Martin Borg

Evidence for efficacy without increased toxicity of hypofractionated radiotherapy for prostate carcinoma: early results of a Phase III randomized trial.

PURPOSE We performed a randomized trial to compare the GI and urogenital toxicity of radiotherapy (RT) for localized (confined to the organ), early-stage (T1-T2N0M0, TNM classification) carcinoma of the prostate, using a conventional (64 Gy in 32 fractions within 6.5 weeks) vs. a hypofractionated (55 Gy in 20 fractions within 4 weeks) schedule and to determine the efficacy of the respective treatment schedules. METHODS AND MATERIALS This report is based on an interim analysis of the first 120 consecutive patients in this Phase III trial after a median follow-up of 43.5 months (range 23-62). RT planning was based on two-dimensional CT data, and the treatment was delivered using a three- or four-field 6-23-MV photon technique. GI and urogenital toxicity (symptom questionnaires incorporating the subjective elements of the late effects of normal tissues-subjective, objective, management, analytic classification of late effects and the European Organization for Research and Treatment of Cancer sexual function questionnaire) were evaluated before RT and 1 month, 1 year, and 2 years after RT completion. The efficacy of RT was assessed clinically (digital rectal examination and radiologic imaging) and biochemically (prostate-specific antigen assay) at baseline, and every 3 months for 2 years after RT and every 6 months subsequently. RESULTS RT, whether conventional or hypofractionated, resulted in an increase in all six symptom categories used to characterize GI toxicity and in four of five symptom categories used to document urinary morbidity 1 month after therapy completion. Sexual dysfunction (based on limited data), which existed in more than one-third of patients before RT, also increased to just more than one-half of patients 1 month after RT. The increase in urinary toxicity after RT was not sustained (diurnal urinary frequency had decreased significantly at 2 years). In contrast, all six symptom categories of GI toxicity remained increased 1 year after RT. Four of the six GI symptom categories (rectal pain, mucous discharge, urgency of defecation, and rectal bleeding) were still increased at 2 years compared with baseline. Except for a slightly greater percentage of patients experiencing mild rectal bleeding at 2 years among those who received hypofractionated RT, no differences were noted in toxicity between the conventional and hypofractionated RT schedule. The mean prostate-specific antigen level was 14.0 +/- 1.0 ng/mL at baseline and declined to a nadir of 1.3 +/- 0.2 ng/mL at a median of 16.8 months (range 0.8-28.3) after RT completion. However, it then rose in 17 patients (8 in the hypofractionated and 9 in the conventional treatment group). Only 8 of these 17 patients were found to have signs of clinical relapse (5 local, 1 regional lymph node, and 2 systemic [bony metastases]) after histopathologic and radiologic reassessment). The remaining 9 patients had biochemical relapse only (defined as three consecutive rises in prostate-specific antigen after nadir). The 4-year biochemical relapse-free survival rate was 85.8% for all patients and did not differ significantly between the two radiation dose schedules (86.2% for the hypofractionated and 85.5% for the conventional fractionation group). CONCLUSION RT for prostate carcinoma, using a three- or four-field 6-23-MV photon technique without posterior shielding of the lateral fields, is an underestimated cause of persistent GI morbidity. The incidence of clinically significant GI and urogenital toxicity after conventional and hypofractionated RT appears to be similar. Hypofractionated RT for carcinoma of the prostate seems just as effective as conventional RT after a median follow-up approaching 4 years.

Chronic effects of therapeutic irradiation for localized prostatic carcinoma on anorectal function.

PURPOSE To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. METHODS AND MATERIALS The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (+/- SD) of 1.4 (+/- 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). RESULTS All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric parameters at 1 year, cf. baseline. The predictor variables used included individual patient tumor and treatment characteristics as well as individual patient symptom scores and parameters of anorectal motor and sensory function at baseline and 4-6 weeks after RTH. The results of the univariate logistical regression analysis showed that (1) frequency of defecation at 4-6 weeks and (2) rectal volumes at baseline both for (a) perception (p < 0.001) and (b) desire to defecate (p < 0.001), predicted significantly for the patients who had symptoms and signs of anorectal dysfunction at 1 year. Individual patient tumor and treatment-related variables tested, in contrast, had no predictive significance. CONCLUSIONS Anorectal symptoms following RTH for prostatic carcinoma are common and persist at least until 1 year after its completion and are associated with objective evidence of heightened rectal sensitivity.

