Dose Fractionation Schedules Research Articles

Randomized Trial Comparing Two Fractionation Schedules for Patients With Localized Prostate Cancer

The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%). Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.

Extracranial Stereotactic Radiation Delivery

Extracranial stereotactic radiation delivery, also known as stereotactic body radiation therapy (SBRT), involves delivering very potent doses of radiation to well-demarcated tumors in the neck, spine, chest, abdomen, and pelvis. Beyond just stereotactic targeting, it represents a formalism of treatment planning and conduct that facilitates the delivery of the most potent dose fractionation schedules ever considered in the field of radiation oncology. In doing so, it uses the most modern technologies to simultaneously hit the target and avoid normal innocent tissues. Clinical results already show that SBRT constitutes a new paradigm in cancer treatment that deserves careful implementation and assessment for the improvement in patient outcomes.

SU-FF-T-379: Biological Radial Dose Functions for Brachytherapy Sources

Purpose: Brachytherapy is often used in combination with external-beam-radiotherapy to deliver a tumoricidal dose, while respecting critical organ tolerances. Its biological equivalence to an external beam dose fractionation has conventionally been considered via only the prescribed dose, preventing the 3D summation of brachytherapy and external beam dose distributions. We investigate a methodology that calculates a brachytherapy dose distribution biologically equivalent to an external beam dose fractionation schedule using a commercial treatment-planning system that has only conventional brachytherapy dose calculation models. Method and Materials: Dose distributions from high-dose-rate (HDR) brachytherapy treatments, including point-source, line-source, planar, and intracavitary gynecological implants were converted to their biological equivalents for corresponding external beam dose fractionations using the linear quadratic equation and an α/β ratio of 10. The radial-dose-function (RDF) values of an Ir-192 source were modified (BRDF) to yield these biologically-equivalent dose distributions using the conventional dose calculation formalism. Use of this formalism was demonstrated by planning an IMRT treatment of cervical cancer constrained by delivered HDR dose distributions. Results: The BRDFs of HDR Ir-192 treatments vary as a function of external beam dose fractionations, the α/β ratio used, and implant geometry. BRDF's dependence on implant geometry is due to the nonlinearity of the linear-quadratic equation. BRDF's have non-unitary values at 1 cm from the source, depending on the equivalence of prescribed external beam and brachytherapy doses. Comparisons between the biological-equivalent dose distributions and the approximations obtained using BRDF showed excellent agreement. Conclusion: A method is proposed to allow calculation of biologically-equivalent brachytherapy dose distribution in commercial treatment planning systems. Preliminary studies using the BRDF demonstrated its usefulness in the IMRT treatment planning when constrained by delivered brachytherapy dose distribution. The process can also be used to review brachytherapy implant dose distributions at conventional external-beam fractionation schedules.

The Role of Altered Fractionation in Head and Neck Cancers.

At the present time, the only rigorously demonstrated therapeutic gain from altered fractionation in the treatment of head and neck cancer is in patients with intermediate stage oropharyngeal cancer treated with hyperfractionation in the Phase III EORTC Trial 2279 I.’ Nevertheless, there is a compelling radiobiological rationale and abundant suggestive evidence from a number of other clinical studies that a therapeutic gain may be realized more generally when conventional fractionation is modified by either reduction in size of dose per fraction, reduction in overall duration of the treatment, or both. This article will briefly review the background radiobiology of altered fractionation schedules and the clinical results that have been reported. The term “altered fractionation” is a relative one, because from the earliest days of radiotherapy there has been lack of agreement as to what constitutes the “norm.” Regimens regarded as conventional differ widely in different parts of the world. For example, in the Manchester school, radical (ie, definitive) treatments for head and neck cancer are dispensed in 16 fractions over 3 weeks while in the United States, most definitive treatments are administered in 35 to 40 fractions over 7 to 8 weeks. Many other variations exist in what is considered conventional therapy. To a large extent, the evolution of “conventional” dose fractionation schedules reflects logistic and financial considerations and the availability of equipment and staff as much as any serious effort to determine which fractionation schedule maximizes the therapeutic advantage. 2,3 Many schedules now considered unconventional have had their proponents in the past, but only recently has sufficient information been available to assess the merits of different fractionation schedules on a radiobiologic basis.

