Simulation dataset of thermal and epithermal neutron self-shielding correction factors for 186W(n,γ)187W reaction rate experiments using tungsten foil targets.

In the experiments of neutron interaction with research samples, the incident neutron energy spectrum, distribution inside the irradiating sample volume, is affected by the unexpected neutron self-shielding effects. The nature of these effects is due to the formation and thickness of the irradiating sample, which significantly causes neutron self-absorption and multiple scattering inside the sample volume. The datasets presented in this article showed the thermal (Gth) and epithermal (Gepi) neutron self-shielding correction factors for the 186W(n,γ)187W neutron capture reaction rate in irradiating tungsten (W) foil samples with different thicknesses. The simulations were performed for three models of surface neutron source's geometries and relative orientations of the irradiating foil samples of isotropic cylinder surface neutron source with foil sample along to the center line, isotropic cylinder neutron source with foil sample flat to the center line, and isotropic spherical neutron source with foil sample placed at the center point. The range of sample thicknesses was from 10 µm to 2.5 mm. The uncertainties for each data point are also reported in the data table, making it more convenient for reuse in related experiments or evaluations.

De novo Versus Secondary Dedifferentiated Chordomas: A Population-Based Analysis and Integrated Individual Participant Data Meta-Analysis.

OBJECTIVE: There is a lack of data about the clinicopathological and molecular characteristics of de novo versus secondary dedifferentiated chordoma (DC). This integrated study aimed to investigate the similarities and differences in clinicopathological manifestations, prognoses, and molecular profiles of these 2 subtypes. METHODS: We accessed the Surveillance, Epidemiology, and End Results (SEER) Program for DC cases from 1975 to 2020. Three electronic databases were also searched for additional DCs. Individual patient data of DC patients from SEER and published literature were combined in integrated analyses. RESULTS: After excluding duplicated patients, we identified 14 and 116 DC patients from SEER and published literature, respectively. There were 74 de novo, 39 secondary, and 18 cases with unknown origin. Our results showed that de novo and secondary DCs were not statistically different in terms of age, gender, primary location, tumor size, distant metastasis at diagnosis, extent of resection, and chemotherapy receipt. There was limited available molecular data for de novo and secondary DCs, though examples TP53 mutations were found in both. In addition, the rates of tumor relapse, metastasis during follow-up, and patient mortality were also comparable between the 2 groups. In the multivariate Cox regression model, we demonstrated that gross total removal and radiotherapy use were associated with prolonged survival of DCs. CONCLUSIONS: De novo and secondary DCs were statistically comparable in terms of patient demographics, clinical manifestations, and prognoses. Gross total excision and radiotherapy were optimal treatments associated with better outcomes of DC patients.

Primary Thyroid Mucoepidermoid Carcinoma (MEC) Is Clinically, Prognostically, and Molecularly Different from Sclerosing MEC with Eosinophilia: A Multicenter and Integrated Study.

Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p < 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p < 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.

Simultaneously Both Expression of LMP-1 and Methylation of E-cadherin: Molecular Biomarker in Stage IV of Nasopharyngeal Carcinoma Patients.

The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.

Survival Outcomes Following Discontinuation of Ipilimumab and Nivolumab for Advanced Melanoma in a Population-based Cohort.