Acute effects of therapeutic irradiation for prostatic carcinoma on anorectal function

Aim—The incidence of anorectal symptoms after radiotherapy (RTH) for localised pelvic malignant disease is unclear. In addition, the effects of pelvic irradiation on both anorectal motility and sensory function are poorly defined. A prospective study was therefore performed on 35 patients (55–82 years of age) with localised prostatic carcinoma before and four to six weeks after RTH to assess its effects on anorectal function. Methods—Anorectal symptoms were assessed by questionnaire. Anorectal pressures at rest and in response to voluntary squeeze, rectal distension, and increases in intra-abdominal pressure were evaluated with perfused sleeve side hole manometry. Rectal sensation was tested during graded balloon distension. Rectal compliance was calculated by the pressure-volume relation obtained during the testing of rectal sensation. Ultrasound was used to determine anal sphincter structure and integrity. Results—RTH had no effect on anal sphincter morphology. The frequency of defecation increased after RTH (7 (3–21) v 10 (3–56) bowel actions a week; p<0.01). After RTH, 16 patients had faecal urgency and eight faecal incontinence, compared with five and one respectively before RTH (p<0.01 for each). Basal and squeeze sleeve recorded pressures were reduced after RTH (54 (3)v 49 (3) mm Hg (p<0.05) and 111 (8)v 102 (8) mm Hg (p<0.01), before and after RTH respectively; means (SEM)). Rectal compliance was reduced after RTH (1.2 v 1.4 mm Hg/ml, p<0.05). After RTH, threshold volumes for perception of rectal distension were lower in the 16 patients who either experienced faecal urgency for the first time (13 patients) or reported worsening of this symptom (three patients) compared with the remaining patients (34 (4)v 48 (5) ml respectively, p<0.05). Conclusion—Faecal incontinence (23%) is a common problem four to six weeks after RTH for prostatic carcinoma and is associated with minor reductions in anal sphincter pressures. The high prevalence of faecal urgency in patients after RTH may be related to alterations in rectal perception of stool.

The role of radiation therapy in the management of sialorrhea.

PURPOSE Sialorrhea is the unintentional loss of saliva and other contents from the mouth. Most patients with this condition are elderly, requiring palliative treatment. These patients have neuropathology with associated poor performance status. Treatment prescribed for this disabling and distressing condition has often been of a surgical nature and described in young patients. It would be inapplicable to the elderly. The aim of this study was to review the role of radiation therapy in the management of sialorrhea. Previous reports are few in number and are cautionary because of adverse effects which have been described, including dryness of the mouth. METHODS AND MATERIALS A total of 34 patients were referred to the Department of Radiation Oncology, Palmerston North Hospital, between 1966 and August 1994, of whom only 1 patient received treatment prior to 1985. Three patients declined treatment and were, therefore, excluded from this review. Thirty-one patients, including 14 males and 17 females, of median age 72 years received 1 or more radiation treatments for sialorrhea. The patients were followed up for a median of 12 months, ranging from 6 months to 27 years. RESULTS Initially, 82% (28/34) of treatments were associated with a satisfactory response. Six patients relapsed, of whom five experienced relapse within 6 months of initial treatment. Two patients were re-treated, one of whom achieved a complete response. Up to the time of review 64% (23/36) of treatments maintained a satisfactory response. The varied fractionation regimens used were not shown to affect the response rate; low doses were shown to be as effective as higher doses, and were not associated with any significant acute or late side effects. Only 4 patients developed long-term side effects. However, response rates were superior for patients treated with electrons, as opposed to orthovoltage therapy, and in particular when electron energies greater than 7 megavolts were used (76% vs. 38% maintained response, p < 0.05). Responses were also superior for patients treated with radiation fields which encompassed both parotid and submandibular glands (74% vs. 33 % maintained response, p < 0.01). CONCLUSIONS Radiation therapy has proven to be a safe and effective treatment in this group of patients, thereby avoiding the adverse effects of anticholinergic medication and invasive surgical procedures.

Renal toxicity after total body irradiation

Abstract Purpose: To evaluate the incidence of renal dysfunction after total body irradiation (TBI). Methods and Materials: Between 1990 and 1997, 64 patients (median age 50 years) received TBI as part of the conditioning regimen before bone marrow transplantation (BMT). Five patients with abnormal renal function at the beginning of treatment or with incomplete data were excluded. All patients received a total of 12 Gy (6 fractions twice daily for 3 consecutive days) prescribed to the peak lung dose (corrected for lung transmission) at a dose rate of 7.5 cGy/min. Renal shielding was not used. Renal dysfunction was assessed on the basis of the serum creatinine levels measured at the start and end of TBI and at 6, 12, 18, and 24 months after completion of BMT. Cox proportional hazard analysis was used to evaluate the various factors known to affect renal function. Results: Only 4 patients had elevated serum creatinine levels at 12 months and subsequently only 2 of the 33 surviving patients had persistent elevated renal serum creatinine levels 24 months after BMT. A fifth patient developed proteinuria and mildly elevated serum creatinine levels at 2.5 years. In 2 patients, the elevation coincided with disease relapse and normalized once remission was achieved. In the third patient, the elevation in serum creatinine levels coincided with relapse of multiple myeloma and the presence of Bence-Jones proteinuria. The fourth patient was the only patient who developed chronic renal failure secondary to radiation nephritis at 2 years. The etiology of the fifth patients rise in creatinine was unknown, but may have been secondary to radiation nephritis. On univariate analysis, but not on multivariate analysis, a significant correlation was found between TBI-related renal dysfunction and hypertension before and after BMT. Conclusion: A dose of 12 Gy at 2 Gy/fraction resulted in only 1 case of radiation nephritis in the 59 patients studied 24 months after the completion of TBI and BMT.

