Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

INTRODUCTION: Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. METHODS: All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. RESULTS: In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. CONCLUSION: Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

INTRODUCTION: The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. METHODS: At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. RESULTS: Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. CONCLUSION: The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

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.

PSMA-PET guided dose-escalated volumetric arc therapy (VMAT) for newly diagnosed lymph node positive prostate cancer: Efficacy and toxicity outcomes at two years.

PURPOSE/OBJECTIVES: There are no published reports of prostate specific membrane antigen (PSMA) positron emission tomography (PET) guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) in newly diagnosed lymph node (LN) positive prostate cancer. We report early toxicity and efficacy outcomes with this approach. MATERIALS/METHODS: Patients with newly diagnosed high-risk prostate cancer were staged using PSMA PET, computed tomography (CT) and bone scans. Patients with LN positive-only metastases were offered curative therapy using 3 months androgen deprivation therapy (ADT) followed by DE-IMRT (using volumetric arc therapy), and 3 years adjuvant ADT. All patients had fiducial marker insertion, with privately insured patients having spacer hydrogel insertion. PET and prostate magnetic resonance imaging were fused with the planning CT. We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45Fx to bilateral elective pelvic LNs. RESULTS: In all, 46 patients were treated, with 83% Gleason 8-10, 67% T3/T4, median number of LNs 2 (range 1-6), and median PET-positive LN volume 1.14 cc (range 0.15-4.14). LNs were outside of standard contouring guidelines in 37% of patients. The mean PET-positive LN clinical target volume dose ranged from 73.3 to 85.9 Gy (median 83.6 Gy). With 24 months median follow-up, two year failure-free survival was 100%, and 2 year overall survival 95.7%. Acute grade 1 and 2 GI toxicity occurred in 48 and 11% of patients, and GU toxicity in 72 and 24%. Late grade 1, 2 and 3 GI toxicity occurred in 13, 2 and 0%, and GU toxicity 28, 13 and 4%. No toxicity was attributable to the high dose LN boost. CONCLUSIONS: PSMA PET-guided DE-IMRT up to 81 Gy to the prostate and involved LNs, and long term ADT, is a promising approach for newly diagnosed LN positive prostate cancer. LN contouring guidelines require re-evaluation in the era of PSMA PET imaging.

Influence of the way results are presented on research interpretation and medical decision making: the PRIMER collaboration randomized studies.

BACKGROUND: The manner of presentation of research results may affect how clinicians interpret research and make clinical decisions. The authors evaluate whether the use of confidence levels improve research interpretation and decision making compared with P values and 95% confidence intervals. METHODS: The 2 Presentation and Interpretation of Medical Research (PRIMER) studies were 3-arm randomized trials. PRIMER 1 presented results of 5 fictitious scenarios with P values (P), P plus 95% confidence intervals (P + CI), or P, CI, and confidence levels (P + CI + CL); PRIMER 2 compared P + CI + CL, P + CI, and P + CL. Clinicians were asked to identify the correct interpretation of scenarios in terms of statistical and clinical significance and then indicate the intended decision making in terms of treatment recommendation. RESULTS: Seventy-five and 246 clinicians participated in PRIMER 1 and PRIMER 2, respectively. In PRIMER 1, P+CI+CL was superior to P + CI and P (P < 0.05); the latter 2 arms did not differ significantly. Decision making was not significantly different between arms. In PRIMER 2, P+CI+CL resulted in better interpretation than P + CI (P = 0.03), with no difference between P + CI and P + CL. In combined analysis, the odds of correct interpretation were higher for P+CI+CL than P+CI (odds ratio = 1.73, P=0.005, 95% CI= 1.19--2.52). Decision making was better for P + CI+ CL (P = 0.03). On multivariate analysis, the P + CI+ CL arm and clinicians with statistics training, not in private practice, or participating in PRIMER 1 had better interpretation. The P + CI+ CL arm was the only factor improving decision making. CONCLUSIONS: Presenting research with a combination of P values, confidence intervals, and confidence levels leads to better interpretation and decision making by clinicians.

Efficacy of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice.

PURPOSE: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. METHODS AND MATERIALS: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. RESULTS: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p = 0.0005) and RO performance (7.6-7.9 of 8, p = 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p = 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. CONCLUSION: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

Design of an internationally accredited radiation oncology resident training program incorporating novel educational models.

