Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

SABR for Early Non-Small Cell Lung Cancer: Changes in Pulmonary Function, Dyspnea, and Quality of Life.

PURPOSE: The aim of this study was to report pulmonary function tests (PFTs) and clinician-reported and patient-reported quality-of-life (QoL) outcomes on a cohort of patients with non-small cell lung cancer (NSCLC) treated with SABR. METHODS AND MATERIALS: A total of 119 patients with NSCLC were treated with SABR in the prospective cohort SSBROC study of patients with T1-T2N0M0 NSCLC. PFTs and QoL measures were obtained at baseline pretreatment and at 6-month intervals. Here we report on the 6- to 18-month time points. Analysis of covariance (ANCOVA) methods adjusting for baseline analyzed potential predictors on outcomes of PFTs and patient-reported dyspnea at 18 months. RESULTS: The only statistically significant decline in PFTs was seen in forced expiratory volume in 1 second (FEV1) at 18 months post-SABR, with a decline of -0.11 L (P = .0087; 95% CI, -0.18 to -0.02). Of potential predictors of decline, only a 1-unit increase in smoking pack-years resulted in a -0.12 change in diffusing capacity for carbon monoxide (P = .026; 95% CI, -0.02 to -0.23) and a 0.003 decrease in FEV1 (P = .026; 95% CI, -0.006 to -0.0004). For patient-reported outcomes, statistically significant worsening in both the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (QLQ-C30 Version 3) and the lung module (QLQ-LC13) dyspnea scores occurred at the 18-month time point, but not earlier. No potential predictors of worsening dyspnea were statistically significant. There was no statistically significant decline in clinician-reported outcomes or global QoL scores. CONCLUSIONS: We found a statistically significant decline in FEV1 at 18 months posttreatment. Smoking pack-years was a predictor for decline in diffusing capacity for carbon monoxide and FEV1 at 18 months. Worsening of patient-reported dyspnea scores was observed, consistent with the expected progression of lung comorbid disease.

Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics?

Purpose: Triple negative breast cancer (TNBC) is a breast carcinoma subtype that neither expresses estrogen (ER) and progesterone receptors (PR) nor the human epidermal growth factor receptor 2 (HER2). Patients with TNBC have been shown to have poorer outcomes mainly owing to the limited treatment options available. However, some studies have shown TNBC tumors expressing androgen receptors (AR), raising hopes of its prognostic role. Patients and Methods: This retrospective study investigated the expression of AR in TNBC and its relationship with known patient demographics, tumor and survival characteristics. From the records of 205 TNBC patients, 36 had available archived tissue samples eligible for AR staining. For statistical purposes, tumors were classified as either "positive" or "negative" for AR expression. The nuclear expression of AR was scored by measuring the percentage of stained tumor cells and its staining intensity. Results: AR was expressed by 50% of the tissue samples in our TNBC cohort. The relationship between AR status with age at the time of TNBC diagnosis was statistically significant, with all AR positive TNBC patients being greater than 50 years old (vs 72.2% in AR negative TNBC). Also, the relationship between AR status and type of surgery received was statistically significant. There were no statistically significant associations between AR status with other tumor characteristics including "TNM status", tumor grade or treatments received. There was no statistically significant difference in median survival between AR negative and AR positive TNBC patients (3.5 vs 3.1 years; p = 0.581). The relationship between OS time and AR status (p = 0.581), type of surgery (p = 0.061) and treatments (p = 0.917) were not statistically significant. Conclusion: The androgen receptor may be an important prognostic marker in TNBC, with further research warranted. This research may benefit future studies investigating receptor-targeted therapies in TNBC.

PSMA-PET-guided dose-escalated volumetric arc therapy for newly diagnosed lymph node-positive prostate cancer: 5 Year outcomes following the FROGG and EviQ node-positive guidelines.

