S. Okkan

Coverage of axillary lymph nodes with high tangential fields in breast radiotherapy

The aim of this study is to evaluate the coverage of axillary nodal volumes with high tangent fields (HTF) in breast radiotherapy and to determine the utility of customised blocking. The treatment plans of 30 consecutive patients with early breast cancer were evaluated. The prescription dose was 50 Gy to the whole breast. Axillary level I-II lymph node volumes were delineated and the cranial border of the tangential fields was set just below the humeral head to create HTF. Dose-volume histograms (DVH) were used to calculate the doses received by axillary nodal volumes. In a second planning set, HTF were modified with multileaf collimators (MLC-HTF) to obtain an adequate dose coverage of axillary nodes. The mean doses of the axillary nodes, the ipsilateral lung and heart were compared between the two plans (HTF vs MLC-HTF) using a paired sample t-test. The doses received by 95% of the breast volumes were not significantly different for the two plans. The doses received by 95% of the level I and II axillary volumes were 16.79 Gy and 11.59 Gy, respectively, for HTF, increasing to 47.2 Gy and 45.03 Gy, respectively, for MLC-HTF. Mean lung doses and per cent volume of the ipsilateral lung receiving 20 Gy (V20) were also increased from 6.47 Gy and 10.47%, respectively, for HTF, to 9.56 Gy and 16.77%, respectively, for MLC-HTF. Our results suggest that HTF do not adequately cover the level I and II axillary lymph node regions. Modification of HTF with MLC is necessary to obtain an adequate coverage of axillary levels without compromising healthy tissue in the majority of the patients.

Insufficiency Fractures After Pelvic Radiotherapy in Patients With Prostate Cancer

PURPOSE To assess the incidence, predisposing factors, and clinical characteristics of insufficiency fractures (IF) in patients with prostate cancer, who received pelvic radiotherapy as part of their definitive treatment. METHODS AND MATERIALS The charts of 134 prostate cancer patients, who were treated with pelvic radiotherapy between 1998 and 2007 were retrospectively reviewed. IF was diagnosed by bone scan and/or CT and/or MRI. The cumulative incidence of symptomatic IF was estimated by actuarial methods. RESULTS Eight patients were identified with symptomatic IF after a median follow-up period of 68 months (range, 12-116 months). The 5-year cumulative incidence of symptomatic IF was 6.8%. All patients presented with lower back pain. Insufficiency fracture developed at a median time of 20 months after the end of radiotherapy and was managed conservatively without any need for hospitalization. Three patients were thought to have metastatic disease because of increased uptake in their bone scans. However, subsequent CT and MR imaging revealed characteristic changes of IF, avoiding any further intervention. No predisposing factors for development of IF could be identified. CONCLUSIONS Pelvic IF is a rare complication of pelvic radiotherapy in prostate cancer. Knowledge of pelvic IF is essential to rule out metastatic disease and prevent unnecessary treatment, especially in a patient cohort with high-risk features for distant spread.

Dosimetric comparison of field in field intensity-modulated radiotherapy technique with conformal radiotherapy techniques in breast cancer

PurposeThe aim of this study was to be able to implement the field-in-field intensity-modulated radiotherapy (FiF) technique in our daily practice for breast radiotherapy. To do this, we performed a dosimetric comparison.Materials and methodsTreatment plans were produced for 20 consecutive patients. FiF plans and conformal radiotherapy (CRT) plans were compared for doses in the planning target volume (PTV), the dose homogeneity index (DHI), doses in irradiated soft tissue outside the target volume (SST), ipsilateral lung and heart doses for left breast irradiation, and the monitor unit counts (MU) required for treatment. Averaged values were compared using Student’s t-test.ResultsWith FiF, the DHI is improved 7.0% and 5.7%, respectively (P < 0.0001) over the bilateral and lateral wedge CRT techniques. When the targeted volumes received 105% and 110% of the prescribed dose in the PTV were compared, significant decreases are found with the FiF technique. With the 105% dose, the SST, heart, and ipsilateral lung doses and the MU counts were also significantly lower with the FiF technique.ConclusionThe FiF technique, compared to CRT, for breast radiotherapy enables significantly better dose distribution in the PTV. Significant differences are also found for soft tissue volume, the ipsilateral lung dose, and the heart dose. Considering the decreased MUs needed for treatment, the FiF technique is preferred over tangential CRT.

Vitamin D Levels in Patients with Breast Cancer: Importance of Dressing Style

BACKGROUND Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments. MATERIALS AND METHODS This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). RESULTS The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (≥25), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively. CONCLUSIONS The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.

