Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

Actual Versus Optimal Radiotherapy Utilisation for Metastatic Cancer Patients in the 45 and Up Study Cohort, New South Wales.

AIMS: Radiotherapy can provide quality of life and/or survival benefits to patients with metastatic cancer on diagnosis (MCOD). However, little is known about radiotherapy utilisation in this population. We compared the optimal radiotherapy rates with actual uptake for people who present with MCOD in the 45 and Up Study cohort, and examined factors associated with utilisation. MATERIALS AND METHODS: In total, 267 153 individuals aged ≥45 enrolled in the Sax Institute's 45 and Up Study completed a baseline questionnaire during 2006-2009, providing sociodemographic and health information and consent for linkage to administrative health databases. Participants diagnosed up to December 2013 with MCOD were identified in the New South Wales Cancer Registry. Radiotherapy receipt was determined from claims to the Medicare Benefits Schedule and/or records in the New South Wales Admitted Patient Data Collection (2006 to June 2016). The Collaboration for Cancer Outcomes, Research and Evaluation optimal utilisation model was adapted for patients with MCOD to provide a benchmark. RESULTS: Of 17 687 participants diagnosed with cancer after completion of the baseline questionnaire, 2392 had MCOD. Of patients with MCOD, 25% had primary lung cancer, which was the most common site. The actual radiotherapy utilisation rate for all patients was 32.3%, lower than the optimal of 45.0%. From multivariable analysis, patients who were aged ≥80 years and/or needed help with daily tasks and/or had a Charlson Comorbidity Index ≥2 were less likely to receive radiotherapy. CONCLUSIONS: Actual uptake of radiotherapy was below optimal. Elderly patients and/or those with more comorbidities were less likely to receive radiotherapy. These results suggest a potential role for advocacy and education around radiotherapy for these patient groups.

Patterns of palliative radiotherapy fractionation for brain metastases patients in New South Wales, Australia.

BACKGROUND AND PURPOSE: There is a paucity of studies examining variation in the use of palliative radiation therapy (RT) fractionation for brain metastases. The aim of this study is to assess variation in palliative RT fractionation given for brain metastases in New South Wales (NSW), Australia, and identify factors associated with variation. MATERIALS AND METHODS: This is a population-based cohort of patients who received whole brain RT (WBRT) for brain metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. RESULTS: Of the 2,698 patients that received WBRT, 1,389 courses (51%) were < 6 fractions, 1,050 courses (39%) were 6-10 fractions, and 259 courses (10%) were > 10 fractions. Older patients were more likely to be treated with shorter courses (P < 0.0001). Patients with primary lung cancers were more likely to receive shorter courses compared with other primary cancers (P < 0.0001). Patients without surgical excision were more likely to receive < 6 fractions compared to those who underwent surgical excision. Shorter courses were more likely to be delivered to patients with the most disadvantaged socioeconomic status (SES) compared with patients with the least disadvantaged SES (P < 0.0001). There were significant fluctuations in the proportion of courses using lower number of fractions over time from 2009 to 2014, but no apparent trend (P = 0.02). There was wide variation in the proportion of shorter courses across residence local health districts, ranging from 24% to 69% for < 6 fractions, 21% to 72% for 6-10 fractions, and 4% to 20% for > 10 fractions (P < 0.0001). CONCLUSION: This study has identified significant unwarranted variations in fractionation for WBRT in NSW. Accelerating the uptake of shorter fractionation regimens, if warranted through evidence, should be prioritised to enhance evidence-based care.

Patterns of use of palliative radiotherapy fractionation for bone metastases and 30-day mortality.

