Clinical outcomes and patterns of care in the treatment of carcinosarcoma of the breast

Purpose: Carcinosarcoma of the breast is a rare yet highly aggressive tumor accounting for \u3c1% of all breast cancers, for which guidance on optimal management and prognosis are sparse. The purpose of this study was to investigate population-based treatment patterns and overall survival (OS) outcomes in patients with this diagnosis. Materials and Methods: We queried the National Cancer Database for patients diagnosed with carcinosarcoma of the breast. All patients included were treated with surgery in the form of mastectomy or lumpectomy, with or without chemotherapy and/or radiation therapy. Patients with metastatic disease were excluded. Kaplan-Meier analysis was used to estimate OS. Univariate and multivariable Cox analyses were used to determine predictive factors of OS. Results: A total of 329 patients from 2004 to 2012 were identified. Median age at diagnosis was 58 years (range, 24-90). Patients had T1 (21%), T2 (44%), T3 (25%), or T4 disease (10%). Most patients were node-negative at diagnosis (77%). Breast conservation surgery was utilized in 33% of patients. Chemotherapy was used in 66% of patients. Less than half (44%) of patients received radiation therapy to a median dose of 50.4 Gy (range 35-56 Gy), with a median 10 Gy boost used in 76%. With a median follow-up of 40.0 months, 3- and 5-year OS for all patients was 74% and 60%, respectively. Kaplan-Meier estimates revealed the 3-yr OS was 80% in patients receiving chemotherapy vs 59% without chemotherapy (P \u3c 0.001). The 3-yr OS was 82% in patients receiving RT vs 66% without RT (P = 0.001). On multivariable analysis, OS was significantly influenced by Charlson-Deyo comorbidity index, insurance status, clinical T stage, surgical margin status, and treatment group, with trimodality therapy (HR: 0.45, 95% CI: 0.27-0.78; P = 0.004) and surgery plus CT (HR: 0.54, 95% CI: 0.33-0.90; P = 0.02) being associated with the greatest OS. Logistic regression revealed only younger patients were more likely to receive trimodality therapy. Conclusions: Carcinosarcoma of the breast is associated with relatively poor rates of OS. The addition of CT and RT to surgery improves OS. Trimodality therapy and surgery plus CT were associated with the greatest OS compared to surgery alone

Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: An integrated clinicopathologic and molecular analysis

BackgroundManagement of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset.MethodsChildren with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation.ResultsOne hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021).ConclusionA high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation

Tectal glioma as a distinct diagnostic entity: a comprehensive clinical, imaging, histologic and molecular analysis

Abstract Tectal glioma (TG) is a rare low-grade tumor occurring predominantly in the pediatric population. There has been no detailed analysis of molecular alterations in TG. Risk factors associated with inferior outcome and long-term sequelae of TG have not been well-documented. We retrospectively studied TGs treated or referred for review at St. Jude Children’s Research Hospital (SJCRH) between 1986 and 2013. Longitudinal clinical data were summarized, imaging and pathology specimen centrally reviewed, and tumor material analyzed with targeted molecular testing and genome-wide DNA methylation profiling. Forty-five patients with TG were included. Twenty-six (57.8%) were male. Median age at diagnosis was 9.9 years (range, 0.01–20.5). Median follow-up was 7.6 years (range, 0.5–17.0). The most common presenting symptoms were related to increased intracranial pressure. Of the 22 patients treated at SJCRH, 19 (86%) required cerebrospinal fluid diversion and seven (32%) underwent tumor-directed surgery. Five patients (23%) received radiation therapy and four (18%) systemic therapy. Ten-year overall and progression-free survival were 83.9 ± 10.4% and 48.7 ± 14.2%, respectively. Long-term morbidities included chronic headaches, visual symptoms and neurocognitive impairment. Lesion ≥3cm2, contrast enhancement and cystic changes at presentation were risk factors for progression. Among those with tumor tissue available, 83% showed growth patterns similar to pilocytic astrocytoma and 17% aligned best with diffuse astrocytoma. BRAF duplication (a marker of KIAA1549-BRAF fusion) and BRAF V600E mutation were detected in 25% and 7.7%, respectively. No case had histone H3 K27M mutation. DNA methylation profile of TG was distinct from other brain tumors. In summary, TG is an indolent, chronic disease with unique clinical and molecular profiles and associated with long term morbidities. Large size, contrast enhancement and cystic changes are risk factors for progression

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy

To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions

Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents

Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results: A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P = .04). Conclusions: SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery

OBJECTIVE The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non.small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31.86 years). The median follow-up was 7.6 months (range 0.5.81.6 months), and the median survival was 9.3 months (range 1.3.81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was . and \u3c 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 . and \u3c 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 . and \u3c 25%, respectively. Lesions \u3e 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 . and \u3c 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 . 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation

Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery

OBJECTIVE The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non.small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31.86 years). The median follow-up was 7.6 months (range 0.5.81.6 months), and the median survival was 9.3 months (range 1.3.81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was . and \u3c 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 . and \u3c 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 . and \u3c 25%, respectively. Lesions \u3e 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 . and \u3c 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 . 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation