Long-term experience with transrectal and transperineal implantations of fiducial gold markers in the prostate for position verification in external beam radiotherapy; feasibility, toxicity and quality of life

Background and purpose

This study presents an overview of the experience with transrectal and transperineal implantations of fiducial markers for position verification in prostate radiotherapy, regarding the practical feasibility, procedure-related toxicity and influence on quality of life (QoL).

Material and methods

Since 2001, 914 patients scheduled for intensity-modulated radiotherapy (IMRT) have received gold markers in the prostate. The incidence of severe toxicity, defined by the CTCAE v3.0, was evaluated retrospectively. The influence on QoL was measured prospectively in 36 patients using a combination of three validated questionnaires: the Rand-36, the EORTC QLQ-C30(+3) and the prostate cancer-specific EORTC QLQ-PR25. Next, the incidence of marker migration was assessed.

Results

From 2001 to 2005, 402 patients received markers via the transrectal route. Two of these patients developed urosepsis (grade 3 toxicity). Since 2005, 512 patients received markers via the transperineal route. No grade 3 or 4 toxicity occurred in this group. No significant and clinically relevant differences were found in QoL between pre- and post-implant measures. In 5 patients marker migration led to discontinuation of the marker-based IMRT.

Conclusions

Clinical use of transperineal-implanted fiducial gold markers for position verification in external beam radiotherapy for prostate cancer is a feasible and safe procedure without influencing patients’ QoL.     

Normative data for the EORTC QLQ-C30 and EORTC-sexuality items in the general Dutch population

Aim

The aim of the present study was to generate Dutch reference data for the EORTC QLQ-C30 and for five sexuality items from the EORTC QL-item bank. Furthermore, to evaluate the relative impact of self-reported health problems on these outcomes and compare the Dutch normative EORTC QLQ-C30 overall QoL with available Scandinavian and German normative data.

Methods

QLQ-C30 and sexual item normative data were obtained from the Health and Health Complaints project from CentERdata. The CentERpanel is an online household panel consisting of more than 2000 Dutch households, representative of the Dutch-speaking population in the Netherlands.

Results

The questionnaire was completed by 1731 (78%) CentERpanel members. For both men and women, functional health (except emotional functioning) decreased with age, and the symptoms pain and fatigue increased with age. Men scored statistically but never clinically significantly better on most functional scales than women. Men reported higher levels of sexual interest and activity than women. All subgroups of participants with health problems reported lower physical and role functioning and overall quality of life (QoL). Those with depression (n = 79) reported functioning scores 20-30 points lower than participants without any condition. Dutch men and women reported high levels of overall QoL as compared to previously published Scandinavian and German normative data.

Conclusion

Age, gender and other health problems are important when comparing QoL and sexuality among different cancer cohorts. Normative data on QoL and sexuality are needed to interpret QoL issues among the growing group of (long-term) cancer survivors.     

Development of a patient-reported questionnaire for collecting toxicity data following prostate brachytherapy

Purpose

To improve a questionnaire used to collect patient-reported outcomes from patients with early stage prostate cancer treated with brachytherapy. A secondary aim was to adapt the Late Effects of Normal Tissue (LENT) subjective toxicity questionnaire for use to collect Common Terminology Criteria for Adverse Events (CTCAE) data, the current preferred platform for assessing radiation toxicity.

Materials and methods

Three hundred and seventy-seven patients were treated with permanent iodine-125 seed implant brachytherapy for early prostate cancer. Toxicity data were collected before and at nine time points post-treatment (0-36 months). Compliance rates for patients completing individual items and item-subsection correlation coefficients were calculated. A factor analysis was carried out to analyse responses to the questionnaire and identify less informative questions, which could be removed. Cronbach’s α coefficient was used to measure reliability.

Results

Two thousand one hundred and eighty-eight questionnaires were analysed. There was poor compliance for questions specifically relating to operations and bowel medication. We found that the division of the questionnaire into subsections based on anatomical site was reasonable and that certain items could be safely removed. The high mean value for Cronbach’s α across all questionnaires (0.752; 95% CI: 0.726-0.779) indicated that the questionnaire was reliable. Fifteen of the 44 questions were removed from the original questionnaires. Questions on urinary incontinence severity, management of urinary and bowel incontinence, effects of reduced flow of urine and the effects of symptoms on activity of daily living and change in sexual function were required to adapt the LENT subjective questionnaire for use to collect CTCAE data.