PURPOSE: Our primary aim was to design a new, internationally accredited, comprehensive radiation oncology (RO) training program for Singaporean residents that satisfied the needs of stake holders and incorporated published evidence. METHODS AND MATERIALS: The evidence-based method included Medline literature review and broad-based training needs assessment. RESULTS: Literature review revealed few studies describing or evaluating RO resident training programs. Our program was designed by incorporating available published research and stakeholder views determined by the training needs assessment. The program includes novel evidence-based educational methods, including individually negotiated learning contracts, a mentor program, logbooks, task-based learning, tutorials, and formative plus summative assessments. The content and structure is consistent with most United States, United Kingdom, and Royal Australian and New Zealand College of Radiologist (RANZCR) guidelines, with resident evaluation via RANZCR examinations. The RANZCR accredited the program in January 2002. CONCLUSION: We recommend institutions or countries introducing or revising RO resident training programs use an evidence-based approach, addressing the needs of stake holders (determined by a comprehensive training needs assessment) and incorporating published research. Novel educational methods may be considered in RO training. This new Singapore program is the first to achieve international accreditation by the RANZCR. It is clear that additional research in the design and evaluation of RO resident training programs is required.

Tailoring distant metastatic imaging for patients with clinically localized undifferentiated nasopharyngeal carcinoma.

PURPOSE: The 2000 practice guidelines of the National Comprehensive Cancer Network recommend World Health Organization Type 2-3 nasopharyngeal carcinoma (NPC) be staged for distant disease using chest X-ray and bone scan. Our aim was to evaluate these modalities plus liver ultrasonography for American Joint Committee on Cancer/International Union Against Cancer 1997 clinical Stage I-IVB NPC. METHODS AND MATERIALS: Between February 1999 and May 2002, all patients with clinical (examination plus CT/MRI of head and neck) Stage I-IVB undifferentiated NPC were prospectively evaluated for distant disease with chest X-ray, liver ultrasonography, and bone scan. Suspicious lesions underwent confirmatory investigation, and patients were reevaluated at 4 months. RESULTS: In the 139 patients evaluated, the positive yield was 3.6% and prevalence was 5.8% (0.7% lung, 2.2% skeletal, and 2.9% liver metastases). The prevalence increased by N stage (p = 0.004) and overall stage (p = 0.05). Compared with N3 disease (odds ratio 1.0), the odds of metastases for N0, N1, and N2 disease was 0, 0.12, and 0.33, respectively. The positive yield was 0%, 1.8%, 4.8%, and 14.3% for N0, N1, N2, and N3 disease, respectively. CONCLUSION: This is the first study to evaluate the use of distant staging investigations for American Joint Committee on Cancer/International Union Against Cancer 1997 staged NPC. We recommend alterations to the 2000 National Comprehensive Cancer Network guidelines as follows: high-risk (N3) disease should be fully staged with chest X-ray, bone scan, and liver ultrasonography; intermediate risk (N1 and N2) disease may be staged using all three modalities on an institutional basis. No evidence supports distant imaging for low-risk (N0 or Stage I) disease.

Estimating risks of radiotherapy complications as part of informed consent: the high degree of variability between radiation oncologists may be related to experience.

PURPOSE: Estimating the risks of radiotherapy (RT) toxicity is important for informed consent; however, the consistency in estimates has not been studied. This study aimed to explore the variability and factors affecting risk estimates (REs). METHODS AND MATERIALS: A survey was mailed to Australian radiation oncologists, who were asked to estimate risks of RT complications given 49 clinical scenarios. The REs were assessed for association with oncologist experience, subspecialization, and private practice. RESULTS: The REs were extremely variable, with a 50-fold median variability. The least variability (sevenfold) was for estimates of late, small intestinal perforation/obstruction after a one-third volume received 50 Gy with concurrent 5-fluorouracil (RE range 5-35%). The variation between the smallest and largest REs in 17 scenarios was >or=100-fold. The years of experience was significantly associated with REs of soft/connective-tissue toxicity (p = 0.01) but inversely associated with estimates of neurologic/central nervous system toxicity (p = 0.08). Ninety-six percent of respondents believed REs were important to RT practice; only 24% rated evidence to support their estimates as good. Sixty-seven percent believed national/international groups should pursue the issue further. CONCLUSION: Enormous variability exists in REs for normal tissue complications due to RT that is influenced by the years of experience. Risk estimation is perceived as an important issue without a good evidence base. Additional studies are strongly recommended.