Didem Çolpan Öksüz

Extraskeletal Ewing's Sarcoma Family of Tumors in Adults: Prognostic Factors and Clinical Outcome

OBJECTIVE The aim of this study was to evaluate prognostic factors, survival rate and the efficacy of the treatment modalities used in patients with extraskeletal Ewings sarcoma. METHODS Data of patients with extraskeletal Ewings sarcoma followed up at our center between 1997 and 2010 were retrospectively analyzed. RESULTS The median age of 27 patients was 24 years (range, 16-54 years). The median follow-up was 31.8 months (range, 6-144 months). Tumor size was between 1.5 and 14 cm (median: 8 cm). Eighty-five percent of patients had localized disease at presentation and 15% had metastatic disease. Local therapy was surgery alone in 16% of patients, surgery combined with radiotherapy in 42% and radiotherapy alone in 27%. All patients were treated with vincristine, doxorubicin, cyclophosphamide and actinomycin-D, alternating with ifosfamide and etoposide every 3 weeks. In patients with localized disease at presentation, the 5-year event-free survival and overall survival were 59.7 and 64.5%, respectively. At univariate analysis, patients with tumor size ≥ 8 cm, high serum lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy and positive surgical margin had significantly worse event-free survival. The significant predictors of worse overall survival at univariate analysis were tumor size 8 ≥ cm, high lactate dehydrogenase, metastasis at presentation, poor histological response to chemotherapy, radiotherapy only as local treatment and positive surgical margin. CONCLUSIONS Prognostic factors were similar to primary osseous Ewings sarcomas. Adequate surgical resection, aggressive chemotherapy (vincristine, doxorubicin, cyclophosphamide and actinomycin-D alternating with ifosfamide and etoposide) and radiotherapy if indicated are the recommended therapy for patients with extraskeletal Ewings sarcoma.

Outcomes following chemoradiotherapy for N3 head and neck squamous cell carcinoma without a planned neck dissection.

OBJECTIVES The optimal management of the N3 neck in head and neck squamous cell carcinoma (HNSCC) remains controversial. We report the outcomes of patients with N3 disease treated with a strategy of concurrent chemo-radiotherapy (CRT)±induction chemotherapy (ICT) without a planned neck dissection. MATERIALS AND METHODS Forty patients with HNSCC N3 disease treated between January 2004 and December 2010 were retrospectively identified. Inclusion criteria for the study were: non-nasopharyngeal HNSCC, N3 nodal disease, intention to treat with CRT±ICT. RESULTS Median age was 60 (range 39-74). Median follow up was 32 months (range 8-88). 34 (85%) of patients received ICT. 35 patients received cisplatin-CRT, 4 carboplatin-CRT and 1 patient was treated with radiotherapy alone due to ICT toxicity. 27 (67.5%) patients had a complete response (CR) to CRT. 5 (12.5%) patients had an incomplete response in both the primary and nodal sites. 8 (20%) patients had a CR in the primary site but incomplete in the nodal regions. The crude rate of regional failure following a CR was 3/27 (11.2%). Isolated regional failure occurred in 1/27 (3.7%) patients who had achieved a CR post-CRT. 3 year overall survival, disease free survival, locoregional control, local control and regional control in the whole cohort were 51.4%, 49.6%, 65.7%, 77.3%, 69.3%, and in patients with a CR were 73.3%, 70.0%, 86.6%, 90.5% and 91.7% respectively. CONCLUSION Isolated regional nodal failure is rare following a complete response to CRT for N3 HNSCC managed without a planned neck dissection.

The Role of Radiotherapy in the Treatment of Primary or Recurrent Desmoid Tumors and Long-Term Results.

