Nonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating ...pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required.
Specialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018. Sample cases were discussed during workshop contact with specifically invited international speakers highly experienced in pancreas SBRT. Furthermore, sample cases were contoured and planned between workshop contact to finalize dose constraints and clinical target volume delineation.
Over 2 separate workshops, consensus was reached on dose and simulation technique. The working group recommended a dose prescription of 40 Gy in 5 fractions. Treatment delivery during end-expiratory breath hold with triple-phase contrast enhanced computed tomography was recommended. In addition, dose constraints, stepwise contouring guidelines, and an anatomic atlas for pancreatic SBRT were developed.
Pancreas SBRT is emerging as a promising treatment modality requiring prospective evaluation in randomized studies. This work attempts to standardize dose, simulation technique, and volume delineation to support the delivery of high quality SBRT in a multicenter study.
Reduction of respiratory tumour motion is important in liver stereotactic body radiation therapy (SBRT) to reduce side effects and improve tumour control probability. We have assessed the ...distribution of use of voluntary exhale breath hold (EBH), abdominal compression (AC), free breathing gating (gating) and free breathing (FB), and the impact of these on treatment time.
We assessed all patients treated in a single institution with liver SBRT between September 2017 and September 2021. Data from pre-simulation motion management assessment using fluoroscopic assessment of liver dome position in repeat breath holds, and motion with and without AC, was reviewed to determine liver dome position consistency in EBH and the impact of AC on motion. Treatment time was assessed for all fractions as time from first image acquisition to last treatment beam off.
Of 136 patients treated with 145 courses of liver SBRT, 68 % were treated in EBH, 20 % with AC, 7 % in gating and 5 % in FB. AC resulted in motion reduction < 1 mm in 9/26 patients assessed. Median treatment time was higher using EBH (39 min) or gating (42 min) compared with AC (30 min) or FB (24 min) treatments.
Motion management in liver SBRT needs to be assessed per-patient to ensure appropriate techniques are applied. Motion management significantly impacts treatment time therefore patient comfort must also be taken into account when selecting the technique for each patient.
Among 61 patients who underwent prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography for oligometastatic renal cell carcinoma, there was a high-impact management ...change due to imaging results in 29 (48%). The detection rate for PSMA-positive disease was 84%.
Prostate-specific membrane antigen (PSMA) is overexpressed in the neovasculature of renal cell carcinoma (RCC). However, there remains limited evidence regarding the use of PSMA positron emission tomography/computed tomography (PET/CT) in RCC.
To assess the impact of PSMA PET/CT in the management of metastatic RCC.
This was a retrospective review of patients who underwent PSMA PET/CT from 2014 to 2020 for restaging or suspected metastatic RCC in a tertiary academic setting.
Management plans before and after PSMA PET/CT were recorded. Impact was classified as high (change of treatment intent, modality, or site), medium (change in treatment method), or low. Secondary outcomes included the patient-level detection rate, PSMA PET/CT parameters, sensitivity, and comparison to CT and, if available, fluorodeoxyglucose (FDG) PET/CT.
Sixty-one patients met the inclusion criteria, of whom 54 (89%) had clear cell RCC. PSMA-positive disease was detected in 51 patients (84%). For 30 patients (49%) there was a change in management due to PSMA PET/CT (high impact, 29 patients, 48%). In 15 patients (25%), more metastases were detected on PSMA PET/CT than on CT. The sensitivity of combined PSMA PET/CT and diagnostic CT was 91% (95% confidence interval 77–98%). In a subcohort of 40 patients, the detection rate was 88% for PSMA and 75% for FDG PET/CT (p = 0.17). The maximum standardised uptake value (SUVmax) was higher for PSMA than for FDG PET/CT (15.2 vs 8.0; p = 0.02). Limitations include selection bias due to the retrospective design, and a lack of corresponding histopathology for all patients.
PSMA PET/CT is a promising imaging modality in metastatic RCC and led to a change in management in 49% of patients. PSMA PET/CT detected additional metastases compared to CT in 25% of patients and registered a significantly higher SUVmax than FDG PET/CT. Prospective studies are required to further define its role.
We report on a group of patients undergoing a new type of imaging for suspected advanced kidney cancer, called PSMA PET/CT. This imaging changed the management plan in 49% of the patients. PSMA PET/CT detected metastases in 84% of our patients and detected more metastases than computed tomography imaging in 25%.
This study aimed to compare the oncological results between unplanned excision (UE) and planned excision (PE) of malignant soft tissue tumor and to examine the impact of residual tumor (ReT) after ...UE. Nonmetastatic soft tissue sarcomas surgically treated in 1996–2012 were included in this study. Disease‐specific survival (DSS), metastasis‐free survival (MFS), and local‐recurrence‐free survival (LRFS) were stratified according to the tumor location and American Joint Committee on Cancer Classification 7th edition stage. Independent prognostic parameters were identified by Cox proportional hazard models. Two‐hundred and ninety PEs and 161 UEs were identified. Significant difference in oncological outcome was observed only for LRFS probability of retroperitoneal sarcomas (5‐year LRFS: 33.0% UE vs. 71.0% PE, P = 0.018). Among the 142 UEs of extremity and trunk, ReT in re‐excision specimen were found in 75 cases (53%). UEs with ReT had significantly lower survival probabilities and a higher amputation rate than UEs without ReT (5‐year DSS: 68.8% vs. 92%, P < 0.001; MFS: 56.1% vs. 90.9%, P < 0.001; LRFS: 75.8% vs. 98.4%, P = <0.001; amputation rate 18.5% vs. 1.8%, P = 0.003). The presence of ReT was an independent poor prognostic predictor for DSS, MFS, and LRFS with hazard ratios of 2.02 (95% confidence interval (CI), 1.25–3.26), 1.62 (95% CI, 1.05–2.51) and 1.94 (95% CI, 1.05–3.59), respectively. Soft tissue sarcomas should be treated in specialized centers and UE should be avoided because of its detrimental effect especially when ReT remains after UE.
