A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer.

OBJECTIVE: Ovarian cancer is one of the most deadly human cancers, resulting in over 15,000 deaths in the US each year. A reliable method that could predict disease outcome would improve care of patients with this disease. The main aim of this study is to identify novel prognostic biomarkers for advanced ovarian cancer. METHODS: We hypothesized that microRNAs (miRNAs) may predict outcome and have examined the prognostic value of these small RNA molecules on disease outcome prediction. miRNAs are a newly identified family of non-coding RNA genes, and recent studies have shown that miRNAs are extensively involved in the tumor development process. We have profiled the expression of miRNAs in advanced ovarian cancer using a novel PCR-based platform and correlated miRNA expression profiles with disease outcome. RESULTS: By performing miRNA expression profiling analysis of 55 advanced ovarian tumors, we have shown that three miR-200 miRNAs (miR-200a, miR-200b and miR-429) in the miR-200b-429 cluster are significantly associated with cancer recurrence and overall survival. Further target analysis indicates that these miR-200 miRNAs target multiple genes that are involved in cancer development. In addition, we have also shown that overexpression of this miR-200 cluster inhibits ovarian cancer cell migration. CONCLUSIONS: miR-200b-429 may be used as a prognostic marker for ovarian cancer outcome, and low-level expression of miR-200 miRNAs in this cluster predicts poor survival. In addition, our study suggests that miR-200 miRNAs could play an important regulatory role in ovarian cancer.

Combined intensity-modulated radiation therapy and brachytherapy in the treatment of cervical cancer.

PURPOSE: This treatment planning study compared pseudo-step-wedge intensity modulation (PSWIM), intensity-modulated radiation therapy (IMRT), and conventional external irradiation, all combined with brachytherapy, for treatment of patients with cervical cancer. METHODS AND MATERIALS: This was a prospective study of 10 patients treated with PSWIM delivering 50.4 Gy to the pelvic lymph nodes and 20 Gy to the cervical tumor. This treatment was compared with a conventional treatment plan with a four-field box to 45 Gy and to an IMRT plan delivering 45 Gy. In each case, brachytherapy was prescribed to a total Point A low-dose-rate equivalent dose of 85 Gy. Total doses to Points A, Point P, the bladder point, and the rectal point were calculated. Acute toxicity and treatment response were prospectively recorded. RESULTS: The mean PSWIM total low-dose-rate equivalent dose to Points A and P (97.3 Gy and 65.1 Gy, respectively) was significantly higher, the mean rectal dose was the same, and the mean bladder dose was higher than with IMRT or four-field box. No acute toxicity of greater Grade 2, as defined by the than Radiation Therapy Oncology Group, was experienced. The positron emission tomography-based treatment response compared favorably with our institutional experience. CONCLUSIONS: Use of PSWIM and brachytherapy delivers significantly more dose to the tumor and lymph nodes than do competing techniques. Rectal doses are comparable. Maximum bladder point doses are higher. Toxicity and tumor response are acceptable.

Evaluating the potential benefit of reduced planning target volume margins for low and intermediate risk patients with prostate cancer using real-time electromagnetic tracking.

PURPOSE: The aim of this study is to quantify and describe the feasibility, clinical outcomes, and patient-reported outcomes of reduced planning target volume (PTV) margins for prostate cancer treatment using real-time, continuous, intrafraction monitoring with implanted radiation frequency transponder beacons. METHODS AND MATERIALS: For this prospective, nonrandomized trial, the Calypso localization system was used for intrafraction target localization in 31 patients with a PTV margin reduced to 2 mm in all directions. A total of 1333 fractions were analyzed with respect to movement of the prostate, pauses and interruptions, and dosimetric data. Pre- and posttreatment quality-of-life scores were tracked at baseline, during treatment, and up to 24 months after treatment. RESULTS: The mean time of daily treatment was 10 minutes, with 96.1% of all treatments falling within a 20-minute treatment window standard. On average, beacon motion exceeded 3 mm during active treatment only 1.76% of the time. The average length of treatment interruption was 34.2 seconds, with an average of 1 interruption every 3.39 fractions. The displacement or excursion of the prostate was the greatest in the superior or inferior dimension (0.11 mm and 0.09 mm, respectively) and anterior or posterior dimension (0.07 mm and 0.13 mm, respectively), followed by the left or right dimension (0.05 mm and 0.06 mm, respectively). At 6 months, patients demonstrated a smaller change in Expanded Prostate Cancer Index Composite scores than the ProtecT comparator group (decreased short-term morbidity). However, in the Bowel and Urinary domains at 12 and 24 months, there was no significant difference. CONCLUSIONS: Our data confirm and support that the use of Calypso tracking with intensity modulated radiation therapy reliably provides minimal disruption to daily treatments and overall time of treatment, with the PTV only moving outside of a 3-mm margin < 2% of the time. The use of a 3-mm PTV margin provides adequate dosimetric coverage while minimizing genitourinary and gastrointestinal toxicity.

Treatment Trends for Stage I Testicular Seminoma in an Equal-Access Medical System.