Conclusions

A questionnaire, validated over 6 years to collect LENT subjective data were adapted and is a reliable approach for collecting CTCAE data after prostate brachytherapy.     

Validity and reliability of the MSKCC Bowel Function instrument in a sample of Italian rectal cancer patients

Aims

The purpose of this study was to translate the Memorial Sloan Kettering Cancer Centre (MSKCC) Bowel Function Instrument into Italian and to test its psychometric validity and reliability in a sample of Italian rectal cancer patients.

Methods

The MSKCC questionnaire was translated into Italian using a standard procedure of double-back translation. Construct validity was tested using a factor analysis and internal reliability was estimated using the Cronbach’s alpha coefficient. Concurrent validity was determined by correlations with European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 quality of life scales. A non-parametric analysis of variance was used to establish the discriminant validity of the questionnaire. Test-retest reliability was assessed using the intra-class correlation coefficient.

Results

124 rectal cancer patients participated in the validation study. The number of missing items was 2.2%. The factorial structure was found to be quite similar to the original one and the internal reliability was 0.7 for urgency, 0.6 for frequency, and 0.7 for dietary subscale. The test-retest reliability was acceptable with one exception: the dietary subscale showed a low reproducibility (ICC = 0.4). All three subscales showed a significant correlation with the QLQ-C30 and QLQ-CR38 domains and were able to discriminate several groups of clinical relevance.

Conclusions

The Italian version of the MSKCC Bowel Function Instrument shows acceptable psychometric properties and can be considered a valuable and specific instrument to assess bowel functions in rectal cancer patients, both for research purposes and in clinical practise.     

Palliative partial pancreaticoduodenectomy impairs quality of life compared to bypass surgery in patients with advanced adenocarcinoma of the pancreatic head

Background

Some surgical centres consider palliative resection (PR) to be superior to double loop bypass (DLB) as treatment for advanced carcinoma of the pancreatic head. We performed a retrospective study with prospectively collected data at a single centre to compare PR and DLB in regard to quality of life (QoL).

Methods

From January 1996 to September 2008, 196 patients were given palliative surgery for advanced pancreatic cancer at the University Hospital of Kiel. Forty-two patients underwent PR and 154 underwent DLB. These groups were compared with regard to survival, post-operative morbidity, and QoL. The EORTC QLQ-C30 was used to assess QoL before surgery, at discharge, three months after surgery, and six months after surgery.

Results

The median survival time after PR was 7.5 months (95% CI: 4.95-10.05) and after DLB was 6 months (95% CI: 4.98-7.02; log rank test: p = 0.066). There were no significant differences in mortality and morbidity rates (7.1% and 45.2% for PR; 3.9% and 38.3% for DLB, respectively). Assessment of QoL indicated that patients who underwent PR had more impairment of some functional metrics and increased symptoms compared to those who underwent DLB.

Conclusion

There was no significant difference in survival or morbidity after PR and DLB, but patients who underwent DLB had better QoL than patients who underwent PR. Therefore, clinicians may want to reconsider the use of PR for patients with advanced pancreatic cancer.     

Quality of life among prostate cancer patients: A prospective longitudinal population-based study

Purpose

To investigate the course of quality of life (QoL) among prostate cancer patients treated with external beam radiotherapy and to compare the results with QoL of a normal age-matched reference population.

Patients and methods

The study population was composed of 227 prostate cancer patients, treated with radiotherapy. The EORTC QLQ-C30 was used to assess QoL before radiotherapy and six months, one year, two years and three years after completion of radiotherapy. Mixed model analyses were used to investigate longitudinal changes in QoL. QoL of prostate cancer patients was compared to that of a normative cohort using a multivariate analysis of covariance.

Results

A significant decline in QoL was observed after radiotherapy (p < 0.001). The addition of hormonal therapy to radiotherapy was associated with a lower level of role functioning. Patients with coronary heart disease and or chronic obstructive pulmonary disease or asthma had a significantly worse course in QoL. Although statistically significant, all differences were classified as small or trivial.

Conclusion

Prostate cancer patients experience a small worsening of QoL as compared with baseline and as compared with a normal reference population. As co-morbidity modulates patients’ post-treatment QoL, a proper assessment of co-morbidity should be included in future longitudinal analyses on QoL.     

Late-onset bowel dysfunction after pelvic radiotherapy: a national survey of current practice and opinions of clinical oncologists

Aims

Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. It is common for patients to develop gastrointestinal symptoms after treatment. The aim of this study was to determine the current practice of clinical oncologists in the UK with respect to late-onset bowel dysfunction after pelvic radiotherapy, and to discuss the wider issues surrounding current and future service provision for this patient group.

Materials and methods

A questionnaire was developed to establish current practice. This was sent to the 314 clinical oncologists in the UK who treat pelvic malignancies up to a maximum of three times.

Results

One hundred and ninety (61%) responses were received. Most oncologists (76%) screen for gastrointestinal dysfunction after pelvic radiotherapy, usually through history taking rather than formal tools. Clinical oncologists view toxicity as a significant problem, with most estimating that up to 24% of patients at 1 year have bowel symptoms. Most oncologists refer less than 50% of their symptomatic patients, with most referring less than 10%. These referrals are 31% to a gastroenterologist, 23% to a gastrointestinal surgeon and 33% to both. Most (58%) do not have access to a gastroenterologist or a gastrointestinal surgeon with a specialist interest in their area. Sixty-five per cent of oncologists think a service is required specifically for patients with bowel dysfunction after pelvic radiotherapy, but half (52%) think that the current service in their area is inadequate.

Conclusions

Clinical oncologists recognise late-onset bowel dysfunction after pelvic radiotherapy as a significant problem, but one that is linked to poor recognition of symptoms and an inadequate patchy service.     

Change of aesthetic and functional outcome over time and their relationship to quality of life after breast conserving therapy

Purpose

We analyzed changes in aesthetic and functional outcome over time after breast conserving therapy. Our special interest resides in the question of whether these aspects gain or loose their influence on quality of life (QoL) with temporal progress.

Patients and methods

This prospective single centre cohort study included 138 patients, treated with breast conserving surgery and consecutive radiotherapy. Patients completed two questionnaires one week and one year after surgery: the BCTOS (Breast Cancer Treatment Outcome Scale) to measure Functional, Aesthetic, and Breast Sensitivity Status and the EORTC (European Organisation for Research and Treatment of Cancer) C30-BR23 to assess QoL. We applied correlation and multiple regression analysis as statistical methods.

Results

Aesthetic and Functional Status did not change significantly over one year, whereas Breast Sensitivity Status and several QoL subscales showed significant improvement (p < 0.0001). Correlations between BCTOS scales and EORTC subscales remain similar over time. Functional and Aesthetic Status kept a strong impact on global health (Spearman’s Rho = −0.28 to −0.45 depending on time of assessment). Increasing age and poorer Functional Status shortly after surgery are predictors of a decline in global health over one year (p < 0.001).

Conclusion

Functional and aesthetic outcome after breast conserving surgery maintain their impact on QoL over a one year follow-up period and are valuable predictors of QoL.     

Palliative prostate radiotherapy for symptomatic advanced prostate cancer

Background and purpose

To report the results for the use of short-course palliative radiotherapy to the prostate for localised symptoms.

Materials and methods

Fifty-eight patients were identified from radiotherapy records between 2003 and 2007. Data were collected retrospectively on patients’ demographics, radiotherapy details and response. Symptoms and toxicity were scored, retrospectively, according to the following scale: 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms.

Results

All the 58 patients had advanced prostate carcinoma. The median age at radiotherapy was 76.6 years (range 54-91). Fifty-six patients (97%) had hormone refractory disease. Twenty-seven patients (47%) had evidence of metastatic disease. 20Gy in 5 fractions was the most commonly used fractionation. The most frequent baseline symptom was haematuria (54%). Eighty-nine percent (31/35) of the patients had a complete or partial resolution of symptoms at 4 months. Response rates for individual symptoms (including unknown responses) were: rectal symptoms (75%), pelvic pain (69%), urinary obstruction (54%) and haematuria (42%). A >50% reduction in PSA occurred in five patients. Toxicity was mild to moderate only and was self-limiting.

Conclusion

Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail.     

A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

Purpose

To determine the maximum tolerated dose (MTD) of oral cisplatin (CP Ethypharm®) in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC) and the recommended dose for phase II trials.

Patients and methods

Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. CP Ethypharm® was administered on five consecutive days every other week for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen patients with locally advanced HNSCC were allocated to four cisplatin dose levels: 10 mg/m²/day: 4 patients; 15 mg/m²/day: 4, 20 mg/m²/day: 5 and 25 mg/m²/day: 5. The inclusion of patients was dictated by occurrence of dose limiting toxicities (DLTs) at each dosing level.