BACKGROUND Desmoid tumors are uncommon and benign mesenchymal neoplasms. The optimal treatment of patients with desmoid tumors is still controversial. Surgery is the primary treatment for locally invasive or recurrent desmoid tumors. Also, radiotherapy is a treatment option for patients at high risk for local failure such as those with positive margins or recurrent and unresectable tumors. AIMS To report our institutional experience and long-term results of patients with desmoid tumors who received radiotherapy. STUDY DESIGN Retrospective cross-sectional study. METHODS Between 1980 and 2009, 20 patients who received radiotherapy (RT) in our institution were analyzed. The majority of patients (80%) were referred with a recurrent tumor after previous surgery. Thirteen patients underwent marginal resection, 4 had wide local excision and 3 patients had only biopsy. Resection margin was positive in 15 (75%) patients. All patients received radiation therapy. The median prescribed dose was 60 Gy. Five patients received less than 54 Gy. RESULTS The median follow-up time was 77.5 months (28-283 months). Nine patients developed local recurrence after RT. Seven local failures (78%) were in field. Time to local recurrence ranged from 3-165 months (median 33 months). The 2-5 year local control (LC) rates were 80% and 69%, respectively. On univariate analysis, the 5 year local control rate was significantly better in the patients treated with ≥54 Gy than in patients who received <54 Gy (p=0.023). The most common acute side effect was grade 1-2 skin toxicity. As a late side effect of radiotherapy, soft tissue fibrosis was detected in 10 patients and lymphangitis was seen in 1 patient. One patient developed radiation-induced sarcoma. CONCLUSION According to our results, radiotherapy is especially effective in recurrent disease and provides a high local control rate in the patients received more than 54 Gy.

Low-grade osteosarcoma, review of 15 cases in a series of 156 osteosarcoma cases.

OBJECTIVE Osteosarcoma of the bone accounts for approximately 20% of all primary malignant bone tumors. Most cases (75-85%) are high-grade osteosarcomas. We aimed to introduce low-grade osteosarcomas that we found by retrospectively scanning our archives because of the diagnostic difficulties, rarity and different therapeutic approach required. MATERIAL AND METHOD We found 156 osteosarcoma cases in the archives of the Department of Pathology of Istanbul University, Cerrahpaşa Faculty of Medicine covering the period 2000 to 2010. These cases included 141 high-grade and 15 low-grade osteosarcomas. RESULTS Low-grade osteosarcomas made up 10.4% of all osteosarcomas. Age and sex distribution were 19 to 54 (median 33.6) with 9 females and 6 males. Most cases were located in the distal femur while others were in the proximal tibia, the left wrist, the distal tibia and the right knee. The tumors were generally made up of relatively well-formed trabeculae of woven bone surrounded by a moderately cellular spindle cell proliferation entangled in collagen fibers. Thirteen cases were reported as parosteal osteosarcoma, one as intramedullary well-differentiated osteosarcoma, and one as low-grade osteosarcoma metastasis in the lung. CONCLUSION Low-grade osteosarcomas account for approximately 3-5% of all osteosarcomas. They are more commonly seen in women and 9 cases out of 6 were female in our series. The average age was 33.6 (19-54). The distal femur was the most common localization as is typical in osteosarcomas. In contrast to high-grade lesions, surgery will be sufficient in low-grade osteosarcomas. The survival rate ranges from 90% to 100%. Differentiating low-grade osteosarcomas from high-grade osteosarcomas and benign lesions and using a multidisiplinary approach for the diagnosis, treatment and follow-up periods are of vital importance.

Ovarian ablation by radiation therapy: Is it still an option for the ablation of ovarian function in endocrine responsive premenopausal breast cancer patients?

Surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21-52 years). RT was given with either Co-60 or 15MV photons of the linear accelerator. The median total dose was 15Gy in 4 consecutive fractions (range 5Gy single fraction-36Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6-167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given.

THE INVESTIGATION OF FETAL DOSES IN MANTLE FIELD IRRADIATION

To determine clinically the fetal dose from irradiation of Hodgkins disease during pregnancy and to quantify the components of fetal dose using phantom measurements. The fetal dose was measured with phantom measurements using thermoluminescent dosemeters (TLDs). Phantom measurements were performed by simulating the treatment conditions on an anthropomorphic phantom. TLDs were placed on the phantom 41, 44, 46.5 and 49.5 cm from the centre of the treatment field. Two TLDs were placed on the surface of the phantom. The estimated total dose to all the TLDs ranged from 8.8 to 13.2 cGy for treatment with (60)Co and from 8.2 to 11.8 cGy for 4 MV photons. It was concluded that the doses in different sections were evaluated to investigate dose changes in different points and depths of fetal tissues in phantom. Precise planning and the use of supplemental fetal shielding may help reduce fetal exposure.