An audit of the indications for and techniques of palliative splenic radiotherapy in the UK

This paper describes a national audit of the indications for, and techniques and toxicity of, palliative splenic radiotherapy in haematological disorders. A postal questionnaire was sent to consultant clinical oncologists treating haematological malignancies in the UK. The response rate was 76%. The audit shows chronic lymphocytic leukaemia, myelofibrosis and chronic myeloid leukaemia to be the most common underlying conditions in which splenic irradiation is used. Painful splenomegaly and hypersplenism were the most common indications. Dose fractionation schedules vary widely across the UK, and also the level of full blood counts used to interrupt radiotherapy. Palliative splenic radiotherapy continues to be widely used in the UK in small numbers of patients and seems to be well tolerated. Re-irradiation for further symptomatic progression is also commonly carried out.

467 oral Evaluation of two dose-fractionation schedules and of prognostic factors in radiotherapy (RT) of metastatic spinal cord compression (MSCC)

467 oral Evaluation of two dose-fractionation schedules and of prognostic factors in radiotherapy (RT) of metastatic spinal cord compression (MSCC)

Radioimmunotherapy in non-Hodgkin's lymphoma (NHL) using a fractionated schedule of DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab

2545 Background: A phase I/II, multi-center, dose-escalation trial was conducted to establish the safety, optimal dosing, and preliminary efficacy of 90Y-epratuzumab administered weekly for 2 or 3 consecutive wks to pts with B-cell NHL who failed ≥1 regimen of standard chemotherapy. Methods: Eligibility criteria included <25% BM involvement, plts >100,000 cells/mm3, and measurable disease by CT with no single mass >10 cm. Pts received 1.5 mg/kg/wk epratuzumab with 111In-epratuzumab co-administered the 1st wk. Twenty-six pts with a median of 3 prior treatments have been treated, including 15 pts without prior bone marrow transplant (BMT) at 5–10 mCi/m2/wk (total 90Y dose, 15–22.5 mCi/m2) and11 pts with prior BMT escalated separately at 2.5–5 mCi/m2/wk (total 90Y dose, 5–10 mCi/m2). Results: Dose escalation is continuing, with no serious AEs considered treatment-related. One pt in each escalation arm had protocol-defined DLT (>12 wk platelet recovery); otherwise, therapy was well tolerated with no significant toxicity besides transient hematologic depression, including 4 pts retreated without additional toxicity. 111In imaging demonstrated antibody tumor targeting, and hot/cold PK demonstrated stability of DOTA chelation ≥1 wk. In 22 pts with treatment evaluations, 13 pts (59%) had an objective response (OR) by IWG criteria, including pts with and without BMT [5/9 (56%) and 8/13 (62%), respectively], with indolent and aggressive disease [8/10 (80%) and 5/12 (42%), respectively], across histologies [follicular NHL, 9/12 (75%); DLCL, 2/4 (50%); mantle cell, 2/6 (33%)], and in pts failing rituximab (9/15, 60%). Most OR's were complete responses (CR/CRu, 9/13, 69%), and 3/5 pts assessed after CR onset now have responses >6 mo, including 2 pts continuing >1 yr. Conclusion: This study shows the feasibility and safety of a dose-fractionation schedule of a 90Y-labeled anti-CD22 Mab, obtaining therapeutic responses across all pt groups, including durable complete responses, and achieving higher cumulative doses than other RAIT agents given as single doses. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics Immunomedics Immunomedics Immunomedics

Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma.

To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. The overall median survival period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were > or =2, there is obvious statistical significance on the prognosis.

