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Purpose: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions., Methods and Materials: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers., Results: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus., Conclusions: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters., Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years., Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067)., Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To define the minimal number of pO(2) measurements, with 90% sensitivity and 90% specificity, needed to categorize cervical tumors as either hypoxic or oxic., Methods and Materials: Using Eppendorf oxygen probe data from our ongoing prospective trial, we simulated the measurement of tumor oxygenation with a smaller number of data points in 135 patients with cervical cancer. The hypoxic proportion, defined as the percentage of pO(2) values <5 mm Hg (HP5), was calculated for each tumor. Hypoxic tumors were defined as those with a median HP5 >50%, and tumors with normal oxygen levels as those with a median HP5 < or =50%. A small number of pO(2) measurements were randomly selected from the Eppendorf measurements in each tumor, or per Eppendorf track, and used to define the tumor as hypoxic or oxic. The sensitivity and specificity were calculated, considering the classification as given by the complete set of Eppendorf measurements as the reference standard., Results: The probability of falsely classifying the tumor decreased as the selected number of pO(2) measurements per tumor increased, and at 16 measurements was approximately 10%. Adding additional measurements per tumor beyond 24 improved the ability to classify the tumor accurately only slightly. The probability of falsely classifying the tumor decreased as the pO(2) measurements per track increased. At five measurements per track, the probability of falsely classifying the tumor was approximately 9%., Conclusion: Approximately 20 measurements per tumor, or five measurements per track, using the Eppendorf pO(2) histograph, are sufficient to categorize cervical tumors as hypoxic or oxic. The results of this study will serve as a guide for research clinicians in the use of this and other systems in the assessment of tumor oxygenation in humans.

Purpose: To determine whether breast pain affects quality of life (QOL) after breast-conserving surgery and tamoxifen (TAM) with or without adjuvant breast radiotherapy (RT)., Methods and Materials: A randomized clinical trial was carried out at the Princess Margaret Hospital between 1992 and 2000 to evaluate the need for breast RT in addition to TAM in women >or=50 years treated with breast-conserving surgery for T1-T2N0 breast cancer. A companion study to assess breast pain was carried out during the last 2 years of the randomized clinical trial. The short-form McGill Pain Questionnaire (SF-MPQ), the European Organization for Research and Treatment of Cancer (EORTC) QOL (QLQ-C30) and EORTC breast cancer module (QLQ-BR23) questionnaires were completed by patients within 1 week of randomization in the randomized clinical trial (baseline) and at 3, 6, and 12 months., Results: Eighty-six patients participated in the breast pain study; 41 received RT plus TAM and 45 received TAM alone. The median age was 70 years (range 51-80). The baseline pain and QOL scores were similar for the two groups. No significant difference was found between the two groups for each scale of the QLQ-C30 and QLQ-BR23 questionnaires at 3, 6, or 12 months (p >0.100), except that at 12 months, the score for role function (QLQ-C30) was higher in the RT plus TAM group than in the RT-only group (p = 0.02). At 3 months, the difference between the mean scores for the SF-MPQ was 0.553 (p = 0.47). At 12 months, the pain scores had decreased in both groups; the difference was 0.199 (p = 0.71). The number of breast operations or surgical complications did not correlate with breast pain in either group. Acute RT toxicity scores did not correlate with breast pain or QOL scores at 12 months., Conclusion: These results suggest that breast RT does not significantly contribute to breast pain or adversely impact the QOL up to 12 months after treatment in postmenopausal patients with node-negative breast cancer who take TAM.

Purpose: To investigate the relations between hypoxia-inducible factor-1 (HIF-1), tumor oxygenation, and clinical correlates in patients with locally advanced carcinoma of the uterine cervix., Methods and Materials: Biopsies from 42 patients with invasive cervical carcinoma and previous polarographic O2 measurements were assessed for the expression of HIF-1alpha using digitized microscopic imaging and analysis., Results: The HIF-1alpha expression levels ranged from <0.1% to 10.7% of the total tumor area; the positive staining was localized exclusively to the nuclei. Three distinct arrangement patterns of HIF-1alpha-positive cells in relation to blood vessels were identified using spatial image mapping: (1) most HIF-1alpha-positive cells were located within the typical oxygen diffusion distance in tissue (< or =150 microm to the nearest blood vessel); (2) most HIF-1alpha-positive cells were located in the vicinity (< or =60 microm) of the blood vessels; and (3) no apparent spatial relationship was found between HIF-1alpha-positive cells and blood vessels. A statistically significant association was found between HIF-1alpha expression and tumor oxygenation (Spearman correlation coefficient = 0.4, p <0.01), as determined with the Eppendorf pO2 histograph. No correlation was found between the level of HIF-1alpha expression and patient outcome, using disease-free survival as the end point., Conclusion: Our results suggest that HIF-1alpha expression may represent a useful biologic marker for hypoxia in uterine cervical cancer.