INTRODUCTION: The Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology Genitourinary Group (FROGG) guidelines and online EviQ protocols incorporate prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) for newly diagnosed lymph node (LN) positive prostate cancer. We evaluated late toxicity and efficacy outcomes following the FROGG and EviQ approach. METHODS: Patients with LN-positive-only metastases on PSMA-PET imaging were offered curative therapy with 3 months neoadjuvant androgen deprivation therapy (ADT) followed by DE-IMRT and 3 years adjuvant ADT. IMRT was delivered via volumetric arc therapy (VMAT). We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45 Fx to elective pelvic nodes, contoured using the PIVOTAL guidelines. RESULTS: Forty-five patients were included. The median number of PET-positive nodes boosted was 2 (range 1-6) and median boost volume 1.16 cc (range 0.15-4.14). Seventeen (38%) patients had PET-positive nodes outside of PIVOTAL contouring guidelines. With 60 months median follow-up, disease-free, metastasis-free, prostate cancer-specific and overall survival were 88.1%, 95.3%, 100% and 91.5%. There were no in-field nodal failures. Late grade 1, 2 and 3 gastrointestinal toxicities occurred in 4%, 2% and 0% of patients, and genitourinary toxicity in 18%, 18% and 4%. Lower limb grade 2 lymphoedema occurred in three patients (7%). CONCLUSION: Outcomes following FROGG guidelines and EviQ are promising, with high long-term disease control and low toxicity. Contouring guidelines require modification due to the high rate of PET-positive nodes demonstrated beyond recommended coverage.

Bone health assessment with dual energy X-ray absorptiometry in men with high-risk prostate carcinoma commencing adjuvant androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is a key component of therapy for patients with high-risk prostate carcinoma, but it may be deleterious for bone health. We sought to determine the frequency of dual energy x-ray absorptiometry (DXA) scanning in patients commencing adjuvant ADT for treatment of high-risk prostate cancer at a large integrated regional cancer centre. Material and methods: The electronic medical records (EMR) of all patients with high-risk prostate carcinoma commenced on adjuvant ADT between January 1, 2016 and December 31, 2017 at the Mid-North Coast Cancer Institute, Coffs Harbour, Australia were reviewed. Patients commenced on neoadjuvant ADT and long-term suppressive ADT for metastatic disease were excluded. The following data were obtained: socio-demographic information, prostate cancer data, ADT details and DXA results. Results: 188 men (mean age ± SD, 75.4 ± 7 years) were commenced on adjuvant ADT for a total duration (mean ± SD) of 23.4 ± 7 months. Most (n = 155/188, 82%) were commenced on leuprorelin acetate. While only 26/188 (14%) had a DXA scan performed prior to ADT, another 133 (71%) had a DXA scan at a median of 20 days (interquartile range 7-98), later. Of the 159 men with DXA readings, 76 (48%) were osteopaenic and 38 (24%) were osteoporotic by DXA criteria. Conclusion: A high level (85%) of DXA scanning in men commencing ADT for prostate cancer can be achieved at a regional centre. The high prevalence (72%) of low bone mass in our unselected cohort underscores the importance of routine DXA scanning to guide bone health management during ADT.

An Unusual Case of Lorlatinib-Induced Pneumonitis: A Case Report.

The discovery of tyrosine kinase oncogenic driver mutations, including anaplastic lymphoma kinase (ALK), has changed the face of non-small cell lung cancer (NSCLC) treatment. Whilst the development of tyrosine kinase inhibitors has improved survival, with their increasing use, it is important to be aware of the risks of rare yet serious adverse events, such as drug-induced pulmonary toxicity. Whilst little is known in regard to drug-induced pneumonitis in the setting of ALK inhibitors, such reactions carry a high morbidity and mortality rate, impacting greatly upon options for further treatment and management. We describe the case of a 73-year-old female with metastatic ALK-positive NSCLC who developed subacute dyspnoea 3 weeks after commencing lorlatinib. She was diagnosed with drug-induced pneumonitis, from which she recovered clinically following the cessation of her targeted therapy. Pneumonitis related to lorlatinib is a rare pulmonary toxicity, and early recognition and intervention is critical to reduce the associated risks of respiratory failure and death.

Prognostic Value of the Neutrophil-Lymphocyte Ratio in Triple Negative Breast Cancer Patients.

OBJECTIVE: To assess the prognostic value of the neutrophil-lymphocyte ratio (NLR) in a cohort of triple-negative breast cancer patients (TNBC) treated in a regional cancer center. METHODS: The electronic medical records of 214 consecutive patients treated with surgery, chemotherapy, and radiotherapy between 2006 and 2016 were reviewed. The prognostic significance of the NLR for disease-free survival (DFS) and overall survival (OS) was examined in relation to clinical and treatment-related factors. Overall survival and DFS were assessed using the Kaplan-Meier method; Cox semi-parametric regression modelling was used for multivariate analysis. RESULTS: Ninety patients were eligible; median follow-up was 45.6 months (range, 6-105 months). The 3-year OS rate was 77.9% and the 5-year OS rate 61.7%. Patients with an NLR of ≤1.7 had significantly better DFS (P=0.029) than patients with an NLR>1.7; OS approached statistical significance (P=0.055). When treatment-related factors - significant on univariate analysis - were entered into the multivariate model, only nodal status N2/N3 remained as significant for DFS (P=0.0078) and advanced T-stage (T3, T4) significant for OS (P=0.014). CONCLUSION: While NLR is associated with survival in TNBC patients on univariate analysis, the prognostic value of NLR is likely due to its association with other clinicopathological factors.

