Survival outcomes for women with a solitary extracranial metastasis from breast cancer.

BACKGROUND: Aggressive metastasis directed treatment of extracranial oligometastatic breast cancer with the aim of increasing disease-free survival has emerged as a new potential treatment paradigm, however there is currently a lack of data to assist in identifying the subset of patients who will potentially benefit most. This single-institute retrospective cohort study aimed to evaluate survival outcomes for patients with a solitary extracranial metastasis from breast cancer and to assess for significant prognostic factors. METHODS AND MATERIALS: Medical records of 70 female breast cancer patients with a solitary extracranial metastasis actively managed at the Peter MacCallum Cancer Centre (PMCC) Melbourne Campus between 2000 and 2019 were reviewed. Kaplan-Meier curves were used to estimate overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS). RESULTS: Median follow-up period was 9.4 years. The study included 40 hormone receptor positive/HER2 negative (HR+HER2-), 14 hormone receptor positive/HER2 positive (HR+HER2+), 3 hormone receptor negative/HER2 positive (HR-HER2+), 9 triple negative (TNBC) and 4 unclassified breast cancer patients. 5-year OS rate for all patients was 46%, LPFS rate was 56% and DPFS was 20%. Tumour receptor group had a statistically significant association with OS and DPFS rates. TNBC patients had significantly poorer OS and DPFS rates in comparison to HR+HER2-patients. CONCLUSION: Among patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

PCP Pincer Complexes of Titanium in the +3 and +4 Oxidation States.

Ti(IV) and Ti(III) complexes using the tBuPCP ligand have been synthesized (tBuPCP = C6H3-2,6-(CH2PtBu2)2). The [tBuPCP]Li synthon can be reacted with TiCl4(THF)2 to form (tBuPCP)TiCl3 (1) in limited yields due to significant reduction of the titanium synthon. The Ti(III) complex (tBuPCP)TiCl2 (2) has been further characterized. This can have half an equivalent of halide abstracted to form [{(tBuPCP)TiCl}2{µ-Cl}][B(C6F5)4] (3) and can also be methylated, forming (tBuPCP)TiMe2 (4). All the Ti(III) complexes have been characterized using EPR and X-ray crystallography, giving insight into their electronic structures, which are further supported by DFT calculations.

The HI-FIVE Trial: A Prospective Trial Using 4-Dimensional 68Ga Ventilation-Perfusion Positron Emission Tomography-Computed Tomography for Functional Lung Avoidance in Locally Advanced Non-small Cell Lung Cancer.

PURPOSE: Functional lung avoidance (FLA) radiation therapy aims to spare regions of functional lung to reduce toxicity. We report the results of the first prospective trial of FLA using 4-dimensional gallium 68 ventilation-perfusion positron emission tomography-computed tomography (68Ga-4D-V/Q PET/CT). METHODS AND MATERIALS: Inclusion criteria required a diagnosis of stage III non-small cell lung cancer and the ability to undergo radical-intent chemoradiation therapy. Functional volumes were generated using planning 68Ga-4D-V/Q PET/CT. These volumes were used to generate a clinical FLA plan to 60 Gy in 30 fractions. The primary tumor was boosted to 69 Gy. A comparison anatomic plan was generated for each patient. Feasibility was met if FLA plans (compared with anatomic plans) allowed (1) a reduction in functional mean lung dose of ≥2% and a reduction in the functional lung volume receiving 20 Gy (fV20Gy) of ≥4%, and (2) a mean heart dose ≤30 Gy and relative heart volume receiving 50 Gy of <25%. RESULTS: In total, 19 patients were recruited; 1 withdrew consent. Eighteen patients underwent chemoradiation with FLA. Of the 18 patients, 15 met criteria for feasibility. All patients completed the entire course of chemoradiation therapy. Using FLA resulted in an average reduction of the functional mean lung dose of 12.4% (SD, ±12.8%) and a mean relative reduction of the fV20Gy of 22.9% (SD, ±11.9%). At 12 months, Kaplan-Meier estimates for overall survival were 83% (95% CI, 56%-94%) and estimates for progression-free survival were 50% (95% CI, 26%-70%). Quality-of-life scores were stable across all time points. CONCLUSIONS: Using 68Ga-4D-V/Q PET/CT to image and avoid functional lung is feasible.

Impact of Medical Operability and Total Metastatic Ablation on Outcomes After SABR for Oligometastases.

