Incidence of Brain Metastases in Nonmetastatic and Metastatic Breast Cancer: Is There a Role for Screening?

BACKGROUND: Current National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines recommend against screening breast cancer patients for asymptomatic brain metastases. Because brain metastases are a major cause of morbidity and mortality from breast cancer, we undertook a literature review to ascertain whether there might be a role for brain metastases screening in high-risk patient subgroups. MATERIALS AND METHODS: A literature search was conducted on the OvidSP platform in the MedLine database, using MeSH terms and subject headings related to breast cancer, brain metastases, and incidence. The search was conducted without language or publication restrictions, and included articles indexed from January 1, 2006 to June 10, 2018. Experimental and observational studies that reported the incidence of brain metastases in patients with nonmetastatic or metastatic breast cancer were included. RESULTS: One hundred seventy studies were identified, with 33 included in the final analysis. Among nonmetastatic breast cancer patients, incidence of brain metastases as site of first recurrence per year of median follow-up ranged from 0.1% to 3.2%. Although incidence of brain metastases was much higher among the metastatic breast cancer population overall, it was particularly high among metastatic HER2-overexpressing (HER2+) and triple-negative populations, ranging between 22% and 36% for the former, and 15%-37% for the latter in the absence of screening. CONCLUSION: In patients with nonmetastatic breast cancer, screening for asymptomatic brain metastases cannot currently be justified. However, due to the high incidence of brain metastases among patients with metastatic HER2+ and triple-negative breast cancer, studies to determine the value of screening for brain metastases should be undertaken in these subgroups.

Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer.

PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. RESULTS: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. CONCLUSION: Cisplatin can be safely delivered with 5-FU-based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study.

PURPOSE: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). METHODS AND MATERIALS: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. RESULTS: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. CONCLUSIONS: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

Complementary and alternative medicine use among women receiving chemotherapy for ovarian cancer in 2 patient populations.

OBJECTIVE: The authors evaluated attitudes toward complementary and alternative medicine (CAM) use in 2 populations of women receiving chemotherapy for epithelial ovarian cancer (EOC). METHODS: Women with EOC currently being treated with chemotherapy at 2 tertiary cancer centers, in Canada and the United Kingdom, completed a self-administered questionnaire on attitudes and perceptions of CAM and types of CAM used within the previous month. RESULTS: One hundred ninety-two patients (94 from Canada, 98 from United Kingdom) completed the questionnaire. Overall, 85 women (44%) were identified as CAM users. Complementary and alternative medicine use was more common among Canadian women (52%) compared with women from the United Kingdom (37%), P = 0.02. Participants used 71 different types of CAM, the majority (61%) taking multiple CAM. The frequency of CAM use was the same in primary compared with recurrent disease. Eighty-nine percent of CAM users considered it important for their oncologist to be aware of CAM use. Canadian women, however, were less likely to inform their physician (Canada: 50%; United Kingdom: 81%), P = 0.02. Motivations for CAM use were the same in both populations including assist healing (60%), boost the immune system (57%), improve quality of life (48%), and relieve symptoms (45%). Thirteen percent thought CAM could cure cancer, whereas 17% thought it would prevent recurrence. CONCLUSIONS: Complementary and alternative medicine use is common in women receiving chemotherapy for EOC. Increasingly, interactions between CAM and prescribed medication are being identified. Oncologists should be aware and actively inquire about CAM use. Although patterns of CAM use differed, the motivation for starting CAM was similar, highlighting the need to address supportive care in all patients.

Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010.

OBJECTIVES: Recent literature has highlighted histological types of ovarian carcinoma as distinct diseases, each with unique clinical and molecular features. Historically, the diagnosis of ovarian clear cell carcinoma (CCC) has been of concern to both patients and physicians due to reports that CCC is associated with a worse prognosis than the more common serous type of ovarian carcinoma (HGSC). This review discusses the unique features of ovarian CCC. METHODS: In June of 2010, a group of researchers and clinicians convened in Vancouver to review and discuss the clinical, pathological, molecular, and treatment-related features of CCC. RESULTS: CCC is the second most common type of ovarian epithelial cancer, representing 5-25% of ovarian carcinomas. It is characterised by its association with endometriosis, and frequent mutations of ARID1A and PIK3CA. Low-stage CCC appears to have a better outcome than stage matched HGSC, while the opposite is true for high-stage disease, suggesting that the current standard treatments applied to HGSC are ineffective for CCC. CONCLUSIONS: Ovarian CCC is highly distinct from HGSC, and a clearer understanding of the basic biology of this disease is needed. Alternative therapies should be explored: irradiation and targeting disease-specific molecular markers should be examined in greater detail. Finally, novel approaches to clinical trial design are needed due to the smaller numbers of patients affected.

A multicenter phase II study of "adjuvant" irinotecan following resection of colorectal hepatic metastases.

OBJECTIVES: This study evaluates the efficacy and toxicity of single-agent irinotecan following hepatectomy for metachronous colorectal metastases, and examines the predictive value of p27 and p53 expression and of microsatellite instability (MSI) status. METHODS: Twenty-nine patients, previously treated with 5-fluorouracil, with operable hepatic colorectal metastases underwent hepatectomy and received adjuvant irinotecan (thrice weekly) for 6 planned cycles. Metastases were examined for p53 and p27 expression by immunohistochemistry and for MSI using mono- and dinucleotide markers. RESULTS: The starting dose of irinotecan was 350 mg/m2 (in 3 patients), 300 mg/m2 (n = 14), and 250 mg/m2 (n = 12). Four patients failed to complete 6 cycles (2 progressive disease and 2 toxicity). Grade > or =3 toxicity was experienced in 8% of cycles (13 of 165). The estimated median relapse-free survival (RFS) was 45.2 months. RFS at 18 months was estimated to be 59% (95% confidence interval [CI], 43-80), 2-year overall survival (OS) was 85% (95% CI, 72-99.8), and the median follow-up was 27.9 months. Six patients (21%) have died; median OS has not been reached. In univariate analyses, p27 and MSI status were not predictive for RFS while p53 approached statistical significance (P = 0.051). Duration of chemotherapy was the only significant predictive factor (P = 0.006). CONCLUSION: The tolerability of this regimen after major liver resection supports further evaluation of irinotecan-based adjuvant chemotherapy in this group of patients.