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PubMed2005

Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg.

In the EORTC-ISG-AGITG trial 946 patients with advanced gastro-intestinal stromal tumours (GIST) were randomised to receive 400 or 800 mg of imatinib daily. An increase in progression free survival (PFS) was demonstrated for patients randomised to the high-dose arm. Patients randomised to low-dose could cross-over to high-dose upon progression. We evaluated the feasibility, safety and efficacy of this policy. Of the 241 patients available for follow-up, 133 patients (55%) crossed over to high-dose imatinib according to the protocol. Of these patients, 92% had not had a prior dose reduction. The cumulative incidence of subsequent dose reductions after cross-over was 17% after six months with 51% discontinuing therapy without requiring a dose reduction. The extent of anaemia and fatigue increased significantly after cross-over, whilst neutropenia was less severe than during low-dose treatment. Objective responses after cross-over included three patients (2%) with a partial response and 36 (27%) with stable disease. The median PFS after cross-over was 81 days, although 18.1% of patients were still alive and progression free one year after cross-over. We conclude that a cross-over to high-dose imatinib is feasible and safe in GIST patients who progress on low-dose therapy.

Adult↗

PubMed2004

Erythrocyte sodium lithium countertransport in renal transplant recipients with mycophenolate mofetil and low-dose cyclosporine.

Hypertension, a common complication after renal transplantation, has many potential etiologies. Erythrocyte sodium lithium countertransport (Na/LiCT) is a sensitive membrane protein that has been observed to be abnormal in several hypertension-related diseases. We have shown that the kinetics of Na/LiCT were abnormal in renal transplant recipients treated with usual dose of cyclosporine (CsA). We postulated that CsA might be a cause of post-renal transplantation hypertension. There is evidence showing that the severity of CsA nephrotoxicity is dependent on the dose. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. We studied the impact of CsA dose reduction in association with MMF on the kinetics of erythrocyte Na/LiCT in renal transplants. In 15 renal allograft recipients, 2 g/d MMF were introduced and the CsA dose reduced to reach whole-blood levels between 70 and 100 ng/mL within 1 month. CsA doses and levels, renal function parameters, blood pressure, and the kinetics of Na/LiCT were evaluated before and 6 months after CsA dose reduction. Overall, renal transplant recipients with usual doses of CsA showed a lower Km with a higher Vmax/Km ratio for erythrocyte Na/LiCT than normal controls (Km, 40 +/- 4 vs 74 +/- 11; P <.05; Vmax/Km, 10.2 +/- 1.7 vs 6.1 +/- 0.9; P <.05). After 6 months of CsA dose reduction, the Km and Vmax/Km of Na/LiCT were similar to those of normal controls (Km, 66 +/- 8 vs 74 +/- 11; P >.05; Vmax/Km, 5.7 +/- 1.2 vs 6.1 +/- 0.9; P >.05). These results demonstrate that reduction of CsA dose in combination with MMF may improve the kinetics of Na/LiCT and lessen the long-term side effects of CsA without increasing the risk of rejection.

Adolescent↗

PubMed1990

Effects of reduction in dose and discontinuation of hydrochlorothiazide in patients with controlled essential hypertension.

We studied the effects of a reduction in dose of hydrochlorothiazide from 50 to 25 mg/d, and its discontinuation for up to 22 months in 36 well-controlled hypertensive patients. Hydrochlorothiazide was discontinued if the diastolic blood pressure remained less than or equal to 94 mm Hg after a 6-month period on the lower dose of hydrochlorothiazide. No other changes were made in medications or diet. Sitting systolic blood pressure rose from 135 +/- 15 mm Hg to 140 +/- 14 mm Hg on reduction of the hydrochlorothiazide dose and rose still further to 145 +/- 20 mm Hg on discontinuation. Even greater increases in standing blood pressure were observed. There were no significant effects on the diastolic blood pressure with reduction of dose or discontinuation of hydrochlorothiazide. A significant decrease in the serum uric acid and a rise in serum potassium occurred. There were no changes in serum glucose or lipids on reduction in the dose of hydrochlorothiazide; whereas, with discontinuation, the serum lipids and hemoglobin A1C fell significantly. These results suggest that the benefits of a reduced dose of hydrochlorothiazide may not be as great as considered heretofore.

