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American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA.

INTRODUCTION: There is wide variation in the indications, treatment regimens, and dosimetry for brachytherapy in the treatment of cancer of the esophagus. No guidelines for optimal therapy currently exist. METHODS AND MATERIALS: Utilizing published reports and clinical experience, representatives of the Clinical Research Committee of the American Brachytherapy Society (ABS) formulated guidelines for brachytherapy in esophageal cancer. RESULTS: Recommendations were made for brachytherapy in the definitive and palliative treatment of esophageal cancer. (A) Definitive treatment: Good candidates for brachytherapy include patients with unifocal thoracic adeno- or squamous cancers < or = 10 cm in length, with no evidence of intra-abdominal or metastatic disease. Contraindications include tracheal or bronchial involvement, cervical esophagus location, or stenosis that cannot be bypassed. The esophageal brachytherapy applicator should have an external diameter of 6-10 mm. If 5FU-based chemotherapy and 45-50-Gy external beam are used, recommended brachytherapy is either: (i) HDR 10 Gy in two weekly fractions of 5 Gy each; or (ii) LDR 20 Gy in a single course at 0.4-1 Gy/hr. All doses are specified 1 cm from the midsource or mid-dwell position. Brachytherapy should follow external beam radiation therapy and should not be given concurrently with chemotherapy. (B) Palliative treatment: Patients with adeno- or squamous cancers of the thoracic esophagus with distant metastases or unresectable local disease progression/recurrence after definitive radiation treatment should be considered for brachytherapy with palliative intent. After limited dose (30 Gy) EBRT, the recommended brachytherapy is either: (i) HDR 10-14 Gy in one or two fractions; or (ii) LDR 20-25 Gy in a single course at 0.4-1 Gy/hr. The need for external beam radiation in newly diagnosed patients with a life expectancy of less than 3 months is controversial. In these cases, HDR of 15-20 Gy in two to four fractions or LDR of 25-40 Gy at 0.4-1 Gy/hr may be of benefit. CONCLUSION: ABS guidelines for esophageal brachytherapy now exist and will be updated by the ABS in the future, as clinical data using more uniform treatment techniques becomes available.

Adenocarcinoma

Fractionated high dose-rate versus low dose-rate regimens for intracavitary brachytherapy of the cervix: equivalent regimens for combined brachytherapy and external irradiation.

The conventional treatment for carcinoma of the uterine cervix is a combination of external teletherapy and low dose-rate (LDR) intracavitary brachytherapy. Recently, however, there has been an increasing trend toward the use of high dose-rate (HDR) brachytherapy, in combination with external irradiation. The question is addressed of designing HDR treatments that will produce equivalent results to the more conventional protocols. We argue that for the unique case of radiotherapeutic treatment of carcinoma of the cervix, the criterion for producing an equivalent treatment should be based on the matching of early, not late, effects. In essence, this is because the dose to the tissues at risk for late effects is usually significantly smaller than the prescribed dose. When this effect is factored in with the different shape of dose-response curves for early and late effects, we conclude that, in the majority of cases, late effects will be no worse in a HDR regimen than a LDR regimen, provided that the corresponding doses have been matched to produce equal early effects. We provide a formalism whereby equivalent protocols can be designed for combined "external + HDR brachytherapy" regimens to match current "external + LDR brachytherapy" schedules. Using extensive basic radiobiological in vitro data derived from various cells of human origin, we provide specific examples of equivalent "external + HDR brachytherapy" regimens for 23 current "external + LDR brachytherapy" commonly-used schedules.

Brachytherapy

Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments.

PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of "pulses," i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term "PDR brachytherapy" is used for treatment schedules with a large number of fractions (at least four per day), while the term "fractionated high dose rate (HDR) brachytherapy" is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. METHODS AND MATERIALS: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both alpha/beta values and the half time for repair of sublethal damage (T 1/2), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of alpha/beta and T 1/2. The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. RESULTS: If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears to be less need for strong fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (slightly) adapted, PDR schedules can be designed using longer pulse intervals of up to 3 h. Schedules with sufficiently long intervals have significant logistic advantages in terms of patient care and treatment tolerance. However, in general, PDR schedules that apply more fractionation have a lower risk of overdosing normal tissues in comparison to fractionated HDR schedules. Applying probable ranges for the values of alpha/beta and T 1/2, the model calculations indicate that the differences in effects between the proposed fractionated HDR and PDR schedules could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. CONCLUSIONS: Pulsed dose rate treatment schedules with longer intervals of up to 3 h appear adequate to replace LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment schedules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical studies.

Brachytherapy

[Bronchoscopic brachytherapy: development of bronchoscopic ultrasonography and brachytherapy for early stage lung cancer of hilar type].

We have recently developed bronchoscopic brachytherapy as a new modality for treating tracheal and bronchial malignancies, and have assessed the feasibility of bronchoscopic ultrasonic diagnosis and bronchoscopic brachytherapy for tracheal and bronchial malignant diseases, using a combination of videobronchoscope, an ultrasonic probe and a high-dose-rate Microselectron. Between September 1992 and December 1994, 34 patients having a total of 34 lesions of the trachea and bronchus received bronchoscopic brachytherapy at the National Cancer Center Hospital. In all 34 of these cases lung cancer was histologically confirmed by biopsy before treatment, although these cancer lesions were roentgenographically occult. Of the 34 patients who received bronchoscopic brachytherapy, 33 patients showed complete response to this therapy. Although 4 patients died of other diseases, the 3-year survival rate was 88.6%. The results of our study show that in such cases bronchoscopic brachytherapy yields a high rate of therapeutic response.

