria R AR Lightsey Judith L JL Okunieff Paul P Daily Karen C KC George Thomas J TJ Zlotecki Robert A RA Trevino Jose J Dang Long H LH

Oncology letters 20161227 3

Chemotherapy and targeted therapies are effective palliative options for numerous unresectable or metastatic cancers. However, treatment resistance inevitably develops leading to mortality. In a subset of patients, systemic therapy appears to control the majority of tumors leaving 5 or less to progress, a phenomenon described as oligoprogression. Reasoning that the majority of lesions remain responsive to ongoing systemic chemotherapy, we hypothesized that local treatment of the progressing lesi ...[more]

PMID: 28454218

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Project description:AimTo evaluate the clinical outcomes of metastatic colorectal cancer (mCRC) patients with oligometastases, oligoprogression, or local control of dominant tumors after stereotactic body radiotherapy (SBRT) and establish a nomogram model to predict the prognosis for these patients.Methods and materialsA cohort of 94 patients with 162 mCRC metastases was treated with SBRT at a single institution. Treatment indications were oligometastases, oligoprogression, and local control of dominant tumors. End points of this study were the outcome in terms of progression-free survival (PFS), overall survival (OS), local progression (LP), and cumulative incidence of starting or changing systemic therapy (SCST). In addition, univariate and multivariable analyses to assess variable associations were performed. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve.ResultsMedian PFS were 12.6 months, 6.8 months, and 3.7 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. 0-1 performance status, < 10 ug/L pre-SBRT CEA, and ≤ 2 metastases were significant predictors of higher PFS on multivariate analysis. Median OS were 40.0 months, 26.1 months, and 6.5 months for oligometastases, oligoprogression, and local control of dominant tumors, respectively. In the multivariate analysis of the cohort, the independent factors for survival were indication, performance status, pre-SBRT CEA, and PTV, all of which were selected into the nomogram. The calibration curve for probability of survival showed the good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for predicting survival was 0.848.ConclusionsSBRT for metastases derived from colorectal cancer offered favorable survival and symptom palliation without significant complications. The proposed nomogram could provide individual prediction of OS for patients with mCRC after SBRT.

Project description:BackgroundOligoprogression is defined as cancer progression of a limited number of metastases under active systemic therapy. The role of metastasis-directed therapy, using stereotactic body radiotherapy (SBRT), is controversial as is the continuation versus switch of systemic therapy. We report outcomes of oligoprogressive patients after SBRT, and compare those patients that continued or switched their current line of systemic therapy.Material/methodsWe included patients who developed up to 5 progressive extracranial metastases under systemic therapy for any solid organ malignancy and were treated with SBRT to all lesions at our institution between 01/2014 and 12/2019. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and the interval to the next systemic therapy line determined using cumulative incidence functions. Multivariable Cox regression models were used to analyze the influence of baseline and post-progression variables on OS, PFS and survival with the next systemic therapy after SBRT.ResultsAmong 135 patients with oligoprogressive disease of which the most common primary tumor was lung cancer (n = 46, 34.1 %), 96 continued their current line of systemic therapy after oligoprogression. Among 39 who switched systemic therapy, 28 (71.8 %) paused or discontinued, while 11 (28.2 %) immediately started another systemic treatment. After a median follow-up of 27.2 months, patients that switched and those who continued systemic therapy after oligoprogression had comparable median OS (32.1 vs. 38.2 months, p = 0.47) and PFS (4.3 vs. 3.4 months, p = 0.6). The intervals to the next systemic therapy line were comparable between both cohorts (p = 0.6). An ECOG performance status of 2 and immediately starting a new systemic therapy after oligoprogression were associated with a poorer survival without next systemic therapy, while the de-novo OMD state was associated with better survival without next systemic therapy compared to the induced state.ConclusionOncological outcomes of patients that continued or switched systemic therapy after SBRT for oligoprogression were comparable, potentially indicating that further lines of treatment may be safely delayed in selected cases.

Project description:PurposeThe use of stereotactic body radiation therapy (SBRT) in pediatric patients has been underreported. We reviewed practice patterns, outcomes, and toxicity of SBRT in this population.Methods and materialsIn this multi-institutional study, 55 patients with 107 non-central nervous system lesions treated with SBRT between 2010 and 2016 were reviewed. Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST v1.1 criteria for soft-tissue and bone lesions, respectively. Patterns of local failure (LF) were assessed dosimetrically. The cumulative incidence of LF and toxicity were estimated accounting for the competing risk event of death. Predictors of LF were identified through joint frailty models for clustered competing risks.ResultsThe median (range) dose/fraction was 7 (4.5-25) Gy, the total (range) dose/site was 35 (12-45), and the median (range) number of fractions was 5 (1-9). The radiographic response rates of bone and soft-tissue lesions were 90.6% and 76.7%, respectively. Symptom improvement was observed for 62% of symptomatic sites. A total of 27 LFs were documented, with 14 in-field, 9 marginal, and 4 out-of-field LFs. The 1-year estimated cumulative LF rate, progression-free survival, and overall survival were 25.2% (95% confidence interval [CI], 17.2%-36.1%), 17.5% (95% CI, 9.0%-34.1%), and 61% (95% CI, 48.9%-76.1%), respectively. Lesion type (soft tissue vs bone) was the only significant predictor of LF on multivariable analysis (P = .04), with increased hazard for soft-tissue lesions. No acute or late toxicity of grade 4 or higher was observed; the estimated 1-year cumulative incidence of late toxicity of any grade was 7.5% (95% CI, 3.6%-12.1%).ConclusionsThe SBRT was well tolerated and resulted in radiographic response and symptom palliation in most pediatric patients with advanced disease. The 1-year cumulative LF rate of 25% will serve as a benchmark for further modifications to radiation therapy indications, parameters, and combination therapy.

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Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

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Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

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