Adult↗

PubMed1988

Scoliosis examinations: organ dose and image quality with rare-earth screen-film systems.

We determined the dose to the breast and evaluated the image quality when various high-speed, rare-earth screen-film systems were used in conjunction with breast dose reduction methods in children undergoing scoliosis examinations. In addition, normalized organ dose to the breast, active bone marrow, thyroid, eyes, ovaries, and testes were measured in a pediatric anthropomorphic phantom comparing the anteroposterior and posteroanterior projections. The average measured dose to the breast was 6.9 and 4.0 mrad (10(-5) Gy), respectively, for nominal 400- and 600-speed, rare-earth screen-film systems used in combination with breast dose reduction methods. The image quality of these systems as evaluated by three radiologists was rated as adequate. The dosimetry results with an anthropomorphic phantom showed that the posteroanterior projection provides approximately a threefold reduction in breast dose as compared with the anteroposterior view. However, the dose to the bone marrow is doubled. Rare-earth screen-film systems used in combination with simple dose-reduction methods can provide adequate image quality for scoliosis examination while significantly reducing the radiation dose to the breast.

Adolescent↗

PubMed2006

Neutropenia and febrile neutropenia in patients with Hodgkin's lymphoma treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy.

When uncomplicated neutropenia during doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy for the treatment of Hodgkin's lymphoma is encountered, it is unclear whether or not treatment should be modified. In the present study, we determined the incidence of neutropenia, febrile neutropenia, and the relationship of febrile neutropenia to grade III/IV neutropenia and dose modification, in a large university patient population. We reviewed the charts of patients diagnosed with Hodgkin's lymphoma between 1 January 1990 and 31 December 2002 who were treated with ABVD chemotherapy, and seen at the University of Iowa with complete diagnosis, staging, and treatment dosing records. Adequate data was available on 894 treatments in 81 patients with Hodgkin's lymphoma treated with ABVD chemotherapy. Grade III/IV neutropenia was present on the scheduled day of treatment in 187 (20.9%) treatments in 64 (79%) patients. Grade III/IV neutropenia was most common at cycle 1 day 15. Febrile neutropenia developed nine times in eight patients, and eight episodes of febrile neutropenia developed when the treatment-day absolute neutrophil count (ANC) > or =1000. Dose delay of >4 days and/or dose reduction to <80% of original doxorubicin dose following grade III/IV neutropenia occurred in 29 of 187 treatments, with no episodes of febrile neutropenia. With grade III/IV neutropenia on the day of therapy, 158 treatments were administered without dose reduction or dose delay with one subsequent episode of febrile neutropenia. Neutropenia during ABVD is common, and dose modification for uncomplicated neutropenia on the day of treatment may not reduce the risk of febrile neutropenia. It may be possible to maintain dose intensity in the face of uncomplicated neutropenia during ABVD therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography.

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing. a dose reduction by 25% has no serious influence on the detection results. whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

Algorithms↗

PubMed2003

Variation in the propensity to release endotoxin after cefuroxime exposure in different gram-negative bacteria: uniform and dose-dependent reduction by the addition of tobramycin.

An aminoglycoside in combination with a beta-lactam antibiotic is often recommended for the treatment of severe infections. The aim of the present study was to study whether cefuroxime-induced endotoxin release could be reduced by addition of tobramycin in different Gram-negative bacteria and how endotoxin release was affected by bacterial killing rate and number of killed bacteria. Three Escherichia coli strains, 1 Klebsiella, 1 Salmonella and 1 Neisseria strain were exposed in vitro to 2, 10 and 50 x minimum inhibitory concentration of cefuroxime, tobramycin or a combination of both. The cefuroxime-induced endotoxin release in the 6 strains varied from 0.1 to 9.9 x 10(-3) EU/killed bacterium. By adding tobramycin, highly significant reductions of 96%, 93%, 97%, 86% and 85% were seen in the 3 E. coli strains and in the Klebsiella and the Salmonella strain, respectively. In the Neisseria strain, the reduction was less. Increasing doses of tobramycin or the combination led to significant endotoxin release reduction in 4/6 strains. In conclusion, addition of tobramycin reduced penicillin-binding protein-3-beta-lactam binding-induced endotoxin release in all tested Gram-negative strains, despite a large interspecies variation in the propensity to release endotoxin. Besides broadening the spectrum and increasing the killing rate, this might be of benefit in the most severe forms of sepsis.

