Late Radiation Side Effects Research Articles

Radiotherapy of Langerhans’ Cell Histiocytosis

This patterns-of-care study was performed to define the current clinical experience with radiotherapy of Langerhans’ cell histiocytosis in adults in Germany and to define open questions resulting from this study. A standardized questionnaire was sent to 198 German radiotherapy institutions. Data about patient characteristics, stage of disease, practice and fractionation of radiotherapy, outcome of therapy, etc. were systematically evaluated. 123 of 198 institutions answered the complete questionnaire (62.1%). Only 23 of the 123 institutions (18.7%) reported experience with radiotherapy of Langerhans’ cell histiocytosis of adults. 18 institutions with 98 patients were evaluable. The majority of patients (72 of 98) was treated on a linear accelerator. The median single dose of radiotherapy was 2 Gy, while the median total dose was 24 Gy. 81 of 89 evaluable patients (91%) reached a local control of the treated lesion(s), 69 of those had a complete remission. Eight of 89 patients (9%) developed an in-field recurrence. 87.8% of patients experienced no acute and 97% of patients no late side effects of radiotherapy. Clinical experience with radiotherapy of Langerhans’ cell histiocytosis in adults in Germany is still very limited. Nevertheless, the clinical results—with high remission and local control rates—confirm the effectiveness of radiotherapy in the multidisciplinary treatment of this disease. Due to the small number of patients in this study despite higher incidence rates, the knowledge of this disease has to be multiplied in Germany. Future patients should be systematically included into a prospective radiotherapy registry.

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

IntroductionRadiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects.MethodsIntrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments.ResultsRadiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects.ConclusionAfter radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.

High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast-conserving surgery: Seven-year results of a comparative study

To report the 7-year results of a prospective study of accelerated partial breast irradiation (APBI) using interstitial high-dose-rate brachytherapy and compare the treatment results with those achieved by standard, whole breast radiotherapy (WBRT), with or without a tumor bed boost (TBB). Between 1996 and 1998, 45 prospectively selected patients with T1N0-N1mi (single nodal micrometastasis), nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI using interstitial high-dose-rate implants. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumor bed plus a 1-2-cm margin. During the same period, 80 patients, who met the eligibility criteria for APBI but who were treated with 50 Gy WBRT with (n = 36) or without (n = 44) a 10-16-Gy TBB, were selected as controls. The median follow-up for the APBI and control groups was 81 and 83 months, respectively. Local control, relapse-free survival, cancer-specific survival, late side effects, and cosmetic results were assessed. The crude rate of total ipsilateral breast failure was 6.7% (3 of 45), 11.4% (5 of 44), and 8.3% (3 of 36) for patients treated with APBI, WBRT, and WBRT + TBB, respectively. The differences in the 5- and 7-year actuarial rates of ipsilateral breast recurrence were not statistically significant among patients treated with APBI (4.4% and 9.0%), WBRT (4.7% and 14.8%), and WBRT + TBB (5.7% and 9.5%). No statistically significant difference in either the 7-year probability of relapse-free survival (79.8%, 73.5%, and 77.7% for APBI, WBRT, and WBRT + TBB, respectively) or cancer-specific survival (93.3%, 92.9%, and 93.9% for APBI, WBRT, and WBRT + TBB, respectively) was found. The 7-year actuarial elsewhere breast failure rate was 9.0% in the APBI group and 8.3% in the control group (p = 0.80). The rate of excellent/good cosmetic results was 84.4% in the APBI group and 68.3% in the control group (p = 0.04). The corresponding rates of asymptomatic fat necrosis were 20.0% and 20.6%. Symptomatic fat necrosis occurred in 1 patient (2.2%) treated with APBI. The incidence of Grade 2 or worse late radiation side effects was similar for both groups (26.7% vs. 28.6%). Accelerated partial breast irradiation using interstitial high-dose-rate implants, with proper patient selection and quality assurance, yields similar 7-year results to those achieved with standard breast-conserving therapy. APBI does not increase the risk of elsewhere breast failures.

Principles and applications of radiation therapy

Radiation therapy is emerging as a beneficial and increasingly accessible treatment option for companion animals with cancer. Various types of radiation are available with different properties that may make one more suitable than another for treating a specific tumor type. Radiation therapy can be used as the sole treatment or as part of a multimodality treatment course to result in local or locoregional tumor control, or as palliative therapy for pain control. When radiation is a potential treatment option, it should be considered early in the decision-making process to ensure that the appropriate diagnostics and other treatment modalities are considered to provide the best potential outcome. This article is intended to provide an overview of the types of radiation therapy that are available, the indications, and the potential acute and late radiation side effects.

