James G. Schwade

Interstitial microwave hyperthermia applicators having submillimetre diameters

Using microscopic techniques we have fabricated interstitial hyperthermia applicators having diameters of 0.20, 0.33 and 0.58 mm, which will fit through catheters of 30, 26 and 22 gauge, respectively. Existing commercial applicators having a diameter of 1.1 mm required 17 gauge (or larger) catheters. Our new applicators, which operate at 915 MHz, are a smaller version of a design used by others. We have characterized our applicators by determining the energy deposition patterns (SAR) in muscle-simulating phantoms. These patterns were determined by measuring the electric field intensity using a miniature implantable isotropic probe having a diameter of 3 mm. Contours of the SAR data for our applicators, as well as a larger commercial applicator, show that all of these applicators exhibit similar heating patterns. Test results suggest that the durability and power handling capability of our submillimetre applicators are adequate for use in patients. Our new applicators should be useful in the percutaneous treatment of deep-seated tumours, intraoperative treatments, and also permit intraluminal or intravascular access to tumours.

The Prognostic Significance of Surgical Staging for Carcinoma of the Endometrium

This study is based on a retrospective review of 156 patients with endometrial carcinoma from 1978 through 1984 who underwent primary surgical evaluation. All cases were retrospectively restaged using the newly adopted FIGO surgical staging. The preoperative FIGO clinical stage distribution for this study was as follows: 121 (77.6%) Stage I, 22 (14.1%) Stage II, 5 (3.2%) Stage III, 2 (1.3%) Stage IV, and 6 (3.8%) unstaged patients. Most patients had TAH-BSO with a collection of peritoneal washings and retroperitoneal lymph node sampling. Surgical staging revealed 122 (78.2%) Stage I, 9 (5.8%) Stage II, 12 (7.7%) Stage III, and 13 (8.3%) Stage IV patients. Surgery upstaged 12.4% of clinical Stage I. In clinical stage II, 59.0% were downstaged while 27.3% were upstaged. For clinical Stage III, 60.6% were upstaged, but no downstaging occurred. No change in stage occurred for clinical Stage IV patients. Ninety-seven surgically staged patients received no adjuvant therapy. The remaining 59 patients had adjunctive treatment which consisted of radiotherapy (59.3%), hormonal therapy (25.4%), chemotherapy (5.1%), or combined modality treatment (10.2%). All patients were followed until death or a minimum of 5 years (60-139 months; median, 82 months) with the exception of 13 patients who were lost to follow-up (2-58 months; median, 34 months). Five-year survival by clinical staging was as follows: 86.2% for Stage I, 85.9% for Stage II, and 0% for Stage III and IV. Five-year survival by surgical staging was 90.6% for Stage I, 85.7% for Stage II, 58.3% for Stage III, and 0% for Stage IV. The 13 patients who were lost to follow-up were censored in all survival analyses at the time of last contact. Stepwise regression analysis using a parametric proportional hazards model identified surgical stage as the most significant prognostic factor (P = 0.02). Univariate analysis showed that patients with surgical Stage IC had significantly worse prognosis (75.0%, 5 years) than those in surgical Stage IA (93.8% 5 YS) or IB (95.4% 5 years). In summary, this study demonstrates that surgical staging as recommended by FIGO is indicated to accurately determine the initial extent of disease in endometrial carcinoma. In addition, surgical staging is the strongest predictor of survival. Deep myometrial invasion appears to be a significant independent prognostic factor within surgical Stage I. The role of adjunctive radiotherapy in Stage I disease awaits the results from an ongoing multi-institutional, prospectively randomized trial.

Application of Robotic Stereotactic Radiotherapy to Peripheral Stage I Non-small Cell Lung Cancer with Curative Intent

AIMS To determine the effectiveness of robotic stereotactic radiotherapy with image guidance and real-time respiratory tracking against early stage peripheral lung cancer. MATERIALS AND METHODS We treated patients with stage I non-small cell lung cancer (NSCLC) with CyberKnife and analysed their clinical characteristics and outcomes. All patients had co-morbid conditions that precluded lobectomy. The clinical target volume (CTV) included the gross tumour volume (GTV) and a 6mm margin in all directions to account for microscopic extension. The planning target volume (PTV) equalled CTV+2mm in all directions for uncertainty. Tumour motion was tracked using a combination of Synchrony and Xsight Spine tracking methods with the aid of a single gold marker implanted in the centre of the tumour, or using the newer Xsight Lung method without markers for selected tumours. A 60-67.5 Gy dose was prescribed to the 60-80% isodose line (median 65%) and given in three to five fractions. Patients were followed every 3 months for a median of 27.5 months (range 24-53 months). RESULTS Of the 67 patients with NSCLC stage IA or IB treated between January 2004 and December 2008, we report the results of a cohort of 31 with peripheral stage I tumours of 0.6-71 cm(3) volume treated between January 2004 and December 2007 with total doses between 60 and 67.5 Gy in three to five fractions. The median D(max) was 88.2 Gy and the median V(95) of the PTV was 99.6% or 27.9 cm(3). No grade 3 or above toxicity was encountered. Four cases of radiation pneumonitis and one case of oesophagitis were observed. In those patients whose pre- and post-treatment results were available, no change in pulmonary function tests was observed. Actuarial local control was 93.2% for 1 year and 85.8% for up to 4.5 years. One-year overall survival was 93.6% and 83.5% for up to 4.5 years, as projected by Kaplan-Meier analyses. CONCLUSIONS In this small cohort of patients with stage I peripheral NSCLC, robotic stereotactic radiotherapy seems to be a safe and obviously superior alternative to conventionally fractionated radiotherapy, with results that may be approaching those obtained with lobectomy without the associated morbidity.

