Wil Dolsma | University Medical Center Groningen (original) (raw)

Papers by Wil Dolsma

Research paper thumbnail of Radiotherapeutisch mogelijkheden voor het kind met een hersentumor

Research paper thumbnail of Existing radiotherapy dose quantification methods in published late effects studies: a review of the literature

Tijdschrift voor Kindergeneeskunde, 2013

Research paper thumbnail of Induction chemotherapy and intensification with autologous bone marrow reinfusion in patients with locally advanced and disseminated breast cancer

European Journal of Cancer, 1993

et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an ... more et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international colaborative study among cancer registries. Int J Cancer 1987, 39,571-585. 20. Hellbardt A, Rene-Olivier M, Obradovic M, Mermillod B, Pannier J-P. The risk of second cancer (sc) in patients treated for testicular seminoma. Int J Rad Oncol Biol Phys 1990, 18, 1327-1331. 21. Kim JH, Chu FC, Woodard HQ, Melamed MR, Huvos A, Cantin J. Radiation-induced soft-tissue and bone sarcoma. Radiology 1978, 129, 501-508. 22. Glanzmann C, Schultz G, Liitolf UM. Lond-term morbidity of adjuvant infradiaphragmatic irradiation in patients with testicular cancer and implications for the treatment of stage I seminoma. Radiother Onco11991, 22, 12-8. 23. Duchesne GM, Horwich A, Dearnaley DP, Nicholls J, et al. Orchidectomy alone for stage 1 seminoma of the testis. Cancer 1990, 65, 1115-1118. 24. yon der Maase H, Engelholm SA, Rcrth M, et al. The DATECA study group. Non-seminomatous testicular germ cell tumours in Denmark 1976-80. Acta Radiol Oncol 1984, 23,255.

Research paper thumbnail of T 3 laryngeal cancer, primary surgery vs planned combined radiotherapy and surgery

Clinical Otolaryngology, 1993

The Dutch Co-operative Head and Neck Oncology Group performed a retrospective, nationwide study o... more The Dutch Co-operative Head and Neck Oncology Group performed a retrospective, nationwide study of laryngeal cancer between 1975 and 1984. The results for T3 laryngeal cancer treated with primary laryngectomy (n = 137) with post-operative radiotherapy when indicated or planned combined (pre-operative) radiotherapy with laryngectomy (n = 113) are analysed. The disease-free survival independent prognostic factors were treatment modality (planned combined treatment fared better, P = 0.001), incomplete resection of disease (P = 0.006), positive lymph nodes in the neck dissection specimen (P = 0.03) and poor differentiation (P = 0.04). Local control (95% vs. 85%, P = 0.01) as well as regional control (96% vs. 79%, P = 0.0001) was improved in the combined group compared with the primary laryngectomy group. Regional control was 69% for N0 patients if the neck nodes were not treated electively, compared with 98% for the planned combined treatment group. It is concluded that elective treatment of the neck nodes in T3 laryngeal cancer is mandatory. Radiotherapy is preferred, since as well as regional control, local control will also improve.

Research paper thumbnail of Guideline adherence for early breast cancer before and after introduction of the sentinel node biopsy

British journal of cancer, Jan 5, 2005

This population-based study aimed to analyse variations in surgical treatment and guideline compl... more This population-based study aimed to analyse variations in surgical treatment and guideline compliance with respect to the application of radiotherapy and axillary lymph node dissection (ALND), for early breast cancer, before and after the sentinel node biopsy (SNB) introduction. The study included 13 532 consecutive surgically treated stage I-IIIA breast cancer patients diagnosed in 1989-2002. Hospitals showed large variation in breast-conserving surgery (BCS) rates, ranging between 27 and 72% for T1 and 14 and 42% for T2 tumours. In multivariate analysis marked inter-hospital and time-dependent variation in the BCS rate remained after correction for case-mix. The guideline adherence was markedly lower for elderly patients. In 25.2% of the patients aged > or = 75 years either ALND or radiotherapy were omitted. The proportion of patients with no ALND after an SNB increased from 1.8% in 1999 to 37.8% in 2002. However, in 2002 also 12.2% of the patients with a positive SNB did not ...

Research paper thumbnail of CHEMO AND RADIOSENSITIVITY TESTING IN A PATIENT WITH ATAXIA TELANGIECTASIA AND HODGKIN DISEASE

Pediatric Hematology and Oncology, 2002

Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersens... more Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or, rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT She was treated with a tailored combined modality approach. No unacceptable toxicity was found, but the girl died of a relapse outside the irradiation field. In comparison with fibroblasts of non-AT patients, the fibroblasts of the patient were 3 times as sensitive for radiotherapy but just 1.2 times as sensitive for doxorubicin. A good correlation was shown between in vitro radio- and chemosensitivity testing and the observed clinical toxicity. The authors suggest, therefore, treating AT patients as much as possible according to standard protocols by adjusting the radiotherapy delivery and the chemotherapy regimen to individual doses derived from in vitro radio- and chemosensitivity testing.

