Laval Grimard

Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer

BACKGROUND The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown. METHODS We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group). RESULTS The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], -2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, -6.9 to 9.8). CONCLUSIONS Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.)

Effect of dose rate on local control and complications in definitive irradiation of T1-2 squamous cell carcinomas of mobile tongue and floor of mouth with interstitial iridium-192.

From 1971 to 1988, 134 T1 and 145 T2 biopsy-proven squamous cell carcinomas of mobile tongue and floor of mouth were definitively managed by iridium-192. Implantations were performed using either guide gutters or afterloading plastic catheters. The prescribed dose at the reference isodose (85% of the basal dose rate, Paris system) was 60-70 Gy. Total dose was not adjusted to dose rate or tumor volume. Results of the 279 implants have been analysed to look for a possible influence of dose rate on local control and necrosis. Follow-up patients free of local recurrence is 1-180 months with average of 51 months. The 279 tumors were divided in four groups according to dose and dose rate: greater than or equal to 62.5 Gy and greater than or equal to 0.5 Gy/h (n = 130), greater than or equal to 62.5 Gy and less than 0.5 Gy/h (n = 36), less than 62.5 Gy and greater than or equal to 0.5 Gy/h (n = 81), less than 62.5 Gy and less than 0.5 Gy/h (n = 32). The four groups were comparable according to age, sex, tumor diameter and macroscopic aspect. At 5 years, the estimated local control (Kaplan Meier) was 93, 87, 79 and 52%, respectively (dose adjusted to dose rate: p less than 0.001, dose rate adjusted to dose: p less than 0.01, Log-rank); the necrosis rate was 44, 24, 37 and 5%, respectively (dose adjusted to dose rate: p = 0.08, dose rate adjusted to dose: p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of curietherapy versus external irradiation combined with curietherapy in Stage II squamous cell carcinomas of the mobile tongue

One hundred and ten patients with Stage II epidermoid carcinomas of the mobile tongue were treated by interstitial irradiation (Group I: 85 patients) or external irradiation to the primary and the regional lymphatics followed by an interstitial boost (Group II: 25 patients). The neck was managed by either an elective neck dissection (43 patients) completed by external irradiation in 13 patients with pathological specimen or close follow-up (40 patients) with therapeutic neck dissection for relapses (7 patients) in Group I. Primary local control was 88% in Group I and 36% in Group II. Regional control was 91% in Group I and 5/6 in Group II for patients whose primary tumor was controlled. Five-year absolute disease-free survival (DFS) was 42% in Group I and 24% in Group II, but there was an imbalance in the distribution of larger tumors favoring Group I. There were 30 radiation-induced complications and four patients required corrective surgery. This retrospective analysis showed better results in patients whose primary was treated by interstitial irradiation alone which has the extra advantage of preserving salivary function.

Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth

From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension.

Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer: a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3).

PURPOSE Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G(1) phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. METHODS AND MATERIALS A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. RESULTS Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). CONCLUSION In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving >/=66 Gy and in patients who smoked during therapy.

Vascular complications of cranial radiation.

ObjectivesCerebral vascular disease has been reported as a long-term complication of cranial radiotherapy. The purpose of this study was to examine the frequency and risk factors associated with development of cerebral vascular disease in children after cranial radiation.Materials and methodsA retrospective chart review of all cancer patients treated between 1985 and 2003 who were under the age of 18 years at the time of initial radiotherapy was performed. Variables examined include diagnosis and site of malignancy, age at the time of radiotherapy, sex, total radiation dosage, number of fractions, duration, and whether the patient had proven cerebral vascular event.ResultsTwo hundred and forty-four patients met the study criteria. One hundred and 13 cases involved tumors of the central nervous system. The remaining patients had systemic neoplastic disease. Post radiation cerebral vascular disease occurred in 11 (5%) patients, and all but one patient had a tumor involving the central nervous system (mainly in the posterior fossa and supratentorial midline).ConclusionThere is an increased risk of cerebral vascular disease after radiation therapy in childhood, especially in children who received high dose radiation at the posterior fossa and supratentorial axial region.