Cefuroxime↗

PubMed1996

Warfarin-fluconazole. III. A rational approach to management of a metabolically based drug interaction.

The results of studies of the effect of fluconazole on cytochrome P450 (P450) 2C9 activity in vivo and in vitro are used to develop an approach to the safe management of the warfarin-fluconazole drug interaction. This approach begins with a determination of an in vitro Ki value (22 microM), which may be used to relate fluconazole plasma concentrations to inhibitory effect on P4502C9 activity and (S)-warfarin half-life. A means for adding fluconazole to a therapeutic regimen of warfarin is proposed that involves a stepped reduction of the warfarin dose over 5 days to a final target daily dose that is determined by the fluconazole dose level. The effect of interindividual pharmacokinetic variability on outcome quality is explored in simulation studies that indicate that a stepped-dose reduction schedule will be superior to a one-time dose reduction. The in vivo K, was found to predict accurately the magnitude of the fluconazole interaction study with another P4502C9 substrate tolbutamide.

Anticoagulants↗

PubMed2000

Chemotherapy with cisplatin, epirubicin and docetaxel in transitional cell urothelial cancer. Phase II trial.

Cisplatin (CDDP), epirubicin (EPI) and docetaxel have single agent activity against urothelial transitional cell carcinoma (TCC). We evaluated the efficacy and toxicity of this combination in locally advanced or metastatic urothelial TCC. Patients with urothelial TCC who had no prior chemotherapy (prior adjuvant chemotherapy > 6 months allowed) were eligible for entry the study. Eligibility criteria were performance status 0-3, granulocyte count (AGC) > or = 1.5 (10(9)/l), platelet count > or = 100 (10(9)/l), clearance creatine > or = 60 ml/min and total bilirubin level < or = 1.5 mg/dl. Treatment consisted of EPI 40 mg/m2 intravenous push, docetaxel 75 mg/m2 in 1 h infusion with premedication and CDDP 75 mg/m2 with pre- and posthydration. Treatment was repeated every 21 days. Antiemetics with dexamethasone and 5-HT3 antagonists were used routinely. Prophylactic haematopoietic growth factors were not used. Patients were evaluated for toxicity weekly and assessed for response every two cycles of treatment. 32 patients were entered into the study and 30 patients (7 with locally advanced and 23 with metastatic disease) were assessable for response. There were 9 (30.0%) complete responses (2, 28.6% in locally advanced and 7, 30.4% in metastatic disease) and 11 (36.7%) partial responses (3, 42.9% in locally advanced and 8, 34.8% in metastatic disease) with an overall response rate (RR) of 66.7% (71.5% in locally advanced, 65.2% in metastatic disease). Overall median survival was 14.5 months (15 months for locally advanced, 12.5 months for metastatic disease). The median duration of response in patients with metastatic disease was 8.5 months. 16 (53.3%) patients required one dose reduction and 5 (16.7%) patients required two dose reductions for a nadir AGC < or = 500/mm3. Four episodes of febrile neutropenia and sepsis occurred. No patient had a dose reduction or treatment delay for any other grade 3/4 toxicity. There were no treatment delays due to myelotoxicity. Alopecia was universal. Non-haematological toxicity including mucositis, fluid retention, allergy, cutaneous toxicity, diarrhoea and neurotoxicity were mild and infrequent. The combination of EPI, docetaxel and CDDP is an active regimen for urothelial TCC. The response rate and toxicity were comparable with the M-VAC (methotrexate, vinblastine, doxorubicin, cisplastin) regimen. Phase III trials comparing this regimen with M-VAC are warranted.