PURPOSE: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites. METHODS AND MATERIALS: Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy. RESULTS: A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED10]≥60 Gy. Cumulative incidence at 5 years of local-only failure was 6%, local and distant 2%, and distant-only 58%. The 3- and 5-year OS [95% confidence intervals {CIs}] were 68% [62-73] and 54% [47-61], and PFS was 20% [15-25] and 14% [10-20]. The 3- and 5-year freedom from systemic therapy [95% CIs] were 40% [34-46] and 31% [24-37], respectively. Seventy-six patients were inoperable and 325 were operable. Operability status was not prognostic for OS (adjusted hazard ratio [HR], 1.0; 95% CI, 0.6-1.7; P = .9) or for PFS (adjusted HR, 1.1; 95% CI, 0.8-1.6; P = .5). Total metastatic ablation was prognostic for OS (adjusted HR, 0.8; 95% CI, 0.4-0.9; P = .032) and for PFS (adjusted HR, 0.6; 95% CI, 0.4-0.8; P = .003). CONCLUSIONS: Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible.

Sigma/pi Bonding Preferences of Solvated Alkali-Metal Cations to Ditopic Arylmethyl Anions.

Arylmethyl anions allow alkali-metals to bind in a σ-fashion to the lateral carbanionic centre or a π-fashion to the aryl ring or in between these extremities, with the trend towards π bonding increasing on descending group 1. Here we review known alkali metal structures of diphenylmethane, fluorene, 2-benzylpyridine and 4-benzylpyridine. Next, we synthesise Li, Na, K monomers of these diarylmethyls using polydentate donors PMDETA or Me6 TREN to remove competing oligomerizing interactions, studying the effect that two aromatic rings has on negative charge (de)localisation via NMR, X-ray crystallographic and DFT studies. Diphenylmethyl and fluorenyl anions maintain C(H)-M interactions regardless of alkali-metal, although the adjacent arene carbons engage in interactions with larger alkali-metals. Introducing a nitrogen atom into the ring (at the 2- or 4-position) encourages relocalisation of negative charge away from the deprotonated carbon and onto nitrogen. Phenyl(2-pyridyl)methyl moves from an enamide formation at one extremity (lithium) to an aza-allyl formation at the other extremity (potassium), while C- or N-coordination modes become energetically viable for Na and K phenyl(4-pyridyl)methyl complexes.

Increasing use of post-mastectomy hypofractionated radiation therapy for breast cancer in Victoria.

INTRODUCTION: The aim of this study was to evaluate the use of post-mastectomy hypofractionationed radiation therapy (HFRT) for breast cancer in Victoria, Australia. METHODS: This is a population-based cohort of women with breast cancer who received post-mastectomy RT to the chest wall with or without nodal irradiation between 2012 and 2017. HFRT was defined as <25 fractions of RT. Data were captured in the Victorian Radiotherapy Minimum Dataset (VRMDS). The changing pattern of HFRT use was evaluated using the Cochran-Armitage test. Patient-, treatment- and institutional-related factors associated with HFRT use were evaluated using multivariable logistic regression. RESULTS: Two thousand and twenty-one women were included in this study, of which 238 (12%) received HFRT. This increased from 8% in 2012 to 18% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (26% in women above 70 years vs 6% in women under 50 years; P < 0.001). Women who did not have nodal irradiation were more likely to have HFRT than those who did (18% vs 9% respectively; P < 0.001). In multivariate analyses, the progressive increase in HFRT use over time remained statistically significant - women treated in 2017 were four times more likely to receive HFRT than those treated in 2012 (95% CI = 2.1-7.7; P < 0.001). Other factors independently associated with increased likelihood of HFRT use included increasing age at RT, and lack of nodal irradiation. CONCLUSION: In this first Australian study evaluating the use of post-mastectomy HFRT, we observed increasing HFRT use in Victoria over time. We anticipate this rising trend will continue in the coming years.

Reversible Dissociation of a Dialumene*.

Dialumenes are neutral AlI compounds with Al=Al multiple bonds. We report the isolation of an amidophosphine-supported dialumene. Our X-ray crystallographic, spectroscopic, and computational DFT analyses reveal a long and extreme trans-bent Al=Al bond with a low dissociation energy and bond order. In solution, the dialumene can dissociate into monomeric AlI species. Reactivity studies reveal two modes of reaction: as dialumene or as aluminyl monomers.

Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases.

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.

Single-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer.

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy. ETHICS AND DISSEMINATION: This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications. TRIALS REGISTRATION NUMBER: NCT03569072; Pre-results.

68 Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer.

