Effect of delay in initiating radiotherapy for patients with early stage breast cancer.

AIMS: For early stage breast cancer, a standard treatment option is partial mastectomy followed by radiation treatment. The 5-year risk of local recurrence ranges from 6-9%. Variable waiting times for radiation treatment of breast cancer in our institution provided an opportunity to evaluate the impact of waiting time on the risk of local recurrence. MATERIALS AND METHODS: Between January 1988 and December 1989, 482 patients with stage I and II breast cancer were treated with radiotherapy in our institution. Information on prognostic factors, such as age, tumour size, histological grade, number of positive lymph nodes and margins of resection, was abstracted from their charts. The interval between date of surgery and date of initial radiation treatment was noted. Dates of local recurrence, metastasis and deaths were recorded. RESULTS: At 5 years, the local recurrence rate was 8%, the metastatic rate 12% and the 'cause-specific' survival rate 90%. In univariate analysis, the risk of local recurrence was associated with younger age, higher histological grade and time to radiation treatment. In the multivariate analysis, the effect of time to radiation treatment on the risk of local recurrence was equivocal. CONCLUSION: Delay in radiation treatment may be associated with an increased risk of local recurrence of breast cancer, at least in our centre. Future research is needed on a larger data set to more accurately estimate the effect of time to radiation treatment on the risk of local recurrence.

Function and health status outcomes in a randomized trial comparing preoperative and postoperative radiotherapy in extremity soft tissue sarcoma.

PURPOSE: Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing preoperative versus postoperative RT is described. PATIENTS AND METHODS: One hundred ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, 6 weeks, and 3, 6, 12, and 24 months after surgery. RESULTS: One hundred eighty-five patients had function data. Patients treated with postoperative RT had better function with higher MSTS (25.8 v 21.3, P <.01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at 6 weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health subscales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first 2 years after treatment. CONCLUSION: The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.

Stereotactic radiation in primary brain tumors in children and adolescents.

To evaluate treatment outcome and morbidity of stereotactic external-beam irradiation (SEBI) in pediatric patients, we reviewed 14 children treated with SEBI, using a 10-MV isocentric linear accelerator at McGill University between 1988 and 1994. The median follow-up was 46 months (range 6-82 months). The median age was 14 years. There were 8 low-grade astrocytomas, 3 neuromas and 4 other histologies. Twelve patients received fractionated treatments. The median collimator diameter was 2.5 cm (range 1-5 cm). The median biological effective dose delivered to the entire tumor volume was 57 Gy for astrocytomas and 43 Gy for the other histologies. The overall actuarial survival rate and disease-free survival rate at 5 years were 83 and 62%, respectively. For the patients with low-grade astrocytomas, the 5-year survival and disease-free survival rates were 100 and 60%, respectively. Four children had recurrence at a median of 37 months. Four patients developed treatment-related complications: 1 had edema alone, 2 had necrosis and 1 had edema associated with necrosis. Neither the physical nor radiobiological parameters were predictive of the treatment outcome or the treatment complications. Stereotactic irradiation is a valid option for progressive nonresectable tumors in children.

Pancreatic cancer as a second tumour following treatment of Hodgkin's disease.

Over the past 30 years, the life expectancy in patients with Hodgkin's disease has greatly improved. However, adverse long-term side-effects are now well recognized and development of second malignancies is one of the most important. We report the case of a patient who developed pancreatic cancer 9 years after treatment, with chemotherapy and radiation, for Hodgkin's disease. The increasing number and variety of solid tumours after curative treatment of Hodgkin's disease points to a need for new, less toxic regimens.

Predictors of delay in starting radiation treatment for patients with early stage breast cancer.

PURPOSE: To describe the factors predicting waiting time for radiation treatment in early breast cancer. MATERIALS AND METHODS: Between January 1992 and December 1993, 739 patients with Stage I and II breast cancer were treated with conservative treatment at three McGill University Hospitals. Waiting time was defined as the interval between the date of surgery and the date of the first radiation treatment. Delay was defined as a waiting time of more than 7 weeks for women who did not receive chemotherapy (Group NC, n = 478), and as a waiting time of more than 24 weeks for those who received chemotherapy (Group C, n = 261). We analyzed predictive factors related to the patient (age, stage, treatment on protocol, income by postal code) and to the referring hospital (university or community hospital). RESULTS: For the entire population, 54% of patients were delayed, 72% in Group NC and 21.4% in Group C. Univariate analysis showed an impact of referring hospital in both groups, and of stage and treatment on protocol in Group C (all p = 0.001). Multivariate analysis showed that delays were significantly less in Group NC for women referred from a community hospital (p = 0.001) and in Group C for women with Stage I disease (p = 0.06), those treated on protocol, and those referred from a university hospital (p = 0.001). CONCLUSION: More than half of patients with early breast cancer waited more than the recommended intervals for radiation therapy. However, lower income breast cancer patients did not wait longer for treatment than higher income patients, possibly a result of the Canadian Medicare system which provides universal access to health care.