Evaluation of apical clips placed during axillary dissection demonstrates potential under-coverage of axillary radiation therapy target volumes during breast cancer regional nodal irradiation.

INTRODUCTION: Evidence-based Australian guidelines (eviQ) recommend adjuvant supraclavicular fossa irradiation after axillary lymph node dissection (ALND) in node-positive breast cancer patients. Disparity between surgically determined versus computed tomography (CT) determined nodal volumes may result in discontiguous nodal volumes and untreated nodal tissue. We examine the extent of untreated nodal tissue in women with breast cancer post-level II or III ALND and adjuvant radiation therapy (RT) using ESTRO contouring guidelines. METHODS: Female breast cancer patients who underwent level II and III ALND with apical clip placement from 2016 to 2020 and CT simulated in supine position were included. CT-defined axillary level II-IV volumes were contoured using ESTRO guidelines. The distance between the apical clip and RT nodal volumes was measured to indicate extent of untreated tissue. RESULTS: Of 34 eligible patients treated by 7 surgeons, 76% had level II ALND and 24% level III ALND. Only 5.9% of clips entirely encompassed the corresponding RT nodal volumes. 55.9% of clips fell within and 44.1% fell inferolaterally outside the corresponding RT nodal volumes. A median 3.6 cm (range 0-7.5 cm) of undissected nodal tissue would not be included within standard RT target volumes following eviQ recommendations. CONCLUSION: There is a disparity between surgically determined versus CT determined axillary nodal volumes, leading to discontiguous nodal volumes and untreated axillary nodal tissue, despite following standard radiation contouring guidelines. Intraoperatively placed apical axillary clips may assist radiation oncologists to accurately delineate undissected nodal tissues at risk.

Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up.

Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.

Machine learning applications in radiation oncology.

Machine learning technology has a growing impact on radiation oncology with an increasing presence in research and industry. The prevalence of diverse data including 3D imaging and the 3D radiation dose delivery presents potential for future automation and scope for treatment improvements for cancer patients. Harnessing this potential requires standardization of tools and data, and focused collaboration between fields of expertise. The rapid advancement of radiation oncology treatment technologies presents opportunities for machine learning integration with investments targeted towards data quality, data extraction, software, and engagement with clinical expertise. In this review, we provide an overview of machine learning concepts before reviewing advances in applying machine learning to radiation oncology and integrating these techniques into the radiation oncology workflows. Several key areas are outlined in the radiation oncology workflow where machine learning has been applied and where it can have a significant impact in terms of efficiency, consistency in treatment and overall treatment outcomes. This review highlights that machine learning has key early applications in radiation oncology due to the repetitive nature of many tasks that also currently have human review. Standardized data management of routinely collected imaging and radiation dose data are also highlighted as enabling engagement in research utilizing machine learning and the ability integrate these technologies into clinical workflow to benefit patients. Physicists need to be part of the conversation to facilitate this technical integration.

Implementation of the Australian Computer-Assisted Theragnostics (AusCAT) network for radiation oncology data extraction, reporting and distributed learning.

INTRODUCTION: There is significant potential to analyse and model routinely collected data for radiotherapy patients to provide evidence to support clinical decisions, particularly where clinical trials evidence is limited or non-existent. However, in practice there are administrative, ethical, technical, logistical and legislative barriers to having coordinated data analysis platforms across radiation oncology centres. METHODS: A distributed learning network of computer systems is presented, with software tools to extract and report on oncology data and to enable statistical model development. A distributed or federated learning approach keeps data in the local centre, but models are developed from the entire cohort. RESULTS: The feasibility of this approach is demonstrated across six Australian oncology centres, using routinely collected lung cancer data from oncology information systems. The infrastructure was used to validate and develop machine learning for model-based clinical decision support and for one centre to assess patient eligibility criteria for two major lung cancer radiotherapy clinical trials (RTOG-9410, RTOG-0617). External validation of a 2-year overall survival model for non-small cell lung cancer (NSCLC) gave an AUC of 0.65 and C-index of 0.62 across the network. For one centre, 65% of Stage III NSCLC patients did not meet eligibility criteria for either of the two practice-changing clinical trials, and these patients had poorer survival than eligible patients (10.6 m vs. 15.8 m, P = 0.024). CONCLUSION: Population-based studies on routine data are possible using a distributed learning approach. This has the potential for decision support models for patients for whom supporting clinical trial evidence is not applicable.