A randomized trial comparing two fractionation schedules for patients with localized prostate cancer

Purpose/Objective: The optimal radiation dose-fractionation schedule for localized prostate cancer is unclear. In Canada, prior to commencement of the study two main schedules were used: 50–52 Gy in 20 fractions over 4 weeks and 64–68Gy in 32–34 fractions over 6–7 weeks. The purpose of this study was to determine if a shorter 4-week radiation schedule was as effective as a longer 6.5-week schedule.

E-8. Evidence-based palliative radiotherapy

Evidence-based medicine has been defined as “the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients” [l]. It relies on quality evidence from well-conducted randomized control trials, and systematic reviews, including (but not confined to) meta-analyses. These reviews frequently result in practice guidelines, defined as “... systematically developed statements to assist provider and patient decisions about appropriate health care for specific clinical circumstances...” [2]. Systematic reviews and evidence based practice guidelines can then be used by health care providers, patients and decision makers (at an institutional or local national level), to achieve a wide range of goals, including provide most effective treatment, improve patient outcome, improve quality of care, minimize practice variations, decrease health care costs by minimizing ineffective treatment, yet still allow for physician autonomy and patients choice. Palliative Radiotherapy for lung cancer (specifically non-small cell lung cancer) is a topic that has been subject to numerous randomized controlled trials, comparing different palliative RT fractionation schemes (summarized in a Cochrane systematic review [3]), immediate vs delayed palliative radiation for asymptomatic patients [4] and palliative radiation +/chemotherapy [5]. Many, but not all, studies comparing different palliative RT regimens have suggested that less protracted radiation protocols provide better palliation, i.e. equivalent symptom control with less toxicity and less burden to the patient and family. Using shorter treatment protocols, approximately 80-85% of patients report improvement in hemoptysis, and 60% improvement in cough; pain improved in 2/3 patients. On average, symptom relief lasted for 50% or more of the patient’s survival time. No dose-fractionation schedule has to date demonstrated a clear superiority in terms of palliation, and until mid-nineties, there was no survival advantage to any of the regimens either. More recently, several studies have demonstrated prolonged survival in the higher dose palliative RT arm of the study: in the MRC trial [6] that difference was seen when comparing 36 Gy/13 fractions to 17 Gy/2 fractions; in the NCIC CTG trial [7] that was seen in patients treated with 20 Gy/5 fractions, as compared to single 10 Gy. This benefit appeared confined to the good performance status patients or those with localized disease (but who were not deemed candidates for aggressive treatment). The main challenge remains how to define and analyze symptom palliation in lung cancer, as a standard definition of palliation is lacking. The degree of improvement in symptoms present at baseline can be used as an index of palliation. However, the effectiveness of palliative radiation may be related to the initial severity of the symptom, not all the patients will have the symptom being assessed, and the timing of response may vary. A broader definition of palliative benefit of treatment would also include stability of mild symptoms and prevention of new symptoms. A method to calculate the palliative benefit of treatment using this broader definition has been described [8], which offers promise as a tool to better assess the benefit of a treatment in the setting where multiple symptoms are common, as is the case in lung cancer. Advances in practising evidence-based palliative radiotherapy will stem from a more uniform approach to analyzing palliation, an emphasis on both the quality of trials and of reporting of those trials [9]; creation and dissemination of systematic reviews and practice guidelines [IO], and attention to factors other than level of evidence which influence medical decisions, including values and beliefs of health care providers and patients, context of the decision and economic studies of impact of intervention, among others.

Radiotherapy for Graves' orbitopathy: results of a national survey.

