Jorgen L. Hansen

American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy.

PURPOSE This report presents an update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer. METHODS Members of the ABS with expertise in cervical cancer formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder, or interstitial applicators for locally advanced cervical cancer. These guidelines were written based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy. RESULTS The ABS affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion before treatment delivery. Applicator placement, dose specification, and dose fractionation must be documented, quality assurance measures must be performed, and followup information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2-Gray (Gy) per fraction radiobiologic equivalence (normalized therapy dose) is 80-90Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed. CONCLUSION These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.

Radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: Rationale and technique

We have recently initiated a program for irradiating small, unresectable arteriovenous malformations (AVMs) in the brain. The treatments are delivered using a modified and carefully calibrated 6 MV linac. We are using high, single doses (15 to 25 Gy) with a goal of sclerosing the vessels and preventing hemorrhages. This technique, radiosurgery, is somewhat controversial in the radiotherapy community. Since the treatment is given in a single sitting, rather than in the more conventional pattern of multiple small daily fractions, there is some concern about late radiation damage to the normal brain tissue. However an extensive review of the literature leads us to the conclusion that if a technique is used that keeps the volume irradiated to high dose small, radiosurgery is a safe and efficacious treatment for small (less than 2.5 cm) AVMs. To decrease the risk of necrosis of normal brain tissue, it is important to confine the high dose region as tightly as possible to the target volume. Precise target localization and patient immobilization is achieved using a stereotactic head frame which is used during angiography, CT scanning, and during the radiation treatment. This minimizes the margin of safety that must be added to the target volume for errors in localization and set-up. The treatment is delivered using multiple noncoplanar arcs, with small, sharp edged X ray beams, and with the center of the AVM at isocenter. This produces a rapid dropoff of dose beyond the target volume. Early results in our first few patients are encouraging.

Age at first birth, parity and risk of breast cancer in a Swedish population

A case-control study was conducted over a period of 11 months in an area containing one-third of the Swedish population. One thousand and one patients participated, constituting 94% of all women newly diagnosed as having breast cancer within the area. They were compared with 1,001 age-matched, non-hospitalized controls without breast cancer, selected by paired sampling from a population register. The risk of breast cancer was slightly, but significantly, related to parity, the standardized relative risk (SRR) being 1.35 for nulliparous women as compared to ever parous. In the different parity groups a risk significantly lower than that for nulliparous women was found only for women with more than 2 children (SRR = 0.59) but the trend with parity was highly significant (P less than 0.001). Age at first birth was not found to be an important risk factor for breast cancer. SRR was lower than for nulliparous women in all groups of women with their first birth before the age of 35 years, but the difference was significant (P less than 0.05) only for those with the first birth between 20 and 24 (SSR = 0.69) and 25 and 29 (SRR = 0.69) years of age. The trend with age at first birth (P less than 0.05) disappeared after stratification for parity, suggesting that it was a confounding factor.

Characteristics of familial breast cancer in sweden: Absence of relation to age and unilateral versus bilateral disease

A case‐control study was conducted to examine the hypothesis that familiality in breast cancer is a heterogeneous entity. A study of 1330 women, recently diagnosed as having breast cancer, compared, by paired sampling from a population register, the same number of age‐matched women without a history of breast cancer. Data obtained by mailed questionnaires revealed a familial history in a first‐degree relative in 149 patients and 90 controls (standardized relative risk/SRR/ = 1.7). The figures for second degree relatives were 115 and 81, respectively (SRR = 1.5). A detailed analysis of age at diagnosis and the occurrence of bilateral disease in the probands and their first‐degree relatives with breast cancer failed to confirm any significant trend towards characterization of familial cases by early occurring or bilateral disease. The SRR for breast cancer in a first‐degree relative was 1.7 for women with unilateral disease and 2.2 for those with bilateral. A slightly higher but nonsignificant relative risk was found for women diagnosed before (SRR = 2.4) than after (SRR = 1.7) 50 years of age. Familial cases did not run a higher risk of developing bilateral disease than nonfamilial—6 and 5%, respectively. No patient or control reported premenopausal and bilateral disease in her mother, whereas three patients and five controls reported these characteristics in one of their sisters. The correlation between age at diagnosis in familial patients and their mothers or sisters with breast cancer was low—0.38 and 0.29, respectively—and there was no correlation with respect to the occurrence of bilateral disease within the families.

