[Show abstract][Hide abstract] ABSTRACT: To study anatomic biologic contouring (ABC), using a previously described distinct halo, to unify volume contouring methods in treatment planning for head and neck cancers.
Twenty-five patients with head and neck cancer at various sites were planned for radiation therapy using positron emission tomography/computed tomography (PET/CT). The ABC halo was used in all PET/CT scans to contour the gross tumor volume (GTV) edge. The CT-based GTV (GTV-CT) and PET/CT-based GTV (GTV-ABC) were contoured by two independent radiation oncologists.
The ABC halo was observed in all patients studied. The halo had a standard unit value of 2.19 +/- 0.28. The mean halo thickness was 2.02 +/- 0.21 mm. Significant volume modification (>or=25%) was seen in 17 of 25 patients (68%) after implementation of GTV-ABC. Concordance among observers was increased with the use of the halo as a guide for GTV determination: 6 patients (24%) had a <or=10% volume discrepancy with CT alone, compared with 22 (88%) with PET/CT (p < 0.001). Interobserver variability decreased from a mean GTV difference of 20.3 cm3 in CT-based planning to 7.2 cm3 in PET/CT-based planning (p < 0.001).
Using the "anatomic biologic halo" to contour GTV in PET/CT improves consistency among observers. The distinctive appearance of the described halo and its presence in all of the studied tumors make it attractive for GTV contouring in head and neck tumors. Additional studies are needed to confirm the correlation of the halo with presence of malignant cells.
International Journal of Radiation OncologyBiologyPhysics 06/2007; 68(2):388-95. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) with the glucose analog [18F]fluro-2-deoxy-D-glucose (FDG) has been accepted as a valuable tool for the staging of lung cancer, but the use of PET/CT in radiation treatment planning is still not yet clearly defined. By the use of (PET/computed tomography (CT) images in treatment planning, we were able to define a new gross treatment volume using anatomic biologic contour (ABC), delineated directly on PET/CT images. We prospectively addressed three issues in this study: (1) How to contour treatment volumes on PET/CT images, (2) Assessment of the degree of correlation between CT-based gross tumor volume/planning target volume (GTV/PTV) (GTV-CT and PTV-CT) and the corresponding PET/CT-based ABC treatment volumes (GTV-ABC and PTV-ABC), (3) Magnitude of interobserver (radiation oncologist planner) variability in the delineation of ABC treatment volumes (using our contouring method).
Nineteen patients with Stages II-IIIB non-small-cell lung cancer were planned for radiation treatments using a fully integrated PET/CT device. Median patient age was 74 years (range: 52-82 years), and median Karnofsky performance status was 70. Thermoplastic or vacuum-molded immobilization devices required for conformal radiation therapy were custom fabricated for the patient before the injection of f-FDG. Integrated, coregistered PET/CT images were obtained and transferred to the radiation planning workstation (Xeleris). While the PET data remained obscured, a CT-based gross tumor volume (GTV-CT) was delineated by two independent observers. The PTV was obtained by adding a 1.5-cm margin around the GTV. The same volumes were recontoured using PET/CT data and termed GTV-ABC and PTV-ABC, correspondingly.
We observed a distinct "halo" around areas of maximal standardized uptake value (SUV). The halo was identified by its distinct color at the periphery of all areas of maximal SUV uptake, independent of PET/CT gain ratio; the halo had an SUV of 2 +/- 0.4 and thickness of 2 mm +/- 0.5 mm. Whereas the center of our contoured treatment volume expressed the maximum SUV level, a steady decline of SUV was noted peripherally until SUV levels of 2 +/- 0.4 were reached at the peripheral edge of our contoured volume, coinciding with the observed halo region. This halo was always included in the contoured GTV-ABC. Because of the contribution of PET/CT to treatment planning, a clinically significant (> or =25%) treatment volume modification was observed between the GTV-CT and GTV-ABC in 10/19 (52%) cases, 5 of which resulted in an increase in GTV-ABC volume vs. GTV-CT. The modification of GTV between CT-based and PET/CT-based treatment planning resulted in an alteration of PTV exceeding 20% in 8 out of 19 patients (42%). Interobserver GTV variability decreased from a mean volume difference of 28.3 cm3 (in CT-based planning) to 9.12 cm3 (in PET/CT-based planning) with a respective decrease in standard deviation (SD) from 20.99 to 6.47. Interobserver PTV variability also decreased from 69.8 cm3 (SD +/- 82.76) in CT-based planning to 23.9 cm3 (SD +/- 15.31) with the use of PET/CT in planning. The concordance in treatment planning between observers was increased by the use of PET/CT; 16 (84%) had < or =10% difference from mean of GTVs using PET/CT compared to 7 cases (37%) using CT alone (p = 0.0035). Conclusion: Position emission tomography/CT-based radiation treatment planning is a useful tool resulting in modification of GTV in 52% and improvement of interobserver variability up to 84%. The use of PET/CT-based ABC can potentially replace the use of GTV. The anatomic biologic halo can be used for delineation of volumes.