Influence of radiation therapy on reconstructive flaps after radical resection of head and neck cancer

This study was undertaken to evaluate the influence of radiotherapy (RT) on reconstructive flaps after radical excision of head and neck cancer. Eighty-eight reconstructive flaps were used in 82 patients who received RT either before (PREOP group, 14 flaps) or after (POSTOP group, 74 flaps) surgery. The success and healing rates of the flaps were evaluated. The success and healing rates were lower in the PREOP group than in the POSTOP group (86% vs 99%,P =0.026 for success; and 64% vs 95%, P=0.003 for healing). The rate of acute radiation reaction in flaps in the POSTOP group was significantly lower than in the surrounding normal tissues (35%vs 84%, P=0.003). Late side effects of RT were rare. Our results suggest good radiation tolerance of reconstructive flaps after radical tumour excision in the head and neck region. Success and healing of the flap are likely to be better if RT is administered after surgery.

766 Poster Development and testing of phase I & II studies of new modalities in the treatment of significant late radiation side effects

766 Poster Development and testing of phase I & II studies of new modalities in the treatment of significant late radiation side effects

Long-term outcome of 56 dogs wioth nasal tumours treated with four doses of radiation at Ointervals of seven days

A retrospective study was undertaken on 56 dogs treated for nasal tumours by megavoltage radiotherapy with a hypofractionated schedule consisting of four doses of 9 Gy given at intervals of...

Long-term experience with carboplatin monotherapy for clinical stage I seminoma: a retrospective single-center study

Objectives. To evaluate the long-term oncologic efficacy and morbidity of carboplatin monotherapy, which was introduced at our department 11 years ago for the treatment of Stage I seminoma. Radiotherapy is the standard treatment of patients with clinical Stage I seminoma. Carboplatin has been advocated as a treatment alternative to avoid the late side effects of radiotherapy and the high recurrence rate of surveillance strategies. Methods. From February 1990 until August 2001, 108 patients received two adjuvant cycles of single-agent carboplatin (400 mg/m 2 body surface on days 1 and 22) 2 weeks after high inguinal orchiectomy. To assess for myelosuppression, complete blood counts were performed at least once a week until the nadir occurred after the second treatment cycle. Results. During a mean follow-up period of 59.8 months (range 6 to 134), 2 patients (1.85%) developed a recurrence (retroperitoneal tumor) within the first year. Both patients received cisplatin-based salvage chemotherapy. At last follow-up, all patients were alive without any evidence of disease. Carboplatin treatment was well tolerated by all patients and was associated with only mild gastrointestinal side effects. Leukopenia was noted in 32 patients (29.6%); 21 (19.4%) of these patients had World Health Organization (WHO) grade 1, 8 (7.4%) had grade 2, 3 (2.8%) had grade 3, and none had grade 4. No patient developed neutropenic fever. Thrombocytopenia was observed in 48 patients (44.4%); of these patients, 38 (35.2%) had WHO grade 1, 5 (4.6%) had grade 2, 2 (1.9%) had grade 3, and 3 (2.8%) had grade 4. Conclusions. From an oncologic standpoint, two cycles of carboplatin monotherapy was highly effective and very well tolerated by all patients.

Results of radiation therapy in 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis.

The records of 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis (WHO Stage 2) were reviewed to determine the efficacy of radiation therapy in this population. Dogs with grade I (n = 1), grade II (n = 16), and grade III (n = 2) cutaneous mast cell tumor were included in this study. All dogs were treated with a combination of pre-irradiation surgical cytoreduction of the primary tumor, irradiation of the primary tumor and regional lymph node, and oral prednisone. Total radiation dose to the primary tumor and regional lymph node ranged from 48 to 57 Gray (Gy). The medial iliac and hypogastric lymph nodes were irradiated prophylactically in 11 dogs with primary tumor of the pelvic limb and positive ipsilateral popliteal lymph node. Total radiation dose to these lymph nodes ranged from 48 to 57 Gy. For all radiation fields, dose per fraction was 3 Gy, and therapy was administered on a Monday through Friday schedule. Acute and late radiation side effects observed in this study were considered acceptable. The median disease-free survival was 1,240 days (95% confidence interval 256 to 2,391 days). The disease-free survival in dogs with stage 2 mast cell tumor suggests that the combination of surgery, irradiation, and prednisone for the primary tumor along with irradiation of the positive lymph node is effective.