Para-aortic irradiation only appears to be adequate treatment for patients with Stage I seminoma of the testis.

PURPOSE: Results of treatment of patients with Stage I seminoma with orchiectomy and radiotherapy are excellent. Even without adjuvant radiotherapy, the relapse rate is only 15-20%; most of the patients fail in the retroperitoneum, with rare failures observed in the pelvis (0.5-2%). In 1991, we began a prospective study evaluating para-aortic lymph node radiation as the only adjuvant treatment for such patients. This paper reports our preliminary results. MATERIALS & METHODS: Between March 1991 and January 1996, 35 patients with histologically proven Stage I seminoma were entered in the study. Median age was 37.9 years (range: 27-65 years). A radical inguinal orchiectomy was performed in all patients. Staging workup consisted of a chest X-ray; B-HCG, alpha-fetoprotein, and CT scan of the abdomen and pelvis in all patients. Lymphangiogram was done in 23 (66%) of 35 patients for further evaluation of the retroperitoneal lymph nodes. Radiotherapy consisted of treatment to the para-aortic region only. Parallel opposed fields extending from the top of T11 to the bottom of L5 were used. The median field size was 8.7 x 21.8 cm (range: 7-11 x 18-26 cm). The median total dose, prescribed at midpoint, was 25 Gy given in 15 daily fractions of 1.66 Gy. Follow-up was performed every 3 months for the first year, every 4-5 months for the second and third years, and every 6 months thereafter. Chest X-ray, tumor markers, and CT scan of the pelvis were performed routinely as part of the follow-up investigation. RESULTS: At a median follow-up of 39.7 months (range: 16-74 months), 34 (97.1%) of 35 patients are alive with no evidence of disease for an overall actuarial survival rate of 97.1% at 5 years and a cause-specific actuarial survival rate of 100%. Treatment morbidity was limited to Grade I-II acute side effects in 18 (51.4%) of 35 patients. No late side effects were seen. CONCLUSION: From our preliminary results, adjuvant radiation treatment limited to the para-aortic lymph node region, without ipsilateral pelvic irradiation, appears to be adequate treatment for Stage I seminoma. Such an approach in our patients resulted in minimal toxicity and excellent disease-free survival.

Parameningeal rhabdomyosarcoma: results of an international workshop.

PURPOSE: A retrospective analysis was performed on children with nonmetastatic rhabdomyosarcomas (RMS) involving a parameningeal site treated by one of the four major cooperative groups: Intergroup Rhabdomyosarcoma Study (IRS), International Society of Pediatric Oncology (SIOP), German Cooperative Group (CWS), and Italian Cooperative Group (ICS) to analyse survival and prognostic factors. METHODS AND MATERIALS: Between 1979 and 1989, 230 children (median age 6 years) were treated in the IRS III, SIOP 84, CWS 81, and ICS 79 studies. All patients received chemotherapy, and 203 were irradiated. Radiotherapy doses were similar in the four studies, although treatment volumes were not similar. The SIOP patients had smaller volumes treated. In addition, the SIOP patients with a low risk of meningeal involvement and children under 5 years of age were not irradiated if they had a complete response (CR) to chemotherapy. Time to initiation of irradiation was earlier in the IRS and Italian studies. RESULTS: Median follow-up was 62 months (range 22-140). The 5-year survival and 5-year event-free survival were better for the IRS study (74% and 71%) than for the other study groups (55% and 36% for SIOP, 47% and 47% for CWS, and 39% and 39% for ICS). The low-risk (LR) patients in the IRS study had improved survival. However, patients with high risk of meningeal involvement had similar survival in all four studies. The most significant prognostic factor was the size of tumor (> 5 cm). CONCLUSION: The improved results from the IRS group, especially among the LR patients, could be related to the IRS treatment employed, particularly the systematic use of radiation, to the inclusion of patients with smaller tumors, and to the routine use of quality control of radiation.