Brachytherapy

Influence of tumoral, radiobiological, and general factors on local control and survival of a series of 361 tumors of the velotonsillar area treated by exclusive irradiation (external beam irradiation+brachytherapy or brachytherapy alone)

PURPOSE: To evaluate statistically the factors influencing the therapeutic results. METHODS AND MATERIALS: A statistical study was carried out concerning 361 patients treated from 1977 to 1991 for velotonsillar carcinoma. They received either brachytherapy alone (18) or a combination of external beam irradiation and brachytherapy (343 patients) using an afterloading iridium technique in plastic tubes. The distribution of patients according to the localization was: 128 tonsils, 134 soft palates, 9 posterior pillars, 63 anterior pillars, and 27 glossotonsillar sulcus. The patients were staged as follows: 90 T1, 141 T2, 119 T3, 2 T4, 9 Tx with 230 N0, 93 N1, 9 N2, 20 N3, and 9 Nx. RESULTS: The results at 5 and 10 years show: local control 80% and 74%, locoregional control 75% and 70%, overall survival 53% and 27%, specific survival 63% and 52%, respectively. The univariate study shows at 5 years a better local control for T1T2 (87%) compared with T3 (67%) with p = 0.00004. The locoregional control is better for N0 (80%) than for N+ (55%) with p = 0.002. This is the same for the overall survival (59% vs. 42%, p = 0.002). Tumors with an extension to the mobile tongue or the base have a poor prognosis (p < 0.002). The radiobiological factors show less recurrences if the total duration of the treatment is < 55 days, the number of days between External Beam Irradiation and brachytherapy is < 20. The security margin seems important also. CONCLUSIONS: For the combination external irradiation and brachytherapy, the multivariate study for local control shows that ony T, localization, and the total duration of treatment are significant. For complications, classified into four grades, only the dose rate is significant.

Adult

Pulsed brachytherapy: the conditions for no significant loss of therapeutic ratio compared with traditional low dose rate brachytherapy.

Pulsed brachytherapy consists of using a stronger radiation source than for traditional low dose-rate brachytherapy, but giving a series of short exposures of 10 to 30 min in every hour, to approximately the same total dose in the same overall time as with the low dose-rate. Calculations based on the linear quadratic model, in which the beta x dose squared component only is assumed to be repairable, and at a monoexponential rate, show that there is no significant loss of therapeutic ratio, defined as tumor damage for a given level of late damage. Some loss of therapeutic ratio would in principle be expected when dose rates are increased, but, in the presently proposed applications, there are so many small pulses (fractions at medium or low dose-rate) that even though repair is not usually complete between them, the relative increase of late damage (in units proportional to log cell kill) is less than 10% more than the increase of tumor damage, except in unlikely conditions that we define. Although these calculations suggest that pulsed brachytherapy should be safe for pulse repetition frequencies up to about 2 hr, using dose rates not exceeding about 3 Gy/hr, we discuss the radiobiological reservations and the limitations of such calculations.

Brachytherapy

Neutron induced brachytherapy: a combination of neutron capture therapy and brachytherapy.

Brachytherapy is a widely used radiation therapy modality while neutron capture therapy is being intensely studied. These methods provide some advantages, but also have limitations that might be ameliorated by combining them. A technique that uses stable solid seeds or needles of Gd which are irradiated in vivo with neutrons has been evaluated. Monte Carlo calculations show that 5000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm3 with a three-plane implant of 9-Gd needles. The tumor to normal tissue advantage of this method is as good as brachytherapy using 60Co seeds. Measurements of prompt gamma dose with films and TLD-700s in a lucite phantom verify the Monte Carlo evaluation. Dose measurements of a Gd needle in air also show that Gd is promising for this form of brachytherapy.

Brachytherapy

Quality assurance in brachytherapy: principles for ionization chamber measurement of absorbed dose close to brachytherapy sources.

At present there exists no standardized procedure for absorbed dose determination with ionization chambers in the vicinity of brachytherapy sources. In this paper, a modification of the IAEA formalism for external photon beams is proposed in order to make it applicable at a reference point 20 mm from brachytherapy sources as well. A non-uniformity correction factor is introduced to correct for the effects of the steep absorbed dose gradient, and it is concluded that reasonable accuracy is possible when the Bragg-Gray principle is assumed to be valid.

Brachytherapy

Quality assurance in brachytherapy: the displacement effect in the vicinity of 60Co and 192Ir brachytherapy sources.

Cylindrical ionization chambers with varying radii have been used to determine the displacement effect at distances between 10 mm and 40 mm from 60Co and 192Ir brachytherapy sources. Agreement with published values of the displacement factor for external 60Co beams is obtained. The shift between the centre of the ionization chamber and the effective point of measurement is found to be only a few per cent of the internal radius of the cylindrical ionization chamber. The shift is found to be dependent on the source to ionization chamber centre distance.

Brachytherapy

Human cervical cancer clearance after 252Cf neutron brachytherapy versus conventional photon brachytherapy.

Tumor clearance pattern was studied for Stage IB carcinoma of the cervix using 252Cf neutron brachytherapy followed by fractionated radiotherapy as compared to conventional therapy using fractionated radiotherapy followed by 137Cs photon low-dose rate (LDR) implant therapy. Reduction in bulk of tumor was assessed by regular and frequent serial clinical observations. The tumor clearance pattern of the neutron-treated patients was greatly accelerated and radically different from those treated using conventional radiation.

Brachytherapy