Residual disease in unplanned excision of soft tissue sarcoma was a poor prognostic predictor for all oncological outcomes. Soft tissue sarcomas should be treated in specialized centers and unplanned excision should be avoided because of its detrimental effect especially when residual disease remains after unplanned excision.
To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer.
Consecutive patients with nonmetastatic squamous cell ...carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome.
Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval CI 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity.
CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.
Image-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and ...without IGRT in prostate cancer patients treated radically.
Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74 Gy in 37 fractions, to 78 Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment.
In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference.
In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.
In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (
F-NaF PET/CT). This imaging technique shows areas of enhanced ...osteoblastic activity and blood flow. In this work,
F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients.
Patients with bone metastases in a prospective trial treated with single fraction SABR received a
F-NaF PET/CT scan prior to and 6 months post-SABR. The SUV
in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose.
Reduction in SUV
was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUV
17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUV
post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy.
F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases.
POPSTAR, 'Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy', Universal Trial Number U1111-1140-7563 , Registered 17th April 2013.
Background
Preoperative radiotherapy (RT) is an important component of the management of retroperitoneal sarcoma (RPS). We aimed to establish the feasibility of this approach by determining the ...accuracy of computed tomography (CT)‐guided core biopsy, proportion of patients completing treatment, rates of acute toxicity and surgical complications, and treatment outcomes.
Methods
This is a retrospective review. Consecutive patients presenting between January 1999 and December 2009 with a diagnosis of either primary or recurrent RPS were identified. Those patients suitable for preoperative RT and surgery were included. Exclusions included presence of metastatic disease, age under 18 years and/or paediatric histology, and treatment with palliative intent.
Results
Twenty‐four patients were included, 14 were males. Median age was 61.4 years. Twenty‐three patients had Stage T2b, high‐grade disease. Twenty patients were treated at initial presentation and four at first local recurrence. Five‐year progression‐free survival, overall survival and local recurrence rates were 48.9, 53.7 and 22%, respectively. A malignant diagnosis was confirmed in all patients who underwent CT‐guided core biopsy; a diagnosis of sarcoma was reached in 90%, histological subtype correctly identified in 66%. All patients in the cohort completed preoperative RT. Grade 3 toxicity occurred in 4% of patients (n = 1). Seventy‐five per cent (n = 18) proceeded to radical resection, where complete macroscopic excision was achieved in all cases. There was no perioperative mortality.
Conclusion
Preoperative RT has low levels of Grades 3 or 4 toxicity, and does not adversely impact surgical management. CT‐guided core biopsy is an accurate means of confirming a diagnosis of RPS prior to definitive treatment.
The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following ...resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR.
and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1–5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post‐treatment to assess longitudinal changes in immune subsets.
The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy.
clinicaltrials.gov ID NCT02855203.
•Prolonged survival has been observed following SABR for oligometastatic clear cell renal cell carcinoma (ccRCC).•Immunotherapy combinations have improved survival in advanced ccRCC.•Pre-clinical models have suggested a synergistic immune-priming effect of SABR.•The RAPPORT trial will evaluate the safety and efficacy of SABR combined with pembrolizumab for oligometastatic ccRCC.
To examine the long-term outcome and patterns of relapse in clinical Stage I testicular seminoma managed with surveillance alone after radical inguinal orchiectomy.
This was a prospective, single-arm ...study. Patients with Stage I testicular seminoma were treated with surveillance alone in accordance with regular, predefined, schedules and investigations.
The study accrued a total of 88 patients between 1985 and 1996. The median age at diagnosis was 34 years. The median tumor size was 3.5 cm. The median follow-up as of June 2003 was 12.1 years. Only 3 patients were lost to follow-up. Of the 88 patients, 71 remained free of relapse and 17 did not. The actuarial relapse-free rate was 83%, 80%, and 80% at 5, 10, and 15 years, respectively. Most relapses (15 of 17) were below the diaphragm. Of the 17 patients with relapse, 14 were treated with radiotherapy and 3 with combination chemotherapy. Only 1 had a second relapse and was further salvaged by chemotherapy. All 17 relapsed patients remained free of recurrence after salvage treatment. None died of seminoma. The statistically significant predictive factor for relapse on the Cox proportional hazards model was the presence of rete testis invasion (hazard ratio 3.5, p = 0.03).
Surveillance with the reservation of radiotherapy or chemotherapy for salvage of relapse is a safe alternative to upfront postoperative adjuvant therapy for Stage I testicular seminoma.
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