Suki Gill

A systematic review of stereotactic radiotherapy ablation for primary renal cell carcinoma

Study Type – Therapy (systematic review)

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

BackgroundImage-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically.MethodsBetween 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment.ResultsIn the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference.ConclusionsIn this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.

Impact of post-therapy positron emission tomography on prognostic stratification and surveillance after chemoradiotherapy for cervical cancer

A study was undertaken to investigate the detection of relapse and survival outcomes in patients with cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post‐therapy 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan.

Late toxicity and biochemical control in 554 prostate cancer patients treated with and without dose escalated image guided radiotherapy.

BACKGROUND AND PURPOSE To compare rates of late gastrointestinal toxicity, late genitourinary toxicity and biochemical failure between patients treated for prostate cancer with implanted fiducial marker image guided radiotherapy (FMIGRT), and those treated without FMIGRT. METHODS AND MATERIALS We performed a single institution retrospective study comparing all 311 patients who received 74 Gy without fiducial markers in 2006 versus all 243 patients who received our updated regimen of 78 Gy with FMIGRT in 2008. Patient records were reviewed 27 months after completing radiotherapy. Biochemical failure was defined using the Phoenix definition. Details of late gastrointestinal and genitourinary toxicities were graded according to CTCAEv4. Moderate/severe toxicity was defined as a grade 2 or higher toxicity. Cumulative incidence and prevalence curves for moderate/severe toxicity were constructed and compared using multistate modeling while biochemical failure free survival was compared using the log rank test. A Cox regression model was developed to correct for confounding factors. RESULTS Median follow-up time for both groups was 22 months. The hazard ratio for moderate/severe late gastrointestinal toxicity in the non-FMIGRT group was 3.66 [95% CI (1.63-8.23), p=0.003] compared to patients in the FMIGRT group. There was no difference in the hazard ratio of moderate/severe late genitourinary toxicity between the two groups (0.44 [95% CI (0.19-1.00)]), but patients treated with FMIGRT did have a quicker recovery from their genitourinary toxicities HR=0.24 [95% CI (0.10-0.59)]. We were unable to detect any differences in biochemical failure free survival between the cohorts HR=0.60 [95% CI (0.30-1.20), p=0.143]. CONCLUSION Despite dose escalation, the use of FMIGRT in radical radiotherapy for prostate cancer significantly reduces the incidence of gastrointestinal toxicity and the duration of late genitourinary toxicity when compared to conventional non-FMIGRT techniques.

Patient-reported complications from fiducial marker implantation for prostate image-guided radiotherapy

OBJECTIVES To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy. METHODS 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale. RESULTS Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5). CONCLUSION Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: A systematic review

Abstract Background. Stereotactic radiotherapy is a non-invasive, ablative technique which may be particularly effective in treating metastatic renal cell carcinoma (RCC). The study objective was to analyse outcomes and toxicity of stereotactic radiotherapy in metastatic RCC. Material and methods. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of Medline was performed in March 2013. Exclusion criteria included mixed histology studies and case series. Local control, overall survival and toxicities were analysed. Results. From 148 publications identified, 16 and 10 publications for cranial and extracranial metastatic RCC met inclusion criteria, respectively. There were 810 intracranial patients and 2433 targets. The weighted local control was 92%. Overall survival ranged from 6.7 to 25.6 months. Significant Grade 3–4 toxicity ranged from 0% to 6%. The weighted rate of treatment-related mortality was 0.6%, all secondary to intratumoral haemorrhage. There were 389 extracranial patients and 730 targets. The weighted local control was 89%. Median overall survival ranged from 11.7 to 22 months. Grade 3–4 toxicity ranged from 0% to 4%. Treatment-related mortality was 0.5%. Conclusion. Stereotactic radiotherapy is associated with excellent local control and low rates of toxicity for intracranial and extracranial metastatic RCC. Future randomised studies are required to confirm the additional benefit of Stereotactic Ablative Body Radiotherapy (SABR) above standard conservative or palliative approaches.

Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial

BACKGROUND The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. METHODS We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. RESULTS Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. CONCLUSION RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration.

An analysis of respiratory induced kidney motion on four-dimensional computed tomography and its implications for stereotactic kidney radiotherapy.

