Kara D. Romano

Choosing a Prescription Isodose in Stereotactic Radiosurgery for Brain Metastases: Implications for Local Control

OBJECTIVEnStereotactic radiosurgery (SRS) achieves excellent local control (LC) with limited toxicity for most brain metastases. SRS dose prescription variables influence LC; therefore, we evaluated the impact of prescription isodose line (IDL) on LC after SRS.nnnMETHODSnA retrospective analysis of patients with brain metastases treated on a Gamma Knife platform from 2004 to 2014 was conducted. Clinical, toxicity, radiographic, and dosimetric data were collected. Cox proportional hazards regression was used to determine progression-free survival (PFS) and competing risks analysis was used to determine predictive factors for LC.nnnRESULTSnA total of 134 patients with 374 brain metastases were identified with a median survival of 8.7 months (range, 0.2-64.8). The median tumor maximum dimension was 8 mm (range, 2-62 mm), median margin dose was 20 Gy (range, 5-24 Gy), and 12-month LC rate was 88.7%. On multivariate analysis, PFS improved with increasing IDL (Pxa0= 0.003) and decreased with non-non-small-cell lung cancer histology (Pxa0= 0.001). Margin dose, tumor size, conformality, and previous whole-brain irradiation failed to independently affect PFS. When adjusting for death as a competing risk, the cumulative likelihood of LC improved with higher IDL (Pxa0= 0.04). The rate of SRS-induced radiographic and clinical toxicity was low (16.6% and 1.5%, respectively), and neither was affected by IDL.nnnCONCLUSIONSnOur results confirm that SRS for brain metastases results in favorable LC, particularly for patients with smaller tumors. We noted that dose delivery to a higher prescription IDL is associated with small but measurable improvements in LC. This finding could be related to higher dose just beyond the radiographically apparent tumor.

More than Just the Number of Brain Metastases: Evaluating the Impact of Brain Metastasis Location and Relative Volume on Overall Survival After Stereotactic Radiosurgery

OBJECTIVEnMost evidence describing outcomes of patients with brain metastases is based on number of brain metastases, rather than location or volume. We evaluated the impact of tumor location and relative volume on overall survival (OS) among a large cohort of patients treated with stereotactic radiosurgery.nnnMETHODSnClinical, radiographic, and dosimetric data were collected on patients treated with first (if multiple) stereotactic radiosurgery for brain metastases. Multivariate analyses were performed to investigate the impact of brain metastasis relative location and volume on OS after stereotactic radiosurgery.nnnRESULTSnAnalysis included 300 patients with 817 tumors (116 patients with single brain metastasis). The most common tumor locations were supratentorial (75% of tumors), cerebellar (19%), and brainstem (5%). Median tumor volume was 0.4 mL (range, 0.003-65.0 mL). Tumor-specific factors associated with inferior OS included brainstem location versus both supratentorial and cerebellum locations for particular assumed values of cube root tumor volume (P < 0.001 for each) and increasing total supratentorial tumor volume (Pxa0= 0.004). Patients with supratentorial tumors and cerebellar tumors demonstrated similar OS, and cube root total tumor volume within the cerebellum and brainstem did not predict for OS.nnnCONCLUSIONSnThe presence of brainstem metastases and cumulative supratentorial tumor volume are adverse features that result in inferior survival. These results can be used to inform patient prognosis and future clinical trial design.

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity

PURPOSEnIn 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period.nnnMETHODS AND MATERIALSnFrom 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded.nnnRESULTSnMedian followup for the LDR and HDR groups was 46xa0months and 12xa0months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, pxa0=xa00.12; and 75% vs. 85%, pxa0=xa00.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, pxa0=xa00.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes.nnnCONCLUSIONSnThis comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging.

Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold

BackgroundTo evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed “HIP.” HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment.MethodsWe identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36xa0months (range 5–36xa0months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.ResultsPatients received a median dose of 42.56xa0Gy in 16 Fractions (Fx) (range 40.05–53.2xa0Gy; and 15–20 Fx). OAR doses were low, with a mean heart dose of 0.37xa0Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (nu2009=u200930) of the cases, with dermatitis being the most common finding (63%). Late grade 1–2 toxicity was present in 42% (nu2009=u200916) of the cases, with hyperpigmentation being the most common finding (nu2009=u20099). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21xa0months, there were no local, regional, or distant failures.ConclusionsWe report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.