Graves' orbitopathy (GO) is a widely accepted indication for radiation therapy (RT). In conjunction with the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD), a national survey was conducted in order to assess whether or not there is a consensus on the indication for RT and various treatment factors which were studied. A questionnaire was circulated to 190 RT institutions to obtain relevant data concerning the patients' workload, stage-dependent indication, and diagnostic procedures, which were considered to be necessary. Further questions addressed details on radiation technique and dose-fractionation schedules, the combined use of corticoids, and salvage RT after previous treatment failure following RT. With a response rate of 152/190 (80%), the survey is nationally representative. Based on the case workload, an estimated annual number of 1,600 GO cases are treated in German radiotherapy departments. With an 88% consensus, stages II-V are the typical indications. 85% considered imaging studies necessary for indication and only 48% for laboratory tests. 76% of the institutions used total doses in the range of 15-20 Gy, and conventional fractionation was most common (57%). 82% used a face mask fixation and 67% CT-based treatment planning. Approximately 50% would prescribe salvage RT, and total doses in the range of 20-40 Gy were considered to be acceptable. The survey revealed a consensus concerning most of the factors studied. We recommend to review the patterns of care for RT of other entities of benign diseases and to implement a quality assurance program both on national and international levels.

Radiation-induced rectal complications are not influenced by age: a dose fractionation study in the rat.

Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats. In this paper, the results of dose fractionation are presented in relation to age at the time of irradiation. Young and older animals were irradiated with single and fractionated doses. After irradiation, rectal complications could lead to occlusion and stenosis, eventually resulting in the clinical symptoms of a megacolon and a possible fistula. For each dose group, cumulative survival rates were obtained with Kaplan-Meier analysis, from which dose-effect curves and the associated LD(50) values for a megacolon/fistula were calculated. The majority of responders died between 8 and 24 weeks after irradiation, irrespective of age. For both age groups, only the fractionation data showed a reduction in the mean latency with increasing dose. In the older age group, 39% of the responders developed a fistula compared to 26% for the younger animals. The LD(50) values increased from around 30 Gy after single doses to nearly 65 Gy after 10 fractions. The increases in LD(50) values with the number of fractions were independent of the age of the rats. For each of the dose fractionation schedules, log-rank testing indicated no significant differences in cumulative survival rates between younger and older animals (P > 0.10). The high alpha/beta ratios obtained for both the young and older animals strongly suggested that the late rectal complications were a consequence of early epithelial injury. Associated histological findings indicated that blood vessel damage, which was already evident at a high incidence at 4 weeks after irradiation, could also play a significant role in the occurrence of consequential late injuries. In conclusion, data obtained for the latent period of rectal occlusion, for the dose-effect curves, for the log-rank testing of cumulative survival rates, and for the alpha/beta ratios strongly support the hypothesis that the incidence of radiation-induced rectal complications is independent of age. Late rectal complications could be a consequence of radiation-induced acute injury.

Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases

Purpose: To compare pain relief among various dose-fractionation schedules of localized radiotherapy (RT) in the treatment of painful bone metastases. Methods and Materials: A systematic search for randomized trials of localized RT on bone metastases using different dose fractionations was performed using Medline (1966 to February 2001) and other sources. The primary outcomes of interest were complete and overall pain relief. The studies were divided into three groups: comparisons of doses given as a single fraction, single vs. multiple fractions, and comparisons of doses given as multiple fractions. The complete and overall pain responses for studies comparing single vs. multiple fractions were pooled. Exploratory analyses of the dose-response relationship, using the biologic effective dose (α/β = 10), were performed using results from all three groups of trials. Results: Two trials comparing single vs. single, eight trials comparing single vs. multiple, and six trials comparing multiple vs. multiple fractions were included. The complete and overall response rates from studies comparing single-fraction RT (median 8 Gy, range 8–10 Gy) against multifraction RT (median 20 Gy in 5 fractions, range 20 Gy in 5 fractions to 30 Gy in 10 fractions) were homogeneous and allowed pooling of data. Of 3260 randomized patients in seven studies, 539 (33.4%) of 1613 and 523 (32.3%) of 1618 patients achieved a complete response after single and multifraction RT, respectively, giving a risk ratio of 1.03 (95% confidence interval 0.94–1.14; p = 0.5). The overall response rate was in favor of single-fraction RT (1011 [62.1%] of 1629) compared with multifraction (958 [58.7%] of 1631; risk ratio 1.05, 95% confidence interval 1.00–1.11, p = 0.04), reaching statistical significance. However, when the analysis was restricted to evaluated patients alone, the overall response rates were similar for single fraction and multifraction RT, at 1011 (72.7%) of 1391 and 958 (72.5%) of 1321, respectively (risk ratio 1.00; p = 0.9). Exploratory analyses by biologic effective dose did not reveal any dose-response relationship among the fractionation schedules used (single 8 Gy to 40 Gy in 15 fractions). Of the other results and observations reported in the trials, only the re-irradiation rates were consistently different between the treatment arms (more frequent re-irradiation in lower dose arms among trials reporting re-irradiation rates). Conclusion: Meta-analysis of reported randomized trials shows no significant difference in complete and overall pain relief between single and multifraction palliative RT for bone metastases. No dose-response relationship could be detected by including data from the multifraction vs. multifraction trials. Additional data are needed to evaluate the role of re-irradiation and the impact of RT on other treatment end points such as quality of life.