Background and purposeStereotactic ablative body radiotherapy (SABR) is an emerging treatment modality for primary renal cell carcinoma. To account for respiratory-induced target motion, an internal target volume (ITV) concept is often used in treatment planning of SABR. The purpose of this study is to assess patterns of kidney motion and investigate potential surrogates of kidney displacement with the view of ITV verification during treatment.Material and methodsDatasets from 71 consecutive patients with free breathing four-dimensional computed tomography (4DCT) planning scans were included in this study. The displacement of the left and right hemi-diaphragm, liver dome and abdominal wall were measured and tested for correlation with the displacement of the both kidneys and patient breathing frequency.ResultsNine patients were excluded due to severe banding artifact. Of 62 evaluable patients, the median age was 68 years, with 41 male patients and 21 female patients. The mean (range) of the maximum, minimum and average breathing frequency throughout the 4DCTs were 20.1 (11–38), 15.1 (9–24) and 17.3 (9–27.5) breaths per minute, respectively. The mean (interquartile range) displacement of the left and right kidneys was 0.74 cm (0.45-0.98 cm) and 0.75 cm (0.49-0.97) respectively. The amplitude of liver-dome motion was correlated with right kidney displacement (r=0.52, p<0.001), but not with left kidney displacement (p=0.796). There was a statistically significant correlation between the magnitude of right kidney displacement and that of abdominal displacement (r=0.36, p=0.004), but not the left kidney (r=0.24, p=0.056). Hemi-diaphragm displacements were correlated with kidney displacements respectively, with a weaker correlation for the left kidney/left diaphragm (r= 0.45, [95% CI 0.22 to 0.63], p=<0.001) than for the right kidney/right diaphragm (r=0.57, [95% CI 0.37 to 0.72], p=<0.001).ConclusionsFor the majority of patients, maximal left and right kidney displacement is subcentimeter in magnitude. The magnitude of kidney motion cannot be reliably estimated from the diaphragmatic, liver dome or abdominal wall surrogates. One explanation may be that the kidneys are not uniformly in contact with the surrogates investigated in this study. Further investigation is required before surrogates of kidney displacement are used for clinical SABR delivery.

Plan of the day selection for online image-guided adaptive post-prostatectomy radiotherapy.

PURPOSE To compare the cone-beam CT (CBCT) soft tissue localization disparity between radiation oncologists (RO) and radiation therapy technologists (RTT) in a novel online protocol of image-guided adaptive radiotherapy to the postoperative prostate bed. METHOD Using the planning CT and pre-treatment CBCTs from the first week of radiotherapy, four adaptive plans of different sizes were derived for each of eight post-prostatectomy patients. Four ROs collectively defined the reference answer, i.e. the plan of the day and isocentre correction for 40 CBCTs taken in weeks 2-6 of treatment for each patient. RTTs were randomly assigned five of these CBCTs; and asked to record their plan of the day selection and isocentre correction. RTT selection and reference answers were compared. The distance between the RTT selection and the reference answer was calculated. RESULTS A total of 33 RTTs took part in this study. The average difference in CTV volume (reference answer-RTT selection) was 1.32 cm(3) (SD 29 cm(3)) overall. The average difference between reference answer and RTT isocentre coordinates was SI 1mm (SD 4.8mm), LR 1.1mm (SD 4.0mm) and AP -0.2mm (SD 3.9 mm). Distance of superior 8mm, inferior 6mm, left 4mm, right 2mm, anterior 6mm and posterior 6mm covered 100% of the CTV in 90% of fractions. CONCLUSION The difference between RTT and RO selection of adaptive volumes is small and can be accounted for in a clinically acceptable CTV to PTV margin. Adaptive post-prostatectomy radiotherapy is feasible, in the setting of an academic center although at the moment, we have insufficient evidence to suggest that margins can yet be reduced with IGART with the current protocol.

Intrafraction Bladder Motion in Radiation Therapy Estimated From Pretreatment and Posttreatment Volumetric Imaging

PURPOSE The use of image guidance protocols using soft tissue anatomy identification before treatment can reduce interfractional variation. This makes intrafraction clinical target volume (CTV) to planning target volume (PTV) changes more important, including those resulting from intrafraction bladder filling and motion. The purpose of this study was to investigate the required intrafraction margins for soft tissue image guidance from pretreatment and posttreatment volumetric imaging. METHODS AND MATERIALS Fifty patients with muscle-invasive bladder cancer (T2-T4) underwent an adaptive radiation therapy protocol using daily pretreatment cone beam computed tomography (CBCT) with weekly posttreatment CBCT. A total of 235 pairs of pretreatment and posttreatment CBCT images were retrospectively contoured by a single radiation oncologist (CBCT-CTV). The maximum bladder displacement was measured according to the patients bony pelvis movement during treatment, intrafraction bladder filling, and bladder centroid motion. RESULTS The mean time between pretreatment and posttreatment CBCT was 13 minutes, 52 seconds (range, 7 min 52 sec to 30 min 56 sec). Taking into account patient motion, bladder centroid motion, and bladder filling, the required margins to cover intrafraction changes from pretreatment to posttreatment in the superior, inferior, right, left, anterior, and posterior were 1.25 cm (range, 1.19-1.50 cm), 0.67 cm (range, 0.58-1.12 cm), 0.74 cm (range, 0.59-0.94 cm), 0.73 cm (range, 0.51-1.00 cm), 1.20 cm (range, 0.85-1.32 cm), and 0.86 cm (range, 0.73-0.99), respectively. Small bladders on pretreatment imaging had relatively the largest increase in pretreatment to posttreatment volume. CONCLUSION Intrafraction motion of the bladder based on pretreatment and posttreatment bladder imaging can be significant particularly in the anterior and superior directions. Patient motion, bladder centroid motion, and bladder filling all contribute to changes between pretreatment and posttreatment imaging. Asymmetric expansion of CTV to PTV should be considered. Care is required in using image-guided radiation therapy protocols that reduce CTV to PTV margins based only on daily pretreatment soft tissue position.