Assessing ISUP prostate cancer grade groups in patients treated with definitive dose escalated external beam radiation.

PURPOSE: The five grade group system has been validated for men treated with radical prostatectomy. However, the prognostic value for men treated with radiation therapy is uncertain, with prior studies utilising old techniques and doses. We aimed to validate the International Society of Urological Pathology (ISUP) groupings for men treated with contemporary radiation therapy. METHODS: Men with localised prostate cancer treated with image-guided, dose-escalated (≥78 Gy) external beam radiation were identified across four institutions. Primary outcome was time to biochemical failure. Harrell's C index assessed performance of the ISUP system against other grading stratifications. RESULTS: 2205 men were included, withmedian follow-up of 5.6 years. Seven-year actuarial rates of biochemical failure for grade groups 1-5 were 9.3%, 10.4%, 13.2%, 12.4% and 23.4%. On multivariate analysis, hazard ratios for biochemical failure were1.19, 1.00, 1.10, 1.05 and 2.10 for grade groups 1-5, relative to 2. P values were only significant for grade group 5. Harrell's C index favoured an alternative three group model (comprising Gleason scores [6 and 3 + 4 = 7] vs [4 + 3 = 7 and 8] vs [9 and 10]) over ISUP grade groups. CONCLUSIONS: The ISUP grade groups were not validated in a contemporary cohort treated with dose-escalated, image-guided radiation therapy. Grade groups 1-4 were not statistically different from each other; however, grade group 5 had a significantly worse prognosis. We identified a new three group model that better predicted biochemical outcomes. Further work is requiredto validate optimal groupings for modern radiation therapy and investigate the contrasting prognostic capability of grade groups in surgical and radiation therapy patients.

Survival outcomes for breast cancer patients who decline recommended treatment: a propensity score-matched analysis.

BACKGROUND: For patients with breast cancer who decline recommended treatments, available data examining survival outcomes are sparse. We compared overall survival and relapse-free survival outcomes between patients with breast cancer who declined recommended primary treatments and those who received recommended primary treatments. METHODS: Using data from the BreastSurgANZ Quality Audit database, a retrospective cohort study was performed for patients diagnosed with breast carcinoma (stage 0-IV) between 2001 and 2014 who were treated in our integrated cancer centre. A propensity score-matched analysis was performed to compare overall survival and relapse-free survival between patients who either declined or received the standard recommended treatment. RESULTS: A total of 56/912 (6.1%) patients declined one or more recommended therapies. Five-year overall survival for those who declined or received treatment as recommended was 81.8% versus 88.9% (P = 0.17), respectively. Ten-year survival was 61.3% versus 67.8% (P = 0.22), respectively. For patients who declined treatments, 5-year relapse-free survival was 72.4%, compared to 87.4% for those who received them (P = 0.005). Ten-year relapse-free survival was 61.0% versus 80.6% (P = 0.002), respectively. On adjusted Cox regression analysis, treatment refusal was associated with poorer relapse-free survival (adjusted hazard ratio 2.76 (95% confidence interval 1.52-5.00), P < 0.001). CONCLUSION: In conclusion, patients who declined recommended treatment for breast cancer had poorer relapse-free survival compared to those who received them. These data may help clinicians assist patients with breast cancer in their decision-making.

Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia.

BACKGROUND: Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014-2018. METHODS: Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. RESULTS: There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014-2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. CONCLUSIONS: Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

Patterns of relapse following hippocampal avoidance prophylactic cranial irradiation for small cell lung carcinoma.