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas

Purpose: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. Methods and Materials: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D prolif of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. Results: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. Conclusions: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials.

348. From conventional averages to individual dose painting in radiotherapy for human tumours: Challenge to non-uniformity

The exploitation of a number of current clinical trials and reports on outcomes after radiation therapy (i.e. breast, head and neck, prostate) in clinical practice reflects many limitations for conventional techniques and dose-fractionation schedules and for “ average ” conclusions. Even after decades of evolution of radiation therapy we still do not know how to optimize treatment for the individual patient and only have “ averages ” and ill-defined “ probabilities ” to guide treatment prescription. Wide clinical and biological heterogeneity within the groups of patients recruited into clinical trials with a few-fold variation in tumour volume within one stage of disease is obvious. Basic radiobiological guidelines concerning average cell killing of uniformly distributed and equally radiosensitive tumour cells arose from elegant but idealistic in vitro experiments and seem to be of uncertain validity. Therefore, we are confronted with more dilemmas than dogmas. Nonlinearity and in homogeneity of human tumour pattern and response to irradiation are discusses. The purpose of this paper is to present and discuss various aspects of non-uniform tumour cell targeted radiotherapy using conformal and dose intensity modulated techniques.

Developments in Radiotherapy

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: <list id="l1" type="5"> <item>Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome.</item><item>Improved treatment results may be expected with even more optimized fractionation schedules.</item><item>The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours.</item><item>Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning.</item><item>More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning.</item><item>New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments.</item><item>New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients.</item><item>Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden.</item></list>

Dose fractionation effects in primary and metastatic human uveal melanoma cell lines.

To investigate the effects of split-dose irradiation on primary and metastatic uveal melanoma cell lines, with a clonogenic survival assay. Appropriate cell concentrations of four primary and four metastatic human uveal melanoma cell lines were cultured for irradiation with single doses and with two equal fractions separated by 5 hours. After irradiation, colony formation was allowed for 7 to 21 days. Two cutaneous melanomas were also tested for comparison. All survival curves were analyzed using the linear quadratic (LQ) model. Specific parameters for the intrinsic radiosensitivity (alpha-component, SF2), for the capacity of repair of DNA damage (beta-component), as well as the alpha/beta ratio were calculated. After single-dose irradiation a wide range in the values of the alpha- and beta-component was obtained for both primary and metastatic uveal melanomas, which resulted in a wide range of alpha/beta ratios. In contrast, calculations based on split-dose data, with which the beta-component could be estimated independent of the alpha-component, indicated that estimates for the capacity of sublethal DNA damage repair was very similar in all cell lines. This indicated that intrinsic factors dominated the radiosensitivity of these cell lines. Split-dose irradiation had little influence on the intrinsic radiosensitivity (alpha-component), but cell survival increased for all cell lines. For the two cutaneous melanomas comparable split-dose results were obtained. For both primary and metastatic uveal melanoma cell lines, data from single and fractionated doses indicate large variations in radiosensitivity, which are mainly dominated by the intrinsic radiosensitivities. Doses of approximately 8 Gy in five fractions would be sufficient to eradicate 10(9) cells (approximately 1 cm3) of the most radioresistant tumor cell lines, but this schedule is an overkill for the radiosensitive tumor cell lines. Based on specific morphologic and histologic tumor markers, more individualized dose fractionation schedules could improve the therapeutic ratio for uveal melanomas.