BACKGROUND AND PURPOSE: Adoption of single-fraction radiation therapy (SFRT) has not been universal in the palliative treatment of bone metastases, despite evidence supporting its safety and efficacy. The aim of this study was to assess SFRT use for bone metastases in New South Wales (NSW), Australia, and the rate of 30-day mortality (30DM). MATERIALS AND METHODS: This is a population-based cohort of patients who received palliative radiation therapy (RT) for bone metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. The proportion of patients dying within 30-days from treatment start date was calculated. RESULTS: Of the 14,602 courses of palliative RT delivered for bone metastases, 30% were SFRT. SFRT was more likely to be delivered to older patients: ≥80 years (34%) versus < 60 years (28%). Patients with lower socioeconomic status (SES) (35%) were more likely to receive SFRT compared with higher SES (25%). SFRT delivered to patients from outer regional area of residence (34%) were higher compared to those from the major city (29%). The proportion of SFRT delivered to patients with comorbidities ≥2 (34%) was higher than patients with no comorbidity (29%). SFRT was associated with higher 30DM of 21% compared with 11% for multi-fraction RT (MFRT). CONCLUSION: SFRT is underused for the treatment of bone metastases in NSW. This is an impetus to develop tools making SFRT obligatory in this setting unless there is good justification not to.

The population benefit of evidence-based radiotherapy: 5-Year local control and overall survival benefits.

BACKGROUND: To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed. METHODS: Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed. FINDINGS: 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model. INTERPRETATION: Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits.

Predicting the cumulative risk of false-positive mammograms.

BACKGROUND: The cumulative risk of a false-positive mammogram can be substantial. We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms. METHODS: We used medical records of 2227 randomly selected women who were 40-69 years of age on July 1, 1983, and had at least one screening mammogram. We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram. RESULTS: Of 9747 screening mammograms, 6. 5% were false-positive; 23.8% of women experienced at least one false-positive result. After nine mammograms, the risk of a false-positive mammogram was 43.1% (95% confidence interval [CI] = 36.6%-53.6%). Risk ratios decreased with increasing age and increased with number of breast biopsies, family history of breast cancer, estrogen use, time between screenings, no comparison with previous mammograms, and the radiologist's tendency to call mammograms abnormal. For a woman with highest-risk variables, the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1% (95% CI = 69.3%-100%) and 100% (95% CI = 99.9%-100%), respectively. A woman with lowest-risk variables had estimated risks of 0.7% (95% CI = 0.2%-1.9%) and 4.6% (95% CI = 1. 1%-12.5%), respectively. CONCLUSIONS: The cumulative risk of a false-positive mammogram over time varies substantially, depending on a woman's own risk profile and on several factors related to radiologic screening. By the ninth mammogram, the risk can be as low as 5% for women with low-risk variables and as high as 100% for women with multiple high-risk factors.

A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer.

AIMS: To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. MATERIALS AND METHODS: The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. RESULTS: If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5-2.8%) and 5 year overall survival 1.2% (0.7-1.9%). CONCLUSIONS: The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable radiotherapy services.

Technology enhancements and changes in radiotherapy throughput in New South Wales.

AIMS: To assess the effect that the age of linear accelerators and recent changes in technology have had on linear accelerator throughput in New South Wales, Australia. MATERIALS AND METHODS: Duration was measured (time of patient entry into the treatment room to time of exit) of each radiotherapy treatment fraction delivered on each linear accelerator over a 5-day period. Patient-, treatment- and equipment-based variables were collected for all treatment fractions, and assessed for their effect on fraction duration. Comparisons were made between these data and similar productivity data collected from a study carried out in 1996. Since the sample sizes for both the study periods were large enough, the distributions of the means were assumed normal (Central Limit Theorem). Specific analyses were carried out to assess the affect that new technologies, such as automatic field-sequencing (AFS) and multi-leaf collimator (MLC), have had on fraction duration. RESULTS: A total of 12 892 treatment fields and 4316 treatment fractions were delivered on 27 linear accelerators over 135 days. Comparison between the 2003 and 1996 productivity data showed an increase in the mean number of patients treated per hour by 11% and fields treated per hour by 31%. The mean number of fields treated per fraction increased by 15%. The mean fraction duration was reduced by 13% for linear accelerators of less than the median age of 7 years that were equipped with MLC/AFS, or both, compared with older linear accelerators without AFS and MLC. This reduction was more obvious for complex techniques, such as four-field breast treatments (27% decrease in fraction duration). The mean number of fields treated per hour was 43% more on the newer machines equipped with AFS and MLC. CONCLUSIONS: An increase in productivity has been observed between the 1996 and 2003 study periods, as measured by patients or fields per hour, despite an increase in treatment complexity as measured by fields per fraction. The application of AFS and MLC, and the use of newer linear accelerators, significantly shortened the mean duration per fraction for the common treatment techniques.

