Molecular and biological rationale of hyperthermia as radio- and chemosensitizer.

Mild hyperthermia, local heating of the tumour up to temperatures <43 °C, has been clinically applied for almost four decades and has been proven to substantially enhance the effectiveness of both radiotherapy and chemotherapy in treatment of primary and recurrent tumours. Clinical results and mechanisms of action are discussed in this review, including the molecular and biological rationale of hyperthermia as radio- and chemosensitizer as established in in vitro and in vivo experiments. Proven mechanisms include inhibition of different DNA repair processes, (in)direct reduction of the hypoxic tumour cell fraction, enhanced drug uptake, increased perfusion and oxygen levels. All mechanisms show different dose effect relationships and different optimal scheduling with radiotherapy and chemotherapy. Therefore, obtaining the ideal multi-modality treatment still requires elucidation of more detailed data on dose, sequence, duration, and possible synergisms between modalities. A multidisciplinary approach with different modalities including hyperthermia might further increase anti-tumour effects and diminish normal tissue damage.

Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS) after primary breast cancer: a systematic review.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is a rare, aggressive disease. The incidence is increasing with the prolonged survival of women irradiated for primary breast cancer. Surgery is the current treatment of choice. Prognosis is poor. This review aims to evaluate all publications on primary treatment of RAAS to identify prognostic factors and evaluate treatment modalities. METHODS: Databases were searched for articles with published individual patient data on prognostic factors, treatment and follow-up of patients with RAAS. A regression analysis was performed to test the prognostic values of age, interval between primary treatment and RAAS, tumour size and grade on the local recurrence-free interval (LRFI) and overall survival (OS). The effects of treatment modalities surgery, radiation (with or without hyperthermia) and chemotherapy or combinations were evaluated. RESULTS: 74 articles were included, representing data on 222 patients. In these patients, the 5-year OS was 43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery and reirradiation and 6% surgery with chemotherapy. The remaining 9% received primary treatments without surgery. Surgery with radiotherapy had a better 5-year LRFI of 57% compared to 34% for surgery alone (p=0.008). The value of other treatment modalities could not be assessed. CONCLUSIONS: This systematic review confirms the poor prognosis of RAAS. Tumour size and age were of prognostic value. The addition of reirradiation to surgery in the treatment of RAAS appears to enhance local control.

Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall.

PURPOSE: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients. PATIENTS AND METHODS: RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These patients had previously undergone breast conserving therapy (BCT, n = 18), mastectomy with irradiation (n=5) or axillary lymph node dissection with irradiation (n = 1). Treatment consisted of surgery followed by reRT + HT (n = 8), reRT + HT followed by surgery (n = 3) or reRT + HT alone (n = 13). Patients received a mean radiation dose of 35 Gy (32-54 Gy) and 3-6 hyperthermia treatments (mean 4). Hyperthermia was given once or twice a week following radiotherapy (RT). RESULTS: The median latency interval between previous radiation and diagnosis of RAS was 106 months (range 45-212 months). Following reRT + HT, the complete response (CR) rate was 56 %. In the subgroup of patients receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates were 91, 46 and 46 %, respectively. In the subgroup of patients without surgery, the rates were 54, 32 and 22 %, respectively. Late grade 4 RT toxicity was seen in 2 patients. CONCLUSION: The present study shows that reRT + HT treatment--either alone or combined with surgery--improves LC rates in patients with RAS.

Negligible influence of comorbidity on prognosis of patients with small cell lung cancer: a population-based study in the Netherlands.

Management of small cell lung cancer (SCLC) among elderly is complex because of decreased organ functions and interactions with comorbidity. Since elderly patients are often excluded from clinical trials, little is known about the way they are treated and outcome. We evaluated the prognostic effects of rising age and comorbidity in unselected Dutch SCLC patients (Eindhoven Cancer Registry). Elderly patients received chemotherapy less often and the dose was also reduced more often. Cardiovascular diseases, hypertension or diabetes lowered the proportion receiving combined chemotherapy and radiotherapy among patients with limited disease. About 80% of the patients receiving chemotherapy suffered from a side effect, which was not related to age. After adjustment for age, gender, stage and treatment modality, comorbidity had a negligible prognostic effect. Chemotherapy (in combination with radiotherapy) seemed to improve survival, however, toxicity and quality of life in these patients should be evaluated thoroughly in future randomized studies.

Results of treatment of the adenocarcinoma of the esophagus.

The results of treatment in 74 patients treated in 1978-1990 for adenocarcinoma of the esophagus were retrospectively analyzed. The overall five-year survival was 7.8%, the median survival 10.0 months. Eighteen patients underwent a resection, in 13 patients with curative and in 5 patients with palliative intent. The median survival for these groups was 13.5 and 5.8 months, respectively. Thirty-one patients were irradiated. The response rate according to the WHO passage score was 79%. The median duration of response and survival was 6.0 and 9.5 months, respectively. Twenty patients were given palliative treatment, in the form of an endoprosthesis (10 patients), an endoprosthesis with chemotherapy (4 patients) or only chemotherapy (6 patients). The median duration of survival of patients in the palliative group was 6.5 months. The data are discussed in relation to results of treatment described in the literature.