AIMS: Induction ipilimumab and nivolumab followed by maintenance nivolumab improve overall survival compared with ipilimumab alone in patients with advanced melanoma, but immune-related adverse events (irAE) occur commonly. The need for induction discontinuation because of irAE and the relationship between irAE and survival in non-trials patients are unclear. MATERIALS AND METHODS: Patients with unresectable stage III-IV melanoma receiving first-line combination immunotherapy at one of six centres between December 2017 and February 2020 outside of trials were identified retrospectively. Landmark 12-week Kaplan-Meier analyses and log-rank tests were used to evaluate associations between discontinuation of induction therapy on overall survival and time to treatment failure (TTF). Multivariable analysis of factors influencing overall survival and TTF was undertaken. RESULTS: Among 95 patients, the median age was 62 years, 38.9% had Eastern Cooperative Oncology Group performance status ≥1 and 22.1% had brain metastases. The median follow-up for the whole cohort was 19.8 months by the reverse Kaplan-Meier method. Any grade and grade 3-4 irAE were noted in 78.9% and 44.2% of the cohort, respectively. 44.2% of patients completed induction immunotherapy, whereas 41.1% did not due to irAE. Twelve-week landmark overall survival and TTF were similar in patients who completed induction versus those who did not due to irAE. On multivariable analysis, any grade irAE (versus none) was associated with longer overall survival (hazard ratio = 0.35, 95% confidence interval 0.15-0.82, P = 0.02) and TTF (hazard ratio = 0.38, 95% confidence interval = 0.17-0.81, P = 0.01). Grade 3-4 irAE correlated with longer TTF (hazard ratio = 0.45, 95% confidence interval = 0.20-1.01, P = 0.05). CONCLUSION: In this population-based cohort, discontinuation of induction immunotherapy as a result of irAE did not adversely affect overall survival or TTF. irAE observed during ipilimumab and nivolumab induction were associated with improved survival outcomes.

Malignant thyroid teratoma: an integrated analysis of case series/case reports.

Malignant thyroid teratoma (MTT) is a very rare thyroid malignancy. These neoplasms have been reported only in case reports and small-sized case series so far. In this study, we searched for MTTs in the Surveillance, Epidemiology, and End Result (SEER) program during 1975-2016. Subsequently, we incorporated the SEER data with published MTT cases in the literature to analyze the characteristics and prognostic factors of MTTs. Integrated data were analyzed using chi-square or Fisher's exact test for categorical covariates, and t-test or Mann-Whitney test for continuous variables. We included 28 studies with 36 MTT cases and found additional 8 cases from the SEER program for final analyses. Our results showed that MTT is typically seen in adult females. These neoplasms were associated with an aggressive clinical course with high rates of extrathyroidal extension (80%) and nodal involvement (62%). During follow-up, the development of recurrence and metastases were common (42% and 46%, respectively), and one-third of patients died at the last follow-up. Large tumor size (P = 0.022) and the presence of metastases during follow-up (P = 0.008) were associated with a higher mortality rate. In conclusion, our study demonstrated the characteristic features of MTT patients and outlined some parameters associated with a negative outcome which could help clinicians better predict the clinical course of these neoplasms.

Clinicopathological Implications of RHOA Mutations in Angioimmunoblastic T-Cell Lymphoma: A Meta-analysis: RHOA mutations in AITL.

BACKGROUND: Studies have recently shown that RHOA mutations play a crucial role in angioimmunoblastic T-cell lymphoma (AITL) pathogenesis. We aimed to pool data from these studies to provide a comparison of clinicopathological features between the RHOA mutant and RHOA wild-type groups in the AITL population. METHODS: We searched PubMed and Web of Science for the keywords "RHOA AND lymphoma" and selected only studies reporting the clinical significance of RHOA mutations in AITL. We calculated the odds ratios (OR) or the mean difference with 95% CI using a random effect model. RESULTS: Our pooled results showed a significant association between RHOA mutations and a T-follicular helper cell (TFH) phenotype, especially CD10 (OR, 5.16; 95% CI, 2.32-11.46), IDH2 mutations (OR, 10.70; 95% CI, 4.22-27.15), and TET2 mutations (OR, 7.03; 95% CI, 2.14-23.12). Although DNMT3A together with TET2 and IDH2 mutations are epigenetic gene alterations, we found an insignificant association between RHOA and DNMT3A mutations (OR, 1.72; 95% CI, 0.73-4.05). No significant associations of RHOA mutations with other clinicopathological features and overall survival were found. CONCLUSIONS: RHOA mutations are strongly correlated with a T-follicular helper cell phenotype and epigenetic mutations such as TET2 and IDH2. Further studies with large AITL samples should be conducted to validate the relationship of TET2, DNMT3A, and RHOA co-mutations.