The development of a new basic treatment equivalent model to assess linear accelerator throughput.

AIMS: The basic treatment equivalent (BTE) model was developed in 1996 in an attempt to improve the measurement of linear accelerator throughput in radiotherapy. This study aimed to assess the effect of treatment set-up and patient characteristics on fraction duration, to update the BTE model and to determine the better throughput measure between fields per hour and BTE per hour. MATERIALS AND METHODS: Stopwatch measurements of the duration of each radiotherapy treatment fraction delivered on each linear accelerator in participating New South Wales radiation oncology departments over a 5-day period in 2003 were undertaken. Patient, equipment and staff data were collected to assess the effect of these variables on fraction duration. A new BTE equation was derived, including the most significant variables. Statistical comparison of fields and BTE per unit time was made to assess the better predictor of fraction duration. RESULTS: Data collected on 27 linear accelerators in 13 departments included a total of 135 days of linear accelerator operation, 4316 fractions and 12 892 treatment fields. Seventeen factors significantly influenced fraction duration (P < 0.01). These accounted for 46% of the total variance in the models. The eight most influential predictors of prolonged fraction duration were included in the BTE model. These were as follows: high number of fields, high number of port films/electronic portal imaging, absence of automatic field-sequencing and multi-leaf collimation, high number of junctions, use of bolus and first fraction of a treatment course. The BTE per hour was shown to be a better predictor of throughput than fields per hour. CONCLUSIONS: The BTE model is a better measure of linear accelerator throughput. It incorporates weightings for treatment and patient factors that significantly influenced fraction duration. This measure could be routinely collected by the radiation oncology departments and included in the electronic radiotherapy information systems.

Evidence-based estimates of the demand for radiotherapy.

There are different methods that may be used to estimate the future demand for radiotherapy services in a population ranging from expert opinion through to complex modelling techniques. This manuscript describes the use of evidence-based treatment guidelines to determine indications for radiotherapy. It also uses epidemiological data to estimate the proportion of the population who have attributes that suggest a benefit from radiotherapy in order to calculate the overall proportion of a population of new cases of cancer who appropriately could be recommended to undergo radiotherapy. Evidence-based methods are transparent and adaptable to different populations but require extensive information about the indications for radiotherapy and the proportion of cancer cases with those indications in the population. In 2003 this method produced an estimate that 52.4% of patients with a registered cancer-type had an indication for radiotherapy. The model was updated in 2012 because of changes in cancer incidence, stage distributions and indications for radiotherapy. The new estimate of the optimal radiotherapy utilisation rate was 48.3%. The decrease was due to changes in the relative frequency of cancer types and some changes in indications for radiotherapy. Actual rates of radiotherapy utilisation in most populations still fall well below this benchmark.

The population benefit of radiotherapy for cervical cancer: local control and survival estimates for optimally utilized radiotherapy and chemoradiation.