High dose-rate tandem and ovoid brachytherapy in cervical cancer: dosimetric predictors of adverse events

BackgroundBrachytherapy (BT) is a vital component of the curative treatment of locally advanced cervical cancer. The American Brachytherapy Society has published guidelines for high dose rate (HDR) BT with recommended dose limits. However, recent reports suggest lower doses may be needed to avoid toxicity. The purpose of this study is to investigate incidence and predictive factors influencing gastrointestinal (GI) and genitourinary (GU) toxicity following HDR intracavitary brachytherapy for locally advanced cervical cancer.MethodsWe retrospectively evaluated a cohort of patients with locally advanced cervical cancer who received CT-based HDR BT. Cumulative doses were calculated using the linear-quadratic model. Statistical analyses were used to investigate clinical and dosimetric predictors of GI and GU toxicity following HDR brachytherapy according to CTCAE v4.0 grading criteria.ResultsFifty-six women with FIGO IB1 – IVA cervical cancer were included. The overall rate of any GU adverse event (Grade 1+) was 23.3% (nu2009=u200913) and severe adverse events (Grade 3+) was 7.1% (nu2009=u20094). Of those, the bladder equivalent dose in 2- Gray (Gy) fractions (EQD2) D2cc was ≥80 for three of the four patients. The overall rate of any GI adverse event was 26.8% (nu2009=u200915) and the rate of severe adverse events was 14.3% (nu2009=u20098). Of those, six of the eight patients had a rectal EQD2 D2ccu2009≥u200965xa0Gy and seven patients had a sigmoid D2ccu2009≥u200965xa0Gy. Amongst clinically meaningful factors for development of adverse events (i.e. diabetes, smoking status, ovoid size, and treatment duration), there were no statistically significant prognostic factors identified.ConclusionsSevere adverse events are observed even with adherence to current ABS guidelines. In the era of recent multi-institutional study results, our data also supports more stringent dosimetric goals. We suggest cumulative D2cc dose limits of: less than 80xa0Gy for the bladder and less than 65xa0Gy for the rectum and sigmoid.

Integration of MRI target delineation into rapid workflow cervical cancer brachytherapy: Impact on clinical outcomes

We evaluated the impact of MRI‐based target delineation on toxicity and tumour control after implementation of a protocol to incorporate MRI while minimizing impact on overall procedural time.

Clinical outcomes of helical conformal versus nonconformal palliative radiation therapy for axial skeletal metastases

PURPOSEnPalliative radiation therapy (RT) for bone metastases has traditionally been delivered with conventional, nonconformal RT (NCRT). Conformal RT (CRT) is potentially more complex and expensive than NCRT, but may reduce normal tissue dose and subsequently toxicity. In this retrospective analysis, we compared CRT with NCRT to investigate the association between conformality and toxicity.nnnMETHODS AND MATERIALSnA retrospective analysis of patients receiving palliative RT for axial skeletal bone metastases from 2012 to 2014 was conducted. Patient and treatment characteristics were obtained including dosimetric variables, acute toxicity, and subjective pain during treatment and in the acute posttreatment period (≤60 days after completion). Statistical analyses included t tests, χ2 tests, and multivariate logistic regression.nnnRESULTSnA total of 179 patients and 254 bone metastases were identified (142 CRT, 112 NCRT). The CRT and NCRT groups were well matched for baseline characteristics (number of fractions, field size, treatment sites, and concurrent chemotherapy). In multivariate logistic regression models, technique (CRT vs NCRT) was not associated with development of acute toxicity. Regarding toxicity, Eastern Cooperative Oncology Group performance status and total dose were significantly associated with a higher rate of acute toxicity during RT (odds ratios, 0.649 and 1.129 and P = .027 and .044, respectively), and only a higher number of vertebral bodies in the treatment field was significantly associated with acute toxicity post-treatment (odds ratios, 1.219, P = .028). CRT was associated with improvement in bone pain during and posttreatment (P = .049 and .045, respectively).nnnCONCLUSIONSnOur results demonstrate no difference in acute toxicity following palliative RT with CRT compared with NCRT for painful bone metastases; however, treatment volume did predict for increased toxicity. Larger studies may further elucidate the value of CRT including the impact of dose escalation for bone metastases and differences in patient reported outcomes between RT techniques.

The Effect of Receptor Status on Mastectomy and Contralateral Prophylactic Mastectomy Rates in Early Stage Invasive Breast Carcinoma

Background: There is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer. Patients and Methods: The National Cancer Database was queried for patients with cT1 to cT3, cN0, and cM0 breast carcinoma from 2004 to 2012. Patients were grouped on the basis of receptor status and surgical management (mastectomy or breast‐conserving surgery [BCS]). Multivariable analyses were performed to investigate factors associated with increased odds of receiving mastectomy over BCS. Among a subgroup of patients who underwent ipsilateral mastectomy, analyses were performed to determine any association between contralateral prophylactic mastectomy (CPM) and receptor status. Results: We found 280,241 patients who met inclusion criteria for analyzing mastectomy or BCS surgical decision. Patients with HER2‐positive (HER2+) tumors (HR+/HER+ and HR−/HER2+) were the most likely to undergo mastectomy (odds ratio [OR], 1.212 and 1.499 respectively, compared with HR+/HER2− patients, each P < .001). HR status alone did not affect ipsilateral surgical management as patients with HR+/HER2− and HR−/HER2− tumors demonstrated similar mastectomy rates (P = .391). Among the 108,018 who underwent mastectomy, 20% underwent CPM. After adjustment, patients with HR+/HER2+, HR−/HER2+, and HR−/HER2− were all more likely to undergo CPM (OR 1.356, 1.608, and 1.358, respectively compared with HR+/HER2− patients, each P < .001). Conclusion: This analysis indicates that patients with early stage breast cancer are more likely to undergo a mastectomy and CPM if they have HER2+ tumors.