Quality control of low dose craniospinal irradiation for low risk medulloblastoma.

Between July 1984 and May 1990, 25 children (median age 9 years) classified as low risk medulloblastoma were treated post-operatively with low dose craniospinal irradiation (25 Gy) followed by a boost to the posterior fossa (total dose 55 Gy), with or without chemotherapy. Simulator and portal films were reviewed for all patients. Doses delivered at the mid cerebral and spinal axis, anterior vertebral body, field junctions and posterior fossa were recalculated and correlated with outcome. Three children were excluded because of inadequate data leaving 22 cases for study. The 5-year actuarial survival is 55%. Nine recurrences and one second tumour (astrocytoma) were observed. Sites of recurrence were either in the posterior fossa (5), in the brain (3), in the spinal axis (1), or combined (2). The dose delivered was within +/- 5% of that prescribed to the brain in 21/22 cases, and to the posterior fossa and the anterior surface of the vertebral body in 17/22 cases. The only patient who received less than 95% of the prescribed dose to the brain (23 Gy) failed in the subfrontal area and olfactory plate. One of the five patients who received less than 95% of the prescribed dose to the posterior fossa (50.3 Gy) failed at the primary site. None of the five patients who received less than 95% of the dose to the spinal axis failed. Quality control of radiation treatment showed that failures could not be correlated with incorrect technique.

Base of skull and cervical spine chordomas in children treated by high-dose irradiation.

PURPOSE: To evaluate the outcome of children with base of skull or cervical spine chordomas treated by high dose irradiation. METHODS AND MATERIALS: Eighteen children, 4 to 18 years of age, with base of skull or cervical spine chordomas, received fractionated high-dose postoperative radiation using mixed photon and 160 MeV proton beams. The median tumor dose was 69 Cobalt Gray-equivalent (CGE) with a 1.8 CGE daily fraction. RESULTS: The median follow-up was 72 months. The 5-year actuarial survival was 68% and the 5-year disease-free survival (DFS) was 63%. The only significant prognostic factor was the location: patients with cervical spine chordomas had a worse survival than those with base of skull lesions (p = 0.008). The incidence of treatment-related morbidity was acceptable: two patients developed a growth hormone deficit corrected by hormone replacement, one temporal lobe necrosis, and one fibrosis of the temporalis muscle, improved by surgery. CONCLUSION: Chordomas in children behave similarly to those in adults: children can receive the same high-dose irradiation as adults with acceptable morbidity.

Postoperative radiotherapy for chondrosarcoma of the L1 vertebral body: a case report.

A 51-year-old man presented with a low-grade chondrosarcoma of the L1 vertebral body, which had been completely resected. Radiotherapy was indicated; however, the close proximity of critical structures such as the spinal cord and the kidneys complicated the delivery of the high radiation dose required. In this paper we present the clinical and technical aspects of the radiotherapy technique used to treat this patient; we also describe the patient immobilization and radiation dose verification techniques used. The patient was treated with 18 MV photons using multiple field arc rotations with fields asymmetric with respect to the rotational axis of the collimator head. The spinal cord was aligned along the horizontal axis of the linear accelerator isocenter, and the patient was immobilized using a 10 degrees styrofoam wedge combined with an Alpha Cradle mold. In this manner, the patient was stabilized in a comfortable position, which facilitated the daily check of the isocenter position within the patient. Radiation dose verification was carried out with films in an anthropomorphic phantom and with an ionization chamber in a water phantom. These measurements confirmed the accuracy of the isodose distributions calculated for the treatment with asymmetric fields in the arc therapy mode. The use of this technique in conjunction with the positioning device permitted the delivery of 64 Gy to the L1 vertebral body with relatively low doses to the critical structures, amounting to 32 Gy at the surface of the spinal cord and less than 16 Gy to half of both kidneys.

Late rectal bleeding following combined X-ray and proton high dose irradiation for patients with stages T3-T4 prostate carcinoma.