Postoperative radiation therapy for squamous cell carcinoma of the head and neck

Purpose: To discuss the role of postoperative radiation therapy (RT) for patients with squamous cell carcinoma of the head and neck. Results: Patients with adverse pathologic features have a high likelihood of local-regional recurrence and a decreased probability of survival after surgery alone. Postoperative RT reduces the risk of local-regional failure and probably improves survival. Patients who are at high risk for recurrence after surgery benefit from more aggressive dose-fractionation schedules that may include altered fractionation to decrease the overall time from surgery to the completion of RT. Adjuvant chemotherapy also appears to improve the probability of cure in high risk patients. Conclusion: Patients who have a high likelihood of local-regional recurrence after surgery have improved disease control and survival after postoperative RT. (Am J Otolaryngol 2003;24:41-50. Copyright 2003, Elsevier Science (USA). All rights reserved.)

Accelerated hypofractionation for early-stage non-small-cell lung cancer

Purpose : To describe the outcome of treating early-stage non-small-cell lung cancer (NSCLC) with an accelerated hypofractionated course of radiotherapy. Methods and Materials : A policy of treating early-stage NSCLC with a dose of 48 Gy in 12 once-daily fractions without elective irradiation of radiologically uninvolved regional nodes was adopted in 1996. We describe the outcome in 33 patients with NSCLC treated with this dose-fractionation schedule. Results : The median patient age was 72.0 years. Most patients (75.8%) were not surgical candidates because of medical comorbidities or old age. For staging, 97.0% underwent CT of the thorax, and mediastinoscopy was performed in 6.1%. All patients had Stage T1-T2N0, except for 4 patients with positive nodes based on pathologically involved or clinically enlarged lymph nodes adjacent to the primary tumor. The overall survival rate was 80.1% at 1 year and 46.0% at 2 years. The median survival was 22.6 months. The cause-specific survival rate was 89.8% at 1 year and 54.1% at 2 years. The recurrence-free survival rate was 66.4% at 1 year and 40.0% at 2 years. Lateral radiotherapy field margins of <2 cm predicted for inferior overall survival, cause-specific survival, and recurrence-free survival on univariate and multivariate analyses ( p <0.05). The most commonly reported toxicities were acute dermatitis (30.3%) and late cutaneous/subcutaneous fibrosis (24.2%). Conclusion : Accelerated hypofractionation for early-stage NSCLC appears to be safe and produces promising early results. Very small radiotherapy field margins may lead to an inferior outcome. Prospective studies are needed to determine the optimal dose-fractionation schedule.

Radiotherapy for Perianal Paget’s Disease

ABSTRACT: The role of radiotherapy in the management of perianal Paget’s disease (PPD) is not well defined in clinical practice or within the medical literature. We present 6 cases, document the radiotherapy details and review our results. A comprehensive literature search has been undertaken attempting to identify all published cases of PPD and survey the number receiving radiotherapy. To further define the role for radiotherapy in PPD these cases have been reviewed. Published results are sporadic and often poorly documented with respect to technical radiotherapy details. Two main roles for radiotherapy in PPD were found. One is as primary treatment for in situ or invasive disease and the other is following surgical relapse ofin-situ or invasive disease. Other possible uses of radiotherapy in PPD such as neoadjuvant or adjuvant treatment or chemo-radiotherapy are discussed. Results of radiotherapy treatment for case of in situ and invasive disease are presented. We disagree with the view in some areas of the surgical literature that radiotherapy has no place in the management of the disease. Despite a thorough surveying of the literature however, precise recommendations on several areas of the technical radiotherapy treatment such as dose-fractionation schedules and field margins are difficult because of the small number of cases and poor general documentation. Our practice recommendations are presented. Radiotherapists should be encouraged to publish their experience in this disease to help define further a role for this treatment.