J.A. Hattangadi

Accelerated Partial Breast Irradiation Using Brachytherapy for Breast Cancer: Patterns in Utilization and Guideline Concordance

BACKGROUND Accelerated partial breast irradiation using brachytherapy (APBIb) is an alternative to whole-breast irradiation (WBI) after breast-conserving surgery. We evaluated patterns of APBIb use with respect to 2009 American Society for Radiation Oncology consensus guidelines (ASTRO-G) in a population-based cohort. METHODS From Surveillance, Epidemiology, and End Results data, we identified 138 815 American women with breast cancer diagnosed between January 1, 2000, and December 31, 2007, who underwent WBI or APBIb after breast-conserving surgery and classified them as suitable, cautionary, or unsuitable for APBIb according to ASTRO-G criteria. Logistic regression was applied to study APBIb use overall and within each guideline category. All P values are from two-sided tests. RESULTS Overall, 2.6% of patients received APBIb, and 65.8% of them were classified as cautionary or unsuitable. APBIb was used by 5% of suitable, 3.4% of cautionary, and 1.6% of unsuitable patients by ASTRO-G criteria (P < .001). APBIb use increased from 0.4% in 2000 to 6.6% in 2007 and varied widely (0%-7%) between localities. Variables associated with APBIb use among suitable patients included other vs white race (odds ratio [OR] = 0.51, P < .001), region (OR = 2.60-8.62, P < .001), and more recent year (OR = 20.3, P < .001). Among cautionary patients, variables associated with APBIb use included black vs white race (OR = 0.76, P = .027), other vs white race (OR = 0.57, P < .001), Hispanic ethnicity (OR = 0.75, P = .036), region (OR = 3.10-10.2, P < .001), nonmetropolitan or rural location (OR = 0.53, P = .012), and more recent year (OR = 17.6, P < .001). Among unsuitable patients, black vs white race (OR = 0.77, P = .008), other vs white race (OR = 0.46, P < .001), region (OR = 3.33-21.6, P < .001), and more recent year (OR = 12.7, P < .001) were associated with APBIb use. CONCLUSIONS APBIb after breast-conserving surgery has been rapidly adopted in the United States. Use varied by race, ethnicity, and widely by region, especially among patients who may not be suitable for this radiation technique.

Accelerated Partial Breast Irradiation With Low-Dose- Rate Interstitial Implant Brachytherapy After Wide Local Excision: 12-Year Outcomes From a Prospective Trial

PURPOSE To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). MATERIALS AND METHODS Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendalls tau (τ(β)) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. RESULTS The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (τ(β) 0.6, p < .0001), lower patient satisfaction (τ(β) 0.5, p < .001), and worse fibrosis (τ(β) 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias ≥1 cm(2). Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (τ(β) 0.3-0.5, p ≤ .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival, and overall survival rate was 85% (95% confidence interval, 70-97%), 72% (95% confidence interval, 54-86%), and 87% (95% confidence interval, 73-99%), respectively. CONCLUSION Low-dose-rate accelerated partial breast irradiation with implant brachytherapy provides acceptable local control in select early-stage BCa patients. However, treatment-related toxicity and cosmetic complications were significant with longer follow-up and at higher doses.

Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma.

Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modalitys ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma.

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

Although adjuvant chemoradiation is used commonly in the United States for the treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy, because the results from randomized trials are conflicting. The authors of this report reviewed their experience in a consecutive, unselected series of patients who received adjuvant 5‐fluorouracil (5‐FU) and radiation therapy (RT) for resected pancreatic adenocarcinoma.

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

PURPOSE To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. METHODS AND MATERIALS All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. RESULTS Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. CONCLUSIONS Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.

Initial management of prostate‐specific antigen‐detected, low‐risk prostate cancer and the risk of death from prostate cancer

The recently published Prostate Cancer Intervention versus Observation Trial (PIVOT) did not identify differences in prostate cancer‐specific mortality or all‐cause mortality among patients with low‐risk disease managed conservatively vs those managed definitively; however, recently published data suggest that older men may harbour more aggressive disease than is identified at biopsy owing to sampling error and undergrading. Whether older men with apparent low‐risk disease are placed at risk of prostate cancer‐specific mortality when managed conservatively remains unknown. The study used population‐level data to show that non‐curative approaches for older men with low‐risk prostate cancer do result in an increased risk of prostate cancer‐specific mortality. Differences between our study and the PIVOT trial include the fact that we included a larger sample size, analysed the data using an ‘as‐treated’ approach, and included a healthier cohort of men as evinced by lower 4‐year all‐cause mortality estimates in our study than in the PIVOT. Our results suggest that older men with apparent low‐risk prostate cancer are at risk of undergrading, which probably explains the differences in prostate cancer‐specific mortality observed between men managed conservatively vs those managed definitively. Our study suggests that alternative approaches to excluding occult, high grade prostate cancer are needed in such men.

