Impact of age on outcomes in young women with breast cancer.

BACKGROUND: In this study, we compared outcomes in young and very young patients with breast cancer (BC). MATERIALS AND METHODS: Between January 1990 to December 2010, 414 young women (age ≤35 years) with BC were registered in the radiotherapy (RT) outpatient department. Patients were divided into young (31-35 years) and very young (18-30 years). They were compared for clinical, pathological characteristics, and treatment-related factors such as RT and systemic therapy. Outcomes compared between the two groups were locoregional recurrence rate (LRR), local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and toxicities. LRFS, DFS, and OS were estimated using the Kaplan-Meier method. RESULTS: Out of 414 patients, 138 and 276 were very young and young, respectively. Clinical, pathological, and treatment characteristics were balanced between the two groups except for more patients in the young group who had pN3 disease and received hormonal therapy; 41 (15%) versus seven (5%) and 171 (62%) versus 62 (45%) in the very young group, respectively. Median follow-up was 84 months (range 12-363 months). LR was seen in 16 (11.6%) and 25 (9%) patients in the very young and young groups, respectively (p = 0.28). The hazard ratios for LR, disease recurrence, and death in the very young group relative to the young group were 1.11 (p = 0.25), 1.0 (p = 1.0), and 1.05 (p = 0.79), respectively. Estimated 10-year LRFS, DFS and OS were 80% versus 86%, 63% versus 61%, and 66% versus 64% in the very young and young groups, respectively. Lymphedema, cardiac toxicity, and second malignancy developed in seven (5%) versus 23 (8%), one (1%) versus three (1%), and seven (5%) versus 18 (7%) patients in the very young and young groups, respectively. CONCLUSION: In very young and young patients with BC, there was no significant difference in LRR, LRFS, DFS, or OS. Toxicities were also comparable between the two groups.

Impact of volume of irradiation on survival and quality of life in glioblastoma: a prospective, phase 2, randomized comparison of RTOG and MDACC protocols.

BACKGROUND: Though conformal partial-brain irradiation is the standard adjuvant treatment for glioblastoma, there is no consensus regarding the optimal volume that needs to be irradiated. European Organisation for Research and Treatment of Cancer (EORTC) and The University of Texas MD Anderson Cancer Center (MDACC) guidelines differ from the Radiation Therapy Oncology Group (RTOG) in their approach toward peritumoral edema, whereas RTOG and MDACC guidelines differ from EORTC in the concept of boost phase. A scarcity of randomized comparisons has resulted in remarkable variance in practice among institutions. METHODS: Fifty glioblastoma patients were randomized to receive adjuvant radiotherapy using RTOG or MDACC protocols. Apart from dosimetric and volumetric analysis, acute toxicities, recurrence patterns, progression-free survival (PFS), overall survival (OS), and quality of life (QoL) were compared using appropriate statistical tests. RESULTS: Both groups were comparable with respect to demographic characteristics. Dosimetric analysis revealed significantly lower boost-phase planning treatment volumes and V60 Gy in the MDACC arm (chi-squared, P = .001 and .013, respectively). No significant differences were observed in doses with respect to organs at risk, acute toxicity, or recurrence patterns (chi-squared, P > .05). On the log-rank test, median PFS (8.8 months vs 6.1 months, P = .043) and OS (17 months vs 12 months, P = .015) were statistically superior in the MDACC group.Age, extent of resection, and proportion of whole brain receiving prescription dose were associated with improved PFS and OS on regression analysis. QoL of patients was significantly better in the MDACC group in all domains except cognitive, as assessed with the EORTC Quality of Life Questionnaire (QLQ-C30) and Brain Cancer Module (QLQ-BN20) (general linear model, P < .05). CONCLUSIONS: Use of limited-margin MDACC protocol can potentially improve survival outcomes apart from QoL of glioblastoma patients, as compared with the RTOG protocol.

Hurdles in radiation planning for glioblastoma: Can delayed-contrast enhanced computed tomography be a potential solution?