Evolving Practice Patterns Over Two Decades (1993-2013) in the Management of Desmoid-type Fibromatosis in British Columbia.

AIMS: Due to the rarity and varied natural history of desmoid-type fibromatosis, evidence-based treatment standards for this disease remain lacking. This study evaluated outcomes in patients with desmoid-type fibromatosis managed at a Canadian institution over two decades. MATERIALS AND METHODS: Records of 227 patients with desmoid-type fibromatosis referred from 1990 to 2013 were retrospectively reviewed to investigate management strategies including active surveillance, surgery, radiation therapy, cryoablation, and systemic therapy, including tamoxifen and chemotherapy. RESULTS: Thirty-two per cent of cases were men, median age 40 years, median tumour size 5.4 cm. Initial treatments were surgery (79%), tamoxifen (13%), radiation therapy (5.0%), chemotherapy (1.8%) and cryoablation (1.2%). Active surveillance was used upfront in 26% of cases, most after 2005. At a median follow-up of 77 months, one patient died of disease, 13 died of unrelated causes and the remainder were alive with no evidence of disease (56%), stable/responding disease (33%) or progressive disease (4%). The recurrence rate was 25% after upfront surgery. Response rates and disease control rates were 40% and 76% for active surveillance; 68% and 96% for radiation therapy; 31% and 67% for tamoxifen; and 53% and 80% for chemotherapy. On univariable analysis, factors associated with a higher recurrence after initial surgery were young age (P = 0.012), male gender (P = 0.012) and extremity location (P = 0.005). On multivariable analysis, only young age was significantly associated with recurrence risk (P = 0.010). CONCLUSIONS: Active surveillance was associated with spontaneous regression and long-term disease control consistent with other studies. Primary radiation therapy appeared to provide a similar response and disease control compared with systemic treatments and may be a viable option for patients who are not candidates for surgery or active surveillance.

Phyllodes tumors of the breast: The British Columbia Cancer Agency experience.

PURPOSE: Phyllodes tumors of the breast are uncommon fibroepithelial lesions for which optimal management remains unclear. This retrospective population-based study reports treatment and outcomes for patients with phyllodes tumors and evaluates characteristics that influence outcome. MATERIALS AND METHODS: Data were analysed on 183 patients with newly diagnosed phyllodes tumors from 1999 to 2014. Five-year Kaplan-Meier local recurrence and survival were compared between cohorts with benign (n=83), borderline (n=50) and malignant phyllodes tumor (n=49) histology. RESULTS: Median (range) follow-up was 65 (0.5-197) months. Local excision was performed in 163 and mastectomy in 19 patients. Eleven patients with malignant phyllodes tumors received radiation therapy. Overall, local recurrence occurred in 8.7%, distant metastases in 4.4%, and cause specific deaths in 3.8%. Five-year Kaplan-Meier outcomes among women with benign, borderline, and malignant phyllodes tumors were: local recurrence 6% vs 9% vs 21%, P=0.131; overall survival 96% vs 100% vs 82%, P=0.002; and disease-free survival 94% vs 91% vs 67%, P<0.001. Five-year Kaplan-Meier local recurrence among women with negative vs close vs positive margins were 8% vs 6% vs 37%, P<0.001. Corresponding rates for intermediate vs pushing vs infiltrative borders were 6% vs 6% vs 33%, P=0.006. Positive margins and infiltrative tumor borders were associated with increased local recurrence (all P≤0.006), and the latter remained significant in exploratory analyses after adjusting for margin status and phyllodes tumor classification. CONCLUSIONS: Five-year outcomes among women with phyllodes tumors were comparable to those reported in the literature. Exploratory analysis has suggested that infiltrative tumor borders may be used in conjunction with margin status to assess local recurrence risk.

Patient preferences for timing and access to radiation therapy.