PURPOSE: Dose escalation for prostate cancer by external beam irradiation is feasible by a 160 MeV perineal proton beam that reduces the volume of rectum irradiated. We correlated the total doses received to portions of the anterior rectum to study the possible relationship of the volume irradiated to the incidence of late rectal toxicity. METHODS: We have randomized 191 patients with stages T3 and T4 prostatic carcinoma to one of two treatment dose arms. These were: 1) 75.6 Cobalt-Gy-equivalent (CGE), 50.4 Gy delivered by 107-25 MV photons followed by 25.2 CGE delivered perineally by protons (Arm 1) or 2) 67.2 CGE delivered by 10-25 MV photons (Arm 2). RESULTS: With a median follow-up of 3.7 years, post-irradiation rectal bleeding (grades 1 and 2 only, none requiring surgery or hospitalization) from telangiectatic rectal mucosal vessels has occurred in 34% of 99 Arm-1 patients and 16% of 92 Arm-2 patients (p = 0.013). Dose-volume histograms (DVHs) for the anterior rectal wall, the posterior rectal wall and the total rectum in 41 patients treated on Arm 1 were calculated from the three dimensional dose distributions. Rectal bleeding has occurred in 14 or 34% of the 41 DVH-analyzed subset of Arm-1 patients. Both the fractional volume of the anterior rectum and the total dose received by fractional volumes of the anterior rectum significantly correlate with the actuarial probability of bleeding. CONCLUSIONS: Clinicians planning dose escalation to men with localized prostate cancer should approve with caution treatment plans raising more than 40% of the anterior rectum to more than 75 CGE without additional effort to protect the rectal mucosa because this late sequela data indicate that more than half of these men will otherwise have rectal bleeding.

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.

Interstitial pneumonitis and venocclusive disease of the liver after bone marrow transplantation.

One hundred and seventy patients were analysed for interstitial pneumonitis and 151 for venocclusive disease of the liver after bone marrow transplantation. We present our results with emphasis on the role of the parameters of single fraction total body irradiation.

[Modern technics of irradiation of brain tumors in children]. / Les techniques modernes d'irradiation des tumeurs cérébrales de l'enfant.

Radiotherapy still represents with surgery the cornerstone in the management of pediatric brain tumors. Techniques of irradiation have benefited greatly from modern imaging, CT scan and MRI for tumor-volume delineation, as well as megavoltage equipment, mainly linear accelerators delivering both high-energy X-Rays and electrons, widely used in cranial-spinal irradiations. Furthermore, new modalities of doses and volumes have been tested in various tumors (medulloblastomas, germ cell tumors...), in studies frequently combining chemotherapy with conventional therapies. Nevertheless, local control remains a major concern in tumors such as brain stem and high grade supratentorial gliomas. Concerning iatrogenic neurological sequelae, particularly harmful in children, limited data suggest an improvement in recent years. This improvement is partly due to the reduced prophylactic doses for the treatment of medulloblastomas, but further long-term observations are necessary. For these reasons, multiple technical innovations have been investigated. Some of them concern irradiation selectivity: stereotactic pencil beams, interstitial brachytherapy, heavy charged particles, 3-dimensional treatment planning. Others aim to increase the irradiation "efficacy": multifractionation, high LET particles, radiation-sensitizers.

Blood cell kinetics and total body irradiation.

The early response of blood cells to irradiation has been studied in leukemia patients who received total body irradiation (TBI) prior to cyclophosphamide and bone marrow transplantation. After a single session treatment (10 Gy in 4 h) the most dramatic variation was observed in the granulocytes. At the end of the irradiation their concentration was 2 to 6 times higher. Because of a subsequent rapid decline, the peak may be overlooked if the blood counts are delayed. Lymphocytes decreased to 50% at the end of the single session TBI and continue to decrease exponentially, with a half time of 30 h. During a fractionated irradiation (11 X 1.2 Gy in 4 days) the lymphocyte number dropped to 60%, 13 h after the first fraction and this decline continued with a half time of 30 h during the treatment. From the data obtained in vivo, a lymphocyte D0 value of 1.2 Gy was computed. The lymphocyte subsets (B.T. OKT4 OKT8) did not exhibit different radiosensitivities either in vivo or in vitro. The disappearance of lethally hit lymphocytes from the blood exhibits a biphasic kinetic: 50% of the cells disappear in a few hours and 50% with a half time at 30 h. Lymphocytes irradiated either in vitro or in vivo when in culture disappear slowly, contrasting with the in vivo findings. It may suggest that lethally hit lymphocytes are quickly removed from the circulating pool in vivo.