AIM: To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. METHODS: All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded. Results of conventional imaging (bone scan, CT and multiparametric magnetic resonance imaging [MRI]) were reviewed and included. RESULTS: One hundred nine men underwent staging PSMA-PET/CT between May 2015 and June 2017; all patients had national comprehensive cancer network (NCCN) intermediate or high-risk prostate cancer and 87% had Gleason score (GS) 4 + 3 or higher. There was positive uptake corresponding to the primary in 108, equivocal in one. All patients with image detected nodal or bony lesions had GS 4 + 3 or more disease. Compared to conventional imaging with bone scan, CT and multiparametric MRI, PSMA-PET/CT upstaged an additional 7 patients (6.4%) from M0 to M1, 16 from N0M0 to N1M0 (14.7%) and downstaged 3 (2.8%) from M1 to M0 disease. CONCLUSION: PSMA-PET/CT identified the primary in 99% of patients, and altered staging in 21% of men with intermediate or high-risk prostate cancer referred for definitive EBRT compared to CT, bone scan and multiparametric MRI. Following this audit, we recommend the routine use of PSMA-PET/CT prior to EBRT in this patient group.

Delineating sites of failure following post-prostatectomy radiation treatment using 68Ga-PSMA-PET.

PURPOSE: To identify sites of failure with 68Ga-PSMA-PET (PSMA-PET) imaging in patients who have Biochemical Failure (BF) following post-prostatectomy radiotherapy. MATERIAL AND METHODS: Between June 2006 and January 2016, 409 men received post prostatectomy intensity modulated radiation treatment (IMRT) with protocolised planning. 310 patients received radiation treatment (RT) to the Prostate Fossa (PF) alone and 99 patients received RT to PF and pelvic lymphatics (PF + LN) usually in combination with androgen deprivation (AD) therapy. Any failure not detected on conventional imaging was delineated with PSMA-PET scanning. Sites of failure were characterised as in-field (PF ±â€¯LN), or out of field (nodal alone, distant metastatic alone (visceral or bone) or multi-site failure). Nodal failure was further divided into pelvic failure and/or distant failure. RESULTS: 119 men developed BF, defined as a PSA rise of >0.2 or greater, above post-RT nadir. Freedom from BF was 71% in the PF group and 70% in the PF + LN group, with median follow up of 52 and 44 months respectively. AD was used concomitantly in 13% of the PF group and 92% of the PF + LN group. 81 patients with BF (68%) had PSMA-PET imaging performed as per study intent, 67 (80%) of whom had PSMA avid disease identified. PSMA-PET delineated in-field failure occurred in 2/50 (4%) of the PF group and 1/17 (6%) in the PF + LN group. Nodal failure alone was 33/50 (66%) for the PF group vs 7/17 (41%) for the PF + LN group. For the nodal only failure patients, 18/33 (55%) had pelvic-only nodal failure in the PF group compared to 1/7 (14%) in the PF + LN group (p = 0.03). 16 (32%) of the PSMA avid failures in the PF group would have been encompassed by standard pelvic lymphatic radiotherapy volumes. CONCLUSION: Post-prostatectomy radiation treatment resulted in excellent in-field control rates. Isolated pelvic nodal failure was rare in those receiving radiotherapy to the prostatic fossa and pelvic nodes but accounted for one third of failures in those receiving PF alone treatment.

Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Detected via Prostate-specific Membrane Antigen Positron Emission Tomography.

BACKGROUND: The management of oligometastatic prostate cancer (PCa) remains controversial, especially following the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging. OBJECTIVE: To assess whether stereotactic body radiotherapy (SBRT) provides a potential for cure in a selected group of patients with oligometastatic PCa in the PSMA-PET era. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, single-centre study of patients with oligometastatic PCa undergoing SBRT from November 2014 to July 2016. We included patients with relapsed PCa receiving SBRT with PSMA-PET-confirmed oligometastases (n=1-3) confined to lymph nodes (LNs) or bone without androgen deprivation therapy. SBRT schedules included 20Gy/1# or 24Gy/2# to bone metastases, and 50Gy/5# or 30Gy/3# to LNs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical failure (BF) defined as a prostate-specific antigen (PSA) level of nadir + 0.2 ng/ml following SBRT. RESULTS AND LIMITATIONS: Fifty-seven patients were eligible, of whom 50 (88%) had undergone radical prostatectomy. The median time from definitive treatment to SBRT was 5.6 yr. A total of 73 lesions were treated: 44 patients had one metastasis, while 13 had two or three. Thirty-seven patients (65%) had LN-only disease, while 18 (31%) had bone-only metastasis. Median follow up was 16 mo. The median biochemical disease-free survival (bDFS) for the cohort was 11 mo, with 31.9% bDFS at 15 mo. All patients with BF (n=43) underwent a repeat PSMA-PET scan, which revealed no in-field failures. Median bDFS was not affected by prostate-specific antigen (PSA) at diagnosis, Gleason score, time from diagnosis to SBRT, site (bone vs LN), PSA doubling time before SBRT, or number of metastases. Failures were somewhat less common in patients with low PSA before SBRT. Toxicity was rare: no patients developed grade ≥2 late toxicity. CONCLUSIONS: SBRT delivered very high rates of local control with minimal toxicity. However, distant recurrences occurred in most patients by 15 mo and did not appear to be predicted by known prognostic factors. PATIENT SUMMARY: In this report, we looked at outcomes after the use of stereotactic body radiotherapy for patients with prostate cancer spread to one to three lymph nodes or bones as detected by positron emission tomography scans. We demonstrated high rates of control of the treated lesions with low toxicity, but by 15 mo more than two-thirds of patients had developed recurrent cancer outside the treated area.

