Dataset Information

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

ABSTRACT: BACKGROUND:We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. METHODS:Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. FINDINGS:The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable. INTERPRETATION:Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.

SUBMITTER: Kunos CA

PROVIDER: S-EPMC4456851 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

Kunos Charles A CA Sherertz Tracy M TM Mislmani Mazen M Ellis Rodney J RJ Lo Simon S SS Waggoner Steven E SE Zanotti Kristine M KM Herrmann Karin K Debernardo Robert L RL

Frontiers in oncology 20150605

<h4>Background</h4>We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers.<h4>Methods</h4>Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common termino ...[more]

PMID: 26097831

Similar Datasets

Project description:BackgroundThe management of vestibular schwannoma has evolved over the past hundred years. In the last decades, surgery has been gradually replaced by radiation therapy as a primary treatment modality, particularly for small tumors, due to the less invasive nature and the compared reported outcomes in tumor control and hearing preservation. However, irradiation sometimes fails to stop tumor growth. In a long-term follow-up after primary fractionated stereotactic radiotherapy, the rate of treatment failure was reported as 3% and needed surgical salvage. For single-fraction modality, Hasegawa et al. reported salvage treatment after primary Gamma Knife radiosurgery in 8%, where 90% of these underwent surgery and 50% of those who were treated with a second gamma knife surgery required surgical intervention later. An increase in tumor volume by more than 10-20%, tumor growth after three years, and no return to pretreatment volume after transient swelling have been considered as tumor recurrence rather than pseudoprogression, a transient increase in tumor volume after radiotherapy that occurs up to 30% of cases. It has been reported that microsurgery after radiotherapy is more difficult, with most authors reporting a loss of defined arachnoid planes and worse cranial nerve outcomes, especially for hearing and facial nerve function.Case descriptionA 43-year-old female patient was incidentally (asymptomatic) diagnosed on a magnetic resonance imaging (MRI) scan harboring a left vestibular schwannoma, grade T2 (Hannover classification), in 2015. Neurologic examination was unremarkable, and audiometry testing was normal. She was initially treated with observation. Three years later, in 2018, the lesion had enlarged, becoming a grade T3a and reaching the cistern of the cerebellopontine angle. The tumor was then treated with fractionated stereotactic radiosurgery (5 sessions of 5 Gy). MRI scans in 2019 and 2020 showed slight tumor growth. This enlargement was attributed to a pseudoprogression after radiosurgery, and only observation was advocated. In 2022, 4 years later, after radiosurgery, the tumor was still growing, and the patient began to suffer from hearing loss. A failure treatment was considered, and microsurgery was indicated. The patient was counseled about the risk of functional nerve impairment, and surgical consent was obtained. A retro sigmoid approach was planned. A gross total resection was attempted due to the clear subperineural plane during tumor dissection and because it was the only option that would provide a cure for the patient. The adjacent neurovascular structures were firmly adhered to the tumor capsule, which represented a major challenge for microdissection. The tumor was soft, without significant bleeding. A total resection was achieved, and the facial nerve was anatomically preserved. The patient developed facial paresis (House-Brackmann III) in the immediate postoperative period, which improved at the 6-month follow-up. Hearing loss did not improve. Postoperative MRI showed total resection.ConclusionMicrosurgery after radiotherapy for vestibular schwannoma is challenging in terms of indication, when to indicate, resection target, difficulty in dissection due to local changes, and outcome. Gross total resection may be considered, as it is the only treatment that may provide a cure for the patient. However, the patient should be counseled about the risks.

Project description:BACKGROUND:Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS:FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ?2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ?4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours >?4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION:The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION:Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

Project description:IntroductionNeoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).MethodsWe identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.ResultsWe included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm3 were smaller tumors (pre-GTV < 15.0 cm3), whereas larger tumors greater than 25.0 cm3 showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.ConclusionPatients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

Project description:BackgroundStereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases.MethodsPatients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life.DiscussionCurrently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure.Trial registrationClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Dataset Information

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

Publications

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets