Andrew McPartlin

Improved accuracy and precision of tracer kinetic parameters by joint fitting to variable flip angle and dynamic contrast enhanced MRI data

To improve the accuracy and precision of tracer kinetic model parameter estimates for use in dynamic contrast enhanced (DCE) MRI studies of solid tumors.

Parametrized rectal dose and associations with late toxicity in prostate cancer radiotherapy

OBJECTIVE We investigated possible associations between planned dose-volume parameters and rectal late toxicity in 170 patients having radical prostate cancer radiotherapy. METHODS For each patient, the rectum was outlined from anorectal junction to sigmoid colon, and rectal dose was parametrized using dose-volume (DVH), dose-surface (DSH) and dose-line (DLH) histograms. Generation of DLHs differed from previous studies in that the rectal dose was parametrized without first unwrapping onto 2-dimensional dose-surface maps. Patient-reported outcomes were collected using a validated Later Effects in Normal Tissues Subjective, Objective, Management and Analytic questionnaire. Associations between dose and toxicity were assessed using a one-sided Mann-Whitney U test. RESULTS Associations (p < 0.05) were found between equieffective dose (EQD23) and late toxicity as follows: overall toxicity with DVH and DSH at 13-24 Gy; proctitis with DVH and DSH at 25-36 Gy and with DVH, DSH and DLH at 61-67 Gy; bowel urgency with DVH and DSH at 10-20 Gy. None of these associations met statistical significance following the application of a Bonferroni correction. CONCLUSION Independently confirmed associations between rectal dose and late toxicity remain elusive. Future work to increase the accuracy of the knowledge of the rectal dose, either by accounting for interfraction and intrafraction rectal motion or via stabilization of the rectum during treatment, may be necessary to allow for improved dose-toxicity comparisons. ADVANCES IN KNOWLEDGE This study is the first to use parametrized DLHs to study associations with patient-reported toxicity for prostate radiotherapy showing that it is feasible to model rectal dose mapping in three dimensions.

Changes in prostate apparent diffusion coefficient values during radiotherapy after neo-adjuvant hormones

Background: Changes in prostate cancer apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) provide a noninvasive method for assessing radiotherapy response. This may be attenuated by neoadjuvant hormone therapy (NA-HT). We investigate ADC values measured before, during and after external beam radiotherapy (EBRT) following NA-HT. Methods: Patients with ⩾T2c biopsy-proven prostate cancer receiving 3 months of NA-HT plus definitive radiotherapy were prospectively identified. All underwent ADC-MRI scans in the week before EBRT, in the third week of EBRT and 8 weeks after its completion. Imaging was performed at 1.5 T. The tumour, peripheral zone (PZ) and central zone (CZ) of the prostate gland were identified and median ADC calculated for each region and time point. Results: Between September and December 2014, 15 patients were enrolled (median age 68.3, range 57–78) with a median Gleason score of 7 (6–9) and prostate-specific antigen (PSA) at diagnosis 14 (3–197) ng/ml. Median period of NA-HT prior to first imaging was 96 days (69–115). All patients completed treatment. Median follow up was 25 months (7–34), with one patient relapsing in this time. Thirteen patients completed all imaging as intended, one withdrew after one scan and another missed the final imaging. PZ and CZ could not be identified in one patient. Median tumour ADC before, during and post radiotherapy was 1.24 × 10−3 mm2/s (interquartile range 0.16 × 10−3 mm2/s), 1.31 × 10−3 mm2/s (0.22 × 10−3 mm2/s), then 1.32 × 10−3 mm2/s (0.13 × 10−3 mm2/s) respectively (p > 0.05). There was no significant difference between median tumour and PZ or CZ ADC at any point. Gleason score did not correlate with ADC values. Conclusions: Differences in ADC parameters of normal and malignant tissue during EBRT appear attenuated by prior NA-HT. The use of changes in ADC as a predictive tool in this group may have limited utility.

Prospective evaluation of relationships between radiotherapy dose to masticatory apparatus and trismus

Abstract Aims: This feasibility study aimed to identify relationships between radiation doses to the masticatory apparatus as a combined block or as individual subunits with changes in trismus following radiotherapy. Material and methods: Twenty patients from a single center were recruited prospectively as part of a randomized trial comparing proactive exercises in the management of trismus. Patients with stage III/IV oral cavity or oropharyngeal squamous cell cancers received intensity-modulated radiotherapy with concurrent systemic therapy. All patients had trismus prior to radiotherapy. Maximal inter-incisor distance (MID) was measured pre- and 6 months from the start of radiotherapy. Bilateral muscles of mastication: medial and lateral pterygoids (MP and LP), masseters (M), temporalis (T), temporomandibular joint (TMJ) were contoured on CT images. The block comprised all muscles excluding the TMJ below the orbital floor. Mean dose, equivalent uniform dose (EUD) and V35–V60 Gy were compared with change in MID. Results: In six patients, the MID deteriorated at 6 months from the start of radiotherapy compared with 14 whose MID improved. No significant association was observed between age, gender, smoking, alcohol status, exercise compliance, cisplatin, tumor site, stage, V35–V60 Gy or EUD with change in MID. A clinical outlier was excluded. Without the outlier (n = 19), a significant association was seen between mean dose and change in MID at 6 months for the ipsilateral block (p = .01), LP (p = .04) and M (p < .01). All patients where trismus deteriorated at 6 months received mean doses >40 Gy to the block. Conclusion: Higher mean radiation doses to the ipsilateral block, LP and M were significantly associated with deterioration in trismus. Limiting dose to these structures to ≤40 Gy for tumors not invading the masticatory muscles may improve treatment-related sequelae. The ipsilateral block, LP and M should be studied further as possible alternative avoidance structures in radiotherapy treatment planning.

EP-1381: ADC of prostate tumour and normal tissue during radiotherapy after neoadjuvant hormone therapy

Conclusion: Despite the numerous publications on focal therapy in prostate cancer, primary FRT is largely unexplored. Radiotherapy appears to be particularly suitable as a focal approach, since it has an established biological basis, known tumoricidal activity, possibility of dose differentiation, large availability of high-precision dose delivery techniques, limited or no invasiveness and familiarity to radiation oncologists and urologists. However, when applied as primary FRT, its use remains investigational since numerous questions remain unmet: consensus on the initial diagnostic tools, the optimization of technical parameters for therapy delivery, follow-up exams and scheduling, tumour control and toxicity profile, response evaluation and failure definition, salvage therapy and costbenefit.

Successful delivery of chemotherapy to treat small-cell prostate cancer in a patient undergoing haemodialysis

We report on the successful treatment of small-cell prostate cancer in a patient undergoing haemodialysis. The therapeutic regimen included 300 mg/m2 of carboplatin and 50 mg/m2 of etoposide coupled with radical radiotherapy. Adjustments to the patients haemodialysis prescription included the use of high flux, a larger dialyser surface area and an increased dialysis time. The parameters used aided tolerance to the drug, allowing the delivery of safe, effective treatment. At an interval of over 12 months post-treatment the patient shows no clinical evidence of recurrent disease. This case provides evidence to encourage the use of chemotherapy in otherwise potentially undertreated haemodialysed patients.

Cisplatin plus capecitabine as first-line chemotherapy for recurrent or metastatic head and neck squamous cell cancer: experience outside of a trial setting.

Purpose: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. Methods: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m2) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m2 twice daily) on days 1-14, for up to 6 cycles. Results: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. Conclusion: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.