PURPOSE: Patient preferences for radiation therapy (rt) access were investigated. METHODS: Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded. RESULTS: Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%-15% preferred 07h30-08h00 or 16h30-17h00; 10% preferred 17h00-18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively. CONCLUSIONS: An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%-20% of rt capacity on weekends and during 07h30-08h00 and 16h30-18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.

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, Allred's 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.

Role of hypofractionated radiotherapy in breast locoregional radiation.

Long-term results of randomised trials have confirmed the safety and efficacy of hypofractionated radiotherapy using approximately 2.6 Gy per fraction to lower total doses of 40-42.6 Gy delivered over 3 weeks, for postoperative treatment of early breast cancer. In these trials, hypofractionated radiotherapy was predominantly used for breast only treatment, while there are fewer trials that specifically examined hypofractionated radiotherapy to the breast plus regional nodes. Hypofractionated locoregional radiation is considered a standard of care in the United Kingdom and in some parts of Canada. We aim to review the radiobiology and normal tissue effects of hypofractionated locoregional radiation and to summarize available published clinical experiences using this treatment strategy as adjuvant therapy after breast conserving surgery or mastectomy for women with early breast cancer.

[Colour-coded duplex-sonography versus scintigraphy. Can scintigraphy be replaced by sonography for diagnosis of functional thyroid autonomy?]. / 99mTc-Szintigraphie versus Farbduplex-Sonographie. Kann zur Diagnose der funktionellen Schilddrüsenautonomie auf die Szintigraphie verzichtet werden?

UNLABELLED: Since the development of colour coded duplex-sonography (ccds), several attempts have been made to implement this technique for diagnosis of focal lesions in the thyroid. There are controversial discussions on whether ccds might replace thyroid scintigraphy in diagnosis of hyperfunctional thyroid nodules. Aim of this study was the comparison of ccds and thyroid scintigraphy in diagnosis of functional thyroid autonomy. PATIENTS, MATERIAL AND METHODS: 192 patients with thyroid nodules > 10mm detected by conventional sonography underwent thyroid scintigraphy. Additionally, these patients were subjected to ccds of the thyroid. In total, 286 thyroid nodules were examined by scintigraphy, ccds and blood tests. RESULTS: Thyroid scintigraphy showed 67% of thyroid nodules as hyperfunctional, 19% indifferent and 14% as hypofunctional. Mean 99mTc uptake of hyperfunctional nodules was 2.19%, of indifferent nodules 1.12% and of hypofunctional nodules 1.06% respectively. The ccds allowed perinodular measurement of flow speed (hyperfunctional: 0.23 ± 0.1 m/s; hypofunctional: 0.22 ± 0.1; indifferent: 0.21 ± 0.09), resistance index (hyperfunctional: 1.21 ± 1.16; hypofunctional: 0.62 ± 0.48; indifferent: 0.93 ± 1.02) and pulsatility index (hyperfunctional: 0.97 ± 0.45; hypofunctional: 0.84 ± 0.4; indifferent: 1.04 ± 0.6) in all nodules as well as intranodular measurement in some of the nodules (24% in hyperfunctional, 2% in indifferent and 15% in hypofunctional nodules). Statistic analysis of the obtained ccds data did not show any practically relevant correlations (p>0.05) with 99mTc uptake, basal TSH, fT3 or fT4. CONCLUSION: Thyroid scintigraphy cannot be replaced by ccds for diagnosis of functional thyroid autonomy. Reliable diagnostics still require a combination of thyroid scintigraphy, sonography and blood tests.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Anemia is a common but neglected complication of adjuvant chemotherapy for early breast cancer.