PURPOSE: Population benefits of radiotherapy if evidence-based guidelines were routinely followed across the entire population are largely unknown. The aim of this study was to investigate population-based benefits for cervical cancer. METHODS: Overall survival (OS) and local control (LC) benefits were investigated. XRT benefit was defined as the absolute benefit of radiotherapy, over no treatment, for radical indications and defined as the benefit of adjuvant radiation over surgery alone for adjuvant indications. The concurrent chemoradiation (CRT) benefit was the incremental benefit of CRT over XRT. Australian population benefits were modeled using decision trees. Citation databases were systematically queried. Meta-analysis was performed if multiple sources of the same evidence level existed. Robustness of the model assumptions was tested through sensitivity analysis. RESULTS: 53% of all cervix patients had adjuvant or curative radiotherapy indications. 96% were for CRT. The estimated 5-year absolute benefits of optimally utilized radiotherapy alone were: LC: 31% (95% Confidence Interval 29%, 34%), OS: 17% (15%, 18%). These were over and above the contribution of other modalities to outcomes. The incremental 5-year absolute benefits of CRT were: LC 4% (2%, 5%), OS 3% (1%, 5%). In sensitivity analysis, the model was robust. CONCLUSIONS: Optimally utilized radiotherapy provides substantial population OS and LC benefits for cervical cancer. Chemoradiation provides a modest population benefit over XRT. The population-based model was robust.

Factors affecting the use of single-fraction radiotherapy for the palliation of bone metastases in Australia.

AIMS: Palliative radiotherapy for bone metastases remains an important treatment in patients with metastatic malignancy. Previous studies have indicated a reluctance to adopt single-fraction treatment despite considerable evidence. This study aims to describe the factors determining the use of palliative radiotherapy in patients with bone metastases and assess whether fractionation patterns have changed over time with emerging evidence. MATERIALS AND METHODS: A retrospective review of radiotherapy databases at Liverpool/Macarthur Cancer Therapy Centre and the Royal Brisbane and Women's Hospital was conducted for the period 1997-2009. Patients receiving palliative radiotherapy for bony metastases were identified and treatment sites were grouped into 'spine', 'limb', 'multiple' or 'other'. Treatment courses were divided into single- or multiple-fraction treatments. The effects of socioeconomic and geographical factors on radiotherapy utilisation and fractionation were assessed. RESULTS: In total, 5683 patients were identified in the cohort; they received a total of 8211 bone treatments. The overall proportion of single-fraction radiotherapy was 29%, with significant variation over the study period (P < 0.001). Age under 70 years and spine or multiple treatment sites were all associated with lower usage of single-fraction radiotherapy on multivariate analysis. Prostate and lung primary sites were associated with higher usage of single-fraction treatment. The proportion of single-fraction treatment remained low (35%), even for patients who survived less than 22 days from their last treatment. Socioeconomic and geographical factors had little effect on the number of fractions used. CONCLUSIONS: The rate of single-fraction radiotherapy for bone metastases has remained low in two large Australian institutions, despite considerable evidence that single-fraction treatment provides equivalent pain relief to fractionated therapy. This trend towards fractionated treatment was largely maintained, even in patients with limited life expectancy. Further measures to increase the rate of single-fraction therapy are needed.

Oropharyngeal cancer in the elderly.

PURPOSE: The poor prognosis of elderly patients in many cancers may be due to less thorough investigation and less aggressive treatment because of the perception that radical treatment will be poorly tolerated and that elderly patients have a limited life expectancy. We wished to assess whether older age is associated with (a) less radical treatment, (b) poorer outcome, or (c) greater toxicity, after adjusting for other possible contributing factors. METHODS AND MATERIALS: A retrospective study of patients with loco-regional oropharyngeal cancer treated between January 1980 and December 1985 was conducted. Patients were treated with radiotherapy, surgery, chemotherapy, or combinations. Cox regression was used to assess age effects while allowing for the influence of other factors. RESULTS: Eighty-eight patients were treated radically and 16 palliatively. Treatment intent (radical or palliative) did not appear to be related to age, before (p = 0.42) or after adjusting for other factors (p = 0.34). In a selected group of 86 radically treated patients ages ranged from 33 to 85 (median 60). There were 35 loco-regional failures and 58 deaths (38 related to oropharyngeal cancer). Older patients were prescribed and received lower doses of radiation. However, older age was not related to the risk of loco-regional recurrence (p = 0.96) or shorter survival (p = 0.67), and was not associated with duration of treatment interruption or severity of toxicity after adjustment for prognostic factors. There was some suggestion of a higher risk of recurrence with increasing age for patients under 70 years but with a risk for patients over 70 at least equal to that of the youngest group. Elderly patients in our study may have been a selected group. CONCLUSION: Older patients with loco-regional oropharyngeal cancer, or at least a subset of them, appear to be able to tolerate radical courses of radiotherapy, and to have similar outcomes as do younger patients.