15-Year Experience of 18F-FDG PET Imaging in Response Assessment and Restaging After Definitive Treatment of Merkel Cell Carcinoma.

UNLABELLED: The objective of this study was to evaluate the utility of (18)F-FDG PET in restaging and response assessment of patients who underwent definitive treatment for Merkel cell carcinoma (MCC). METHODS: A retrospective review of patients undergoing (18)F-FDG PET imaging for MCC between January 1997 and October 2010 at the Peter MacCallum Cancer Centre with follow-up until February 2015 was performed. Data analysis was performed on patients who were treated definitively and underwent post-treatment PET imaging performed either as a restaging scan for ongoing monitoring, suspicion of recurrence, or assessment for suitability of salvage treatment or as response assessment within 1-6 mo of treatment. Management plans were recorded prospectively before (18)F-FDG PET imaging and compared with post-imaging management to assess the impact of the study as per our previously defined categories: high if the primary treatment modality or intent was changed and medium if the radiotherapy technique or dose was altered. In total, 62 patients were included in the analysis. Thirty-six patients underwent 53 restaging scans, and 37 patients underwent a response-assessment scan. The median follow-up of patients in the restaging group was 5.3 y (95% confidence interval [CI], 4.6-9.4), and it was 5.7 y (95% CI, 4.3-10.8) in the response-assessment group. RESULTS: Restaging (18)F-FDG PET scans had a high impact in 24 of 53 cases (45%) and a medium impact in 6 of 53 cases (11%). In the response-assessment group, 24 of 37 patients had a complete metabolic response (CMR). Patients without a CMR had a 15% 1-y overall survival (95% CI, 0.04-0.55). Those with a CMR had an 88% 2-y overall survival (95% CI, 0.75-1.00) and a 68% 5-y overall survival (95% CI, 0.49-0.95). The presence of a CMR (P < 0.001) and nodal involvement (P = 0.016) were statistically significant prognostic factors for overall survival. CONCLUSION: (18)F-FDG PET imaging had a high impact on restaging after definitive treatment in patients with MCC. Metabolic response was significantly associated with overall survival. (18)F-FDG PET may play an important role in ongoing post-treatment management of MCC.

18F-FDG PET provides high-impact and powerful prognostic stratification in the staging of Merkel cell carcinoma: a 15-year institutional experience.

UNLABELLED: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited evidence on the role of PET scanning. The primary aim of this study was to assess the impact of (18)F-FDG PET in the staging and management of MCC. METHODS: A single-institution review using clinical outcome data collected until February 2012 was performed of patients with MCC who underwent staging PET scanning between January 1997 and October 2010. Management plans were recorded prospectively at the time of the PET request, and follow-up outcomes were recorded retrospectively. The clinical impact of PET was scored using our previously published criteria: "high" if the PET scan changed the primary treatment modality or intent; "medium" if the treatment modality was unchanged but the radiation therapy technique or dose was altered. The primary objective was to test the hypothesis that the true proportion of patients who have a high- or medium-impact scan would be greater than 25%. RESULTS: The median follow-up of 102 consecutive patients was 4.8 y. The results of staging PET had an impact on patient management in 37% of patients (P < 0.003). High- and medium-impact scans were recorded for 22% and 15% of patients, respectively. PET staging results differed from conventional staging results in 22% of patients, with PET upstaging 17% and downstaging 5%. The 3- and 5-y overall survival was 60% (95% confidence interval, 50%-71%) and 51% (95% confidence interval, 41%-64%), respectively. In stratification by PET-defined stage, the 5-y overall survival was 67% for patients with stage I/II disease but only 31% for patients with stage III disease (log-rank P < 0.001). The 5-y cumulative incidence of locoregional failure, distant failure, and death was 16.6%, 22.3% and 14.3%, respectively. On multivariate analysis, only PET stage (P < 0.001) and primary treatment modality (P = 0.050) were significantly associated with overall survival. The primary treatment modality was not associated with progression-free survival when stratification was by tumor stage. CONCLUSION: The use of (18)F-FDG PET scans had a great impact on patients and may play an important role in the prognostic stratification and treatment of this disease.

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.