Effect of intersource spacing on local control and complications in brachytherapy of mobile tongue and floor of mouth

From 1971 to 1988, 133 T1 and 141 T2 biopsy-proven squamous cell carcinomas of mobile tongue and floor of mouth were definitively managed by Iridium-192. Implantations were performed using either guide gutters or afterloading plastic catheters. The prescribed dose at the reference isodose (85% of the basal dose rate, Paris system) was 60-70 Gy. Total dose was not adjusted to dose rate or tumor volume. Results of the 274 implants have been analysed to look for a possible influence of intersource spacing on local control and necrosis. Follow up for patients free of local recurrence is 1-180 months with median of 35 months. The 274 tumors were divided into two groups according to intersource spacing: 9-14 mm (n = 204), and 15-20 mm (n = 70). At 5 years, the estimated local control (Kaplan Meier) was 86% and 76%; respectively (p = 0.13); the necrosis rate was 33% and 46%, respectively (p = 0.04). Multivariate analysis shows that dose and activity of wires were significantly related to local control, while only tumor site was predictive of necrosis; there was a non-statistically significant relationship between intersource spacing of wires and local control (p = 0.055). When considering only patients with oral tongue cancers, necrosis was significantly related to activity of wires (p = 0.013), and there was a non-significant trend to a relationship between necrosis and intersource spacing (p = 0.066) and tumor diameter (p = 0.065). For patients with floor of mouth cancer, none of these factors was significantly related to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dosimetry of intraluminal brachytherapy

Dose specification in intraluminal brachytherapy varies considerably in the literature. A terminology is proposed, inspired from the Paris System of interstitial brachytherapy, to define some dosimetric guidelines. The dose is specified in the central plane which is a plane perpendicular to the source and passing through its centre. The reference dose rate is calculated in this plane. The treated volume is the volume encompassed by the reference isodose. The hyperdose sleeve is the volume receiving a dose equal to or greater than twice the reference dose. A study of the dose distribution along a linear source of iridium-192 was undertaken. Results obtained, also valid for caesium-137 and cobalt-60, show that the radius of the hyperdose sleeve is relatively independent of the length of the source. It is approximately 0.6 times the distance between the source axis and the point of dose specification when the active length varies from 3 to 20 cm. Reporting not only the dose, but also the thickness of tissue covered by the reference isodose and the thickness of tissue included in the hyperdose sleeve, is recommended to assist in evaluation of the results of treatment and to facilitate the exchange of clinical information in intraluminal brachytherapy. Practical examples are given.

A new combined approach in the conservative management of rectal cancer

Between 1980 and 1987, 25 patients with rectal cancer were treated with a combination of preoperative external irradiation of 35 Gy in 15 fractions over 3 weeks which was followed, 6 to 8 weeks later, by a tumorectomy and peroperative placement of a plastic tube loop for post-operative interstitial therapy by iridium-192. This boost dose was 20 Gy (Paris System) for submucosal lesions (seven patients) and 25 Gy for intramural (eight patients) and extramural (ten patients) lesions. With a mean follow-up of 40.5 months, there have been five local recurrences, the latest occurring 16 months post-tumorectomy. Two of these five patients are alive and disease-free 1 year post salvage abdominoperineal resection. The 20 patients with local control have preserved a full functional sphincter and 19 of them are disease-free; there were few complications. This sphincter preserving combined approach seems promising for patients with tumors of the middle and lower rectum who cannot undergo major surgery and for selected patients who refuse abdominoperineal resection.

Interstitial low‐dose‐rate brachytherapy in the treatment of recurrent head and neck malignancies

Recurrent head and neck malignancies are therapeutically challenging. Brachytherapy is a retreatment alternative to external‐beam radiation therapy (EBRT).