Adult↗

PubMed2004

Infusion pump dose error reduction systems: trends in purchasing and use.

Over the last three years, infusion pump suppliers have begun introducing dose error reduction systems. The primary function of these systems is to reduce pump programming errors and associated injuries to patients. However, these systems can offer other benefits as well. In this article, we describe ways that hospitals can use dose error reduction system data to improve patient care and staff efficiency. We also detail the fees that accompany this new software and discuss the potential for increasing patient safety using wireless capabilities.

Infusion Pumps↗

PubMed2026

De-escalation of radiotherapy in HPV-negative non-nasopharyngeal head and neck squamous cell carcinoma: a systematic review.

BACKGROUND: Definitive and postoperative radiotherapy are central components of treatment for head and neck squamous cell carcinoma (HNSCC) but are associated with significant toxicities that can impair long-term function and quality of life. De-escalation strategies, aiming to reduce treatment-related morbidity while maintaining tumor control, have attracted increasing interest. However, most research has focused on HPV-positive oropharyngeal carcinoma. Systematic evidence for HPV-negative disease remains limited. METHODS: PubMed and EMBASE were searched for prospective studies investigating radio(chemo)therapy de-escalation in HPV-negative, HPV-unspecified, or mixed non-nasopharyngeal HNSCC populations. CLINICALTRIALS: gov was searched for ongoing prospective trials. Data extraction and verification were performed independently by three investigators. RESULTS: Screening of 3156 records identified 14 published prospective studies, 10 in the definitive and four in the postoperative setting. Strategies included reduction or omission of elective nodal volumes, dose reduction, and combined approaches. Additionally, 23 ongoing prospective trials were identified. Across studies, elective nodal failure rates were consistently low (0-4.6%), with most recurrences occurring within high-dose volumes rather than de-escalated elective regions. Randomized evidence for elective nodal dose reduction is mixed: two trials maintained regional control and reduced acute toxicity, whereas another was stopped for futility. CONCLUSION: Available evidence on de-escalation in HPV-negative HNSCC is limited, derived primarily from small, heterogeneous phase II studies with mixed HPV populations. Although data are promising in selected settings, notably for elective nodal control, the randomized evidence for elective nodal dose reduction is conflicting, and further adequately designed prospective randomized trials are required.

Humans↗

PubMed1999

Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks.

OBJECTIVE: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. METHOD: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. RESULTS: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. CONCLUSIONS: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms.

Adult↗

PubMedDate not supplied

Exhaling a budesonide inhaler through the nose results in a significant reduction in dose requirement of budesonide nasal spray in patients having asthma with rhinitis.

Budesonide, an inhaled corticosteroid is used routinely in the treatment of bronchial asthma and rhinitis. Although inhaled corticosteroids in therapeutic doses are unlikely to result in systemic side effects, there is as yet skepticism about their routine and prolonged use. The aim of this study was to determine whether budesonide inhalation through a metered dose inhaler, when exhaled through the nose could result in a reduction in the dose requirement of budesonide metered nasal spray in patients having perennial allergic asthma with rhinitis. This study was an open, parallel, comparative, crossover trial in which 49 young patients having perennial allergic asthma with rhinitis were divided into two groups and administered either a combination of budesonide metered dose inhaler with a budesonide nasal spray or a budesonide inhaler alone, which was to be exhaled through the nose. Both groups were later crossed over and weekly symptom scores and peak nasal inspiratory flow rates were monitored during each phase of the study. Finally, patients who volunteered from both groups were instructed to note the reduction in dose requirement of budesonide nasal spray while using a budesonide inhaler and exhaling it through the nose. The results of this study reveal that when a budesonide inhaler is exhaled through the nose, it results in an improvement in symptom scores and peak nasal inspiratory flow rates, which were significantly less than those obtained in the group using both a budesonide nasal spray and a metered dose inhaler. In addition, exhaling budesonide through the nose results in a 40.1% reduction in the dose requirement of a budesonide nasal spray, which is statistically significant (p < 0.001).

Administration, Inhalation↗

PubMed2004

A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer.

