BackgroundWe sought to determine the role of abdominal reirradiation for patients presenting with recurrent or new primary gastrointestinal (GI) malignancies. At our institution, we have established a hyperfractionated, accelerated reirradiation regimen consisting of 39 Gray (Gy) in 26 twice-daily fractions. Although this regimen is used frequently in the pelvis, we sought to determine its toxicity and efficacy for abdominal tumors.MethodsTwenty-four patients who received abdominal reirradiation with a hyperfractionated, accelerated approach from 2000 to 2017 were identified. Overall survival (OS) and local progression-free survival (LPFS) were calculated using the Kaplan-Meier method. Several patient, tumor and treatment characteristics were evaluated on univariate analyses for association with OS and LPFS using a Cox proportional hazards model.ResultsOf the twenty-four patients identified, the majority (n = 11, 46%) had pancreatic adenocarcinoma as their primary disease but also included upper GI adenocarcinoma (n = 4), colon adenocarcinoma (n = 3), hepatobiliary cancers (n = 4) and other malignancies (n = 2). The majority of patients received 45–50.4Gy in 1.8Gy fractions as their initial abdominal radiation course. The median reirradiation dose was 39Gy in 26 twice-daily fractions with a minimum six hour interval. The median [interquartile range (IQR)] interval between the courses of radiotherapy was 28 [18.6–38.9] months. Only palliative reirradiation intent was associated with decreased OS. While colon adenocarcinoma primary was significantly associated with increased LPFS, the sample size was small (n = 3). The 1-yr rate of LPFS was 38%. The median [IQR] duration of freedom from local progression was 8 [3.8–19.2] months. The 1-year OS was 50% and the median (IQR) OS was 14 [6.3–19.6] months. Thirteen patients (54%) had acute side effects with one patient experiencing G3 nausea and one experiencing a G4 bleed; the remaining patients experienced G1-G2 symptoms.ConclusionHyperfractionated, accelerated reirradiation to the abdomen was relatively well-tolerated but provided limited local control to recurrent or second primary abdominal malignancies. Reirradiation could play a role in treating these patients with palliative or curative intent, but alternative strategies for delivering increased biologically effective dose should be further explored.
Background: Select patients with rectal adenocarcinoma with metastatic disease at presentation can be cured with multimodality management. However, the optimal components and sequencing of therapy is unknown. The aim of this study is to evaluate outcomes for patients treated with chemotherapy, short course radiation therapy (SCRT) and surgical resection. Methods: Patients with newly diagnosed metastatic rectal adenocarcinoma who received SCRT from 2010-2016 were identified. All patients were evaluated by a multidisciplinary team and deemed candidates for treatment with curative intent. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Patient, tumor and treatment characteristics were evaluated as prognostic factors using a Cox proportional hazards model. Results: Thirty-four patients were included with a median [interquartile range (IQR)] follow-up of 25 (14.75-42.25) months; 26 patients (76.5%) received definitive surgery for their rectal tumor, and 24 patients (70.6%) received definitive local management of metastatic disease. One-, 2-and 3-year OS were 97%, 86.2% and 76.0%, respectively, and 1-, 2-, and 3-year PFS were 52.1%, 22.7% and 17%, respectively. On multivariate analysis, definitive management of metastases was associated with improved OS [hazard ratio (HR) 0.03, 95% confidence interval (CI): 0.01-0.33]; P=0.003, and ≤2 months of neoadjuvant chemotherapy was associated with decreased OS (HR 11.7, 95% CI: 2.11-106; P=0.004). Conclusions: These findings suggest that SCRT can be successfully integrated into a definitive, multidisciplinary approach to metastatic rectal adenocarcinoma. Benefits to this approach include decreased time off systemic therapy as compared to standard course RT. Further study is needed to determine the optimum interval between SCRT and surgery.
Purpose Patients with small cell lung cancer (SCLC) who have brain metastases require whole-brain radiation therapy (WBRT). When there is no emergent indication for WBRT, patients may receive systemic therapy first and WBRT afterward. In scenarios when systemic therapy is initiated first, it has not been previously investigated whether delaying WBRT is harmful. Methods and Materials The National Cancer Database was queried (2004-2016) for patients with SCLC with brain metastases who received 30 Gy in 10 fractions of WBRT. Patients were divided into groups based on whether they received early WBRT (3-14 days after initiation of chemotherapy) or late WBRT (15-90 days after initiation of chemotherapy). Demographic and clinicopathologic categorical variables were compared between those who had early WBRT (3-14 days) and those who had late WBRT (15-90 days). Factors predictive for late WBRT were determined. Overall survival (OS), which was defined as days from diagnosis to death, was evaluated and variables prognostic for OS were determined. Results A total of 1082 patients met selection criteria; 587 (54%) had early WBRT and 495 (46%) received late WBRT. Groups were similarly distributed aside from days from initiating chemotherapy to initiating WBRT ( P < .001). The early WBRT group had a median of 7 days (interquartile range [IQR], 5-10 days) from initiating chemotherapy to initiating WBRT and the late WBRT group had a median of 34 days (IQR, 21-57 days). On binary logistic regression analysis, a longer time interval between diagnosis and the start of systemic therapy was predictive for later WBRT. Median OS was 8.7 months for early WBRT and 7.5 months for late WBRT (hazard ratio [HR], 1.165; P = .008). Early WBRT ( P = .02), female sex ( P = .045), and private insurance ( P = .04) were favorable prognostic factors for OS on multivariable analysis, whereas older age ( P = .006) was an unfavorable prognostic factor. Conclusions Patients with SCLC and brain metastases who received early WBRT were found to have a modest improvement in OS compared with patients who received late WBRT. These findings suggest that early WBRT should be offered to patients who have brain metastases, even in the absence of an indication for emergent WBRT.
Historically, the effort by academia and industry to develop new chemical entities into lifesaving drugs has limited success in meeting the demands of today’s healthcare. Repurposing drugs that are originally approved by the United States Food and Drug Administration or by regulatory authorities around the globe is an attractive strategy to rapidly develop much-needed therapeutics for oncologic indications that extend from treating cancer to managing treatment-related complications. This review discusses computational approaches to harness existing drugs for new therapeutic use in oncology.
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