Results

The most frequently experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed, including three at 25 mg/m² level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m² level (grade 3 GI disorders), one at 10 mg/m² level (grade 4 mucositis). PK analysis showed no significant difference of C_max values between day 1 and day 5 of treatment at each dose level (total & ultrafilterable platinum).

Conclusion

Due to 3 DLTs experienced at 25 mg/m²/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m²/day.     

Tobacco smoking and long-lasting symptoms from the bowel and the anal-sphincter region after radiotherapy for prostate cancer

Background and purpose

Tobacco smoking can cause vascular injury, tissue hypoxia and fibrosis as can ionizing radiation. However, we do not know if tobacco smoking increases the risk of long-term side effects after radiotherapy for prostate cancer.

Methods

We identified 985 men treated with radiotherapy for prostate cancer between 1993 and 2006. In 2008, long-lasting symptoms appearing after radiotherapy for prostate cancer were assessed through a study-specific questionnaire as were smoking habits and demographic factors of all these men. In the questionnaire the prostate-cancer survivors were asked to report symptom occurrence the previous six months.

Results

We obtained information on tobacco smoking from 836 of the 985 prostate-cancer survivors with a median time to follow-up of six years (range 2-14 years). The prevalence ratio of defecation urgency among current smokers compared to never smokers was 1.6 (95% CI 1.2-2.2). Corresponding prevalence ratio for diarrhea was 2.8 (95% CI 1.2-6.5), the sensation of bowel not completely emptied after defecation 2.1 (95% CI 1.3-3.3) and for sudden emptying of all stools into clothing without forewarning 4.7 (95% CI 2.3-9.7).

Conclusion

Tobacco smoking among prostate-cancer survivors treated with radiotherapy increases the risk of certain long-lasting symptoms from the bowel and anal-sphincter region.     

Mammary fat necrosis following radiotherapy in the conservative management of localized breast cancer: Does it matter?

Purpose

Fat necrosis is a well-described and relatively common complication arising from post-lumpectomy irradiation of the breast, most commonly breast brachytherapy. We wish to assess the clinical significance of fat necrosis resulting from post-lumpectomy breast irradiation.

Methods

We reviewed the literature to determine the overall incidence and significance of fat necrosis to determine whether or not fat necrosis poses a significant clinical problem.

Results

Fat necrosis occurs in up to one-quarter of patients following post-lumpectomy breast irradiation. Only rarely is invasive intervention required however, it does significantly degrade the quality of all modalities of breast imaging.

Conclusions

Fat necrosis is a common complication of radiotherapy which rarely requires therapeutic intervention. However, post-therapeutic clinical imaging such as mammography, ultrasound and magnetic resonance imaging are affected which may result in additional diagnostic procedures up to and including biopsy.     

Multivariate analysis of quality of life outcome for nasopharyngeal carcinoma patients after treatment

Purpose

The study analyzed the prognostic factors of quality of life (QoL) for patients with nasopharyngeal carcinoma (NPC) after treatment, with focusing on the therapeutic benefits of the technological advances in radiotherapy (RT).

Materials and methods

A cross-sectional investigation was conducted to assess the QoL of 356 NPC patients with cancer-free survival of more than 2 years. Among them, 106 patients were treated by two-dimensional RT (2DRT), 108 by 2DRT plus three-dimensional conformal RT (3DCRT) boost, 58 by 3DCRT alone, and 84 by intensity-modulated RT (IMRT). The QoL was assessed by the EORTC QLQ-C30 questionnaire and QLQ-H&N35 module. The clinical difference of QoL scores between groups was calculated using Cohen’s D coefficient.

Results

We found NPC survivors who had a higher education level or annual family income and who had received more advanced RT treatments had better QoL outcomes. Compared with 2DRT, the impact of 3DCRT was small on most scales and moderate (Cohen’s D: 0.53-0.67) on emotional functioning, pain, and mouth opening; the impact of IMRT was moderate on nine scales and large (Cohen’s D: 0.80-0.88) on swallowing, social eating, teeth, and mouth opening.

Conclusions

In addition to socioeconomic levels, advances in RT technique played a significant role in improving QoL of NPC patients.     

Identifying afterloading PDR and HDR brachytherapy errors using real-time fiber-coupled Al2O3:C dosimetry and a novel statistical error decision criterion

Background and purpose

The feasibility of a real-time in vivo dosimeter to detect errors has previously been demonstrated. The purpose of this study was to: (1) quantify the sensitivity of the dosimeter to detect imposed treatment errors under well controlled and clinically relevant experimental conditions, and (2) test a new statistical error decision concept based on full uncertainty analysis.