Research paper thumbnail of Renal function after unilateral nephrectomy for Wilms' tumour: the influence of radiation therapy

European Journal of Cancer, 1996

The effect of therapy on renal function after unilateral nephrectomy for Wihns' tumour was studie... more The effect of therapy on renal function after unilateral nephrectomy for Wihns' tumour was studied. In the second year following unilateral nephrectomy, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated simultaneously by measuring 1251-iothalamate clearance and 1311-hippurate clearance. Of 41 evaluable patients, 29 received chemotherapy as sole treatment modality following nephrectomy (group 1); 12 patients additionally received radiation therapy to a field that included the remaining kidney (group 2). Results were expressed as standard deviation scores (zscores). In group 1, mean z-score for GFR was -0.27 (94.6% of normal) and in group 2 mean z-score was -1.51 (72.7% of normal for two kidneys) (P= 0.022, Mann-Whitney U-test). Mean z-score for ERPF was -0.09 (97.0%) in group 1 and -1.53 (73.8%) in group 2 (P=O.O39). It was concluded that the combination of chemotherapy and radiation therapy, in contrast to chemotherapy alone, negatively affects the ability of the remaining kidney to adjust its function after the loss of its counterpart.

Research paper thumbnail of Systolic and diastolic dysfunction in long-term adult survivors of childhood cancer

European Journal of Cancer

Anthracyclines Radiotherapy Toxicity Childhood cancer Survivors Long-term Echocardiography Systol... more Anthracyclines Radiotherapy Toxicity Childhood cancer Survivors Long-term Echocardiography Systolic function Diastolic function A B S T R A C T Aim: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS)

Research paper thumbnail of Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

British Journal of Cancer, 1997

Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed... more Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed by ablative chemotherapy and chest irradiation. One patient died of subacute heart failure 3 months after ablative chemotherapy. At a minimum of 1 year's follow-up (range 1-11 years) left vertricular ejection fraction (LVEF) was marginally abnormal in 4 of 27 disease-free survivors. One exceptional patient who received two transplantations is alive, with serious heart failure occurring after the second ablative chemotherapy. Including this patient, the percentage of patients free of clinical and subclinical cardiac dysfunction at 7 years is 78% (95% Cl 61-95%). After ablative chemotherapy, cardiotoxicity was rarely life-threatening. The impact of subclinical cardiotoxicity in the long term is not clear and needs continued evaluation.

Research paper thumbnail of Intensive chemotherapy with autologous bone marrow transfusion as primary treatment in women with breast cancer and more than five involved axillary lymph nodes

European Journal of Cancer, 1994

Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutiv... more Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutive studies of high-dose chemotherapy using autologous bone marrow transplantation (ABMT) to assist haematological recovery. In the first study, 25 patients were treated with cyclophosphamide (160-200 mg/kg) as the sole chemotherapy; in the second (26 patients), the cycle of high-dose cyclophosphamide (with or without 800-1,200 mg/m 2 etoposide) was repeated as induction treatment. In the first study, response was high [14 complete responses (CR), 7 partial responses (PR)] but was not increased by repeating the cycle (15 CR, 8 PR), and survival was slightly worse in the second trial. In the third study, 15 patients were treated with doxorubicin, vincristine and etoposide for two cycles and then with 200 mg/kg cyclophosphamide. Although high-dose cyclophosphamide increased the complete response rate, the additional responses were short-lived. In the final study, an attempt was made to increase the initial CR rate by combination chemotherapy using carboplatin (400-600 mg/m2), etoposide (120 mg/ m 2 × 4) and either high-dose cyclophosphamide (40 mg/kg × 4) or melphalan (140 mg/m2). Although all nine patients responded, none underwent a CR. The long-term survival (up to 7 years) does not appear to be different from that in comparably selected cases treated with conventional chemotherapy.

Research paper thumbnail of Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer

Breast Cancer Research and Treatment, 1996

Background This trial studied the disease-free survival after high-dose chemotherapy in patients ... more Background This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer. Patients and methods Thirty women, mean age 42.2 years (range 33–55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were eligible if they were ≤ 55 years of age, had achieved complete remission within 6 months of the initiation of chemotherapy, and had a WHO performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180 mg/m2 and mitoxantrone 60 mg/m2 both divided over 3 days. On day 7 bone marrow and/or peripheral stem cells were infused. After bone marrow recovery, external beam radiation was administered to sites of previous metastatic disease in 15 patients. Results Apart from leuko- and thrombocytopenia, mucositis was the major side effect. One patient died during the bone marrow transplant period due to an aspergillus infection. The median follow-up since highdose chemotherapy is 25 months (range 13 to 56 months). The median disease-free survival since high-dose chemotherapy is 27 months and the disease free survival is still 43% with an overall survival of 53% at 3 years. In two patients tumor relapse occurred only in the brain; in one patient the only relapse sign was a meningeal carcinosis. At the moment 17 patients are disease-free (13+–56+) months after high-dose chemotherapy. Conclusion Until now this high-dose regimen in selected patients with complete remission after induction chemotherapy for metastatic breast cancer has a promising disease free survival.