OBJECTIVE: Conformal radiation is the standard of care in treatment of glioblastoma. Although co-registration of magnetic resonance imaging (MRI) with early contrast enhanced computed tomography (CECT) is recommended for target delineation by consensus guidelines, ground realities in developing countries often result in availability of less-than-ideal MR sequences for treatment planning. Purpose of this study is to analyze the impact of incorporation of delayed-CECT sequences for radiation planning in glioblastomas, as an adjunct or alternative to MRI. METHODS: Case records of all patients of glioblastoma treated at our center between 2011 and 2014 were retrospectively evaluated. Gross treatment volumes were delineated on T1 contrast MRI (m-GTV), early CECT (e-GTV) and delayed CECT (d-GTV); volumetric comparisons were made using repeated measures analysis of variance and pair-wise analysis. RESULTS: Although 96% of registered patients underwent postoperative MRI, only 38% of them had desirable sequences suitable for co-registration. Median duration between acquisition of postoperative MRI and surgery was 45 days (range, 33-60), whereas that between MRI and treatment-planning CT was 5 days (range, 1-10). Statistically significant differences (P < 0.0001) were obtained between mean volumes of e-GTV (41.20cc), d-GTV (58.09cc) and m-GTV (60.52cc). Although the mean GTV increased by 46% between early CECT and MRI, the difference was only 4% between delayed CECT and MRI. CONCLUSION: Delayed CECT is superior to early CECT for co-registration with MRI for target delineation, especially when available MR sequences are less-than-ideal for treatment planning, and can be considered as the most appropriate adjunct as well as an alternative to MRI, compared to early CECT.

Biomarkers in triple negative breast cancer: A review.

Breast cancer is an intrinsically heterogeneous disease. In the world about 1 million cases of breast cancer are diagnosed annually and more than 170000 are triple-negative. Characteristic feature of triple negative breast cancer (TNBC) is that it lacks expression of oestrogen, progesterone and human epidermal growth factor receptor-2/neu receptors. They comprise 15%-20% of all breast cancers. We did a systematic review of PubMed and conference databases to identify studies published on biomarkers in TNBC. We included studies with biomarkers including: Epidermal growth factor receptor, vascular endothelial growth factor, c-Myc, C-kit and basal cytokeratins, Poly(ADP-ribose) polymerase-1, p53, tyrosinase kinases, m-TOR, heat and shock proteins and TOP-2A in TNBC. We also looked for studies published on synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. TNBC is a complex disease subtype with many subclasses. Majority TNBC have a basal-like molecular phenotype by gene expression profiling. Their clinical and pathologic features overlap with hereditary BRCA1 related breast cancers. Management of these tumours is a challenge to the clinician because of its aggressive behaviour, poor outcome, and absence of targeted therapies. As the complexity of this disease is being simplified over time new targets are also being discovered for the treatment of this disease. There are many biomarkers in TNBC being used in clinical practice. Biomarkers may be useful as prognostic or predictive indicators as well as suggest possible targets for novel therapies. Many targeted agents are being studied for treatment of TNBC.

Pediatric astroblastoma: a rare case with a review of the literature.

Astroblastoma is a rare glial tumor with uncertain histopathological origin and unpredictable clinical behavior. We present a case of an 11-year-old girl who presented with headache and blurring of vision for 2 months. A well-demarcated mass was found in the right frontoparietal lobe on a brain MRI. The patient was treated with total tumor resection followed by postoperative radiotherapy. Histologically, the features were suggestive of high-grade astroblastoma. The patient is alive and disease free 23 months after surgery. The characteristic radiological and histopathological features and treatment of this case are described with a literature review.

Primary sinonasal malignant melanoma: a clinicopathologic and prognostic study.

We conducted a retrospective study to evaluate the clinicopathologic features and prognostic factors associated with primary sinonasal malignant melanoma. We reviewed the records of 10 patients-7 men and 3 women, aged 35 to 70 years (mean: 51.4)-who had been treated at our referral center over a 9-year period. The tumors were located in the nasal cavity in 7 patients and in a paranasal sinus in the other 3. Medial maxillectomy was performed in 4 patients, wide local excision in 3, and endoscopic excision in 2; the remaining patient, who had presented with a liver metastasis, received chemotherapy and palliative local radiotherapy. Two patients who presented with a neck node metastasis also underwent concurrent radical neck dissection. Follow-up ranged from 8 to 70 months (median: 25). Only 4 patients remained alive through the duration of follow-up. The 2- and 5-year survival rates were 60 and 40%, respectively. Based on the findings of our small study, we conclude that primary sinonasal malignant melanoma carries a generally poor prognosis despite aggressive treatment. The primary cause of death in our series was a distant metastasis (n = 5) despite adequate locoregional control in most cases. This finding confirms the aggressive nature of this disease. Other factors that appeared to be associated with a poor prognosis were (1) older age, (2) a primary tumor location in a paranasal sinus, (3) an advanced tumor stage, (4) an external approach to surgery, and (5) the absence of adjuvant radiotherapy.

Nonbreast second malignancies after treatment of primary breast cancer.

PURPOSE: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. METHODS AND MATERIALS: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. RESULTS: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. CONCLUSION: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.