In this study, we set out to determine the frequency and severity of anemia and the corrective interventions used during adjuvant chemotherapy for breast cancer.We conducted a retrospective electronic chart review of 702 patients who received adjuvant breast cancer chemotherapy at four BC Cancer Agency centres in 2002 and 2003. For these patients, we recorded the initial hemoglobin reading and the date of the first hemoglobin reading in the ranges 110-119 g/L, 100-109 g/L, 90-99 g/L, and <90 g/L. We also recorded any discussion about, or delivery of, interventions for anemia [transfusion, epoetin (epo) or both].Median age of the study population was 51 years, and it varied with chemotherapy type. Among the patients, 12% had a hemoglobin reading <120 g/L before the start of chemotherapy. Overall, the proportion of patients with at least one hemoglobin reading <120 g/L was 78%; <110 g/L, 54%; <100 g/L, 31%; and <90 g/L, 14%. Depending on chemotherapy type, a hemoglobin reading <100 g/L occurred in 5% to 54% of patients. Intervention rates increased as hemoglobin declined. For 99 patients with a hemoglobin reading <90 g/L, a discussion of anemia was documented in the treatment chart in 49% of cases, a transfusion was delivered in 23%, epo was used in 11%, and transfusion and epo were both delivered in 5%.Anemia was relatively common and varied with chemotherapy type. Documentation of a discussion of anemia occurred in fewer than 20% of the patients with a hemoglobin reading of 90-99 g/L and in only half the patients with a hemoglobin reading <90 g/L. Intervention rates were low at hemoglobin readings for which randomized trials have shown that intervention can improve quality of life.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Short communication: Setup variations in locoregional radiotherapy for breast cancer: an electronic portal imaging study.

Recent trials demonstrating a survival benefit with locoregional radiotherapy (LRRT) to the chest wall and regional nodes in women with node-positive breast cancer have led to increased use of complex techniques to match three or more radiation fields, but information on setup reproducibility with LRRT for breast cancer is scarce. This study reports the magnitude and directions of random and systematic deviations in LRRT for breast cancer using an offline electronic portal imaging verification protocol. Electronic portal images (EPIs) of 46 consecutive women treated with LRRT for breast cancer from March 2001 to February 2002 with LRRT were analysed. Comparisons of EPIs to the corresponding digitally reconstructed radiographs were performed offline with anatomy matching. Displacements in mm were recorded in the superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP) directions. Random errors ranged from 2.0 mm to 2.5 mm for the breast/chest wall tangential treatments and 2.3 mm to 3.9 mm for the supraclavicular nodal treatments. Systematic errors occurred to a greater degree in the AP direction for the tangential fields and in the ML direction for the supraclavicular field. Displacements of > or =10 mm were found in 1.2% of breast/chest wall tangential treatments and in 6.2% of supraclavicular nodal treatments. These data demonstrate that EPI is a useful tool to verify setup reproducibility in LRRT for breast cancer.

CT slice index and thickness: impact on organ contouring in radiation treatment planning for prostate cancer.

OBJECTIVE: To assess the impact of CT slice index and thickness (3 mm versus 5 mm) on (i) prostate volume, dimensions, and isocenter coordinates, (ii) bladder and rectal volumes, and (iii) DRR quality, in the treatment of prostate cancer. METHODS: 16 patients with prostate cancer underwent two planning CT-scans using 3 and 5 mm slice index/thickness. Prostate, bladder, and rectum were outlined on all scans. Prostate isocenter coordinates, maximum dimensions, and volumes were compared along with bladder and rectal volumes. Bladder volumes and maximum diameters were further investigated using a second observer. A comparative analysis of DRR quality was conducted as well as a dosimetric analysis using DVH. RESULTS: The differences in measurements of prostate volume, isocenter coordinates and maximum dimensions between the 3 and 5 mm scans, were small and not statistically significant. Similar finding was seen for rectal volume. However, bladder volume was always larger on the 3 mm scan (mean difference=27.9 cc; SE=4.8 cc; 95% CI: 17.7-38.2 cc; p<0.001) and the findings were reproduced with the second observer (mean difference=31.9 cc; SE=4.7 cc; 95% CI: 21.9-41.9 cc; p<0.001). The differences in volume are caused by a slight increase in (1) the measurement of the longitudinal dimensions on the 3 mm scans, and (2) the slice by slice measured bladder area on the 3 mm scans. The latter is due to partial volume effect. The 3 mm DRR were slightly better than the 5 mm DRR. The bladder DVH differed significantly in some patients. CONCLUSION: Bladder volume is significantly larger on the 3 mm scans. Differences in contoured areas may be accounted for, in part, by the partial volume effect.