Research paper thumbnail of Guideline adherence for early breast cancer before and after introduction of the sentinel node biopsy

British Journal of Cancer, 2005

This population-based study aimed to analyse variations in surgical treatment and guideline compl... more This population-based study aimed to analyse variations in surgical treatment and guideline compliance with respect to the application of radiotherapy and axillary lymph node dissection (ALND), for early breast cancer, before and after the sentinel node biopsy (SNB) introduction. The study included 13 532 consecutive surgically treated stage I -IIIA breast cancer patients diagnosed in 1989 -2002. Hospitals showed large variation in breast-conserving surgery (BCS) rates, ranging between 27 and 72% for T1 and 14 and 42% for T2 tumours. In multivariate analysis marked inter-hospital and time-dependent variation in the BCS rate remained after correction for case-mix. The guideline adherence was markedly lower for elderly patients. In 25.2% of the patients aged X75 years either ALND or radiotherapy were omitted. The proportion of patients with no ALND after an SNB increased from 1.8% in 1999 to 37.8% in 2002. However, in 2002 also 12.2% of the patients with a positive SNB did not have an ALND. Guideline compliance for BCS, with respect to radiotherapy and ALND, fell since the SNB introduction, from 96.1% before 2000 to 91.4% in 2002 (Po0.001). Noncompliance may however reflect patient-tailored medicine, as for elderly patients with small, radically resected primary tumours. The considerable variation in BCS-rates is more consistent with variations in surgeon preferences than patient's choice.

Research paper thumbnail of Long term treatment related upper limb morbidity and quality of life after sentinel lymph node biopsy for stage I or II breast cancer

Ejso, 2006

Background: In a prospective study, long term upper-limb morbidity, perceived disabilities in act... more Background: In a prospective study, long term upper-limb morbidity, perceived disabilities in activities of daily life (ADL) and quality of life (QOL) were assessed before and 2 years after sentinel lymph node biopsy (SLNB) or axillary lymph node dissections (ALND) for breast cancer. Methods: Two hundred and four patients with stage I/II breast cancer, mean age 55.6 years (SD: 11.6) entered the study and 181 patients (89%) could be evaluated after 2 years. Fifty-seven patients underwent SLNB (31%) and 124 patients underwent an ALND (69%). Assessments included pain, shoulder range of motion, muscle strength, arm volume, perceived shoulder disability in ADL and QOL. Results: Significant (P!0.05) changes between before and 2 years after surgery were found in almost all assessments of shoulder function, ADL and several QOL subscales. Patients in the ALND group showed significant more changes in range of motion (ROM), grip strength, arm volume, ADL and QOL physical-and role functioning, pain and sleeplessness and arm symptoms compared to the SLNB group. Multivariate linear regression analysis showed that ALND could predict decrease of ROM, grip strength, ADL and physical functioning (QOL) and increase of arm volume, pain and arm symptoms score (QOL). Radiation on the axilla predicts an additional decrease in shoulder ROM and increase of arm volume. Conclusion: Two years after surgery for breast cancer, patients show significantly less treatment related upper limb morbidity, perceived disability in ADL and worsening of QOL after SLNB compared with ALND. q

Research paper thumbnail of Treatment-related upper-limb morbidity one year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for stage I or II breast cancer

Annals of Surgical Oncology, 2004

Background: In a prospective study, upper limb morbidity and perceived disability/activities of d... more Background: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).

Research paper thumbnail of Short-term morbidity of the upper limb after sentinel lymph node biopsy or axillary lymph node dissection for Stage I or II breast carcinoma

Cancer, 2003

BACKGROUND. The goals of sentinel lymph node biopsy (SLNB) are to improve axillary staging and re... more BACKGROUND. The goals of sentinel lymph node biopsy (SLNB) are to improve axillary staging and reduce unnecessary axillary lymph node dissections (ALND), thereby reducing treatment-related upper-limb morbidity. In the current prospective study, short-term upper-limb morbidity was assessed after SLNB and/or ALND.