BACKGROUND: The practice patterns for adjuvant therapies for stage I seminoma are rapidly evolving, and surveillance is currently preferred. How these recommendations have affected contemporary practice in an equal-access US population is unknown. MATERIALS AND METHODS: A total of 436 men diagnosed with clinical stage IA-IB seminoma from 2001 to 2011 were identified in the Automated Central Tumor Registry (ACTUR). The ACTUR is the cancer registry system for the Department of Defense. Logistic regression models analyzed the association between patient characteristics and adjuvant therapy. Overall and recurrence-free survival were determined from Kaplan-Meier analysis. RESULTS: The use of adjuvant radiotherapy in this population decreased significantly from 2001 to 2011. In 2001, 83.9% of patients received radiotherapy compared with only 24.0% in 2011. During that period, a concomitant increase occurred in the use of chemotherapy from 0% to 38.0%. A later year of diagnosis was significantly associated with a greater rate of receiving chemotherapy relative to radiotherapy (P < .001 for 2006-2011 vs. 2001-2005; relative rate ratio, 19.3; 95% confidence interval [CI], 8.04-46.13). A later year of diagnosis was not significantly associated with the receipt of surveillance (P = .412 for 2006-2011 vs. 2001-2005; odds ratio, 0.83; 95% CI, 0.54-1.29). Black race or age was not significantly associated with adjuvant therapy. With a median follow-up period of 4.7 years, the 5-year overall and recurrence-free survival rates were 98.0% and 77.0%, respectively. CONCLUSION: The use of adjuvant radiotherapy has been replaced by chemotherapy for clinical stage I testicular seminoma in an equal-access system. The lack of an increase in active surveillance in our cohort might represent overtreatment of the population.

Deep inspiration breath hold with electromagnetic confirmation of chest wall position for adjuvant therapy of left-sided breast cancer: Technique and accuracy.

PURPOSE: With most patients now living long after their breast cancer diagnosis, minimizing long-term side effects of breast cancer treatment, such as reducing late cardiac and pulmonary side effects of radiation therapy (RT), is particularly important. It is now possible to use an electromagnetic tracking system to allow real-time tracking of chest wall (CW) position during the delivery of RT. Here, we report our experience using electromagnetic surface transponders as an added measure of CW position during deep inspiration breath hold (DIBH). METHODS AND MATERIALS: We conducted a single-institution institutional review board-approved retrospective review of 15 female left-sided breast cancer patients treated between July 2012 and June 2013 with conventional whole breast radiation. We compared daily port films with treatment planning digitally reconstructed radiographs to establish daily setup accuracy, then used Calypso tracings to compare the position of the CW during the daily port film with the position of the CW during that day's treatment to determine the reproducibility of the breath hold position. Finally, we created competing treatment plans not using DIBH and used a paired t test to compare mean heart (MH) and left anterior descending (LAD) coronary artery dose between the 2 techniques. RESULTS: Mean total error (inter- and intrafraction) was dominated by interfraction error and was greatest in the longitudinal direction with a mean of 2.13 mm and 2 standard deviations of 8.2 mm. DIBH significantly reduced MH and LAD dose versus free breathing plans (MH, 1.26 Gy vs 2.84 Gy, P ≤ .001; LAD, 5.49 Gy vs 18.15 Gy, P ≤ .001). CONCLUSIONS: This study demonstrates that DIBH with electromagnetic confirmation of CW position is feasible, and allows potential improvement in the accurate delivery of adjuvant RT therapy for breast cancer.

Prospective clinical trial of positron emission tomography/computed tomography image-guided intensity-modulated radiation therapy for cervical carcinoma with positive para-aortic lymph nodes.

PURPOSE: To describe a more aggressive treatment technique allowing dose escalation to positive para-aortic lymph nodes (PALN) in patients with cervical cancer, by means of positron emission tomography (PET)/computed tomography (CT)-guided intensity-modulated radiation therapy (IMRT). Here, we describe methods for simulation and planning of these treatments and provide objectives for target coverage as well as normal tissue sparing to guide treatment plan evaluation. METHODS AND MATERIALS: Patients underwent simulation on a PET/CT scanner. Treatment plans were generated to deliver 60.0 Gy to the PET-positive PALN and 50.0 Gy to the PALN and pelvic lymph node beds. Treatment plans were optimized to deliver at least 95% of the prescribed doses to at least 95% of each target volume. Dose-volume histograms were calculated for normal structures. RESULTS: The plans of 10 patients were reviewed. Target coverage goals were satisfied in all plans. Analysis of dose-volume histograms indicated that treatment plans involved irradiation of approximately 50% of the bowel volume to at least 25.0 Gy, with less than 10% receiving at least 50.0 Gy and less than 1% receiving at least 60.0. With regard to kidney sparing, approximately 50% of the kidney volume received at least 16.0 Gy, less than 5% received at least 50.0 Gy, and less than 1% received at least 60.0 Gy. CONCLUSIONS: We have provided treatment simulation and planning methods as well as guidelines for the evaluation of target coverage and normal tissue sparing that should facilitate the more aggressive treatment of cervical cancer.