Lung Metastases Treated by CyberKnife® Image-Guided Robotic Stereotactic Radiosurgery at 41 Months

Objectives: Based on the reported success of stereotactic body radiotherapy in treating extracranial tumors, we used CyberKnife® (Accuray Incorporated, Sunnyvale, CA) to treat patients with metastatic lung cancer. Methods: This is a retrospective report of treatment details and outcomes of 35 patients, ranging in age from 33 to 91 years, with 69 histologically proven pulmonary metastases, treated by image-guided robotic stereotactic radiosurgery at the CyberKnife® Center of Miami, between March 2004 and August 2007. Tumor volumes ranged from 0.7 mL to 152 mL. Total doses ranged from 5 to 60 Gy delivered in one to four fractions with an equivalent dose range from 6 to 110 Gy NTD delivered in 2-Gy fractions assuming an α/β of 20 Gy. Results: All patients tolerated radiosurgery well with fatigue as the main side effect. Grade 3 and grade 4 pulmonary toxic reactions were observed in one patient who had undergone a repeat treatment. Of the 35 treated patients, 27 (77%) were still alive at a median 18-month (range 2–41 mo) follow-up. Local control was 71% with 25 tumors showing a complete response, 16 a partial response, and 7 stable with disease. Eight had progressive disease. Conclusions: The delivery of precisely targeted radiation doses to lung tumors in a hypofractionated fashion is feasible and safe. image-guided robotic stereotactic radiosurgery of pulmonary metastases with the CyberKnife® achieves good rates of local disease control with limited toxicity to surrounding tissues and in many cases may be beneficial for patients for whom surgery is not an option.

Stereotactic target point verification of an X ray and CT localizer

Stereotactic radiosurgery with a linear accelerator requires the accurate determination of a target volume and an accurate match of the therapeutic radiation dose distribution to the target volume. X ray and CT localizers have been described that are used to define the target volume or target point from angiographic or CT data. To verify the accuracy of these localizers, measurements were made with a target point simulator and an anthropomorphic head phantom. The accuracy of determining a known, high contrast, target point with these localizers was found to be a maximum of +/- 0.5 mm and +/- 1.0 mm for the X ray and CT localizer, respectively. A technique using portal X rays taken with a linear accelerator to verify the target point is also described.

In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines

Background. This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation‐modulation effects of recombinant α‐IFN and β‐IFN on two different human cervical cancer cell lines: ME‐180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated.

Hyperfractionated radiation therapy and 5-fluorouracil, cisplatin, and mitomycin-C (+/- granulocyte-colony stimulating factor) in the treatment of patients with locally advanced head and neck carcinoma.

The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte‐colony stimulating factor (G‐CSF) was added during the second phase of this study.

Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: A potentially lethal complication

New multi-programmable pacemakers frequently employ complementary metal oxide semiconductors (CMOS). This circuitry appears more sensitive to the effects of ionizing radiation when compared to the semiconductor circuits used in older pacemakers. A case of radiation induced runaway pacemaker in a CMOS device is described. Because of this and other recent reports of radiation therapy-induced CMOS type pacemaker failure, these pacemakers should not be irradiated. If necessary, the pacemaker can be shielded or moved to a site which can be shielded before institution of radiation therapy. This is done to prevent damage to the CMOS circuit and the life threatening arrythmias which may result from such damage.

Early results of CyberKnife image-guided robotic stereotactic radiosurgery for treatment of lung tumors

Objective: To determine if image-guided robotic stereotactic radiosurgery (IGR-SRS) by CyberKnife achieves acceptable local control in resectable but medically inoperable patients with non-small cell lung cancer (NSCLC) or pulmonary metastasis, and to evaluate control rates and toxicity. Methods: Treatment details and outcomes were reviewed for 95 patients (age range 33–96 years) with 136 histologically proven cancers treated by IGR-SRS at the CyberKnife Center of Miami between March 2004 and March 2007. Tumor volumes ranged from 1.2 cc to 338 cc. Targeting was accomplished using combined skeletal alignment and real-time tracking via fiducials placed within the tumor. Total doses ranged from 15 to 67.5 Gy delivered in 1 to 5 fractions. Results: Of the 95 patients treated, 78 (82%) are still alive at 1 to 36 months post-treatment. Nineteen patients have died, four from disease other than cancer progression. All patients but one achieved at least partial response to treatment and tolerated radiosurgery well. For the majority of our patients, fatigue had been the main side effect. Conclusions: The delivery of precisely targeted high radiation doses with surgical precision to lung tumors in a hypo-fractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery (IGR-SRS) of lung tumors with the CyberKnife achieves excellent rates of local disease control with limited toxicity to surrounding tissues, and in many cases may be curative for patients for whom surgery is not an option.

Radiosurgery target point alignment errors detected with portal film verification.

Stereotactic radiosurgery with a linear accelerator requires an accurate match of the therapeutic radiation distribution to the localized target volume. Techniques for localization of the target volume using CT scans and/or angiograms have been described. Alignment of the therapeutic radiation distribution to the intended point in stereotactic space is usually accomplished using precision mechanical scales which attach to the head ring. The present work describes a technique used to verify that the stereotactic coordinates of the center of the intended radiation distribution are in agreement with the localized target point coordinates. This technique uses anterior/posterior and lateral accelerator portal verification films to localize the stereotactic coordinates of the center of the radiation distribution with the patient in the treatment position. The results of 26 cases have been analyzed. Alignment errors of the therapeutic radiation distribution in excess of 1 mm have been found using the portal film verification procedure.