Research paper thumbnail of Aggressive fibromatosis (non-familial desmoid tumour): Therapeutic problems and the role of adjuvant radiotherapy

British Journal of Surgery, 1995

Aggressive fibromatosis is a rare soft tissue tumour with a high tendency to local recurrence, ev... more Aggressive fibromatosis is a rare soft tissue tumour with a high tendency to local recurrence, even after apparently adequate resection. Wide local excision with a margin of at least 3 cm, depending on the anatomical location, should be performed to improve rates of recurrent disease. There is no consensus concerning the role of radiotherapy in the treatment of these lesions. The clinical findings of 39 cases diagnosed between 1972 and 1991 were reviewed retrospectively. Local control was effected in 19 of 32 patients treated with surgery alone after a median (range) follow-up of 72 (18–236) months. There were 40 cases of recurrent fibromatosis in 15 patients. Local control was obtained in 13 of 14 patients who received radiotherapy using a wide-field technique and doses of more than 50 Gy over a period of 5 weeks after marginal or incomplete resection of primary or recurrent lesions (P < 0.001). The results suggest that in a selected group of patients with aggressive fibromatosis radiotherapy may effectively achieve control of residual disease after surgery without marked disfigurement and loss of function.

Research paper thumbnail of Treatment-Related Upper Limb Morbidity 1 Year after Sentinel Lymph Node Biopsy or Axillary Lymph Node Dissection for Stage I or II Breast Cancer

Annals of Surgical Oncology, 2004

Background: In a prospective study, upper limb morbidity and perceived disability/activities of d... more Background: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).

Research paper thumbnail of Three-Dimensional Conformal Simultaneously Integrated Boost Technique for Breast-Conserving Radiotherapy

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To compare the target coverage and normal tissue dose with the simultaneously integrated... more Purpose: To compare the target coverage and normal tissue dose with the simultaneously integrated boost (SIB) and the sequential boost technique in breast cancer, and to evaluate the incidence of acute skin toxicity in patients treated with the SIB technique. Methods and Materials: Thirty patients with early-stage left-sided breast cancer underwent breast-conserving radiotherapy using the SIB technique. The breast and boost planning target volumes (PTVs) were treated simultaneously (i.e., for each fraction, the breast and boost PTVs received 1.81 Gy and 2.3 Gy, respectively). Three-dimensional conformal beams with wedges were shaped and weighted using forward planning. Dosevolume histograms of the PTVs and organs at risk with the SIB technique, 28 ؋ (1.81 ؉ 0.49 Gy), were compared with those for the sequential boost technique, 25 ؋ 2 Gy ؉ 8 ؋ 2 Gy. Acute skin toxicity was evaluated for 90 patients treated with the SIB technique according to Common Terminology Criteria for Adverse Events, version 3.0. Results: PTV coverage was adequate with both techniques. With SIB, more efficiently shaped boost beams resulted in smaller irradiated volumes. The mean volume receiving >107% of the breast dose was reduced by 20%, the mean volume outside the boost PTV receiving >95% of the boost dose was reduced by 54%, and the mean heart and lung dose were reduced by 10%. Of the evaluated patients, 32.2% had Grade 2 or worse toxicity. Conclusion: The SIB technique is proposed for standard use in breast-conserving radiotherapy because of its dose-limiting capabilities, easy implementation, reduced number of treatment fractions, and relatively low incidence of acute skin toxicity.

Research paper thumbnail of 236 Health-related quality of life in patients with early stage breast cancer treated with breast conserving surgery and radiotherapy

Research paper thumbnail of Comparison of normal tissue dose with three-dimensional conformal techniques for breast cancer irradiation including the internal mammary nodes

International Journal of Radiation Oncology Biology Physics, 2005

To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with thre... more To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with three commonly used strategies, by analyzing the dose to the heart and other organs at risk. Four different three-dimensional conformal dose plans were created for 30 breast cancer patients. The IMN were enclosed with the Para Mixed technique by a widened mediolateral tangent photon beam and an anterior electron beam, with the Patched technique by an anterior electron beam, with the Standard technique by an anterior photon and electron beam, and with the PWT technique by partially wide tangents. All techniques were optimized for conformality and produced equally adequate target coverage. Heart dose was lowest with the Para Mixed and Patched technique for all patients and with the PWT technique for right-sided treatment only. Lung dose was highest with the PWT, lowest with the Patched, and intermediate with the Para Mixed and Standard techniques. Skin dose was highest with the Patched, lowest with the PWT, and intermediate with the Para Mixed and the Standard techniques. The Para Mixed technique resulted in a 13-Gy lower dose in an overlap area, and the PWT technique was the only technique that incorporated considerable volumes of the contralateral breast. The Para Mixed technique yielded the overall best results. No other technique resulted in a lower heart dose. Lung and skin were equally spared instead of one of them being compromised, and the contralateral breast was avoided.

