Gokhan Ozyigit

Patterns of failure in patients receiving definitive and postoperative IMRT for head-and-neck cancer.

PURPOSE To analyze the patterns of locoregional failure in patients with head-and-neck cancer treated with inverse planning intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Between February 1997 and December 2000, 165 patients with histologically confirmed head-and-neck cancer were treated using a parotid-sparing inverse planning IMRT protocol. Thirty-nine patients who received either palliative repeat irradiation or IMRT as a boost were excluded from this analysis, leaving 126 patients for this analysis. Of the 126 patients, 30 were women and 96 were men (median age 56 years, range 13-84). Fifty-two patients (41%) received definitive IMRT. Of the 52 patients, 17 were treated with RT alone and 35 with concurrent cisplatin-based chemotherapy regimens. Seventy-four patients (59%) received postoperative IMRT. The median follow-up was 26 months (range 12-55). IMRT was used only in the upper neck for salivary sparing. The lower neck was treated with a conventional AP low-neck port abutted to the inferior IMRT dose distribution border. The radiation dose was prescribed to the two clinical target volumes (CTVs) according to the assumed risk of containing disease. The mean dose for definitive IMRT patients was 72.64 +/- 4.83 Gy to CTV1 and 64.34 +/- 5.15 Gy to CTV2. The mean dose to CTV1 and CTV2 in postoperative cases was 68.53 +/- 4.71 Gy and 60.95 +/- 5.33 Gy, respectively. The locations of failure were analyzed. RESULTS Seventeen locoregional failures (persistent or recurrent disease) were found. Of these 17 failures, 9 (53%) were inside CTV1. One failure (6%) was marginal to CTV1 but inside CTV2. One failure (6%) occurred outside CTV1 but inside CTV2. Another failure was marginal to CTV2. Of the 17 failures, 5 (28%) were found outside of the IMRT field and in the lower neck. Dose-volume histogram analysis revealed that for all but 1 patient, the recurrent/persistent disease within the CTVs received comparable or superior dose coverage relative to the CTV. The 2-year actuarial locoregional control rate was 85%, and the ultimate locoregional control rate after surgical salvage was 89%. We observed no dermal failure and only one marginal failure in the region adjacent to the spared parotid glands. CONCLUSION We have shown that the target definition and coverage for patients treated with IMRT for parotid sparing is adequate. The predominant tumor failure within CTV1 may imply the need to identify patients with radioresistant tumor subvolumes (such as hypoxic regions) within the CTV. This information would assist in discriminating a subgroup of tumors for a more aggressive and target-specific therapeutic approach.

DETERMINATION AND DELINEATION OF NODAL TARGET VOLUMES FOR HEAD-AND-NECK CANCER BASED ON PATTERNS OF FAILURE IN PATIENTS RECEIVING DEFINITIVE AND POSTOPERATIVE IMRT

PURPOSE We present the guidelines for target volume determination and delineation of head-and-neck lymph nodes based on the analysis of the patterns of nodal failure in patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS Data pertaining to the natural course of nodal metastasis for each head-and-neck cancer subsite were reviewed. A system was established to provide guidance for nodal target volume determination and delineation. Following these guidelines, 126 patients (52 definitive, 74 postoperative) were treated between February 1997 and December 2000 with IMRT for head-and-neck cancer. The median follow-up was 26 months (range 12-55), and the patterns of nodal failure were analyzed. RESULTS These guidelines define the nodal target volume based on the location of the primary tumor and the probability of microscopic metastasis to the ipsilateral and contralateral (Level I-V) nodal regions. Following these guidelines, persistent or recurrent nodal disease was found in 6 (12%) of 52 patients receiving definitive IMRT, and 7 (9%) of 74 patients receiving postoperative IMRT had failure in the nodal region. CONCLUSION On the basis of our clinical experience in implementing inverse-planning IMRT for head-and-neck cancer, we present guidelines using a simplified, but clinically relevant, method for nodal target volume determination and delineation. The intention was to provide a foundation that enables different institutions to exchange clinical experiences in head-and-neck IMRT. These guidelines will be subject to future refinement when the clinical experience in head-and-neck IMRT advances.