International Journal of Radiation OncologyBiologyPhysics 11/2005; 63(4):1016-23. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gemcitabine, a widely reported radiosensitizer, was found to increase and decrease radiation survival of HeLa cells under different treatment conditions. A 24 h exposure at 10 or 20 nM increased S phase cells and radiation survival, with a dose modification factor (DMF) of 0.82 or 0.78, respectively. Shortening exposure time avoided cell cycle effect and eliminated increases of radiation survival. Treatment for 1 h showed no change in radioresponse (DMF of 1.03) at 20 nM versus radiosensitization at 1, 2, or 20 microM (DMF of 1.66). These results document an enhanced radiation survival while confirming reported radiosensitization under different conditions. Such findings may impact drug dosimetry.
Cancer Letters 01/2003; 187(1-2):179-83. · 5.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The radioactive gold grain applicator and seeds offer the flexibility necessary for effective use in the treatment of difficult sites of head-and-neck cancers. This study reviews our experience with gold grain (198Au) implants in locally advanced head-and-neck cancer to demonstrate their efficacy and feasibility.
This study reviewed the charts of 94 patients who were treated with gold grain implants (1970-1995) and who were treated with radioactive 198Au implants. Thirty-seven of the subjects had implants located in the head-and-neck region, and these form the basis for this report. Of these, eight of the cases were located in the supraglottic larynx, five in the nasopharynx, four in the retromolar trigone, two in the oral cavity, four in the base of the tongue, four in the maxillary antrum, four in the palate, two in metastatic cervical lymph nodes (of unknown primary tumor), two in the tonsillar fossa, one in the pyriform fossa, and one in the posterior pharyngeal wall. Twenty-eight were recurrent cases after prior surgeries and radiation. Six were residual locally advanced cases, and 3 patients had their implants for a second primary tumor in an area that had been irradiated before. The gold grains were inserted with a Royal Marsden gun and 198Au, 130-180 MBq per seed. The median number of seeds implanted was 34. The total radiation dose, delivered at a margin of 0.5 cm around the target volume, ranged from 40 to 120 Gy, with a median of 80 Gy.
Complete local control was achieved in 33% and was contingent on two factors: (1) the size of the lesion implanted and (2) the histology and possible primary tumor site. In 19 tumors with a diameter greater than 2.5 cm, only 2 (11%) had complete tumor control. Conversely, 9 of 14 patients (64%) who had lesions smaller than 2.5 cm experienced successful local control (p = 0.002). Palatal-adenoid-cystic tumors had an average progression-free survival of 52 months, compared with 13, 9, and 4 months, respectively, in nasopharyngeal, oropharyngeal, and supraglottic squamous cell carcinoma. Palliation was successfully accomplished in 76% of the cases. Cessation of bleeding occurred in 50% of the subjects, pain control was achieved in 88%, and 60% experienced relief of dysphagia.
Gold grain implants have a role in the palliation of recurrent head-and-neck tumors, particularly for sites difficult to reach via other techniques, such as the supraglottic larynx, base of the tongue, hypopharynx, and the nasopharynx. Local control is best achieved in lesions less than 2.5 cm in dimension and is most successful in slow-growing tumors.
[Show abstract][Hide abstract] ABSTRACT: Cancer that recurs after surgery and radiation therapy remains a major problem. The claimed effectiveness of thermobrachytherapy in patients with this problem prompted the present study. Forty-six lesions (20 head and neck, 18 pelvic, seven chest wall, and one limb sarcoma) in 38 patients were treated with interstitial hyperthermia that sandwiched the use of Ir-192 with the aim of delivering 2,000-6,000 cGy, depending on prior dose and tissue tolerance. Complete regression occurred in 19 (54%) of 35 evaluable cases. More than 58,000 measured temperature points were analyzed to develop a representative quantitative measure, the "modal thermal dose," that represented the temperature reported most often during heating sessions. The pattern was plotted in each case. No significant relation was found between heating patterns and tumor response. Of all the prognostic factors studied, the radiation dose was the most significant, with a complete response rate being 78% when the total radiation dose exceeded 6,000 cGy, compared with 8% when the dose was lower than 5,000 cGy (P less than .005). The tumor volume also was important, with smaller lesions responding much better than larger ones (P = .1).