Materials and methods

Phantom studies of two gynecological cancer PDR and one prostate cancer HDR patient treatment plans were performed using tandem ring applicators or interstitial needles. Imposed treatment errors, including interchanged pairs of afterloader guide tubes and 2-20 mm source displacements, were monitored using a real-time fiber-coupled carbon doped aluminum oxide (Al₂O₃:C) crystal dosimeter that was positioned in the reconstructed tumor region. The error detection capacity was evaluated at three dose levels: dwell position, source channel, and fraction. The error criterion incorporated the correlated source position uncertainties and other sources of uncertainty, and it was applied both for the specific phantom patient plans and for a general case (source-detector distance 5-90 mm and position uncertainty 1-4 mm).

Results

Out of 20 interchanged guide tube errors, time-resolved analysis identified 17 while fraction level analysis identified two. Channel and fraction level comparisons could leave 10 mm dosimeter displacement errors unidentified. Dwell position dose rate comparisons correctly identified displacements ?5 mm.

Conclusion

This phantom study demonstrates that Al₂O₃:C real-time dosimetry can identify applicator displacements ?5 mm and interchanged guide tube errors during PDR and HDR brachytherapy. The study demonstrates the shortcoming of a constant error criterion and the advantage of a statistical error criterion.     

Can nurses manage gastrointestinal symptoms arising from pelvic radiation disease?

Aims

About 17,000 patients receive radiotherapy for pelvic cancer in the UK annually. Up to 50% are left with altered bowel function affecting quality of life. The UK National Cancer Survivorship Initiative Vision acknowledges that the needs of cancer survivors are not being met and challenges professionals to develop new models of care.

Materials and methods

A prospective, observational qualitative study was carried out to assess whether nurse-delivered care is feasible for patients with radiotherapy-induced bowel dysfunction. The experience of a senior nurse, directed by an algorithm of investigation with a comprehensive treatment pathway, is reported.

Results

Over 12 months, 59 new and 103 follow-up appointments were managed by the nurse. In total, 37 women and 73 men, with a median age of 69 years, were seen; 9 had been treated for gastrointestinal, 33 for gynaecological and 68 for urological cancers, 26 months (median) previously. Sixty minutes (new consultations) (median, range 35-80) and 40 minutes (follow-up consultations) (range 20-85) were required. Ordering investigations, treatment initiation, long-term care planning and discharge seemed to be manageable in 83% of patients.

Conclusion

An experienced nurse, working within a defined scope of practice, with medical support can manage care in patients with mild or moderate symptoms arising after pelvic radiotherapy. An ongoing randomised controlled trial is assessing patient outcomes.     

Partial breast irradiation for locally recurrent breast cancer within a second breast conserving treatment: Alternative to mastectomy? Results from a prospective trial

Purpose

To assess the outcome of multi-catheter pulse dose rate (PDR) brachytherapy of re-irradiation for local ipsilateral breast tumour recurrence (IBTR) in regard to local control, survival, morbidity and quality of life (QoL).

Patients and methods

Between 1999 and 2006, 39 patients were included with histologically confirmed IBTR, Karnofsky index ?80% and refusal of mastectomy. Exclusion criteria were multicentric invasive growth pattern, unclear surgical margins, distant metastasis and a postoperative breast not suitable for interstitial brachytherapy. Primary endpoint was local tumour control. Morbidity, cosmetic outcome and QoL were assessed in 24/39 patients.

Results

The five year actuarial local control rate was 93% after a mean follow up of 57 (±30) months with two second local relapses. Overall survival and disease free survival, both at 5 years, were 87% and 77%, respectively. Late side effects Grade 1-2 were observed in 20/24 patients after a mean follow-up of 30 (±18) months. Late side effects ?Grade 3 occurred in 4/24 patients. Cosmetic outcome was excellent to fair in 76% of women. Overall QoL was comparable to a healthy control group. Mean scores of scales and items of QLQ-BR23 were comparable to primary breast conserving therapy.

Conclusions

Accelerated PDR-brachytherapy following breast conserving surgery (BCS) for local IBTR results in local tumour control comparable to mastectomy. Morbidity is moderate; the cosmetic outcome is good and hardly any impairment on QoL is observed.     