Boost irradiation of breast carcinoma: teletherapy vs. brachytherapy

Background: The results of adjuvant radiotherapy including a boost dose after breast-conserving surgery of mamma carcinoma were retrospectively analysed to relate local tumor control, survival, and cosmetic results to the boost technique. Material and methods: The study included 229 female patients who were treated in the period 1986–1997. Group A consisted of patients where the primary irradiation was hyperfractionated (two fractions per day) and the boost was applied by reduced portals, also at two fractions per day. In group B the ‘boost’ was applied interstitially intraoperatively and the ‘primary’ irradiation followed at one fraction per day. The cosmetic results and the late changes to the mamma were the subjects of follow-up examinations and were assessed using the EORTC score. Results: 129 patients formed group A, median follow-up 4.2 years, and 100 patients with median follow-up of 9.4 years formed group B. 59% of group A and 60% of group B were in stage pT1, 38% and 39% were in pT2, and 25% and 39% were in stage N1 or N2 (no significant differences). Tumors were mostly poorly to moderately differentiated. The upper outer quadrant was most afflicted. Local recurrence occurred in two and five cases, lymph-node recurrence in two cases each, while there were ten and 12 cases of distant metastases. There were no deaths in group A and in group B six with obvious distant metastases and eight with other causes of death. The cosmetic results and late side-effects (induration, teleangiectasis, ulcers) were significantly worse in the interstitial group B. Multivariate analysis revealed that only the total applied dose significantly affected the severity of late radiation side-effects. The cosmetic results worsened with time, the tendency for lymph edemas in the irradiated side increased. Induration decreased continuously after pure teletherapy but increased continuously after interstitial therapy. These trends did not change in either group. Conclusions: Both therapy schemes resulted in successful local tumor control with good cosmetic results and few side effects, but the interstitial boost therapy was clearly less favourable. Longer-term follow-up is required to compare the late side-effects even further.

Sequence analysis of the ATM gene in 20 patients with RTOG grade 3 or 4 acute and/or late tissue radiation side effects

Purpose: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe adverse reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. Material and Methods: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 (RTOG) acute and/or late tissue radiation side effects by reaction severity. DNA from the peripheral blood of patients was isolated. All 66 exons and adjacent intron regions of the ATM gene were PCR-amplified and examined for mutations by a combination of agarose gel electrophoresis, single-stranded conformational polymorphism (SSCP) analysis, and exon-scanning direct sequencing. Results: Only 2 of the patients revealed altogether four heteroallelic sequence variants. The latter included two single-base deletions in different introns, a single-base change causing an amino acid substitution in an exon, and a large insertion in another intron. Both the single-base deletions and the single-base change represent known polymorphisms. The large insertion was an Alu repeat, shown not to give rise to altered gene product. Conclusions: Despite high technical efforts, no unequivocal ATM mutation was detected. Nevertheless, extension of similar studies to larger and differently composed cohorts of patients suffering severe adverse effects of radiotherapy, and application of new technologies for mutation detection may be worthwhile to assess the definite prevalence of significant ATM mutations within the group of radiotherapy patients with adverse reactions. To date, it must be recognized that our present results do not suggest that heterozygous ATM mutations are involved in clinically observed radiosensitivity but, rather, invoke different genetic predisposition or so far unknown exogenous factors.

Relapse and subarachnoid dissemination of a pineal germinoma 14 years after radiation therapy

Intracranial germinomas are rare tumours which are highly curable with radiotherapy. In recent years treatment with chemotherapy has gained importance. Recurrence and dissemination is seen in about 10–20% of cases within the first 2 years after diagnosis; late recurrence and dissemination is very rare. We describe a patient with a recurrent germinoma 14 years after radiotherapy of a pineal tumour. We further report the management with chemotherapy, the late side effects of radiotherapy and the course of the disease with its fatal dissemination. We conclude that the use of radiotherapy, despite being highly effective, is clearly limited by its late side-effects. New regimens with chemotherapy seem promising but proved to be less effective in our case with tumour seeding throughout the subarachnoid space.

