An improved technique for breast cancer irradiation including the locoregional lymph nodes

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The Toxicity of Radiotherapy Following High-dose Chemotherapy With Peripheral Blood Stem Cell Support in High-risk Breast Cancer: A Preliminary Analysis

High-dose chemotherapy with autologous bone marrow and/or peripheral blood stem cell (PBSC)support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has been reported to be associated with morbidity and mortality resulting from pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-dose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thiotepa and carboplatin, in patients with high-risk breast cancer. In two randomised single institution studies, 70 consecutive patients received anthracycline-containing adjuvant chemotherapy (FEC: S-fluorouracil, epirubicin and cyclophosphamide) followed by radiotherapy to achieve maximal local control. Of these patients, 34 received high-dose CTC with autologous PBSC support. All patients tolerated the full radiation dose in the planned time schedule. Radiation pneumonitis was observed in 5 patients (7O), 4 of whom had undergone high-dose chemotherapy (P= 0.38). All 5 responded favourably to prednisone. Fatal toxicities were not observed. Myelosuppression did not require interruption or untimely discontinuation of the radiotherapy, although significant reductions in median nadir platelet counts and haemoglobin levels were observed in patients who had received high-dose chemotherapy (Z’= 0.0001). The median nadir of WBC counts was mildly but significantly decreased during radiotherapy (P= 0.01). Red blood cell or platelet transfusions were rarely indicated. Adequate radiotherapy for breast cancer can be safely administered after high-dose CTC with autologous PBSC support. Radiation-induced myelotoxicity is clearly enhanced following CTC, but this is of little clinical significance. Radiation pneumonitis after high-dose therapy may occur more often in patients with a history of lung disease or after a relatively high radiation dose to the chest wall. Other high-dose regimens, particularly those incorporating drugs with known pulmonary toxicity (such as BCNU), may predispose patients to radiation pneumonitis

The Toxicity of Radiotherapy Following High-dose Chemotherapy With Peripheral Blood Stem Cell Support in High-risk Breast Cancer: A Preliminary Analysis

High-dose chemotherapy with autologous bone marrow and/or peripheral blood stem cell (PBSC)support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has been reported to be associated with morbidity and mortality resulting from pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-dose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thiotepa and carboplatin, in patients with high-risk breast cancer. In two randomised single institution studies, 70 consecutive patients received anthracycline-containing adjuvant chemotherapy (FEC: S-fluorouracil, epirubicin and cyclophosphamide) followed by radiotherapy to achieve maximal local control. Of these patients, 34 received high-dose CTC with autologous PBSC support. All patients tolerated the full radiation dose in the planned time schedule. Radiation pneumonitis was observed in 5 patients (7O), 4 of whom had undergone high-dose chemotherapy (P= 0.38). All 5 responded favourably to prednisone. Fatal toxicities were not observed. Myelosuppression did not require interruption or untimely discontinuation of the radiotherapy, although significant reductions in median nadir platelet counts and haemoglobin levels were observed in patients who had received high-dose chemotherapy (Z’= 0.0001). The median nadir of WBC counts was mildly but significantly decreased during radiotherapy (P= 0.01). Red blood cell or platelet transfusions were rarely indicated. Adequate radiotherapy for breast cancer can be safely administered after high-dose CTC with autologous PBSC support. Radiation-induced myelotoxicity is clearly enhanced following CTC, but this is of little clinical significance. Radiation pneumonitis after high-dose therapy may occur more often in patients with a history of lung disease or after a relatively high radiation dose to the chest wall. Other high-dose regimens, particularly those incorporating drugs with known pulmonary toxicity (such as BCNU), may predispose patients to radiation pneumonitis

Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement

Background. Uncontrolled studies suggest that high-dose chemotherapy is beneficial in patients with breast cancer and multiple metastases to the axillary lymph nodes. Many physicians accept this treatment as standard care. We aimed to assess adjuvant high-dose chemotherapy in breast cancer in a phase II randomised trial. Methods. 97 women aged younger than 60 years, who had breast cancer with extensive axillary-node metastases (confirmed by a tumour-positive infraclavicular lymph-node biopsy), received three courses of up-front chemotherapy (FE120C). This regimen consisted of cyclophosphamide 500 mg/m2, epirubicin 120 mg/m2, and 5-fluorouracil 500 mg/m2 once weekly for 3 weeks. After surgery, stable patients or those who responded to chemotherapy were randomly assigned conventional therapy (fourth course of FE120C, followed by radiation therapy and 2 years of tamoxifen [40 patients]) or high-dose therapy (identical treatment but an additional high-dose regimen and peripheral-blood progenitor-cell [PBPC] support after the fourth FE120C course [41 patients]). This high-dose regimen comprised cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, and carboplatin 1600 mg/m2. The primary endpoint was overall and disease-free survival. All analyses were by intention to treat. Findings. No patients died from toxic effects of chemotherapy. With a median follow-up of 49 (range 21-76) months, the 4-year overall and relapse-free survivals for all 97 patients were 75% and 54% respectively. There was no significant difference in survival between the patients on conventional therapy and those on high-dose therapy. Interpretation. High-dose therapy is associated with substantial cost and acute toxic effects, but also has potentially irreversible long-term effects. Until the benefit of this therapy is substantiated by large-scale phase III trials, high-dose chemotherapy should not be used in the adjuvant treatment of breast cancer, apart from in randomised studies

Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation.

BACKGROUND: Radiotherapy prevents local recurrence of breast cancer after breast-conserving surgery. We evaluated the effect of a supplementary dose of radiation to the tumor bed on the rates of local recurrence among patients who received radiotherapy after breast-conserving surgery for early breast cancer. METHODS: After lumpectomy and axillary dissection, patients with stage I or II breast cancer received 50 Gy of radiation to the whole breast in 2-Gy fractions over a five-week period. Patients with a microscopically complete excision were randomly assigned to receive either no further local treatment (2657 patients) or an additional localized dose of 16 Gy, usually given in eight fractions by means of an external electron beam (2661 patients). RESULTS: During a median follow-up period of 5.1 years, local recurrences were observed in 182 of the 2657 patients in the standard-treatment group and 109 of the 2661 patients in the additional-radiation group. The five-year actuarial rates of local recurrence were 7.3 percent (95 percent confidence interval, 6.8 to 7.6 percent) and 4.3 percent (95 percent confidence interval, 3.8 to 4.7 percent), respectively (P<0.001), yielding a hazard ratio for local recurrence of 0.59 (99 percent confidence interval, 0.43 to 0.81) associated with an additional dose. Patients 40 years old or younger benefited most; at five years, their rate of local recurrence was 19.5 percent with standard treatment and 10.2 percent with additional radiation (hazard ratio, 0.46 [99 percent confidence interval, 0.23 to 0.89]; P=0.002). At five years in the age group 41 to 50 years old, no differences were found in rates of metastasis or overall survival (which were 87 and 91 percent, respectively). CONCLUSIONS: In patients with early breast cancer who undergo breast-conserving surgery and receive 50 Gy of radiation to the whole breast, an additional dose of 16 Gy of radiation to the tumor bed reduces the risk of local recurrence, especially in patients younger than 50 years of age

Do clinical characteristics and outcome in nonagenarians with a hip fracture differ from younger patients?

Aim: To compare clinical characteristics and outcome of nonagenarian hip fracture patients with younger patients aged 65-89years. Methods: This was a cohort follow-up study of admissions for a hip fracture between 2005-2010 (mean follow up of 3.5years) in two teaching hospitals in the Netherlands; 230 nonagenarians and 1014 patients aged 65-89years were included. Clinical characteristics, adverse events, mobility and mortality were compared. Results: Nonagenarians were more likely to be female and anemic (both P<0.001), and had more trochanteric fractures (P=0.005). The number of American Society of Anesthesiologists III/VI classified patients did not differ between the two groups. During the hospital stay, adverse events were more frequently observed in nonagenarians compared with younger patients (P<0.001). The length of stay was significantly longer in nonagenarians (P<0.001), and the 90-day readmission rate was similar. Absolute mortality was higher in nonagenarians (P<0.001), excess mortality, however, was comparable. Before admission, 40.0% of the nonagenarians lived in their own home, and 40.9% had returned 3months postfracture. The rate of returning to their own home was lower compared with younger patients (P<0.001). Prefracture mobility was worse in nonagenarians compared with the younger group, but 3months after discharge, the number of patients that regained prefracture mobility was comparable in both age groups. Conclusions: Nonagenarian hip fracture patients differ significantly from younger patients aged 65-89years with respect to clinical characteristics and long-term outcome. However, almost half of the nonagenarians returned to their own home and more than half regained their prefracture level of mobility. Given these findings, prevention strategies for hip fracture and adverse events during hospital stay that focus particularly on frail nonagenarians are highly recommended

AN UPDATE ON BETER, THE DUTCH NATIONWIDE SURVIVORSHIP CARE PROGRAMME FOR HODGKIN LYMPHOMA SURVIVORS

Biological, physical and clinical aspects of cancer treatment with ionising radiatio