Research paper thumbnail of Radiotherapeutisch mogelijkheden voor het kind met een hersentumor

Research paper thumbnail of Existing radiotherapy dose quantification methods in published late effects studies: a review of the literature

Tijdschrift voor Kindergeneeskunde, 2013

Research paper thumbnail of Induction chemotherapy and intensification with autologous bone marrow reinfusion in patients with locally advanced and disseminated breast cancer

European Journal of Cancer, 1993

et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an ... more et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin's disease: an international colaborative study among cancer registries. Int J Cancer 1987, 39,571-585. 20. Hellbardt A, Rene-Olivier M, Obradovic M, Mermillod B, Pannier J-P. The risk of second cancer (sc) in patients treated for testicular seminoma. Int J Rad Oncol Biol Phys 1990, 18, 1327-1331. 21. Kim JH, Chu FC, Woodard HQ, Melamed MR, Huvos A, Cantin J. Radiation-induced soft-tissue and bone sarcoma. Radiology 1978, 129, 501-508. 22. Glanzmann C, Schultz G, Liitolf UM. Lond-term morbidity of adjuvant infradiaphragmatic irradiation in patients with testicular cancer and implications for the treatment of stage I seminoma. Radiother Onco11991, 22, 12-8. 23. Duchesne GM, Horwich A, Dearnaley DP, Nicholls J, et al. Orchidectomy alone for stage 1 seminoma of the testis. Cancer 1990, 65, 1115-1118. 24. yon der Maase H, Engelholm SA, Rcrth M, et al. The DATECA study group. Non-seminomatous testicular germ cell tumours in Denmark 1976-80. Acta Radiol Oncol 1984, 23,255.

Research paper thumbnail of T 3 laryngeal cancer, primary surgery vs planned combined radiotherapy and surgery

Clinical Otolaryngology, 1993

The Dutch Co-operative Head and Neck Oncology Group performed a retrospective, nationwide study o... more The Dutch Co-operative Head and Neck Oncology Group performed a retrospective, nationwide study of laryngeal cancer between 1975 and 1984. The results for T3 laryngeal cancer treated with primary laryngectomy (n = 137) with post-operative radiotherapy when indicated or planned combined (pre-operative) radiotherapy with laryngectomy (n = 113) are analysed. The disease-free survival independent prognostic factors were treatment modality (planned combined treatment fared better, P = 0.001), incomplete resection of disease (P = 0.006), positive lymph nodes in the neck dissection specimen (P = 0.03) and poor differentiation (P = 0.04). Local control (95% vs. 85%, P = 0.01) as well as regional control (96% vs. 79%, P = 0.0001) was improved in the combined group compared with the primary laryngectomy group. Regional control was 69% for N0 patients if the neck nodes were not treated electively, compared with 98% for the planned combined treatment group. It is concluded that elective treatment of the neck nodes in T3 laryngeal cancer is mandatory. Radiotherapy is preferred, since as well as regional control, local control will also improve.

Research paper thumbnail of Guideline adherence for early breast cancer before and after introduction of the sentinel node biopsy

British journal of cancer, Jan 5, 2005

This population-based study aimed to analyse variations in surgical treatment and guideline compl... more This population-based study aimed to analyse variations in surgical treatment and guideline compliance with respect to the application of radiotherapy and axillary lymph node dissection (ALND), for early breast cancer, before and after the sentinel node biopsy (SNB) introduction. The study included 13 532 consecutive surgically treated stage I-IIIA breast cancer patients diagnosed in 1989-2002. Hospitals showed large variation in breast-conserving surgery (BCS) rates, ranging between 27 and 72% for T1 and 14 and 42% for T2 tumours. In multivariate analysis marked inter-hospital and time-dependent variation in the BCS rate remained after correction for case-mix. The guideline adherence was markedly lower for elderly patients. In 25.2% of the patients aged > or = 75 years either ALND or radiotherapy were omitted. The proportion of patients with no ALND after an SNB increased from 1.8% in 1999 to 37.8% in 2002. However, in 2002 also 12.2% of the patients with a positive SNB did not ...

Research paper thumbnail of CHEMO AND RADIOSENSITIVITY TESTING IN A PATIENT WITH ATAXIA TELANGIECTASIA AND HODGKIN DISEASE

Pediatric Hematology and Oncology, 2002

Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersens... more Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or, rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT She was treated with a tailored combined modality approach. No unacceptable toxicity was found, but the girl died of a relapse outside the irradiation field. In comparison with fibroblasts of non-AT patients, the fibroblasts of the patient were 3 times as sensitive for radiotherapy but just 1.2 times as sensitive for doxorubicin. A good correlation was shown between in vitro radio- and chemosensitivity testing and the observed clinical toxicity. The authors suggest, therefore, treating AT patients as much as possible according to standard protocols by adjusting the radiotherapy delivery and the chemotherapy regimen to individual doses derived from in vitro radio- and chemosensitivity testing.

