Ferah Yildiz

Salvage reirradiaton with stereotactic body radiotherapy for locally recurrent head-and-neck tumors.

PURPOSE In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. METHODS AND MATERIALS From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. RESULTS Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4-17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. CONCLUSIONS Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with considerable 1-year survival is achieved with a relatively high rate of morbidity and related mortality.

Conventional external radiotherapy in the management of clivus chordomas with overt residual disease.

Abstract Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasising tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery.Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3–7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator-based stereotactic radiosurgery after subtotal excision and external irradiation.The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4–43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas.

Comparison of AJCC 1988 and 1997 classifications for nasopharyngeal carcinoma

PURPOSE A comparison of American Joint Committee on Cancer (AJCC) 1988 and 1997 nasopharyngeal carcinoma (NPC) classifications was made in terms of patient distribution and efficacy in predicting prognosis. METHODS AND MATERIALS Between 1993-1997, 90 patients (64 M, 26 F) with non-metastatic NPC were treated. The mean age was 42.02 (range: 9-82) years old. Histopathological diagnosis was WHO 2 and 3 in 83 (92.2%) patients. All patients were prospectively staged using AJCC 1988 and modified Hos classifications (1989) and these data were stored in a computer database. Retrieval of this information enabled us to restage patients according to the AJCC 1997. Median follow-up was 38 months. RESULTS According to the AJCC 1988 there were 2 (2.2%), 6 (6.7%), 13 (14.4%), and 69 (76.7%) patients in Stage I, II, III and IV, respectively. Same figures were 8 (8.8%), 21 (23.3%), 26 (28.9%), and 35 (38.8%), according to AJCC 1997. Three year overall survival (OS) rates were 100%, 100%, 67%, and 62% for patients Stage I, II, III, and IV according to the AJCC 1988 and 100%, 72%, 65%, and 55%, (I vs. IV; p = 0.03, I vs. III; p = 0.05) respectively, according to the AJCC 1997. Three year loco-regional relapse free survival (LRRFS) rates were 50%, 100%, 100%, and 83% (I vs. III; p = 0.03) for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 88%, 90%, 89%, and 85% according to the AJCC 1997. Three year distant metastasis free survival (DMFS) rates were 100%, 100%, 82%, and 67% for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 100%, 74%, 80%, and 57% (I vs. IV; p = 0.03) according to the AJCC 1997. We did not observe any significant difference in LRRFS among T stages for both staging system and the N stage was the primary determinant for DMFS in both systems. CONCLUSIONS We observed a better patient distribution with AJCC 1997 comparing to AJCC 1988. The new classification also attained better statistical significances among stages in the OS and DMFS rates.

A Retrospective Comparison of Robotic Stereotactic Body Radiotherapy and Three-Dimensional Conformal Radiotherapy for the Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

PURPOSE We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT). METHODS AND MATERIALS Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation. RESULTS The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival. CONCLUSION Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.

Percent positive axillary lymph node metastasis predicts survival in patients with non-metastatic breast cancer

Purpose. We retrospectively evaluated the impact of percent positive axillary nodal involvement on the therapeutic outcomes in patients with non-metastatic breast cancer receiving postmastectomy radiotherapy and chemotherapy. Materials and methods. Between January 1994 and December 2002, the medical records of 939 eligible non metastatic breast carcinoma patients were analyzed. Chest wall radiotherapy was indicated in case of positive surgical margin, tumor size equal or more than 4 cm, skin-fascia invasion. Lymphatic irradiation was applied for more than three metastatic axillary lymph nodes, incomplete axillary dissection (<10 lymph nodes), extracapsular extension or perinodal fat tissue invasion. A total dose of 50 Gy was given to chest wall and lymph node regions with 2 Gy daily fractions. Statistical analyses were performed by Kaplan-Meier method, Log-rank test and Coxs regression analysis. Results. The median follow-up for all patients alive was 62 months. The 5-year overall survival (OS) and disease-free survival (DFS) for entire cohort were 81%, and 65%, respectively. Univariate analysis for OS revealed significance for tumour size (≤5 cm vs. >5cm, p<0.001), metastatic nodal involvement (0 vs. 1–3 vs. >4 LN, p<0.001), percent positive nodal involvement ([metastatic nodes/total nodes removed]×100; 0 vs.≤25% vs. 26–50% vs. >50%, p<0.001), surgical margin status (negative vs. positive, p=0.05), and hormonal treatment (present vs. absent, p=0.03). DFS had similarly significance for age (≤40 years vs. >40 years, p=0.006), tumour size (0.02), metastatic nodal involvement (p<0.001), percent positive nodal involvement (p<0.001), and perinodal invasion (present vs. absent, p=0.01). Multivariate analysis revealed significance for tumour size, percent positive nodal involvement, hormonal treatment, and surgical margin status for OS. Age and percent positive nodal involvement were found to be significant for DFS. Conclusion. Percent positive nodal involvement was found to be a significant prognostic factor for survival in all end-points.