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.

The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network

PURPOSE The aim of this study was to assess the outcome of patients with primary spinal myxopapillary ependymoma (MPE). MATERIALS AND METHODS Data from a series of 85 (35 females, 50 males) patients with spinal MPE were collected in this retrospective multicenter study. Thirty-eight (45%) underwent surgery only and 47 (55%) received postoperative radiotherapy (RT). Median administered radiation dose was 50.4 Gy (range, 22.2-59.4). Median follow-up of the surviving patients was 60.0 months (range, 0.2-316.6). RESULTS The 5-year progression-free survival (PFS) was 50.4% and 74.8% for surgery only and surgery with postoperative low- (<50.4 Gy) or high-dose (>or=50.4 Gy) RT, respectively. Treatment failure was observed in 24 (28%) patients. Fifteen patients presented treatment failure at the primary site only, whereas 2 and 1 patients presented with brain and distant spinal failure only. Three and 2 patients with local failure presented with concomitant spinal distant seeding and brain failure, respectively. One patient failed simultaneously in the brain and spine. Age greater than 36 years (p = 0.01), absence of neurologic symptoms at diagnosis (p = 0.01), tumor size >or=25 mm (p = 0.04), and postoperative high-dose RT (p = 0.05) were variables predictive of improved PFS on univariate analysis. In multivariate analysis, only postoperative high-dose RT was independent predictors of PFS (p = 0.04). CONCLUSIONS The observed pattern of failure was mainly local, but one fifth of the patients presented with a concomitant spinal or brain component. Postoperative high-dose RT appears to significantly reduce the rate of tumor progression.

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.

Clinical experience of head-and-neck cancer IMRT with serial tomotherapy

New radiotherapy planning and delivery techniques are undergoing rapid progress and change due to computer hardware and software technologies that have led to the development of sophisticated 3-dimensional (3D) radiation treatment planning and computer-controlled radiation therapy delivery systems. Intensity-modulated radiation therapy (IMRT) is the most recent and advanced form of external beam radiation therapy often used to perform 3D conformal radiotherapy. It represents one of the most important technical advances in radiotherapy. IMRT has the potential to achieve a much higher degree of target conformity and normal tissue sparing than most other treatment techniques, especially for target volumes at risk with complex shapes and concave regions such as head-and-neck cancer. In this review, we summarize our own IMRT treatment techniques with serial tomotherapy and our clinical experience with 126 patients with head-and-neck IMRT.

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.

Investigating in-field and out-of-field neutron contamination in high-energy medical linear accelerators based on the treatment factors of field size, depth, beam modifiers, and beam type

PURPOSE We analysed the effects of field size, depth, beam modifier and beam type on the amount of in-field and out-of-field neutron contamination for medical linear accelerators (linacs). METHODS Measurements were carried out for three high-energy medical linacs of Elekta Synergy Platform, Varian Clinac DHX High Performance and Philips SL25 using bubble detectors. The photo-neutron measurements were taken in the first two linacs with 18 MV nominal energy, whereas the electro-neutrons were measured in the three linacs with 9 MeV, 10 MeV, 15 MeV and 18 MeV. RESULTS The central neutron doses increased with larger field sizes as a dramatic drop off was observed in peripheral areas. Comparing with the jaws-shaped open-field of 10 × 10 cm, the motorised and physical wedges contributed to neutron contamination at central axis by 60% and 18%, respectively. The similar dose increment was observed in MLC-shaped fields. The contributions of MLCs were in the range of 55-59% and 19-22% in Elekta and Varian linacs comparing with 10 × 10 and 20 × 20 cm open fields shaped by the jaws, respectively. The neutron doses at shallow depths were found to be higher than the doses found at deeper regions. The electro-neutron dose at the 18 MeV energy was higher than the doses at the electron energies of 15 MeV and 9 MeV by a factor of 3 and 50, respectively. CONCLUSION The photo- and electro-neutron dose should be taken into consideration in the radiation treatment with high photon and electron energies.