Research paper thumbnail of Renal function after unilateral nephrectomy for Wilms' tumour: the influence of radiation therapy

European Journal of Cancer, 1996

The effect of therapy on renal function after unilateral nephrectomy for Wihns' tumour was studie... more The effect of therapy on renal function after unilateral nephrectomy for Wihns' tumour was studied. In the second year following unilateral nephrectomy, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated simultaneously by measuring 1251-iothalamate clearance and 1311-hippurate clearance. Of 41 evaluable patients, 29 received chemotherapy as sole treatment modality following nephrectomy (group 1); 12 patients additionally received radiation therapy to a field that included the remaining kidney (group 2). Results were expressed as standard deviation scores (zscores). In group 1, mean z-score for GFR was -0.27 (94.6% of normal) and in group 2 mean z-score was -1.51 (72.7% of normal for two kidneys) (P= 0.022, Mann-Whitney U-test). Mean z-score for ERPF was -0.09 (97.0%) in group 1 and -1.53 (73.8%) in group 2 (P=O.O39). It was concluded that the combination of chemotherapy and radiation therapy, in contrast to chemotherapy alone, negatively affects the ability of the remaining kidney to adjust its function after the loss of its counterpart.

Research paper thumbnail of Systolic and diastolic dysfunction in long-term adult survivors of childhood cancer

European Journal of Cancer

Anthracyclines Radiotherapy Toxicity Childhood cancer Survivors Long-term Echocardiography Systol... more Anthracyclines Radiotherapy Toxicity Childhood cancer Survivors Long-term Echocardiography Systolic function Diastolic function A B S T R A C T Aim: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS)

Research paper thumbnail of Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

British Journal of Cancer, 1997

Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed... more Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed by ablative chemotherapy and chest irradiation. One patient died of subacute heart failure 3 months after ablative chemotherapy. At a minimum of 1 year's follow-up (range 1-11 years) left vertricular ejection fraction (LVEF) was marginally abnormal in 4 of 27 disease-free survivors. One exceptional patient who received two transplantations is alive, with serious heart failure occurring after the second ablative chemotherapy. Including this patient, the percentage of patients free of clinical and subclinical cardiac dysfunction at 7 years is 78% (95% Cl 61-95%). After ablative chemotherapy, cardiotoxicity was rarely life-threatening. The impact of subclinical cardiotoxicity in the long term is not clear and needs continued evaluation.

Research paper thumbnail of Intensive chemotherapy with autologous bone marrow transfusion as primary treatment in women with breast cancer and more than five involved axillary lymph nodes

European Journal of Cancer, 1994

Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutiv... more Since 1980, 75 patients with small-cell lung cancer (SCLC) have been entered into four consecutive studies of high-dose chemotherapy using autologous bone marrow transplantation (ABMT) to assist haematological recovery. In the first study, 25 patients were treated with cyclophosphamide (160-200 mg/kg) as the sole chemotherapy; in the second (26 patients), the cycle of high-dose cyclophosphamide (with or without 800-1,200 mg/m 2 etoposide) was repeated as induction treatment. In the first study, response was high [14 complete responses (CR), 7 partial responses (PR)] but was not increased by repeating the cycle (15 CR, 8 PR), and survival was slightly worse in the second trial. In the third study, 15 patients were treated with doxorubicin, vincristine and etoposide for two cycles and then with 200 mg/kg cyclophosphamide. Although high-dose cyclophosphamide increased the complete response rate, the additional responses were short-lived. In the final study, an attempt was made to increase the initial CR rate by combination chemotherapy using carboplatin (400-600 mg/m2), etoposide (120 mg/ m 2 × 4) and either high-dose cyclophosphamide (40 mg/kg × 4) or melphalan (140 mg/m2). Although all nine patients responded, none underwent a CR. The long-term survival (up to 7 years) does not appear to be different from that in comparably selected cases treated with conventional chemotherapy.

Research paper thumbnail of Phase II study of intensive chemotherapy with autologous bone marrow transplantation in patients in complete remission of disseminated breast cancer

Breast Cancer Research and Treatment, 1996

Background This trial studied the disease-free survival after high-dose chemotherapy in patients ... more Background This trial studied the disease-free survival after high-dose chemotherapy in patients in complete remission of metastatic breast cancer. Patients and methods Thirty women, mean age 42.2 years (range 33–55) with metastatic breast cancer, received high-dose chemotherapy in a phase II study. Patients were eligible if they were ≤ 55 years of age, had achieved complete remission within 6 months of the initiation of chemotherapy, and had a WHO performance scale of 0 or 1. The high-dose regimen consisted of melphalan 180 mg/m2 and mitoxantrone 60 mg/m2 both divided over 3 days. On day 7 bone marrow and/or peripheral stem cells were infused. After bone marrow recovery, external beam radiation was administered to sites of previous metastatic disease in 15 patients. Results Apart from leuko- and thrombocytopenia, mucositis was the major side effect. One patient died during the bone marrow transplant period due to an aspergillus infection. The median follow-up since highdose chemotherapy is 25 months (range 13 to 56 months). The median disease-free survival since high-dose chemotherapy is 27 months and the disease free survival is still 43% with an overall survival of 53% at 3 years. In two patients tumor relapse occurred only in the brain; in one patient the only relapse sign was a meningeal carcinosis. At the moment 17 patients are disease-free (13+–56+) months after high-dose chemotherapy. Conclusion Until now this high-dose regimen in selected patients with complete remission after induction chemotherapy for metastatic breast cancer has a promising disease free survival.

