Stereotactic Radiosurgery for Gynecologic Cancer

Kunos, Charles; Brindle, James; Debernardo, Robert

doi:10.3791/3793

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…It may be envisioned that a second-line radiochemotherapy strategy could emerge for the management of incompletely responding persistent or recurrent ovarian cancers. Here, radiosurgery (41) could target and ablate sites of chemorefractory ovarian cancer while cabazitaxel provides radiosensitization and independent cytotoxicity. The combination of radiosurgery and concomitant chemotherapy (i.e., gemcitabine and carboplatin) is already being studied in a phase I clinical trial (listed at as NCT01652794).…”

Section: Discussionmentioning

confidence: 99%

Cabazitaxel-Induced Stabilization of Microtubules Enhances Radiosensitivity in Ovarian Cancer Cells

2013

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Background: Up to 40% of women with ovarian cancer have short disease-free intervals due to molecular mechanisms of chemotherapy resistance. New therapeutic strategies are sought. Ovarian cancers are sensitive to radiochemotherapy. The taxane cabazitaxel (XRP6258, Jevtana) promotes tubulin assembly and stabilizes microtubules against depolymerization in cells, acting similarly in mechanism to paclitaxel. Here, sequences of cabazitaxel-radiation co-administration are tested for drug-alone cytotoxicity and optimal radiosensitization.Materials and Methods: SKOV3, OVCAR3, and TOV-112D ovarian cancer cells were administered cabazitaxel 24 h before (first), 18 h before (second), together (third), or 24 h after (fourth) a single radiation dose, and then, investigated by clonogenic assay and flow cytometric assays. Radiation dose-cell survival data were fitted by two-stage multivariate analyses of variance. High-content flow cytometry partitioned cabazitaxel effects into G2-phase versus M-phase events by DNA content, cyclin A2, and phospho-S10-histone H3 (PHH3). Paclitaxel served as a comparator.Findings: Cabazitaxel cytotoxicity and radiosensitization were dose dependent. Cabazitaxel added 24 h before radiation was the most lethal schedule. DNA content measurements by flow cytometry showed that cabazitaxel-treated cells accumulated in the radiosensitive G2/M 4C DNA complement compartment. Cytometry also showed that surviving cabazitaxel-induced cell cycle arrested cells resolve the arrest by entering 4C or by 8C DNA complement cell cycles.Interpretation: The radiosensitizing effect of cabazitaxel was schedule dependent, due to cell cycle redistribution, and best when cabazitaxel was given 24 h before radiation. Clinical trials of administering both cabazitaxel and radiation should be explored in women with chemoresistant ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Cabazitaxel-Induced Stabilization of Microtubules Enhances Radiosensitivity in Ovarian Cancer Cells

2013

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“…Fixed tungsten circular collimators (5–60 mm) or a tungsten-copper alloy iris aperture collimated a 6 MV radiation beam. For additional details, the reader is referred to a peer-reviewed, video-complemented algorithm for the three outpatient robotic SBRT treatment sessions (Kunos et al, 2012b). …”

Section: Methodsmentioning

confidence: 99%

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

Kunos¹,

Brindle²,

Waggoner³

et al. 2012

Front. Oncol.

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Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers. Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan–Meier method and the Cox proportional hazards model was used to control for prognostic variables. Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5). Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway. Funding: Case Comprehensive Cancer Center.

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“…Stereotactic radiosurgery has been evaluated in several retrospective studies of metastatic gynecological malignancies and has demonstrated activity at various doses and schedules. Particularly in patients with small tumor burden at recurrence and good performance status, the use of stereotactic body radiation therapy (SBRT) to treat FDG-PET avid para-aortic disease has shown a 4-year local control rate of 67.4%, with low incidence of G3-4 complications (Choi et al, 2009; Kunos et al, 2012a,b). More prospective studies are needed to confirm the role of molecular imaging as a routine examination during the follow-up of these patients (Elit et al, 2010).…”

Section: Evaluation Of Treatment Response and Disease Recurrencementioning

confidence: 99%

The role of PET/CT in cervical cancer

Herrera¹,

Prior²

2013

Front. Oncol.

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In locally advanced cervical cancer, 18F-fluorodeoxyglucose (FDG) positron emission tomography – computed tomography (PET/CT) has become important in the initial evaluation of disease extent. It is superior to other imaging modalities for lymph node status and distant metastasis. PET-defined cervical tumor volume predicts progression-free and overall survival. Higher FDG uptake in both primary and regional lymph nodes is strongly predictive of worse outcome. FDG-PET is useful for assessing treatment response 3 months after completing concurrent chemo-radiotherapy (CRT) and predicting long-term survival, and in suspected disease recurrence. In the era of image-guided adaptive radiotherapy, accurately defining disease areas is critical to avoid irradiating normal tissue. Based on additional information provided by FDG-PET, radiation treatment volumes can be modified and higher doses to FDG-positive lymph nodes safely delivered. FDG-PET/CT has been used for image-guided brachytherapy of FDG-avid tumor volume, while respecting low doses to bladder and rectum. Despite survival improvements due to CRT in cervical cancer, disease recurrences continue to be a major problem. Biological rationale exists for combining novel non-cytotoxic agents with CRT, and drugs targeting specific molecular pathways are under clinical development. The integration of these targeted therapies in clinical trials, and the need for accurate predictors of radio-curability is essential. New molecular imaging tracers may help identifying more aggressive tumors. 64Cu-labeled diacetyl-di(N(4)-methylthiosemicarbazone) is taken up by hypoxic tissues, which may be valuable for prognostication and radiation treatment planning. PET/CT imaging with novel radiopharmaceuticals could further impact cervical cancer treatment as surrogate markers of drug activity at the tumor microenvironment level. The present article reviews the current and emerging role of PET/CT in the management of cervical cancer.

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Stereotactic Radiosurgery for Gynecologic Cancer

Cited by 12 publications

References 17 publications

Cabazitaxel-Induced Stabilization of Microtubules Enhances Radiosensitivity in Ovarian Cancer Cells

Cabazitaxel-Induced Stabilization of Microtubules Enhances Radiosensitivity in Ovarian Cancer Cells

Phase II Clinical Trial of Robotic Stereotactic Body Radiosurgery for Metastatic Gynecologic Malignancies

The role of PET/CT in cervical cancer

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