Review of MammoSite brachytherapy: Advantages, disadvantages and clinical outcomes

Background. The MammoSite® radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. Material and methods. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Results. Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of ≥7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5–25%). Conclusion. Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer providing good local control, minimal complication rate and excellent cosmesis.

The role of the breast care nurse during treatment for early breast cancer: The patient’s perspective

Abstract INTRODUCTION: Women who are diagnosed with breast cancer require the support of a range of people during their treatment. Although the role of the breast care nurse in providing support has recently been investigated in several Australian studies the patients’ perspective on the role of the breast care nurse in Australian hospitals has not previously been described in detail. The aim of this paper is to explore patients’ perspectives on the role of the breast care nurse. METHODS: In-depth interviews were conducted with 18 women who had completed treatment for early breast cancer. The women were asked to describe their experiences from the time of diagnosis through to treatment completion. Thematic analysis was used to analyse the data. FINDINGS: Breast cancer patients repeatedly emphasised the importance of the role of their breast care nurses throughout their experience of breast cancer. The support that breast care nurses provided incorporated the following components: communication, rapport and an awareness of the women’s needs, availability, reassurance and practical information. CONCLUSION: This study provides an understanding of women’s perspectives on the role of breast care nurses and confirms that breast care nurses play an important support role during the experience of early breast cancer. Oncology clinics should focus on ensuring that all women who are diagnosed with breast cancer have adequate access to the support that breast care nurses are able to provide.

A Systematic Review of Intraoperative Radiotherapy in Early Breast Cancer

A systematic review was undertaken to assess the safety and efficacy of intraoperative radiotherapy (IORT) in early breast cancer compared with breast conserving surgery with postoperative radiotherapy. Literature databases were searched up to March 2002 inclusive. IORT studies of any design and breast conserving therapy randomised controlled trials with sample sizes greater than 500 patients (with at least one arm of breast conserving therapy (BCT)) and systematic reviews on BCT published since 1992, were included for comparison. Seven unique IORT studies were located; one randomised controlled trial, one study with a concurrent control group and five case series. Minor postoperative complications were reported following IORT. Short-term results were similar for both treatment modalities in terms of local recurrence, disease-free and overall survival. However, the current evidence base is poor, making definitive assessment on IORT very difficult. Further research is required to clarify several issues such as identification of the most appropriate subgroups of patients for IORT, a comparison of the currently available mobile IORT technologies, establishing whether IORT is most appropriate as a boost replacement dose or replacement for all postoperative radiotherapy, the examination of how biological repair processes may differ between the two treatment modalities and determining precisely where local recurrences originate with respect to the original tumour site.

Radiotherapy in fascial fibromatosis: A case series, literature review and considerations for treatment of early‐stage disease

Palmar and plantar fascial fibromatoses are benign hyperproliferative disorders of the deep fascia of the palm and sole. This study seeks to examine the role of radiotherapy in the management of fascial fibromatosis.

Prostate-specific antigen (PSA) rate of decline post external beam radiotherapy predicts prostate cancer death

BACKGROUND AND PURPOSE To assess the association between PSA velocity (PSAV) in the first 24 months after external beam radiotherapy (EBRT) and prostate cancer-specific mortality (PCSM) and all cause mortality. MATERIALS AND METHODS All eligible patients in the South Australian (SA) Prostate Cancer Clinical Outcomes registry were followed. 848 Patients treated by definitive EBRT with more than one PSA recorded in the two year post-treatment were included. We calculated PSAV by linear regression. RESULTS The mean number of PSA measurements in the 2year period was 4.4 (SD1.9). The median PSAVs across quartiles (Q1-Q4) were -4.17, -1.29, -0.38 and 0.20ng/ml/yr. In multivariable analysis, a U-shaped relationship was seen between PSAV and PCSM with Q1-Q4 hazard ratios (HR) being 3.82 (1.46-10.00), 3.07 (1.10-8.58), 1, 5.15 (1.99-13.30) respectively. HR for all cause mortality in a similar model were 1.79 (1.07-2.98), 1.55 (0.93-2.59), 1.00 and 1.74 (1.04-2.90) for Q1 to Q4 respectively. A rapid PSA decline in the first year was a strong predictor of PCSM. However, in the second year PSA increase was positively associated with PCSM. CONCLUSION A rapid decline in PSA in the first year following EBRT is positively associated with PCSM. This may be a useful early indicator of the need for additional therapies.