Research paper thumbnail of Guideline adherence for early breast cancer before and after introduction of the sentinel node biopsy

British Journal of Cancer, 2005

This population-based study aimed to analyse variations in surgical treatment and guideline compl... more This population-based study aimed to analyse variations in surgical treatment and guideline compliance with respect to the application of radiotherapy and axillary lymph node dissection (ALND), for early breast cancer, before and after the sentinel node biopsy (SNB) introduction. The study included 13 532 consecutive surgically treated stage I -IIIA breast cancer patients diagnosed in 1989 -2002. Hospitals showed large variation in breast-conserving surgery (BCS) rates, ranging between 27 and 72% for T1 and 14 and 42% for T2 tumours. In multivariate analysis marked inter-hospital and time-dependent variation in the BCS rate remained after correction for case-mix. The guideline adherence was markedly lower for elderly patients. In 25.2% of the patients aged X75 years either ALND or radiotherapy were omitted. The proportion of patients with no ALND after an SNB increased from 1.8% in 1999 to 37.8% in 2002. However, in 2002 also 12.2% of the patients with a positive SNB did not have an ALND. Guideline compliance for BCS, with respect to radiotherapy and ALND, fell since the SNB introduction, from 96.1% before 2000 to 91.4% in 2002 (Po0.001). Noncompliance may however reflect patient-tailored medicine, as for elderly patients with small, radically resected primary tumours. The considerable variation in BCS-rates is more consistent with variations in surgeon preferences than patient's choice.

Research paper thumbnail of Long term treatment related upper limb morbidity and quality of life after sentinel lymph node biopsy for stage I or II breast cancer

Ejso, 2006

Background: In a prospective study, long term upper-limb morbidity, perceived disabilities in act... more Background: In a prospective study, long term upper-limb morbidity, perceived disabilities in activities of daily life (ADL) and quality of life (QOL) were assessed before and 2 years after sentinel lymph node biopsy (SLNB) or axillary lymph node dissections (ALND) for breast cancer. Methods: Two hundred and four patients with stage I/II breast cancer, mean age 55.6 years (SD: 11.6) entered the study and 181 patients (89%) could be evaluated after 2 years. Fifty-seven patients underwent SLNB (31%) and 124 patients underwent an ALND (69%). Assessments included pain, shoulder range of motion, muscle strength, arm volume, perceived shoulder disability in ADL and QOL. Results: Significant (P!0.05) changes between before and 2 years after surgery were found in almost all assessments of shoulder function, ADL and several QOL subscales. Patients in the ALND group showed significant more changes in range of motion (ROM), grip strength, arm volume, ADL and QOL physical-and role functioning, pain and sleeplessness and arm symptoms compared to the SLNB group. Multivariate linear regression analysis showed that ALND could predict decrease of ROM, grip strength, ADL and physical functioning (QOL) and increase of arm volume, pain and arm symptoms score (QOL). Radiation on the axilla predicts an additional decrease in shoulder ROM and increase of arm volume. Conclusion: Two years after surgery for breast cancer, patients show significantly less treatment related upper limb morbidity, perceived disability in ADL and worsening of QOL after SLNB compared with ALND. q

Research paper thumbnail of Treatment-related upper-limb morbidity one year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for stage I or II breast cancer

Annals of Surgical Oncology, 2004

Background: In a prospective study, upper limb morbidity and perceived disability/activities of d... more Background: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).

Research paper thumbnail of Short-term morbidity of the upper limb after sentinel lymph node biopsy or axillary lymph node dissection for Stage I or II breast carcinoma

Cancer, 2003

BACKGROUND. The goals of sentinel lymph node biopsy (SLNB) are to improve axillary staging and re... more BACKGROUND. The goals of sentinel lymph node biopsy (SLNB) are to improve axillary staging and reduce unnecessary axillary lymph node dissections (ALND), thereby reducing treatment-related upper-limb morbidity. In the current prospective study, short-term upper-limb morbidity was assessed after SLNB and/or ALND.