The doses received by the breast during mantle radiotherapy.

PURPOSE: To accurately measure the dose received by the breast during mantle radiotherapy. METHODS AND MATERIALS: A phantom containing lung-equivalent material was used to measure the doses received by the breast during mantle radiotherapy given by anterior and posterior opposing fields. These were measured using thermoluminescent dosimeters and compared with point dose calculations obtained by computer planning. RESULTS: Most of the breast lies under the lung shields or inferior to the mantle field, but the upper outer quadrant of the breast remains unshielded. In the unshielded areas of the breast, the average dose measured was nearly 13% higher than the dose prescribed at the central axis. In the shielded parts of the breast, the average measured dose was nearly 10% of the dose prescribed at the central axes, decreasing from 18% superiorly to 4% inferiorly. The posterior field contributed 45% to the dose in the breast, even though doses were prescribed at the midplane. The computer calculations systematically varied from measured doses by up to 35%, becoming less accurate towards the inferior edge of the field. CONCLUSIONS: In a conventional course of mantle radiotherapy (for example, 36 Gy in 20 fractions), most of the breast is shielded but will receive a dose of 3-4 Gy, higher than expected largely due to internally scattered radiation passing through the lungs from the posterior field. Computer dose calculations may poorly reflect actual off-axis doses in large fields with complex shielding, containing inhomogeneous tissue.

Split-course accelerated therapy in head and neck cancer: an analysis of toxicity.

PURPOSE: To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. METHODS AND MATERIALS: SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. RESULTS: Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). CONCLUSION: Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered.

The role of the gallium scan in primary extranodal lymphoma.

UNLABELLED: The purpose of this study was to examine the factors influencing gallium scan positivity for patients with primary extranodal lymphoma and to examine the role of the gallium scan in staging the disease and assessing response to initial treatment. METHODS: Ninety-two patients with extranodal lymphoma who had a gallium scan were reviewed. The influences of tumor site, size, grade and the presence of clinically detectable disease after biopsy on the rate of gallium scan positivity were analyzed. The role of the gallium scan in staging and selecting treatment was assessed. Nineteen patients had a gallium scan to assess their response to treatment, and its predictive value was reviewed. RESULTS: The overall gallium scan positivity (sensitivity) rate was 70%. This rate was low in patients whose extranodal lymphoma occurred in skin, intestine and testis, or was low grade (0%-25%). When these patients were excluded, the rate rose to 88%. Gallium scan positivity was not related to the presence of clinically detectable disease after biopsy and there was insufficient data about tumor size to determine a relationship. The gallium scan increased the disease stage in six patients (7%) and changed the initial treatment in six patients (7%). The gallium scan became negative in 15 (79%) of those patients who had a gallium scan to assess their response to treatment. All but two of these patients remain alive with a median follow-up of 3.75 yr. CONCLUSION: The gallium scan was rarely positive for patients with skin, intestinal, testicular and low-grade lymphomas, but was otherwise comparable to lymphoma arising in lymph nodes. The result affected staging or treatment in seven patients (8%). After treatment, an initially-positive gallium scan usually became negative, a conversion associated with a favorable outcome.

The effect of waiting for radiotherapy for grade III/IV gliomas.

