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A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases

Brennan, Cameron; Yang, T Jonathan; Hilden, Patrick; Zhang, Zhigang; Chan, Kelvin; Yamada, Yoshiya; Chan, Timothy A; Lymberis, Stella C; Narayana, Ashwatha; Tabar, Viviane; Gutin, Philip H; Ballangrud, Ase; Lis, Eric; Beal, Kathryn
PURPOSE: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. METHODS AND MATERIALS: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age >/=18 years, and Karnofsky performance status (KPS) >/=70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). RESULTS: The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (>/=3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). CONCLUSIONS: Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors >/=3 cm with superficial dural/pial involvement demonstrate the highest risk of LF.
PMCID:5736310
PMID: 24331659
ISSN: 0360-3016
CID: 746042

Predictors of acute gastrointestinal toxicity during pelvic chemoradiotherapy in patients with rectal cancer

Yang, T Jonathan; Oh, Jung Hun; Son, Christina H; Apte, Aditya; Deasy, Joseph O; Wu, Abraham; Goodman, Karyn A
BACKGROUND:This study was conducted to identify the factors associated with acute gastrointestinal (GI) toxicity during pelvic chemoradiotherapy (PCRT) in patients with rectal cancer. METHODS:We analyzed 177 patients with rectal cancer treated from 2007 through 2010. Clinical information, including weekly diarrhea and proctitis toxicity grade during PCRT, was recorded. GI structures including bowel and anal canal were contoured. The associations between toxicity and clinical and dosimetric predictors were tested. RESULTS:The median age was 60; 76 patients were women; 98 were treated with intensity-modulated radiotherapy (IMRT) and 79 with 3D conformal RT (3DCRT). A higher rate of grade 2+ diarrhea was observed in the women, starting at week 4 (24% women vs. 11% men, P = .01; week 5: 33% vs. 12%, P = .002), as well as in all the patients treated with 3DCRT (22% vs. 12% IMRT, P = .03; week 5: 32% vs. 11%, P = .001). On multivariate analysis, the normal tissue complication probability (NTCP) model including bowel V45 (bowel volume receiving ≥45 Gy) showed that being female, and use of 3DCRT, was most predictive of grade 2+ diarrhea (area under the curve [AUC] = 0.76; R S = 0.35; P < .001). A higher rate of grade 2+ proctitis was seen in patients <60 years of age starting at week 3 (21% vs. 9%, P = .02; week 4: 35% vs. 16%, P = .003). The NTCP model including anal canal V15 and younger age was most predictive of grade 2+ proctitis (AUC = 0.67; R S = 0.25; P < .001). CONCLUSIONS:Women and all patients who were treated with 3DCRT had higher rates of grade 2+ diarrhea, and the younger patients had a higher rate of grade 2+ proctitis during PCRT. The use of more stringent dosimetric constraints in higher risk patients is a strategy for minimizing toxicity.
PMCID:3849899
PMID: 24312686
ISSN: 1934-7820
CID: 5770852

Tumor bed delineation for external beam accelerated partial breast irradiation: a systematic review

Yang, T Jonathan; Tao, Randa; Elkhuizen, Paula H M; van Vliet-Vroegindeweij, Corine; Li, Guang; Powell, Simon N
In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1-2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer's ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed.
PMID: 23806188
ISSN: 1879-0887
CID: 5770842

Radiation therapy in the management of breast cancer

Yang, T Jonathan; Ho, Alice Y
Radiation therapy (RT) plays an essential role in the management of breast cancer by eradicating subclinical disease after surgical removal of grossly evident tumor. Radiation reduces local recurrence rates and increases breast cancer-specific survival in patients with early-stage breast cancer after breast-conserving surgery and in node-positive patients who have undergone mastectomy. This article reviews the following topics: (1) the rationale for adjuvant RT and the evidence for its use in noninvasive and invasive breast cancer, (2) RT delivery techniques for breast-conserving therapy such as hypofractionated RT, partial breast irradiation, and prone irradiation, and (3) indications for PMRT.
PMID: 23464696
ISSN: 1558-3171
CID: 5770832