OBJECTIVE: To determine the activity and tolerability of weekly docetaxel in patients with platinum-resistant mullerian origin tumors. METHODS: Patients with persistent disease, or those recurring less than 6 months after receiving platinum-containing therapy, were eligible for this phase II study. Docetaxel was initially administered at a dose of 40 mg/m(2) on days 1, 8, and 15, with a cycle length of 28 days. This starting dose was subsequently reduced to 30 mg/m(2) due to toxicity. Dexamethasone prophylaxis was administered at a dose of 4 mg PO every 12 hours for 3 doses, starting 12 hours before each dose of docetaxel. RESULTS: Thirty-two patients were enrolled, with a median age of 59 years. The majority of patients received a median of 3 prior regimens, with 45% of the study group having received 4 or more prior regimens. The overall response rate in 29 evaluable patients was 6.9%, with no complete responses. Seventeen percent of patients experienced stable disease. Dose reduction or delay was required in 10 of the first 22 patients enrolled, prompting a reduction in the starting dose to 30 mg/m(2). Hematologic toxicity was generally tolerable, and no patient experienced febrile neutropenia. Non-hematologic toxicity was generally grade 1 in nature, although a combination of multiple low grade toxicities occurring in an individual patient oftentimes mandated dose reduction. CONCLUSIONS: Weekly docetaxel demonstrated modest activity in a heavily pre-treated, platinum-resistant population. A starting docetaxel dose of 30 mg/m(2) would be reasonable for future studies exploring the utility of weekly dosing in less heavily pre-treated patients.

Aged↗

PubMedDate not supplied

Hypothetical mortality risk associated with spiral computed tomography of the maxilla and mandible.

In the present study, dose measurements have been conducted following examination of the maxilla and mandible with spiral computed tomography (CT). The measurements were carried out with 2 phantoms, a head and neck phantom and a full body phantom. The analysis of applied thermoluminescent dosimeters yielded radiation doses for organs and tissues in the head and neck region between 0.6 and 16.7 mGy when 40 axial slices and 120 kV/165 mAs were used as exposure parameters. The effective dose was calculated as 0.58 and 0.48 mSv in the maxilla and mandible, respectively. Tested methods for dose reduction showed a significant decrease of radiation dose from 40 to 65%. Based on these results, the mortality risk was estimated according to calculation models recommended by the Committee on the Biological Effects of Ionizing Radiations and by the International Commission on Radiological Protection. Both models resulted in similar values. The mortality risk ranges from 46.2 x 10.6 for 20-year-old men to 11.2 x 10(-6) for 65-year-old women. Using 2 methods of dose reduction, the mortality risk decreased by approximately 50 to 60% to 19.1 x 10(-6) for 20-year-old men and 5.5 x 10(-6) for 65-year-old women. It can be concluded that a CT scan of the maxillofacial complex causes a considerable radiation dose when compared with conventional radiographic examinations. Therefore, a careful indication for this imaging technique and dose reduction methods should be considered in daily practice.

Adult↗

PubMed2000

Adverse effects and other safety aspects of the hepatitis C antivirals.

The preferred treatment for patients with chronic hepatitis C, either treatment-naive, relapsers or nonresponders to IFN monotherapy, is now IFN-ribavirin combination treatment. The adverse effects of IFN are well established and familiar to hepatologists all over the world. More than 25,000 patients worldwide have been treated with combination therapy. Patients re-treated with a combination regimen are more likely to tolerate IFN better than treatment-naive patients, probably due to better case selection. The safety profile of regimens containing IFN-alpha plus ribavirin is generally consistent with the safety profile of each agent when employed in monotherapy; there is little or no synergistic toxicity. Anorexia, dyspnoea, cough, pruritus and rash are the only adverse events reported at a consistently higher frequency with combination treatment, and are usually mild to moderate in severity and rarely result in dose reductions or discontinuation. The primary cause of dose reduction for combination therapy is haemolytic anaemia, which can be managed effectively. The most common reason for discontinuation of therapy for either type of therapy is psychiatric problems, especially depression, which seems to be closely related to the duration of treatment. In patients receiving combination therapy, anaemia and depression need close monitoring, and dose modification in some cases. Strict guidelines for dose reduction and discontinuation are essential to prevent serious adverse events. Because of the teratogenic risk from ribavirin, pregnancy is contraindicated in patients or their partners during and 6 months after treatment.

