Role of radiation therapy for renal tumors.
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ABSTRACT:
SUBMITTER: Parashar B
PROVIDER: S-EPMC3930657 | biostudies-other | 2014 Mar
REPOSITORIES: biostudies-other
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Project description:Advancements in radiation delivery technology have made it feasible to treat tumors with ablative radiation doses via stereotactic ablative radiation therapy (SAbR) at locations that were previously not possible. Renal cell cancer (RCC) was initially thought to be radioresistant, even considered toxic, in the era of conventional protracted course radiation. However, SAbR has been demonstrated to be safe and effective in providing local control to both primary and metastatic RCC by using ablative radiation doses. SAbR can be integrated with other local and systemic therapies to provide optimal management of RCC patients. We will discuss the rationale and available evidence for the integration and sequencing of SAbR with local and systemic therapies for RCC.
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Project description:Radiotherapy has been a longstanding treatment option for low-grade glioma. Improvements in tumor control and radiation-related toxicity may be attributed to advances in neuroimaging as well as radiotherapy planning and delivery. The discovery of various molecular prognostic factors have aided in patient selection for radiotherapy. These prognostic and predictive factors may also play a key role in determining which patients are likely to benefit most from combined systemic therapy and radiation.
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Project description:The incidence of brain tumors in the elderly population has increased over the last few decades. Current treatment includes surgery, radiotherapy and chemotherapy, but the optimal management of older patients with brain tumors remains a matter of debate, since aggressive radiation treatments in this population may be associated with high risks of neurological toxicity and deterioration of quality of life. For such patients, a careful clinical status assessment is mandatory both for clinical decision making and for designing randomized trials to adequately evaluate the optimal combination of radiotherapy and chemotherapy.Several randomized studies have demonstrated the efficacy and safety of chemotherapy for patients with glioblastoma or lymphoma; however, the use of radiotherapy given in association with chemotherapy or as salvage therapy remains an effective treatment option associated with survival benefit. Stereotactic techniques are increasingly used for the treatment of patients with brain metastases and benign tumors, including pituitary adenomas, meningiomas and acoustic neuromas. Although no randomized trials have proven the superiority of SRS over other radiation techniques in older patients with brain metastases or benign brain tumors, data extracted from recent randomized studies and large retrospective series suggest that SRS is an effective approach in such patients associated with survival advantages and toxicity profile similar to those observed in young adults. Future trials need to investigate the optimal radiation techniques and dose/fractionation schedules in older patients with brain tumors with regard to clinical outcomes, neurocognitive function, and quality of life.
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Project description:PurposeOligoprogression, defined as limited sites of progression on systemic therapy, in patients with metastatic renal cell carcinoma (mRCC) is not uncommon, possibly because of inter- and intratumoral heterogeneity. We evaluated the effect of stereotactic ablative radiation therapy (SAbR) for longitudinal control of oligoprogressive mRCC.Methods and materialsPatients with extracranial mRCC were included in this retrospective analysis if they progressed in ≤3 sites on systemic therapy while demonstrating response/stability at other sites and received SAbR to all progressing sites without switching systemic therapy. Our primary endpoint was modified progression-free survival (mPFS), which we calculated from the start of SAbR to the start of a subsequent systemic therapy, death, or loss to follow-up.ResultsWe identified 36 patients with a median follow-up of 20.4 months (interquartile range, 10.9-29.4). Forty-three sites were treated with SAbR with a median dose of 36 Gy (range, 18-50) in 3 fractions (range, 1-5). Median time to SAbR from the start of systemic therapy was 11.4 months (interquartile range, 6.1-17.1). Median mPFS was 9.2 months (95% confidence interval [CI], 5.9-13.2). Patients receiving SAbR while on immunotherapy exhibited a longer median mPFS (>28.4 months, log-rank P = .0001) than patients not on immunotherapy (9.2 months). Median overall survival from SAbR administration was 43.4 months (95% CI, 21.5-not Reached). The 1-year local control rate was 93% (95% CI, 78.7-97.5). Most SAbR-related toxicities were grade 1 to 2 (33% of patients), with one grade 5 hemoptysis event possibly related to SAbR or disease progression.ConclusionsSAbR has the potential to extend the the duration of current systemic therapy for selected patients with mRCC, preserving subsequent therapies for later administration possibly enabling longer treatment duration.
