A systematic overview of radiation therapy effects in soft tissue sarcomas

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for soft tissue sarcomas (STS) is based on data from five randomized trials. Moreover, data from 6 prospective studies, 25 retrospective studies and 3 other articles were used. In total, 39 scientific articles are included, involving 4579 patients. The results were compared with those of a similar overview from 1996 which included 3344 patients. The conclusions reached can be summarized as follows: The well-established prognostic factors for tumour-related death from STS-histological grade, tumour size and age-are well documented. The importance of superficial versus deep site as well as the anatomic site is also reaffirmed to some extent. There is strong evidence that adjuvant radiotherapy improves the local control rate in combination with conservative surgery in the treatment of STS of extremities and trunk in patients with negative, marginal or minimal microscopic positive surgical margins. A local control rate of 90% has been achieved. Improvement is obtained with radiotherapy added in the case of intralesional surgery, but the local control rate is somewhat lower. More studies are needed on this issue. For STS in other anatomic sites, retroperitoneum, head and neck, breast and uterus, there is only weak indication of a benefit for the local control rate, with the use of adjuvant radiotherapy. There is still insufficient data to establish that preoperative radiotherapy is favourable compared to postoperative radiotherapy for local control in patients presenting primarily with large tumours. One small study has shown a possible survival benefit for preoperative radiotherapy. There is fairly good evidence to suggest that the preoperative setting results in more wound complications. There is no randomized study comparing external beam radiotherapy and brachytherapy. The data suggest that external beam radiotherapy and low dose rate brachytherapy result in comparable local control for high-grade tumours. Some patients with low-grade soft tissue sarcomas benefit from external beam radiotherapy in terms of local control. Brachytherapy with low dose rate for low-grade tumours seems to be of no benefit, but data are sparse. The available data are inconclusive concerning the effect of intraoperative high dose rate radiotherapy for retroperitoneal STS. Further studies are needed. Neutron radiotherapy might be beneficial for patients with low- and intermediate-grade tumours considered inoperable and for those operated with intralesional margins. More severe side effects for neutrons have been registered. In two small studies investigating hyperfractionation schedules there was no indication of improvements compared to daily fractions of 2 Gy Further studies should be encouraged. One small study using preoperative limb perfusion with TNFalpha melphalan and +/-interferon gamma combined with postoperative radiotherapy in the case of marginal or positive surgical margin has shown excellent local control without enhanced morbidity

A systematic overview of radiation therapy effects in brain tumours

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for brain turnouts is based on data from 9 randomized trials and 1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective studies and 4 other articles were used. In total, 19 scientific articles are included, involving 4266 patients. The results were compared with those of a similar overview from 1996 including 11252 patients. The conclusions reached can be summarized as follows: The conclusion from SBU 129/2 that curative treatment is not available for patients with high-grade malignant glioma (grade III and IV) is still valid. The survival benefit from postoperative radiotherapy compared to supportive care only or chemotherapy is about 3-4 months, as demonstrated in earlier randomized studies. Quality of life is now currently estimated and considered to be of major importance when reporting the outcome of treatment for patients with brain tumours. There is no scientific evidence that radiotherapy using hyper- and hypofractionation leads to longer survival for patients with high-grade malignant glioma than conventional radiotherapy There is large documentation, but only one randomized study. There is some documentation to support the view that patients with grade IV glioma and poor prognosis can be treated with hypofractionation and with an outcome similar to that after conventional fractionation. A shorter treatment time should be convenient for the patient. Documentation of the benefit of a radiotherapy boost with brachytherapy is limited and no conclusion can be drawn. There is no scientific evidence that radiotherapy prolongs life for patients with low-grade glioma. There are some data supporting that radiotherapy can be used to treat symptoms in patients with low-grade glioma. As no controlled studies have been reported, no firm conclusion can be drawn

A systematic overview of radiation therapy effects in breast cancer

A systematic review of radiation therapy trials in several turnout types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41204 patients. The results were compared with those of a similar overview from 1996 including 285982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the turnout bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn

Cisplatin pharmacokinetics and pharmacodynamics in patients with squamous-cell carcinoma of the head/neck or esophagus

The pharmacokinetics of total platinum (Pt) in plasma and cisplatin (CDDP)-DNA adducts in different cell types were described in ten patients with squamous-cell carcinoma of the head/neck or esophagus after their first cycle of chemotherapy containing a CDDP dose of 100 mg/m2. Nephrotoxicity was studied in terms of urinary excretion of marker proteins (protein HC, IgG, and albumin). Pharmacodynamic relationships between pharmacokinetic parameters and toxicity were investigated. A population-based model with limited sampling was found feasible for producing pharmacokinetic information, in accordance with literature data. The kinetics of two normal cell types with different turnover (lymphocytes and buccal cells) appeared to have different kinetic profiles of CDDP-DNA adducts. Analysis of urinary excretion of marker proteins (protein HC, albumin, and IgG) showed that the nephrotoxicity was displayed first as tubular damage and later as impaired glomerular barrier function. There were indications that tubular nephrotoxicity may be predicted by pharmacokinetic parameters of plasma Pt. We found older patients to have a lower Pt clearance and more extensive early tubular damage. There was no correlation between CDDP-DNA adducts in normal cells and nephrotoxicity. Larger studies are warranted to define the pharmacokinetic window of CDDP. Limited sampling for analysis of CDDP pharmacokinetics may then be a possible avenue for individualizing the dose and, thus, improving the clinical use of the drug

Risk factors for post-treatment hypogonadism in testicular cancer patients.

OBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)). RESULTS: HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460). CONCLUSIONS: It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH

Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution

CAM2028, a vehicle that forms a bioadhesive lipid barrier when applied to the oral mucosa, was developed as a carrier system for local delivery of benzydamine, an NSAID used for pain relief in oral mucositis. This trial compared the analgesic effect of CAM2028 plus benzydamine (CAM2028-benzydamine) with unmedicated CAM2028 (CAM2028-control) for the treatment of oral mucositis in patients with head-and-neck cancer. Thirty-eight study participants were enrolled during their 3rd to 4th week of radiation therapy. Participants were required to have symptomatic oral mucositis (WHO Grade 2 or above) at screening and pain scores of at least 6 on an 11-point Likert scale at screening and on each day before treatment with study medication. After undergoing radiation, patients were administered a single dose of CAM2028-control or CAM2028-benzydamine 2 days apart, in a randomized crossover fashion. Pain was assessed over the following 8 h. With both treatments, patients experienced a mean 40 % decrease in pain intensity at 6 h (the primary study endpoint). Both treatments resulted in significant pain relief within 5 min of application that was evident during the entire 8-h assessment period. There was no difference in pain relief between the two interventions at any time point. Both treatments were safe and well tolerated. CAM2028-benzydamine and CAM2028-control were both efficacious in reducing pain in patients with oral mucositis related to radiation therapy for head-and-neck cancer. Analgesic effects of both medications were immediate, clinically significant, and persistent for up to 8 h