Andrea Lo

Long-Term Outcomes and Complications in Patients With Craniopharyngioma: The British Columbia Cancer Agency Experience

PURPOSE We report long-term outcomes and complications of craniopharyngioma patients referred to our institution. METHODS AND MATERIALS Between 1971 and 2010, 123 consecutive patients received primary treatment for craniopharyngioma in British Columbia and were referred to our institution. The median age was 30 years (range, 2-80 years). Thirty-nine percent of patients were treated primarily with subtotal resection (STR) and radiation therapy (RT), 28% with STR alone, 15% with gross total resection, 11% with cyst drainage (CD) alone, 5% with CD+RT, and 2% with RT alone. Eight percent of patients received intracystic bleomycin (ICB) therapy. RESULTS Median follow-up was 8.9 years, and study endpoints were reported at 10 years. Ten-year Kaplan-Meier progression-free survival (PFS) was 46%. Patients treated with STR+RT or CD+RT had the highest PFS (82% and 83%, respectively). There were no significant differences between PFS after adjuvant versus salvage RT (84% vs 74%, respectively; P=.6). Disease-specific survival (DSS) was 88%, and overall survival (OS) was 80%. Primary treatment modality did not affect DSS or OS, while older age was a negative prognostic factor for OS but not DSS. Kaplan-Meier rates for visual deterioration, anterior pituitary hormone deficiency, diabetes insipidus, seizure disorder, and cerebrovascular events (CVE) due to treatment, not tumor progression, were 27%, 76%, 45%, 16%, and 11%, respectively. The CVE rate was 29% in patients who received ICB compared to 10% in those who did not (P=.07). CONCLUSIONS We report favorable PFS in patients with craniopharyngioma, especially in those who received RT after surgery. DSS and OS rates were excellent regardless of primary treatment modality. We observed a high incidence of hypopituitarism, visual deterioration, and seizure disorder. Eleven percent of patients experienced CVEs after treatment. There was a suggestion of increased CVE risk in patients treated with ICB.

Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

PURPOSE To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. METHODS AND MATERIALS Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. RESULTS Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. CONCLUSIONS The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA>1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

The Impact of Peer Review of Volume Delineation in Stereotactic Body Radiation Therapy Planning for Primary Lung Cancer: A Multicenter Quality Assurance Study

Introduction: Although the value of peer review is increasingly recognized, there is little research documenting its impact in the setting of stereotactic body radiation therapy (SBRT) for lung cancer. This study determines the dosimetric effect of peer review of tumor and normal tissue contouring in lung SBRT planning. Methods: Forty anonymized lung SBRT plans were retrospectively evaluated post treatment. Each plan was independently reviewed by two to three radiation oncologists using established institutional guidelines. For each structure, reviewers recorded recommendations for “no change,” “minor change,” “major change,” or “missing contour” and provided a modified or new contour as needed. Dose–volume histograms were analyzed for dosimetric violations. Results: Among 472 contoured structures evaluated, recommendations from peer review were 107 major change (23%), 176 minor change (37%), 157 no change (33%), and 32 missing (7%). Common major changes involved the skin (n = 20), heart (n = 18), and proximal bronchial tree (n = 15). Dose constraints were not achieved for 25 new or recontoured structures (5%), of which 17 involved the planning target volume (PTV). Among cases with PTV violations, the mean prescription dose coverage to the modified PTVs was 90%, compared with the protocol standard of greater than or equal to 95% coverage. The remaining violations involved the ribs (n = 5), spinal canal (n = 2), and heart (n = 1). Conclusions: Peer review of structure contouring resulted in significant changes in lung SBRT plans. Recontouring of several plans revealed violations of dose limits, most often involving inadequate PTV coverage. Peer review, especially of target volume delineation, is warranted to improve consistency and quality in lung SBRT planning.

Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast

BACKGROUND In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allreds subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level. PATIENTS AND METHODS From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras. RESULTS Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P < 0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P < 0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET. CONCLUSIONS ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

Patterns of Recurrence After Low-Dose-Rate Prostate Brachytherapy: A Population-Based Study of 2223 Consecutive Low- and Intermediate-Risk Patients

OBJECTIVES This study examined patterns of recurrence after low-dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). METHODS AND MATERIALS A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. RESULTS At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse. In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. CONCLUSIONS In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.

A Cross-Sectional Cohort Study of Cerebrovascular Disease and Late Effects After Radiation Therapy for Craniopharyngioma.

The study objective was to describe radiation‐induced vascular abnormalities, stroke prevalence, and stroke risk factors in survivors of childhood craniopharyngioma.

A Patient-centered Approach to Evaluate the Information Needs of Women With Ductal Carcinoma In Situ.

Objective: To evaluate the information needs of ductal carcinoma in situ (DCIS) patients. Methods: Four focus groups involving 24 previously treated DCIS patients were conducted to develop a comprehensive list of questions they felt were important to have answered at the time of diagnosis. Using a survey, a separate group of patients treated for DCIS then rated the importance of having each of these questions addressed before treatment decision making. Response options were “essential,” “desired,” “not important,” “no opinion,” and “avoid.” For each essential/desired question, respondents specified how addressing it would help them: “understand,” “decide,” “plan,” “not sure,” or “other.” Results: Focus group participants generated 117 questions used in the survey. Fifty-seven patients completed the survey (55% response rate). Respondents rated a median of 66 questions as essential. The most commonly cited reason for rating a question essential was to “understand,” followed by to “decide.” The top questions women deemed essential to help them understand were disease specific, whereas the top questions deemed essential to help women decide were predominantly treatment specific, pertaining to available options, recurrence and survival outcomes, and timelines to decide and start treatment. Conclusions: DCIS patients want a large number of questions answered, mostly for understanding, and also for deciding and planning. A core set of questions that most patients consider essential for decision making has been formulated and may be used in the clinical setting and in research to develop educational resources and decision-making tools specific to DCIS.