Does rectum and bladder dose vary during the course of image-guided radiotherapy in the postprostatectomy setting?

Aims and Background To assess the variations in actual doses delivered to the rectum and bladder in the course of postprostatectomy radiotherapy using kilovoltagecone-beam computed tomography datasets acquired during image-guided radiotherapy. Methods and Study Design Twenty consecutive patients treated with intensity-modulated or intensity-modulated arc therapy to the prostate bed were retrospectively evaluated. Both the planning tomography and kilovoltage-cone-beam computed tomography were acquired with an empty rectum and a half-full bladder. Target localization was performed on the basis of soft tissue matching using cone-beam computed tomography scans before each treatment fraction. A total of 16 cone-beam computed tomography scans per patient (acquired at the first 5 fractions and twice weekly thereafter) were used for the assessments. The bladder and rectum were recontoured offline on each cone-beam computed tomography scan by a single physician, and the delivered doses were recalculated. The variations in certain dose-volume parameters for the rectum and bladder (BD2cc, RD 2cc, V40%, V50%, V60%, V65%) were analyzed using the paired t test. Results Most of the dose volume variations for rectum and bladder were significantly higher than predicted (P <0.05) for the 320 kilovoltage-cone-beam computed tomography sets, except for the doses received by 2 cc of the bladder and V50 and V60 of the rectum. The dose-volume parameters of the bladder did not meet our criteria of V65 ≤25% and V40 ≤50% in 10% and 20% of the patients, respectively. None of the dose-volume histograms showed rectal V65 ≥17%; however, the rectal V40 ≤35% dose constraint was not met in 11 patients. For all patients, the ANOVA test revealed no significant difference between the variations. Conclusion Actual doses delivered during treatment were found to be higher than predicted, but the majority of calculated bladder and rectal doses remained in the limits of our plan acceptance criteria. Interfraction variability of the rectum and bladder is a major concern in the postprostatectomy radiotherapy setting, even when patients are instructed about rectal and bladder preparation before the radiotherapy course. Image guidance with cone-beam computed tomography at each treatment fraction may offer a viable tool to account for interfraction variations of the rectum and bladder throughout the treatment course.

Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.

Aims and Background There is limited data regarding outcomes of Ewings sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewings sarcoma family of tumors. Methods and Study Design From 1992–2008, 90 adolescents and adults with Ewings sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. Results The median age was 21 years (range, 13–50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7–167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis. Conclusions We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

Long-Term Treatment Results in Soft Tissue Sarcomas of the Thoracic Wall Treated with Pre-or-Postoperative Radiotherapy - a Single Institution Experience

OBJECTIVE To evaluate the long term results among patients with soft tissue sarcoma of the thoracic wall. MATERIALS AND METHODS Twenty-six patients who were treated with pre-or postoperative radiotherapy between December 1980-December 2007, with a diagnosis of soft tissue sarcoma of the thoracic wall were retrospectively evaluated. RESULTS The median age was 44 years (14-85 years) and 15 of them were male. A total of 50% of patients were grade 3. The most common histologic type of tumor was undifferentiated pleomorphic sarcoma (26.9%). Tumor size varied between 2-25 cm (median 6.5 cm). Seventeen of the cases had marginal and 9 had wide local resection. Four cases received preoperative radiotherapy and 22 postoperative radiotherapy. Six of the patients with large and high grade tumors received chemotherapy. Median follow-up time was 82 months (9-309 months). Local recurrence and metastasis was detected in 34.6% and 42.3% of patients, respectively. Five- year local control (LC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) were 62%, 38%, 69%, and 76% respectively. On univariate analysis, the patients with positive surgical margins had a markedly lower 5-year LC rate than patients with negative surgical margin, but the difference was not significant (43% vs 78%, p=0.1). Five-year DFS (66% vs 17%) and DSS (92% vs 60%) rates were significantly worse for the patients who had high grade tumors (p=0.01, p=0.008 respectively). CONCLUSIONS Tumor grade and surgical margin are essential parameters for determining the prognosis of thoracic wall soft tissue sarcoma both in our series and the literature.

Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study

PURPOSE Turkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study. PATIENTS AND METHODS Totally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control. RESULTS The median follow-up time was 59 (21-220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control. CONCLUSION In our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.