Vaginal high dose rate brachytherapy alone in patients with intermediate- to high-risk stage I endometrial carcinoma after radical surgery.

The objective of this study was to analyze the efficacy and morbidity of vaginal cuff brachytherapy alone in intermediate- to high-risk stage I endometrial cancer patients after complete surgical staging. Between October 1994 and November 2005, 128 patients with intermediate- to high-risk stage I endometrial adenocarcinoma were treated with high dose rate (HDR) brachytherapy alone after complete surgical staging. The intermediate- to high-risk group was defined as any stage I with grade 3 histology or stage IB grade 2 or any stage IC disease. The comprehensive surgery was in the form of total abdominal hysterectomy, bilateral salpingo-oophorectomy in addition to infracolic omentectomy, and routine pelvic and para-aortic lymphadenectomy. The median number of the lymph nodes dissected was 33. The median age at the time of diagnosis was 60 years. Forty patients were staged as IB (grade 2: 25 and grade 3: 15), and 88 patients were staged as IC (grade 1: 31, grade 2: 41, and grade 3: 16). A total dose of 27.5 Gy with HDR brachytherapy, prescribed at 0.5 cm, was delivered in five fractions in 5 consecutive days. Median follow-up was 48 months. Six (4.7%) patients developed either local recurrence (n= 2) or distant metastases (n= 4). Five-year overall survival and disease-free survival (DFS) rates are 96% and 93%, respectively. Only age was found to be significant prognostic factor for DFS. Patients younger than 60 years have significantly higher DFS (P= 0.006). None of the patients experienced grade 3/4 complications due to the vaginal HDR brachytherapy. Vaginal cuff brachytherapy alone is an adequate treatment modality in stage I endometrial adenocarcinoma patients with intermediate- to high-risk features after complete surgical staging with low complication rates.

Comparison of intracavitary brachytherapy and stereotactic body radiotherapy dose distribution for cervical cancer.

PURPOSE To compare the dose distribution characteristics of stereotactic body radiotherapy (SBRT) with intracavitary high-dose-rate (HDR) brachytherapy in patients with cervical carcinoma. METHODS AND MATERIALS HDR intracavitary brachytherapy treatment plans for 11 women with cervical carcinoma were evaluated in this analysis. The total HDR brachytherapy dose was 28Gy given in four fractions. HDR brachytherapy was delivered with the microSelectron HDR therapy unit (Nucletron B. V., Veenendaal, The Netherlands). SBRT plans for each patient were generated with MultiPlan for CyberKnife Robotic Radiosurgery System (Accuray Inc., Sunnyvale, CA). The dose distributions, dose-volume histograms, and maximum dose points of the target and critical organs were recorded for both plans. RESULTS SBRT yielded significantly better target coverage; the median target coverage for the 100% isodose line was 50.7% for HDR brachytherapy plans, whereas it was 99.1% for SBRT plans. The dose distributions for critical organs were similar in both types of plans. The exceptions were the 25% isodose being significantly better in brachytherapy plans for rectum, and the 100% isodose exposure being higher in brachytherapy plans for rectum, bladder, and sigmoid colon. Some significant differences were also found in maximum doses received by a 2-cc volume of bladder in favor of SBRT plans. In addition, maximum bone marrow doses were significantly higher in SBRT plans. CONCLUSION SBRT plans achieved better target coverage and better dose distributions to critical organs except bone marrow compared with HDR brachytherapy plans in patients with locally advanced cervical cancer.

Two cases of Stevens–Johnson syndrome: toxic epidermal necrolysis possibly induced by amifostine during radiotherapy

Amifostine is a phosphorylated aminothiol prodrug that provides selective cytoprotection against the toxic effects of radiotherapy and chemotherapy for a number of normal tissues while affording little protection to tumoral tissue. Allergic reactions with amifostine are rarely reported in the literature. Stevens±Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are closely related severe, acute mucocutaneous reactions mostly elicited by drugs. SJS refers to cases with less than 10% of body surface involvement and TEN to those with more than 30% involvement; those with cutaneous detachment between 10 and 30% may be labelled as SJS±TEN overlap. We report two patients who developed SJS and SJS±TEN during amifostine treatment; to our knowledge these are the first reports of such an association for this kind of reaction.

BASAL CELL CARCINOMAS DEVELOPING IN A CASE OF MEDULLOBLASTOMA ASSOCIATED WITH GORLIN'S SYNDROME

We report a case of a 20-year-old male with Gorlins syndrome (nevoid basal cell carcinoma syndrome), developing multiple basal cell carcinomas within irradiation fields 10 years after the treatment of medulloblastoma.

Robotic stereotactic body radiotherapy in the treatment of sinonasal mucosal melanoma: Report of four cases

Sinonasal mucosal melanoma (SNMM) is a rare entity originating from melanocytes of the sinonasal mucosa. Postoperative radiotherapy is recommended in all cases to increase local control. However, external radiotherapy is rarely used as a definitive treatment modality. In this report, we present 4 cases of SNMM treated with CyberKnife (Accuray, Sunnyvale, CA).