The relationship between morbidity after axillary surgery and long-term quality of life in breast cancer patients: The role of anxiety

Aims

Although arm/shoulder morbidity after sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) has been studied before, information is lacking concerning self-imposed restrictions in activities and long-term consequences of both surgical procedures in relationship to quality of life (QoL) and anxiety.

Methods

Eighty-nine disease-free breast cancer survivors completed a set of questionnaires assessing arm/shoulder symptoms, limitations in daily life, anxiety and QoL. Also, the ipsi- and contra lateral arm circumference and the range of shoulder motion were measured.

Results

Fifty-one women had SLNB, 25 had SLNB followed by ALND and 13 had ALND. Although ALND patients experienced more shoulder symptoms, limitations in daily life and imposed more restrictions on themselves than SLNB patients, no significant differences during physical examination were found. A decreased range of motion and a higher score on trait anxiety resulted in a lower QoL. Trait anxiety and perceived limitations in daily life predicted long-term quality of life.

Conclusions

There is a discrepancy between experienced and measured limitations in range of shoulder motion. Anxiety and self-imposed restrictions play an important role in predicting long-term QoL and should get the necessary attention when addressing shoulder symptoms in breast cancer patients.     

Carbogen and nicotinamide in locally advanced bladder cancer: Early results of a phase-III randomized trial

Purpose

Phase II studies in laryngeal and bladder carcinoma of accelerated radiotherapy with carbogen and nicotinamide (RT + CON) suggested a therapeutic advantage. Therefore, a randomized phase-III trial of RT + CON in locally advanced bladder carcinoma compared to radiotherapy (RT) alone was undertaken.

Methods

One hundred and sixty-five patients with muscle-invasive transitional cell bladder carcinoma were randomized to RT alone and 168 to RT + CON. This paper reports on compliance and toxicity to nicotinamide (NAM) and carbogen and on early radiation-induced adverse bowel and urinary events.

Results

Of those receiving RT + CON, 65-69% accepted all doses of NAM. Sixty-four percent of patients presented Grade ?1 NAM toxicity (nausea or vomiting), which was severe in 13%. Compliance to carbogen was 85% and none (32 fractions) and 2% (20 fractions) of patients presented severe toxicity. The highest prevalence of severe radiation acute morbidity was seen for urinary frequency (RT: 18% and RT + CON: 15%) and for diarrhea (RT: 3% and RT + CON: 5%).

Conclusions

There is no indication of an increase in radiation-induced morbidity by combining the tumour radiosensitizers carbogen and nicotinamide with radiotherapy. Late morbidity and treatment outcome will ultimately determine if there is a therapeutic benefit.     

An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry

Purpose

To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment.

Methods and materials

The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated.

Results and conclusions

Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.     

Combination therapy of imatinib mesylate and interferon-alpha demonstrates minimal activity and significant toxicity in metastatic renal cell carcinoma: results of a single- institution phase II trial

Background

Renal cell carcinoma (RCC) is characterized by increased expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF)-β, both of which contribute to its angiogenic phenotype. Interferon-α (IFN-α) improves survival in patients with metastatic RCC, perhaps partly because of its antiangiogenic properties. Imatinib mesylate inhibits PDGF-mediated signal transduction and might thus have antiangiogenic activity as well.

Patients and Methods

Patients with metastatic RCC were treated with IFN-α (9 × 10⁶ IU subcutaneously 3 times weekly) and oral imatinib mesylate (600 mg daily starting on day 8). Therapy was continuous, and response was evaluated at 8-week intervals using the Response Evaluation Criteria in Solid Tumors. Baseline plasma PDGF-AA, PDGF-AB, and PDGF-BB levels were obtained.

Results

Between January 2003 and January 2005, 17 patients were treated. One patient (6%) had a partial response, 4 (24%) had stable disease, 7 (41%) had progressive disease, and 5 (29%) were unevaluable because of early withdrawal secondary to toxicity. Median time to progression (TTP) using the Kaplan-Meier method was 8 weeks, and median overall survival was 17.8 months. Six patients (35%) withdrew from therapy because of toxicity, and 9 patients (53%) experienced ≥ 1 grade 3/4 toxicity. Platelet-derived growth factor AA, AB, and BB plasma levels did not correlate with TTP or overall survival.

Conclusion

Based on a response rate of only 6%, a median TTP of 2 months, and significant toxicities, further study of IFN-α in combination with imatinib mesylate is not recommended in patients with metastatic RCC.