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Project description:We investigated the possibility of using a pharmacologic agent to modulate viral gene expression to target radiotherapy to tumor tissue. In a mouse xenograft model, we had previously shown targeting of [(125)I]2'-fluoro-2'-deoxy-beta-D-5-iodouracil-arabinofuranoside ([(125)I]FIAU) to tumors engineered to express the Epstein-Barr virus thymidine kinase (EBV-TK). Here we extend those results to targeting of a therapeutic radiopharmaceutical [(131)I]FIAU to slow or stop tumor growth or to achieve tumor regression. These outcomes were achieved in xenografts with tumors that constitutively expressed the EBV-TK. With naturally infected EBV tumor cell lines (Burkitt's lymphoma and gastric carcinoma), activation of viral gene expression by pretreatment with bortezomib was required. Marked changes in tumor growth could also be achieved in naturally infected Kaposi's sarcoma herpesvirus tumors after pretreatment with bortezomib. Bortezomib-induced enzyme-targeted radiation therapy illustrates the possibility of pharmacologically modulating tumor gene expression to result in targeted radiotherapy.
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Project description:Immunotherapy, particularly immune-checkpoint inhibition, is producing encouraging clinical responses and affecting the way numerous cancers are treated. Yet immune-checkpoint therapy is not effective for many patients, and even those who initially respond can experience relapse, fueling interest in finding new processes or tools to improve the effectiveness of these novel therapeutics. One such tool is radiation. Both preclinical and clinical studies have demonstrated that the systemic effects of immunotherapy can be amplified when it is used in combination with radiation and, conversely, that the immunogenic effects of local irradiation can be amplified and extended to distant sites when used with immunotherapy. We review how stereotactic ablative radiation therapy, a technique specifically indicated for tumors treated with immune-checkpoint inhibitors, can potentiate the effects of immune-checkpoint therapy. We further explore how these novel therapeutics may transform radiation, previously considered a local treatment option, into powerful systemic therapy.
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Project description:PurposeTo quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen.Methods and materialsWe identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 vs >100 Gy10). Comparisons were made using log-rank testing.ResultsThirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy10 (3-year local control 65%, P < .001).ConclusionsStereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy10 are utilized.
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Project description:PurposeStereotactic body radiation therapy (SBRT) has demonstrated clinical benefits for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and nearby organs at risk can limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiation therapy (SFRT) may address this limitation because this technique can deliver high-dose radiation to discrete subvolume vertices inside a tumor target while restricting the remainder of the target to a safer lower dose. Indeed, SFRT, such as GRID, has been used to treat large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT delivered with arc-based therapy, which may allow for safe, high-quality SBRT for large and/or deep tumors.Methods and materialsHerein, we report the results of a dosimetry and quality assurance feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥10 cm in an axial dimension. Prior computed tomography simulation scans were used to generate volumetric modulated arc therapy Lattice SBRT plans that were then delivered on clinically available Linacs. Quality assurance testing included external portal imaging device and ion chamber analyses.ResultsAll generated plans met the standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101. Additionally, we provide a step-by-step approach to generate and deliver Lattice SBRT plans using commercially available treatment technology.ConclusionsLattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer who need palliation of large tumors (NCT04553471, NCT04133415).
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Project description:Despite the historically limited role of radiotherapy in the management of primary hepatic malignancies, modern advances in treatment design and delivery have renewed enthusiasm for radiation as a potentially curative treatment modality. Surgical resection and/or liver transplantation are traditionally regarded as the most effective forms of therapy, although the majority of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma present with locally advanced or unresectable disease on the basis of local vascular invasion or inadequate baseline hepatobiliary function. In this context, many efforts have focused on nonoperative treatment approaches including novel systemic therapies, transarterial chemoembolization, ethanol ablation, radiofrequency ablation, and stereotactic body radiation therapy (SBRT). This review aims to summarize modern advances in radiotherapy, particularly SBRT, in the treatment of primary hepatic malignancies.
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Project description:The ability of tumors to evade detection by the immune system via inducing immunosuppression prompted the therapeutic development of immune checkpoint inhibitors. In our recent review, we discussed findings from preclinical and clinical investigations of these agents utilized in combination with radiation inducing abscopal (systemic) antitumor effects.
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