[Uterine and ovarian metastases 28 years after the discovery of breast cancer]. / Métastases utérines et ovariennes 28 ans après la survenue d'un cancer du sein.

INTRODUCTION: Breast cancer seldom leads to uterine metastases, but more frequently spreads to the ovaries. OBSERVATION: A 72 year-old woman treated 28 years earlier for a breast cancer (conservative treatment and ovarian castration through radiotherapy) presented with metrorrhagia. The hysteroscopy and uterine curettage were normal. Three months later she presented with bone pains and pain along the course of the femoral nerve. The clinical examination revealed the existence of left axillary and sub-clavicle adenopathies. A biopsy of the lymph nodes showed a lobular adenocarcinoma with positive hormonal receptors. The clinical and biological state of the patient improved under treatment with tamoxifen and aredia. Eight months later the patient complained of pelvic pains. The ultrasound examination showed a pelvic tumour situated at the fundus of an enlarged uterus, as well as peritoneal effusion. The patient underwent a total hysterectomy and multiple biopsies that revealed diffuse metastases of a lobular adenocarcinoma spreading to the neck and the body of the womb, the mesosalpinx, the left ovary and the epiploon. The patient died less than a year after the first symptoms had appeared. DISCUSSION: Uterine metastases of extrapelvic origin are rare. Breast cancer is the first cause of this dissemination. It is generally invasive, lobular, and frequently spreads to the ovaries. In the case reported here, what is remarkable is the exceptionally long period between the discovery of a breast cancer and the apparition of metastases. Hence, in order to detect a primary or secondary ovarian or uterine cancer, it is important to emphasize the necessity of systematic pelvic examination in patients treated for breast cancer.

Osteopontin and its receptor alphavbeta(3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially.

Osteopontin is an arginine-glycine-aspartic acid-containing acidic glycoprotein component of the extracellular matrix that is postulated to bind to integrin receptors at the cell surface to mediate cellular adhesion and migration during embryo implantation. The primary aim of this study was to examine the uterine expression of osteopontin throughout the menstrual cycle in normal fertile controls sampled prospectively based on urinary LH surge detection. Expression of osteopontin was documented using Northern blot analysis, in situ hybridization, and immunohistochemistry. Furthermore, the temporal pattern of osteopontin expression was compared with that of its receptor, the alphavbeta3 integrin. Using Ishikawa cells, a well differentiated endometrial adenocarcinoma cell line, the in vitro regulation of osteopontin and its receptor alphavbeta3 integrin was studied. By Northern blot analysis, osteopontin mRNA appears during the early secretory phase, with maximal expression occurring in mid to late secretory-phase endometrium. The in situ hybridization analyses showed that osteopontin mRNA specifically localized in epithelial cells within the endometrium. Immunostaining of osteopontin was detected in the glandular secretions and on the apical portions of surface (luminal) epithelium. The patterns of expression of osteopontin by Northern blotting, in situ hybridization, and immunohistochemistry are remarkably similar to the pattern for the alphavbeta3 integrin. Despite these similarities in distribution, in vitro studies demonstrate that osteopontin and beta3 integrin subunit expression are differentially regulated. The expression of osteopontin was primarily induced in response to progesterone, whereas the beta3 integrin subunit was up-regulated by epidermal growth factor or heparin-binding epidermal growth factor. The differential regulation of these two endometrial proteins suggests the existence of two separate pathways regulating epithelial gene expression in human endometrium during the window of implantation. In adhesion assays using Ishikawa cells, alphavbeta3 but not alphavbeta5 or beta1 integrins appear to be the primary receptors for osteopontin. These findings may better define the factors that favor the development of a receptive endometrium.