Prostatic Duct Adenocarcinoma: Clinical Characteristics, Treatment Options, and Outcomes – a Rare Cancer Network Study

Background: To evaluate the clinical characteristics, contemporary treatment options, and outcome of prostatic duct adenocarcinoma (PDA), we initiated a Rare Cancer Network (RCN) study. Materials and Methods: Six member institutions of the RCN collected clinical data on 31 patients. Treatment consisted of definitive radiotherapy in 14 patients and radical prostatectomy in 16 patients. One patient was treated with androgen deprivation alone. The mean follow-up period was 56 months. Results: Of the 14 patients managed with radiotherapy, 1 patient developed bone metastases and died of prostate cancer, and 1 patient had a biochemical relapse 8 years after definitive radiotherapy. Of the 16 patients who underwent radical prostatectomy, 2 patients developed bone metastases, one of who died of disease. Three patients that relapsed after prostatectomy were successfully salvaged with radiotherapy. The patient that was treated with androgen deprivation alone developed bone metastases at 10 months, was treated with chemotherapy, and was alive after 22 months. Conclusions: Our results suggest that PDA is a cancer with a behavior similar to that of high Gleason grade acinar carcinoma. Good local control can be achieved by either radiation or surgery. Postoperative radiotherapy seems to work as an adjuvant or salvage treatment, and most tumors appear to respond to androgen deprivation.

The Application of Positron Emission Tomography/Computed Tomography in Radiation Treatment Planning: Effect on Gross Target Volume Definition and Treatment Management

AIMS To analyse the effect of the use of molecular imaging on gross target volume (GTV) definition and treatment management. MATERIALS AND METHODS Fifty patients with various solid tumours who underwent positron emission tomography (PET)/computed tomography (CT) simulation for radiotherapy planning from 2006 to 2008 were enrolled in this study. First, F-18 fluorodeoxyglucose (FDG)-PET and CT scans of the treatment site in the treatment position and then a whole body scan were carried out with a dedicated PET/CT scanner and fused thereafter. FDG-avid primary tumour and lymph nodes were included into the GTV. A multidisciplinary team defined the target volume, and contouring was carried out by a radiation oncologist using visual methods. To compare the PET/CT-based volumes with CT-based volumes, contours were drawn on CT-only data with the help of site-specific radiologists who were blind to the PET/CT results after a median time of 7 months. RESULTS In general, our PET/CT volumes were larger than our CT-based volumes. This difference was significant in patients with head and neck cancers. Major changes (> or =25%) in GTV delineation were observed in 44% of patients. In 16% of cases, PET/CT detected incidental second primaries and metastatic disease, changing the treatment strategy from curative to palliative. CONCLUSIONS Integrating functional imaging with FDG-PET/CT into the radiotherapy planning process resulted in major changes in a significant proportion of our patients. An interdisciplinary approach between imaging and radiation oncology departments is essential in defining the target volumes.

Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients

The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I–III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10–14, 15–19, 20–24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1–95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients.

Is Administration of Trastuzumab an Independent Risk Factor for Developing Osteonecrosis of the Jaw Among Metastatic Breast Cancer Patients Under Zoledronic Acid Treatment

AbstractOne of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients’ ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13–82) and the mean number of ZA infusions was 38 (range: 15–56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer.

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival.

Replacement of the tumor bed following oncoplastic breast-conserving surgery with immediate latissimus dorsi mini-flap.

The aim of the present study was to evaluate the geographic variability of the tumor bed following oncoplastic breast-conserving surgery (OP-BCS), and to assess its relevance for radiotherapy planning. In this prospective study, pre- and postoperative computerized tomography (CT) scans of 22 patients with early-stage breast cancer were fused. The preoperative gross tumor volume or excisional biopsy cavity were contoured under the guidance of preoperative radiological images. Postoperative lumpectomy cavities were contoured under the guidance of surgical clips. The conformity index (CI) was calculated and defined on a scale between 0 and 1, where 0 indicated no overlap and 1 indicated 100% concordance. Associations between CI and the number of clips, time interval between surgery and CT scans, pathological tumor size and age were assessed using independent sample testing. The median CI was 0.07 (in five cases, 1, and in eight cases, 0). The lumpectomy cavity shifted from the primary location in 36.4% of the cases. Median shifts between the isocenters of pre- and postoperative volumes were measured as 1.02 cm (range, 0.4–4.43 cm) in the x, 1.07 cm (range, 0.05–5.67 cm) in the y, and 1.12 cm (range, 0–3.75 cm) in the z directions. Only the clip number was determined to be significantly associated with CI (P=0.017). Pre- and postoperative tumor bed volumes were fully superposed in five of the 22 cases. The present study has shown that the tumor bed is markedly replaced following OP-BCS with latissimus dorsi mini-flap (LDMF) reconstruction. Special care should therefore be taken when defining the lumpectomy cavity following OP-BCS with LDMF reconstruction.