“Assessing the methodological quality of systematic reviews in radiation oncology: A systematic review”

OBJECTIVE The objective of our study was to evaluate the methodological quality of systematic reviews and meta-analyses in Radiation Oncology. METHODS A systematic literature search was conducted for all eligible systematic reviews and meta-analyses in Radiation Oncology from 1966 to 2015. Methodological characteristics were abstracted from all works that satisfied the inclusion criteria and quality was assessed using the critical appraisal tool, AMSTAR. Regression analyses were performed to determine factors associated with a higher score of quality. RESULTS Following exclusion based on a priori criteria, 410 studies (157 systematic reviews and 253 meta-analyses) satisfied the inclusion criteria. Meta-analyses were found to be of fair to good quality while systematic reviews were found to be of less than fair quality. Factors associated with higher scores of quality in the multivariable analysis were including primary studies consisting of randomized control trials, performing a meta-analysis, and applying a recommended guideline related to establishing a systematic review protocol and/or reporting. CONCLUSIONS Systematic reviews and meta-analyses may introduce a high risk of bias if applied to inform decision-making based on AMSTAR. We recommend that decision-makers in Radiation Oncology scrutinize the methodological quality of systematic reviews and meta-analyses prior to assessing their utility to inform evidence-based medicine and researchers adhere to methodological standards outlined in validated guidelines when embarking on a systematic review.

Documentation of Late-Effects Risks and Screening Recommendations for Adolescent and Young Adult Central Nervous System, Soft Tissue, or Bone Tumor Survivors Treated with Radiotherapy in British Columbia, Canada

PURPOSE To assess the documentation of late-effects (LE) risks and screening recommendations in medical records of adolescent and young adult central nervous system (CNS), soft tissue, and bone tumor survivors. METHODS The medical records of all patients diagnosed with a CNS neoplasm, an arteriovenous malformation, a soft tissue, and bone tumor, at ages 15-39 years, treated between 1985 and 2010 with radiation therapy in the province of British Columbia, Canada, surviving >5 years, alive, and discharged to the community were assessed. The documentation of LE risks and screening recommendations were analyzed descriptively. RESULTS In the medical records of 132 CNS tumor survivors and 94 soft tissue or bone tumor survivors, 15% and 13% included no documentation of LE risks, 21% and 22% included only nonspecific documentation, and 64% and 65% minimal documentation, respectively. Documentation of at least one specific LE risk increased significantly among CNS tumor patient charts (from 29% in 1980-1989, to 67% in 1990-1999, to 88% in 2000-2010, χ2 [2, N = 132] = 32.257, p < 0.000) and soft tissue or bone tumor patient charts (from 47% [1980-1989] to 56% [1990-1999] to 78% [2000-2010], χ2 [2, N = 94] = 6.702, p = 0.035). There was no documentation of a screening recommendation in 75% of CNS tumor patient charts and 91% of soft tissue and bone tumor charts. CONCLUSION The documentation of LE risks and screening recommendations has been limited, highlighting the need to improve written communication with primary care providers.

Quantification of large scale DNA organization for predicting prostate cancer recurrence: DNA Organization Predicts Recurrence

This study investigates whether Genomic Organization at Large Scales (which we propose to call GOALS) as quantified via nuclear phenotype characteristics and cell sociology features (describing cell organization within tissue) collected from prostate tissue microarrays (TMAs) can separate biochemical failure from biochemical nonevidence of disease (BNED) after radical prostatectomy (RP). Of the 78 prostate cancer tissue cores collected from patients treated with RP, 16 who developed biochemical relapse (failure group) and 16 who were BNED patients (nonfailure group) were included in the analyses (36 cores from 32 patients). A section from this TMA was stained stoichiometrically for DNA using the Feulgen–Thionin methodology, and scanned with a Pannoramic MIDI scanner. Approximately 110 nuclear phenotypic features, predominately quantifying large scale DNA organization (GOALS), were extracted from each segmented nuclei. In addition, the centers of these segmented nuclei defined a Voronoi tessellation and subsequent architectural analysis. Prostate TMA core classification as biochemical failure or BNED after RP using GOALS features was conducted (a) based on cell type and cell position within the epithelium (all cells, all epithelial cells, epithelial >2 cell layers away from basement membrane) from all cores, and (b) based on epithelial cells more than two cell layers from the basement membrane using a Classifier trained on Gleason 6, 8, 9 (16 cores) only and applied to a Test set consisting of the Gleason 7 cores (20 cores). Successful core classification as biochemical failure or BNED after RP by a linear classifier was 75% using all cells, 83% using all epithelial cells, and 86% using epithelial >2 layers. Overall success of predicted classification by the linear Classifier of (b) was 87.5% using the Training Set and 80% using the Test Set. Overall success of predicted progression using Gleason score alone was 75% for Gleason >7 as failures and 69% for Gleason >6 as failures.