Sequence-analysis of the ATM-gene in twenty patients with RTOG grade 3 or 4 severe acute and/or late tissue radiation side effects

Sequence-analysis of the ATM-gene in twenty patients with RTOG grade 3 or 4 severe acute and/or late tissue radiation side effects

Hypofractionated radiotherapy for invasive bladder cancer

Background and purpose: The policy of the Radiotherapy Department of St. Thomas' Hospital in London for patients with invasive bladder cancer, used to be treatment with hypofractionated radiotherapy. The advantages of this fractionation scheme included reduction of the number of treatment sessions and better use of limited resources. Our results after hypofractionation were compared to series with more conventional radiotherapy. Material and methods: Between 1975 and 1985, 123 patients with a T2–T3 transitional cell carcinoma of the bladder were treated by a radical course of hypofractionated radiotherapy. Local control, survival and morbidity rates were analysed retrospectively. Results: The actuarial local control rates at 5 and 10 years were 31 and 29%, respectively. The actuarial cancer-specific 5- and 10-year survival rates were 48 and 39%, respectively. Acute side effects were observed in 87% of patients. The actuarial overall and severe late complication rates at 5 years were 33 and 9%, respectively. The local control, survival and early side effect rates we found, were in the same range as those reported in literature. Late radiation side effects however, were more common after hypofractionated radiotherapy compared to conventional radiotherapy schedules. Conclusions: We conclude that the potential advantage of a reduced number of treatment sessions may be lost in the long term, because of the higher incidence of late morbidity after hypofractionated radiotherapy. Hypofractionation however, remains a valuable technique for palliation and deserves further investigation for radical treatment where access to equipment is difficult or resources are limited.

Acute and late side effects of radiotherapy for ocular disease: an overview.

Acute and late side effects of radiotherapy for ocular disease: an overview.

1000 Organ conservation in bladder cancer

The use of radical radiotherapy for localised muscle-invasive bladder cancer carries the potential disadvantages compared to cystectomy of local tumour relapse, the formation ofnew tumours of the bladder urotheIium, and the possibility of late radiation side effects on the bladder. The benefits of this approach include physiological micturition and the preservation of sexual potency. Previous trials have not demonstrated inferior survival in patients with T3 bladder cancer managed by radical radiotherapy reserving salvage cystectomy for those who recur. However, these trials have not been large. We have recently re-analysed the Institute of Urology trial which registered 189 patients between 1965 and 1976 to determine long-term results. The 5 year survival in 91 patients randomised to radical radiotherapy was 27.9% (19.1–37.8%). Whereas for 98 patients randomised to radiotherapy + cystectomy, the 5 year survival was 39.8% (30.3–49.8%). Since this trial, there have been advances in both radiotherapy and surgery. Conformal radiotherapy offers the potential for reducing radiation side-effects. Additionally, we have completed a study of accelerated fractionation treated to doses between 57.6 and 64 Gy in 32 fractions over 26 days. Eighty five patients were treated in this study and of 70 who had check cystoscopy at 3–6 months, a pathological complete response was seen in 80% with 2 further patients demonstrating carcinoma in situ only. We conclude that a trial is required based on modem staging and treatment techniques to compare radiotherapy and cystectomy for localised muscle invasive bladder cancer.

Long-term follow-up of young children with brain tumors after irradiation

Purpose : Young children with brain tumors are at high risk of developing late sequelae after curative radiotherapy. A retrospective study was undertaken to determine the frequency and severity of neurological deficits, endocrine dysfunction, and intellectual disabilities. Methods and Material : One hundred and fifty-six children age ≤ 3 years were treated between 1952 and 1986 with radiotherapy. Of the 57 survivors, 47 had surgery, 12 chemotherapy and 24 children received cranio-spinal radiotherapy. Late radiation side effects were assessed with a clinical examination, blood tests and an interview. Results : The median follow-up was 13 years and the actuarial survival at 5 and 10 years was 49% and 44%, respectively. No, or only a mild, handicap was noted in 24 patients, while 21 had moderately severe and 16 severe disabilities. Children with supratentorial tumors had more abnormal neurological findings compared to those with infratentorial malignancies ( p < 0.001). Eighty percent of children had endocrine abnormalities, which were more marked in children with parasellar tumors ( p < 0.001). Twenty-one children were mentally retarded. In a multivariate analysis epilepsy emerged as the only significant variable independently associated with poor cognitive function. Conclusion : Long-term morbidity was found to be disabling in 58% of the surviving children. These findings encourage the development of treatment strategies designed to reduce toxicity.

En-bloc irradiation of tumours of the head and neck and their lymphatics. II. Early results and side effects.

The results and side effects of en-bloc irradiation of ear, nose and throat tumours and their lymphatics showed that the technique had been successful in nasopharyngeal carcinoma, but poor in carcinoma of the hypopharynx. Marked early and late radiation side effects were relatively common in high age and with certain tumour sites, whereas no correlation could be demonstrated with total absorbed dose, fractionation, cumulative radiation effect or major surgery.