Antiviral Agents↗

PubMed2004

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck.

PURPOSE: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients. EXPERIMENTAL DESIGN: Seventy-two patients enrolled. Eligibility criteria included recurrent or second primary HNC, metastases or expected 2-year survival <20%. Chemoradiotherapy consisted of 5-fluorouracil, 600 mg/m(2)/d, for 5 days; paclitaxel, 100 mg/m(2) on Day 1; and concurrent 1.5 Gy twice-daily radiation for 5 days. Gemcitabine was dose escalated, 50-300 mg/m(2) on day 1. Cycles repeated every 14 days until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: neutropenic fever; grade > or =4 neutropenia or thrombocytopenia for >4 days; grade > or =4 mucositis or dermatitis for >7 days; or grade 3 toxicity necessitating chemotherapy dose reductions. Non-DLT dose reductions in 5-fluorouracil and/or paclitaxel were allowed. RESULTS: Seventy-nine percent of assessable patients experienced a clinical response. Five-year actuarial survival is 33.0%, and locoregional control is 61.4%. The recommended phase II dose of gemcitabine in this regimen is 100 mg/m(2) during cycles 1-5 (1 of 7 patients with DLT) or 200 mg/m(2) delivered only during cycles 3-5 (3 of 19 with DLT). Grades 3 and 4 mucositis (56 and 21%, respectively) and dermatitis (25 and 21%, respectively) were common. CONCLUSIONS: Gemcitabine, 5-fluorouracil, paclitaxel, and twice-daily radiation, delivered on alternating weeks, is active in patients with poor-prognosis HNC, although severe mucositis limits the clinical applicability of this regimen. Refinements in radiotherapy, including intensity-modulated radiation therapy, may improve the tolerance for this regimen.

Adolescent↗

PubMed2004

Breathing adapted radiotherapy of breast cancer: reduction of cardiac and pulmonary doses using voluntary inspiration breath-hold.

BACKGROUND AND PURPOSE: Adjuvant radiotherapy of breast cancer using wide tangential photon fields implies a risk of late cardiac and pulmonary toxicity. This CT-study evaluates the detailed potential dosimetric consequences of applying breathing adapted radiotherapy (BART), and the feasibility of a monitored voluntary breath-hold technique for right-sided as well as for left-sided tumours. PATIENTS AND METHODS: After breast-conserving surgery, 16 patients were CT-scanned in distinct respiratory phases using the varian real-time position management system for the monitoring of respiratory anterioposterior chest wall excursion. Each patient underwent three scans: during free breathing (FB), voluntary expiration breath-hold (EBH) and voluntary deep inspiration breath-hold (DIBH). For each scan, an optimised treatment plan was designed with conformal tangential fields encompassing the clinical target volume (CTV) of the breast and ipsilateral internal mammary nodes, and an anterior supraclavicular field. RESULTS: Breath-hold was well accepted by the patients, with a median duration of 24 s for both EBH and DIBH. The mean anterioposterior chest wall excursions were 2.5, 2.6 and 4.1 mm during FB, EBH and DIBH, respectively. During EBH, the mean front chest wall position was 2.7 mm posterior to its mid-FB position, and during DIBH 12.6 mm anterior to its mid-FB position. For right-sided tumours, the median ipsilateral relative lung volume receiving >50% of the prescribed CTV dose was 39, 49 and 32% for FB, EBH and DIBH, respectively. For left-sided tumours, the corresponding percentages were 37, 46 and 31%. The median heart volume receiving >50% of the prescription dose was reduced from 8% for FB to 1% for DIBH, and the median left anterior descending coronary artery volume was reduced from 54 to 5%. CONCLUSIONS: Irradiated cardiac volumes can consistently be reduced for left-sided breast cancers using DIBH for wide tangential treatment fields. Additionally, substantial dose reductions in the lung are observed for both right- and left-sided tumours.

Aged↗