Planned two-fraction proton beam stereotactic radiosurgery for high-risk inoperable cerebral arteriovenous malformations.

PURPOSE To evaluate patients with high-risk cerebral arteriovenous malformations (AVMs), based on eloquent brain location or large size, who underwent planned two-fraction proton stereotactic radiosurgery (PSRS). METHODS AND MATERIALS From 1991 to 2009, 59 patients with high-risk cerebral AVMs received two-fraction PSRS. Median nidus volume was 23 cc (range, 1.4-58.1 cc), 70% of cases had nidus volume ≥ 14 cc, and 34% were in critical locations (brainstem, basal ganglia). Median AVM score based on age, AVM size, and location was 3.19 (range, 0.9-6.9). Many patients had prior surgery or embolization (40%) or prior PSRS (12%). The most common prescription was 16 Gy radiobiologic equivalent (RBE) in two fractions, prescribed to the 90% isodose. RESULTS At a median follow-up of 56.1 months, 9 patients (15%) had total and 20 patients (34%) had partial obliteration. Patients with total obliteration received higher total dose than those with partial or no obliteration (mean dose, 17.6 vs. 15.5 Gy (RBE), p = 0.01). Median time to total obliteration was 62 months (range, 23-109 months), and 5-year actuarial rate of partial or total obliteration was 33%. Five-year actuarial rate of hemorrhage was 22% (95% confidence interval, 12.5%-36.8%) and 14% (n = 8) suffered fatal hemorrhage. Lesions with higher AVM scores were more likely to hemorrhage (p = 0.024) and less responsive to radiation (p = 0.026). The most common complication was Grade 1 headache acutely (14%) and long term (12%). One patient developed a Grade 2 generalized seizure disorder, and two had mild neurologic deficits. CONCLUSIONS High-risk AVMs can be safely treated with two-fraction PSRS, although total obliteration rate is low and patients remain at risk for future hemorrhage. Future studies should include higher doses or a multistaged PSRS approach for lesions more resistant to obliteration with radiation.

Advancing age within established Gleason score categories and the risk of prostate cancer‐specific mortality (PCSM)

Study Type – Prognosis (case series)

Prognostic Factors for stereotactic radiosurgery-treated patients with cerebral metastasis: Implications on randomised control trial design and inter-institutional collaboration

INTRODUCTION Defining key prognostic factors for patients with cerebral metastases who underwent stereotactic radiosurgery (SRS) treatment will greatly facilitate future clinical trial designs. METHODS We adopted a two-phase study design where results from one cohort were validated in a second independent cohort. The exploratory analysis reviewed the survival outcomes of 1017 consecutive patients (with 3610 metastases) who underwent Gamma radiosurgery at the University of California, San Diego (UCSD)/San Diego Gamma Knife Center (SDGKC). Multivariate analysis was performed to identify prognostic factors. Results were validated using data derived from 2519 consecutive patients (with 17,498 metastases) treated with SRS at the Katsuta Hospital. RESULTS For the SDGKC cohort, the median overall survival of patients following SRS was 7 months. Two year follow-up data were available for 85% of the patients. Multivariate analysis found that patient age, Karnofsky Performance Status, systemic cancer status, tumour histology, number of metastasis and cumulative tumour volume independently associated with overall survival (p<0.001). All statistical associations were validated by multivariate analysis of data derived from the Katsuta Hospital cohort. CONCLUSIONS This is the first integrated study that defined prognostic factors for SRS-treated patients with cerebral metastases using an inter-institutional validation study design. The work establishes a model for collaborative interactions between large volume centers and provides prognostic variables that should be incorporated into future clinical trial design.

Radiation recall myositis in pediatric Ewing sarcoma

Radiation recall is a rare and poorly understood phenomenon, characterized by an acute inflammatory reaction within the previously irradiated area, triggered by a precipitating systemic agent. This reaction typically affects the skin, and radiation recall myositis in the absence of cutaneous involvement has rarely been described in the literature. In this report, we present two cases of radiation recall in pediatric Ewing sarcoma patients receiving successive proton radiotherapy and chemotherapy, with magnetic resonance imaging (MRI) of muscle edema within the prior radiation fields. Pediatr Blood Cancer 2012;59:570–572.