A phase I-II trial of cisplatin, hyperthermia and radiation in patients with locally advanced malignancies

A Phase I-II trial testing the addition of systemic cisplatin (CDDP) to local hyperthermia and radiation was conducted to determine the dose of cisplatin that is tolerable once weekly for 6 weeks and to estimate the therapeutic potential of this trimodality combination in patients with locally advanced malignancies. Cisplatin at 20 mg/m2 (4 patients), 30 mg/m2 (8 patients), and 40 mg/m2 (12 patients) was given rapidly (over 5-10 min) i.v. after prehydration with 1 liter of normal saline. After approximately two-thirds of the cisplatin dose had been delivered, microwave hyperthermia was begun and continued for 60 min; the target minimum tumor temperature was 43 degrees C. Following hyperthermia, a 400 cGy fraction of radiation was delivered to the tumor. On other days during the treatment weeks, additional 200 cGy fractions were given to total doses of 6,000-6600 cGy in patients with full radiation tolerance or 2400-3600 cGy in patients with limited radiation tolerance. The 24 patients in this trial had a median age of 57 years and the predominant sites/tumor types were head and neck/squamous cell carcinoma (9) and chest wall/breast adenocarcinoma (9). Seventeen of the 24 treated tumors (70%) had previously been irradiated. Eighteen patients (75%) had received prior chemotherapy and nine patients (38%) had previously been treated with cisplatin. Bone marrow suppression was dose limiting in patients heavily pretreated with chemotherapy and chest wall radiation. No significant toxicities were observed at the 20 and 30 mg/m2 dose levels, but 5 of the 12 patients (42%) treated at 40 mg/m2 required modification of the cisplatin dose because of blood count suppression in four patients and mild renal dysfunction in one patient. Each of the patients with bone marrow suppression, however, had been heavily pretreated except for one patient with thrombocytopenia due to hypersplenism. Nausea and vomiting were mild with use of a standard, multiagent antiemetic regimen. Twelve patients (50%) attained a complete regression (CR) and 12 patients (50%) a partial regression (PR). Complete regression appeared to correlate with small tumor volumes (115 cc for CR versus 199 cc for PR patients) and higher tumor temperatures (4.6 average minimum equivalent minutes at 43 degrees C in CR versus 2.0 min in PR patients). Local toxicities included second degree burns in 12 patients (50%) and third degree burns in 6 (25%), but all burns healed in 4-12 weeks without surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer: long-term results from Dana-Farber Cancer Institute study 94-153.

The authors present long‐term results from a phase 2 study that assessed the efficacy of transrectal ultrasound hyperthermia plus radiation with or without androgen suppression for the treatment of locally advanced prostate cancer.

Familiality in breast cancer: a case-control study in a Sweden population.

1330 consecutively diagnosed breast-cancer patients, and an equal number of paired aged-matched controls without breast cancer, were investigated for a familial history of breast cancer. Patients and controls received identical questionnaires. One relative or more with breast cancer was reported by 18.6% of the patients and by 12.3% of the controls, giving a standardized relative risk (SRR) of 1.6 (P < 0.01). One or more first-degree relatives with breast cancer were reported by 11.2% of the patients and by 6.8% of the controls, with an SRR of 1.7 (P < 0.01). For second-degree relatives the SRR was 1.5 (P < 0.05). Of the patients, 3.9% had mothers with breast cancer compared to 2.7% of the controls (SRR = 1.4, N.S.). One or more sisters with breast canceer were reported by 10.1% of the patients and by 5.1% of the controls (SRR = 2.0, P < 0.01). No distinct difference in familiality between the different age groups was found.

Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields

PurposeTo assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSite™ applicator and compare to those produced by whole breast external beam radiotherapy (WBRT).Materials and methodsDosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400 cGy was 1 cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10 Gy or more (V10) and the dose received by 20 cc of the structure (D20), were calculated as well as the maximum and mean doses received.ResultsFifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925–1380 cc. Cardiac volumes ranged from 337–551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction.ConclusionThis study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets.Trial registrationDana Farber Trial Registry number 03-179

Design of an ultrasonic therapy system for breast cancer treatment

This paper describes the design of a novel ultrasonic therapy system dedicated to the breast cancer treatment and the theoretical investigation of the heating characteristics of the system. The applicator is a cylinder comprised of a stack of rings. Each ring has up to 48 transducers mounted on the inside of the ring and directed towards the centre. The transducers operate in one of two frequency bands (1.8-2.8 MHz and 4.3-40.8 MHz), arranged alternately in each ring. During treatment the patient is positioned in prone position, with the breast immersed in water and surrounded by this array. This design was modelled and optimized by 3-D simulations for a variety of treatment conditions. The simulated results demonstrate that the system has an excellent capability to achieve and maintain a temperature distribution (41.5-44 degrees C) in a quadrant to a whole breast. Initial experiments using a single ring of transducers has been performed to verify the power deposition calculation.