AIM: To determine the effect of waiting time for radiotherapy on the overall survival of patients with high-grade gliomas. METHODS: We examined records of patients with grade III/IV gliomas who were referred to radiotherapy after surgery or biopsy - ECOG <3, any age, radical intent or palliative intent with dose >50 Gy, no interstitial or radiosurgery boost. Waiting time was defined in two ways, time from biopsy to radiotherapy and time from presentation to radiotherapy department to start of radiotherapy. RESULTS: There were 182 patients in the study having a median survival of 8.5 months, with a median follow up of 10.5 months. The group comprised of 63 (35%) grade III and 119 (65%) grade IV gliomas. Median times and ranges from biopsy and presentation to treatment were 26 days (4-78 days) and 15 days (1-62 days), respectively. The median dose was 60 Gy in a median of 30 fractions over a median of 46 days. Tumour progression before and during radiotherapy occurred in seven patients (4%) and 19 patients (11%), respectively. One hundred and seventy-nine patients died of disease. The seven patients whose tumour progressed before radiotherapy were excluded from the analysis of prognostic variables. In a multivariate analysis the variables that were significantly associated with worse survival were older age, reduced dose and prolonged waiting time from presentation. The risk of death increased by 2% for each day of waiting for radiotherapy. CONCLUSION: The study showed longer waiting time from presentation at radiotherapy department to treatment to be a significant predictor of overall survival for patients with high-grade glioma.

The effect of treatment time and treatment interruption on tumour control following radical radiotherapy of laryngeal cancer.

A significant effect of overall treatment time on local control was found in a retrospective review of 1012 radically irradiated squamous cell carcinomas of the larynx. The actuarial local relapse free rate (LRFR) at 5 years for the whole group was 59%. The effect of treatment time on local control was modelled to the linear-quadratic equation. Using logistic regression analysis treatment time and dose were significant (p = 0.008 and p = 0.04, respectively). When the analysis was adjusted for the influence of stage and laryngeal subsite treatment time remained a significant prognostic factor (p = 0.02). The derived value of gamma/alpha was 0.7 Gy/day and when adjusted for stage and sub-site 0.8 Gy/day. This equates to a dose increment to maintain iso-effective local control of 0.64 Gy/day and 0.73 Gy/day respectively for daily fractions of 2.5 Gy and an assumed alpha/beta for tumour of 25 Gy. To provide an estimate of the clinical impact of treatment interruptions not compensated for by dose escalation a Cox regression was performed. Significant variables were T stage, N stage, sex, total dose and total length of treatment interruption. Using the proportional hazard model it was calculated that each day of treatment interruption resulted in an increase in the hazard of local relapse by 4.8% (p = 0.006). Based on our data it was calculated that this would result in a decrease in local control of 1.4% for each day of uncompensated treatment interruption.

Does waiting time affect the outcome of larynx cancer treated by radiotherapy?

AIM: To determine the impact of waiting for radiotherapy on local control in early larynx cancer treated by radiotherapy alone. METHODS: Records of patients with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres. Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2) time from presentation to radiation department to start of radiotherapy and (3) the minimum of (1) and (2). Time to relapse was the major end point. RESULTS: There were 581 patients with a median follow-up of 6.8 years. Stage distribution was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18. Median times from biopsy, presentation and minimum time to treatment were 24, 16 and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31 days. The median dose was 61 Gy in a median of 30 fractions over a median 46 days. Local recurrence occurred in 126 patients. The actuarial recurrence free rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant predictors of relapse were higher T stage, longer treatment duration and increasing field area. Waiting time was not significantly associated with local relapse. CONCLUSION: This study did not show longer waiting time to be a significant predictor of relapse in early larynx cancer. Other end-points which are relevant, such as quality of life, have not been examined. Longer treatment times were significantly associated with relapse.

Influence of radiotherapy treatment time on control of laryngeal cancer: comparisons between centres in Manchester, UK and Toronto, Canada.

A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6-0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data).(ABSTRACT TRUNCATED AT 250 WORDS)