BACKGROUND: Hippocampal avoidance techniques are an evolving standard of care for patients undergoing cranial irradiation. Our aim was to assess the oncological outcomes and patterns of failure following hippocampal avoidance prophylactic cranial irradiation (HA-PCI) as a standard of care in unselected patients with both limited and extensive stage small cell lung carcinoma. MATERIALS AND METHODS: Consecutive patients with small cell lung carcinoma with a complete (limited stage) or good partial (extensive stage) response following chemotherapy were eligible to receive HA-PCI, with a total dose of 25 Gray in 10 fractions. All patients had a negative baseline MRI brain scan with gadolinium prior to HA-PCI. Patients had baseline and follow up Common Toxicity Criteria Adverse Event assessments. Following completion of HA-PCI, all patients had three-monthly MRI brain scans with gadolinium until confirmation of intracranial relapse, as well as three-monthly CT of the chest, abdomen and pelvis. Overall and progression-free survival were calculated using the Kaplan-Meier method. RESULTS: A total of 17 consecutive patients, 9 men and 8 women, with a mean age of 70 years received HA-PCI between May 2016 and June 2020 after completion of their initial chemotherapy. There were no Grade 4 or greater adverse events. No patient had an isolated hippocampal avoidance zone relapse alone; three of 17 patients had multifocal relapses that included the hippocampal avoidance zone. CONCLUSION: In our series, there were no hippocampal only relapses and we conclude that HA-PCI is a safe alternative to standard PCI in the setting of small cell lung cancer.

Long-term outcomes of patients with conserved breast cancer treated with adjuvant hypofractionated prone breast intensity-modulated radiation therapy.

INTRODUCTION: New techniques for adjuvant radiation therapy after breast conservation include prone positioning, hypofractionation and intensity-modulated radiation therapy (IMRT). Long-term evaluations of this combination are lacking, and we report our own experience. METHODS: Patients with invasive breast cancer followed for a minimum 36 months post-IMRT were eligible. Dose used was 40 Gray in 15 fractions over 3 weeks to the whole breast via forward-planned prone, whole breast IMRT. A 10 Gy in 5 fraction supine boost was offered. RESULTS: Between January 2012 and January 2020, 2199 patients had breast conservation and adjuvant radiation: 489 received hypofractionated prone breast IMRT, with 155 eligible for our evaluation. Median follow-up was 52 months. Median age was 62 (range 36-80), 78.7% were T1, 20.6% were T2, and 12.3% were node-positive. Grade was 1 in 26.5%, 2 in 43.9% and 3 in 29.7%; 87.1% were oestrogen receptor positive, 3.2% were HER2 positive, and 11.0% were triple negative. 58.6% received a boost, 74.8% endocrine therapy and 32.3% chemotherapy. No patient developed local recurrence. One regional recurrence was successfully salvaged. Six patients (3.9%) developed metastases, and 1.9% died. Five-year actuarial local recurrence-free, regional recurrence-free and breast cancer-specific survival rates were 100.0%, 98.2% and 94.8%. Late grade 1 and 2 breast pain occurred in 20.0% and 1.3% of patients. Only 11.0% had new pain compared to pre-radiation. No patient developed radiation-induced pneumonitis, pulmonary fibrosis, rib fracture or cardiac toxicity. All patients scored cosmesis as 'good' or better. CONCLUSION: Adjuvant hypofractionated prone breast IMRT has excellent locoregional control and minimal toxicity.

Effect of Clinical and Treatment Factors on Survival Outcomes of Triple Negative Breast Cancer Patients.

PURPOSE: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors. PATIENTS AND METHODS: The electronic records of 214 consecutive TNBC patients treated with surgery followed by radiotherapy at the Mid North Coast Cancer Institute between 2006 and 2016 were reviewed. Overall survival and DFS times were analyzed using the Kaplan-Meier method; multivariate Cox proportional hazard regression modelling was used to assess the significance of prognostic factors. RESULTS: The majority of tumors were T1 (51.9%), followed by T2 (39.2%) and T3 (6.1%). For the whole group, mean DFS was 106.4 (SD 48.7) months; OS 109.4 (SD 52.1) months. Radiotherapy technique, fractionation protocol and laterality were not significant factors for DFS or OS (p>0.05). However, compared to breast conservation, mastectomy was associated with poorer DFS (mean 114.2 vs 65.2 months; p<0.0001) and poorer OS (mean 115.5 vs 80.5 months; p=0.0015). The mastectomy group had fewer patients with tumor size T1 (p=0.001) and higher proportions of T3 (p=0.001) and T4 (p=0.02). On multivariate analysis, tumor size T3/T4 and nodal status N2/N3 were significant factors for reduced DFS (p=0.023 and p=0.0003 respectively). Tumor size T3/T4 was the only significant prognostic factor for reduced OS (p=0.019). CONCLUSION: Advanced disease exhibited by tumor size > 5cm and positive nodal status is associated with poorer DFS in TNBC patients. Radiotherapy technique or fractionation protocol were not associated with differences in DFS or OS in our patient cohort.