[Show abstract][Hide abstract] ABSTRACT: The T-cell subsets of 129 patients with cancer were counted before and after radiation therapy. The cells were labeled with monoclonal antibodies that were specific for each type of T cell. Significant changes after therapy were decreases in the proportion of T-helper/inducer cells, pan-T cells, and in the ratio of T-helper/inducer to T-suppressor/cytotoxic cells. There was an increase in the percentage of T-suppressor/cytotoxic cells. When the site of the primary cancer was considered, genitourinary cancer and cancer of the head and neck both showed a decreased percentage of T-helper/inducer cells and a reduced ratio of T-helper/inducer to T-suppressor/cytotoxic cells. The percentage of pan-T cells in head and neck cancer and the ratio of T-helper/inducer to T-suppressor/cytotoxic cells in breast cancer were decreased. The percentage of T-helper cells was particularly decreased by radiation therapy in advanced stages of cancer, in higher grade tumors, and in larger tumors. The absolute numbers of various T-cell subsets were decreased in all groups.
[Show abstract][Hide abstract] ABSTRACT: The effect of heat on 1,4-dihydroxy-5,8-bis[2-[(2-hydroxyethyl)amino]ethylamino]-9, 10-anthracenedione dihydrochloride (DHAD; mitoxantrone, NSC 301739) cytotoxicity was studied in V79 Chinese hamster cells. An overnight exposure to the drug at 40 degrees C enhanced drug damage in chromosome aberrations, culture growth, and cellular reproductive integrity. Preincubation of cells overnight in medium containing no drug at this temperature also showed some enhancement in subsequent DHAD lethality (at 37 degrees C as well as 43 degrees C). Short exposures (1 h) to DHAD at 43 degrees C was more damaging than were exposures at 37 degrees C. This was also true for cells in the plateau phase of culture growth. As compared with exponentially growing cells, plateau-phase cells were more resistant to DHAD.
Cancer Research 09/1985; 45(8):3593-7. · 8.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chinese hamster V79 cells were exposed to spirogermanium (SG), and their mitotic activity, population growth, plating efficiency, viability (dye exclusion), and clonogenicity were assayed. Mitotic frequency of cultures in SG decreased initially with increasing drug concentration and later plateaued at varying levels depending on drug concentration. Cultures continuously exposed to SG showed drug concentration-dependent growth inhibition, with no effect at 0.1-0.2 micrograms/ml and increasing toxicity above 0.5 microgram/ml. Cytolysis was enhanced by the simultaneous presence of amphoterocin B and by exposing cells to SG at 42 degrees C. Hypoxia protected cells from drug-induced lysis. The loss of membrane-intact cells was inversely related with population density at the time of drug exposure. Short exposures (up to 5 hours) at 20 micrograms/ml showed that cell killing was primarily through reduction of dye-excluding cells within a matter of hours and secondarily through loss of proliferative capacity. Prolonged drug contact (24 hours) at lower concentrations (1-5 micrograms/ml) accentuated the effect on clonogenicity. These results suggest that for clinical potency, prolonged drug contact may be beneficial.
American Journal of Clinical Oncology 07/1983; 6(3):331-7. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cell-mediated immune status of 147 patients who received radiotherapy was evaluated using in vitro tests (PHA, E-rosette and spontaneous blastogenesis) both before and 6 weeks after the end of radiation. All patients had verified malignancies, involving the bronchus in 29 cases, breast in 28, female genital system in 26, head and neck in 20 and bladder in 15. Patients suffering from bronchogenic carcinomas or malignancies of the head and neck showed a relative high degree of immune suppression. Our findings indicate a trend towards some improvement in PHA reactivity, as well as in as the percentage of E-rosette-forming cells after treatment, which is more noticeable in patients with pelvic or breast tumors. A relationship seems to exist between the tumor load and the immune status, which reverts to a normal pattern when the former is extinguished. Moreover, patients with poor clinical response display a profoundly depressed level of immune status without any improvement after treatment.
Cancer 04/1978; 41(3):1076-86. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The role of radiotherapy in the management of rectal and rectosigmoid cancer is still far from clear. Our experience with 98 patients is presented: eight patients were treated with radical radiotherapy, 13 received postoperative radiation, and 67 were treated for palliative purposes only (bleeding, pain, mass, and fistulation). Satisfactory results were demonstrated in all three categories, and sterilization of disease by radiation was histologically proven in three cases. The necessity of high-dose radiation for the achievement of optimum results is demonstrated, and the techniques and problems are described.
American Journal of Roentgenology 12/1976; 127(5):841-5. · 2.90 Impact Factor