Sedat Koca

Multivariate analysis of prognostic factors in 75 patients with soft tissue sarcoma

The results of 75 patients with soft-tissue sarcomas treated by the combination of local surgical excision plus postoperative radiotherapy are reported. Thirty-five tumors were situated in the extremities, 32 in the trunk, and eight in the head and neck. Twenty-eight tumors were high grade, 33 intermediate and 14 low grade. Sixty-two patients had complete resections (wide or marginal) and 13 incomplete resections (intralesional). Radiation was administered with a shrinking-field technique (median total dose, 64 Gy; range, 50-78). Twenty-five patients developed local recurrence (33%). The 5-year local control rate was 67%. On univariate analysis, a tumor site other than extremity (p < 0.05), unfavorable histology (p < 0.01), and incomplete resection (p < 0.01) were poor risk factors for local recurrence. When multivariate analysis were performed, only incomplete resection (relative risk (RR) 7.2) remained a poor risk factor. The 5-year overall survival rate was 50.5% for the entire group. Following a univariate analysis of host tumor and treatment-related factors, a tumor site other than extremity (p < 0.05), high tumor grade (p < 0.01) unfavorable histology (p < 0.05), and incomplete tumor resection (p < 0.01) were found to significantly increase the risk of further tumor death. Multivariate analysis found high tumor grade (RR 5.6), and incomplete resection (RR 7) to be independent poor risk factors for survival.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1, 69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours (p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA (p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients (p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion (p = 0.01), 34.8% for positive margins versus 78.1 for negative margins (p < 0.0001). After a multivariate analysis, tumour grade (p = 0.026) and presence of positive margins (p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

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.

Toxic Epidermal Necrolysis after Cranial Radiotherapy and Phenytoin Treatment

Background: There are few reports about Stevens-Johnson syndrome, a bullous form of erythema multiforme, that can develop in patients treated with cranial irradiation and antiepileptic drugs, especially with phenytoin. We present a patient who developed toxic epidermal necrolysis, a rare and severe form of Stevens-Johnson syndrome, during cranial radiotherapy and phenytoin treatment. Case Report: A 65-year-old male patient with stage IIIB non-small cell lung carcinoma developed a brain metastasis. The patient was treated with phenytoin and dexamethasone. Palliative total cranial irradiation was performed. On the 23rd day of phenytoin administration, erythema and edema in the radiotherapy area and lips, as well as widespread maculopapular eruptions and rashes in the upper thoracic area were observed. The dermal lesions progressed to bullae and subsequently toxic epidermal necrolysis covering 70% of the whole body surface developed. The patient died within 15 days of appearance of the lesions due to secondary infections, despite supportive and symptomatic treatment. Conclusion: Although toxic epidermal necrolysis is a rare toxicity it must always be considered during cranial irradiation and antiepileptic prophylaxis.

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 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.

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.

Neoadjuvant Treatment with Preoperative Radiotherapy for Extremity Soft Tissue Sarcomas: Long-Term Results from a Single Institution in Turkey

BACKGROUND To assess the long term clinical outcome of preoperative radiotherapy with or without chemotherapy followed by limb sparing surgery in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. MATERIALS AND METHODS Sixty patients with locally advanced STS were retrospectively analyzed. The median tumor diameter was 12 cm. All patients were treated with preoperative radiotherapy delivered with two different fractionation schedules (35Gy/10fr or 46-50Gy/23-25fr). Neoadjuvant chemotherapy was added to 44 patients with large and/or high grade tumors. Surgery was performed 2-6 weeks after radiotherapy. Chemotherapy was completed up to 6 courses after surgery in patients who had good responses. RESULTS Median follow-up time was 67 months (8-268 months). All of the patients had limb sparing surgery. The 5-year local control (LC), disease free (DFS) and overall survival (OSS) rates for all of the patients were 81%, 48.1% and 68.3% respectively. 5-year LC, DFS and cause specific survival (CSS) were 81.7%, 47%, 69.8%, and 80%, 60%, 60% in the chemoradiotherapy and radiotherapy groups, respectively. On univariate analysis, patients who were treated with hypofractionation experienced significantly superior LC, DFS and CSS rates with similar rates of late toxicity when compared with patients who were treated with conventional fractionation and statistical significance was retained on multivariate analysis. CONCLUSIONS Treatment results are consistent with the literature. As neoadjuvant chemoradiotherapy provides effective LC and CSS with acceptable morbidity, it should be preferred for patients with large and borderline resectable STS.