Choosing between conventional and hypofractionated prostate cancer radiation therapy: Results from a study of shared decision-making.

AIM: To evaluate patient choice of prostate cancer radiotherapy fractionation, using a decision aid. BACKGROUND: Recent ASTRO guidelines recommend patients with localised prostate cancer be offered moderately hypofractionated radiation therapy after discussing increased acute toxicity and uncertainty of long-term results compared to conventional fractionation. MATERIALS AND METHODS: A decision aid was designed to outline the benefits and potential downsides of conventionally and moderately hypofractionated radiation therapy. The aid incorporated the ASTRO guideline to outline risks and benefits. RESULTS: In all, 124 patients with localised prostate cancer were seen from June-December 2018. Median age was 72 (range 50-90), 49.6 % were intermediate risk (50.4 % high risk). All except three patients made a choice using the aid; the three undecided patients were hypofractionated. In all, 33.9 % of patients chose hypofractionation: falling to 25.3 % for patients under 75 years, 24.3 % for patients living within 30 miles of the cancer centre, and 14.3 % for patients with baseline gastrointestinal symptoms. On multivariate analysis, younger age, proximity to the centre, and having baseline gastrointestinal symptoms significantly predicted for choosing conventional fractionation. Insurance status, attending clinician, baseline genitourinary symptoms, work/carer status, ECOG, cancer risk group and driving status did not impact choice. Reasons for choosing conventional fractionation were certainty of long-term results (84 %) and lower acute bowel toxicity (51 %). CONCLUSIONS: Most patients declined the convenience of moderate hypofractionation due to potentially increased acute toxicity, and the uncertainty of long-term outcomes. We advocate that no patient should be offered hypofractionation without a thorough discussion of uncertainty and acute toxicity.

Mathematical oncology and it's application in non melanoma skin cancer - A primer for radiation oncology professionals.

Cancers of the skin (the majority of which are basal and squamous cell skin carcinomas, but also include the rarer Merkel cell carcinoma) are overwhelmingly the most common of all types of cancer. Most of these are treated surgically, with radiation reserved for those patients with high risk features or anatomical locations less suitable for surgery. Given the high incidence of both basal and squamous cell carcinomas, as well as the relatively poor outcome for Merkel cell carcinoma, it is useful to investigate the role of other disciplines regarding their diagnosis, staging and treatment. Mathematical modelling is one such area of investigation. The use of mathematical modelling is a relatively recent addition to the armamentarium of cancer treatment. It has long been recognised that tumour growth and treatment response is a complex, non-linear biological phenomenon with many mechanisms yet to be understood. Despite decades of research, including clinical, population and basic science approaches, we continue to be challenged by the complexity, heterogeneity and adaptability of tumours, both in individual patients in the oncology clinic and across wider patient populations. Prospective clinical trials predominantly focus on average outcome, with little understanding as to why individual patients may or may not respond. The use of mathematical models may lead to a greater understanding of tumour initiation, growth dynamics and treatment response.

Collaborative implementation of stereotactic ablative body radiotherapy: A model for the safe implementation of complex radiotherapy techniques in Australia.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) for lung cancer is a modality of treatment that has improved outcomes for lung cancer patients. However, radiotherapy for lung cancer is underutilized and fewer than half of elderly patients with non-small cell lung cancer (NSCLC) receive active treatment. The purpose of this study is to report on a collaboration in implementing an NSCLC SABR (stereotactic ablative body radiation) program safely, efficiently, and uniformly across several centers, including regional sites. The first aim of this paper is to detail the collaboration and implementation that started in 2013 and is ongoing. The second aim of this paper is to document early toxicities and quality of life outcomes. METHOD: A tripartite approach was used to develop the protocol and networks required for the implementation of SABR across multiple sites in NSW. Departments starting the programmes were supported and physics credentialing with central site submission was required before commencing the treatment. Additional ongoing support was available via an email discussion group involving all members of the collaboration. RESULTS: Between July 22, 2013 and February 22, 2016, 41 patients were enrolled with 34 patients in active follow up. The toxicity profile so far is similar to those of published studies with no appreciable effect on quality of life outcomes. CONCLUSION: The collaboration formed an effective framework in facilitating the implementation of SABR across several sites in NSW and could be used as a model for the safe and uniform implementation of new technologies in Australia.