Research paper thumbnail of Aggressive fibromatosis (non-familial desmoid tumour): Therapeutic problems and the role of adjuvant radiotherapy

British Journal of Surgery, 1995

Aggressive fibromatosis is a rare soft tissue tumour with a high tendency to local recurrence, ev... more Aggressive fibromatosis is a rare soft tissue tumour with a high tendency to local recurrence, even after apparently adequate resection. Wide local excision with a margin of at least 3 cm, depending on the anatomical location, should be performed to improve rates of recurrent disease. There is no consensus concerning the role of radiotherapy in the treatment of these lesions. The clinical findings of 39 cases diagnosed between 1972 and 1991 were reviewed retrospectively. Local control was effected in 19 of 32 patients treated with surgery alone after a median (range) follow-up of 72 (18–236) months. There were 40 cases of recurrent fibromatosis in 15 patients. Local control was obtained in 13 of 14 patients who received radiotherapy using a wide-field technique and doses of more than 50 Gy over a period of 5 weeks after marginal or incomplete resection of primary or recurrent lesions (P < 0.001). The results suggest that in a selected group of patients with aggressive fibromatosis radiotherapy may effectively achieve control of residual disease after surgery without marked disfigurement and loss of function.

Research paper thumbnail of Treatment-Related Upper Limb Morbidity 1 Year after Sentinel Lymph Node Biopsy or Axillary Lymph Node Dissection for Stage I or II Breast Cancer

Annals of Surgical Oncology, 2004

Background: In a prospective study, upper limb morbidity and perceived disability/activities of d... more Background: In a prospective study, upper limb morbidity and perceived disability/activities of daily life (ADLs) were assessed before and 1 year after sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).

Research paper thumbnail of Three-Dimensional Conformal Simultaneously Integrated Boost Technique for Breast-Conserving Radiotherapy

International Journal of Radiation Oncology Biology Physics, 2007

Purpose: To compare the target coverage and normal tissue dose with the simultaneously integrated... more Purpose: To compare the target coverage and normal tissue dose with the simultaneously integrated boost (SIB) and the sequential boost technique in breast cancer, and to evaluate the incidence of acute skin toxicity in patients treated with the SIB technique. Methods and Materials: Thirty patients with early-stage left-sided breast cancer underwent breast-conserving radiotherapy using the SIB technique. The breast and boost planning target volumes (PTVs) were treated simultaneously (i.e., for each fraction, the breast and boost PTVs received 1.81 Gy and 2.3 Gy, respectively). Three-dimensional conformal beams with wedges were shaped and weighted using forward planning. Dosevolume histograms of the PTVs and organs at risk with the SIB technique, 28 ؋ (1.81 ؉ 0.49 Gy), were compared with those for the sequential boost technique, 25 ؋ 2 Gy ؉ 8 ؋ 2 Gy. Acute skin toxicity was evaluated for 90 patients treated with the SIB technique according to Common Terminology Criteria for Adverse Events, version 3.0. Results: PTV coverage was adequate with both techniques. With SIB, more efficiently shaped boost beams resulted in smaller irradiated volumes. The mean volume receiving >107% of the breast dose was reduced by 20%, the mean volume outside the boost PTV receiving >95% of the boost dose was reduced by 54%, and the mean heart and lung dose were reduced by 10%. Of the evaluated patients, 32.2% had Grade 2 or worse toxicity. Conclusion: The SIB technique is proposed for standard use in breast-conserving radiotherapy because of its dose-limiting capabilities, easy implementation, reduced number of treatment fractions, and relatively low incidence of acute skin toxicity.

Research paper thumbnail of 236 Health-related quality of life in patients with early stage breast cancer treated with breast conserving surgery and radiotherapy

Research paper thumbnail of Comparison of normal tissue dose with three-dimensional conformal techniques for breast cancer irradiation including the internal mammary nodes

International Journal of Radiation Oncology Biology Physics, 2005

To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with thre... more To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with three commonly used strategies, by analyzing the dose to the heart and other organs at risk. Four different three-dimensional conformal dose plans were created for 30 breast cancer patients. The IMN were enclosed with the Para Mixed technique by a widened mediolateral tangent photon beam and an anterior electron beam, with the Patched technique by an anterior electron beam, with the Standard technique by an anterior photon and electron beam, and with the PWT technique by partially wide tangents. All techniques were optimized for conformality and produced equally adequate target coverage. Heart dose was lowest with the Para Mixed and Patched technique for all patients and with the PWT technique for right-sided treatment only. Lung dose was highest with the PWT, lowest with the Patched, and intermediate with the Para Mixed and Standard techniques. Skin dose was highest with the Patched, lowest with the PWT, and intermediate with the Para Mixed and the Standard techniques. The Para Mixed technique resulted in a 13-Gy lower dose in an overlap area, and the PWT technique was the only technique that incorporated considerable volumes of the contralateral breast. The Para Mixed technique yielded the overall best results. No other technique resulted in a lower heart dose. Lung and skin were equally spared instead of one of them being compromised, and the contralateral breast was avoided.