Implementation of 26 Gy in five fractions over 1 week adjuvant radiotherapy for breast cancer: Prospective report of acute skin toxicity and consideration of resource implications.

PURPOSE: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. MATERIALS AND METHODS: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar-Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. RESULTS: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. CONCLUSION: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis.

BACKGROUND: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. METHODS: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. FINDINGS: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. INTERPRETATION: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.

Ovarian function after chemotherapy in young breast cancer survivors.

BACKGROUND: As cure rates for breast cancer improve, there is increasing evidence that late effects of treatment-and impaired fertility in particular-are emerging as important concerns among young breast cancer survivors. Older reports have evaluated the occurrence of amenorrhea after treatment, but few data have been reported about the incidence of biochemical evidence for impaired ovarian function in patients who do not become overtly menopausal. METHODS: We conducted a cross-sectional study evaluating anti-Müllerian hormone (amh) in premenopausal chemotherapy-treated breast cancer survivors and control patients. Random serum levels of amh and other relevant clinical data were collected for 100 premenopausal chemotherapy-treated breast cancer survivors and 76 control subjects. Subgroup analyses were performed for women with regular menstrual cycles at the time of amh testing. RESULTS: After adjustment for age, amh was significantly lower in the overall group of patients receiving chemotherapy (p = 0.002) and in the subgroup reporting normal cycles (p = 0.03). Cyclophosphamide produced a significant dose-dependent reduction in amh (p < 0.001); trastuzumab was associated with increased amh in survivors with normal cycles. Overall, serum amh in survivors was roughly equivalent to that measured in control patients 12 years older. CONCLUSIONS: Young breast cancer survivors often experience significant impairment of ovarian function despite having normal menstrual cycles after treatment. Those results have important implications for patient counselling and the timing of possible referral to a fertility specialist.

A clinical review of treatment outcomes in glioblastoma multiforme--the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival?

OBJECTIVE: Glioblastoma multiforme (GBM) accounts for up to 60% of all malignant primary brain tumours in adults, occurring in 2-3 cases per 100,000 in Europe and North America. In 2005, a Phase III clinical trial demonstrated a significant improvement in survival over 2, and subsequently 5, years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT). The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice. METHODS: This was a retrospective study including all patients with histologically proven GBM diagnosed from 1999 to 2008 and treated with adjuvant RT at our institution. A total of 273 patients were identified. Statistical analysis was carried out using SPSS® v.18 (SPSS, Chicago, IL). RESULTS: The median survival for the whole group (n=273) over the 10-year period was 7.6 months (95% confidence interval 6.7-8.4 months). Overall, the cumulative probability of survival at 1 and 2 years was 31.5% and 9.4%, respectively. In total, 146 patients received radical RT. 103 patients were treated with radical RT and TMZ and 43 patients received radical RT alone. The median survival for patients receiving radical RT with TMZ was 13.4 months (95% CI 10.9-15.8 months) vs 8.8 months for radical RT alone (95% CI 6.9-10.7 months, p=0.006). 2-year survival figures were 21.2% vs 4.7%, respectively. On multivariate analysis, independent predictors of survival included Karnofsky Performance Status, RT dose, TMZ and extent of surgery. The strongest predictors of poorer outcome based on the hazard ratio were palliative RT, followed by not receiving TMZ chemotherapy, then KPS <90 and a biopsy only surgical approach. CONCLUSION: This paper demonstrates improved survival outcomes consistent with those published in the literature for the addition of concurrent and adjuvant TMZ to radical RT for the treatment of GBM. Although 63% of patients seen in the clinic were suitable for a combined modality approach, the prognosis for the lower Radiation Therapy Oncology Group classes still remains poor.

Pelvic radiotherapy in patients with hydronephrosis in stage IIIB cancer of the cervix: renal effects and the optimal timing for urinary diversion?

BACKGROUND AND PURPOSE: Many patients with Stage IIIB cervix cancer (Ca) and hydronephrosis will require ureteral stenting. The timing is important as delays or prolonged overall treatment times adversely affect outcome. Our aim was to measure the effect of pelvic radiotherapy (R/T) on renal function and identify a subset of patients at high risk of acute urinary obstruction during R/T. PATIENTS AND METHODS: From 1/1/2000 to 1/1/2002, all patients with Stage IIIB cervix Ca and hydronephrosis were analysed retrospectively. To quantify the impact of pelvic R/T, all eligible patients from 1/7/2002-1/7/2004 had prospectively recorded baseline biochemistry, creatinine clearance and renal ultrasounds; these were repeated weekly to detect any change in renal function or degree of hydronephrosis. RESULTS: 13 eligible patients were analysed retrospectively, 5 with unilateral hydronephrosis with 40% requiring urinary diversion (UD). 8 had bilateral hydronephrosis, with 75% requiring UD; 50% before R/T and 35% during R/T. Average creatinine clearance (CrCl) was 74 mL/min (1.24 mL/s) in unilateral hydronephrosis , bilateral = 52 mL/min (0.87 mL/s), in those stented during R/T it was < 40 mL/min (0.67 mL/s). The resulting break in R/T was 6 and 19 days. In the prospective study, 5 patients were eligible and 4 consented. 75% had unilateral hydronephrosis and did not require UD with an average CrCl = 71 mL/min (1.19 mL/s). 1 patient with bilateral hydronephrosis had a CrCl of < 20 mL/min (0.33 mL/s) with bilateral stents placed before R/T. CONCLUSIONS: Patients with bilateral hydronephrosis and a low CrCl < 50 mL/min (0.84 mL/s) should be considered for elective UD prior to R/T. Pelvic R/T did not induce any deterioration in renal function or degree of hydronephrosis.

A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology.

OBJECTIVES: To review and document the changing patterns in diagnosis, causes and treatment of bacterial infections of the central nervous system (CNS) in a national neurosurgical unit only in patients from whom a specimen was obtained for culture. METHODS: The case notes, radiological results and laboratory records of all 163 patients in our institution who underwent a neurosurgical procedure between 1988 and 2000 for a CNS abscess in a national center were reviewed retrospectively. Those patients from whom there were no operative specimens (i.e. neurosurgical intervention was not performed) and who were treated empirically were excluded, as were patients with mycobacterial infection. RESULTS: The mean age of the 163 patients was 35.2 years. Headache, pyrexia and an altered mental state were the commonest presentations. The frontal lobe was the commonest anatomical site (62 patients, 38%) and the majority of abscesses occurred following community infections such as sinusitis and mastoiditis; no primary source could be identified in 32 (20%) patients. Bacteria were isolated from 73% of patients and polymicrobial infections occurred in 29 (17.7%) patients. Anaerobes accounted for only 13.6% of isolates and methicillin-resistant Staphylococcus aureus (MRSA) was isolated on five occasions, all in the last five years of this review. Sixteen (9.8%) patients died prior to discharge or transfer back to the original referring hospital and 18 (11%) patients developed epilepsy. CONCLUSION: There was a relatively high incidence of polymicrobial infection but the number of specimens with anaerobes was small, which may be because of the use of empiric metronidazole before surgical intervention. Most infections were community-acquired and responded well to a combination of surgical drainage and antibiotic therapy. The emergence of MRSA in this group of patients is, however, worrying.