BACKGROUND:Stereotactic ablative body radiotherapy (SABR) is a non-invasive therapy for inoperable primary renal cell carcinoma. However, long-term prospective clinical trial data are scarce. We aimed to use pooled data from two clinical trials (FASTRACK and FASTRACK II) to evaluate activity and safety of SABR in the long term. METHODS:In this pooled analysis, we used data from FASTRACK, a single-institutional, phase 1, prospective clinical trial conducted at the Peter MacCallum Cancer Centre (Melbourne, VIC, Australia), and FASTRACK II, an international, non-randomised, phase 2 clinical trial conducted in seven academic hospitals in Australia and one in the Netherlands. The treatment protocol, inclusion and exclusion criteria, and dose constraints were the same in both trials. Patients had primary renal cell carcinoma and were deemed medically inoperable or high-risk for surgery, were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 2 or less, tumours of 10 cm or less in maximal dimension, and N0-N1 disease. Tumours 4 cm or smaller in FASTRACK II and smaller than 5 cm in FASTRACK received a single fraction of 26 Gy and larger tumours received 42 Gy in three fractions 48 h apart. Local control (freedom from local progression) was the primary endpoint, assessed using Response Evaluation Criteria in Solid Tumours (version 1.1) criteria. The analyses were conducted only in patients who commenced protocol treatment. Safety was evaluated with the Common Terminology Criteria for Adverse Events in participants who started protocol treatment. A patient representative was involved in the study design and conduct of FASTRACK II. Both trials were registered with ClinicalTrials.gov (FASTRACK: NCT01676428; FASTRACK II: NCT02613819) and are both completed. FINDINGS:108 patients were enrolled between June 28, 2012, and Oct 17, 2014 (FASTRACK), and between July 28, 2016, and Feb 27, 2020 (FASTRACK II). Five patients did not receive treatment (one opted for surgery, three did not meet dose constraints and were withdrawn, and one died before treatment). Median age was 76·9 years (IQR 70·0-81·9). 74 (72%) of 103 patients analysed were male and 29 (28%) were female. Race and ethnicity data were not collected. The median follow-up was 5·0 years (IQR 2·3-6·0). Local control at 1 year was 100%, at 3 years was 98% (89-100), and at 5 years was 98% (89-100), with local progression occurring in only one patient who had both local and distant progression at 28 months. Eight (8%) patients had grade 3 adverse events: abdominal or flank pain (four [4%] patients), nausea or vomiting (two [2%]), colonic obstruction (two [2%]), fatigue (one [1%]), and colitis or diarrhoea (one [1%]). All grade 3 or worse adverse events occurred within 2 years of SABR delivery. No grade 4 adverse events or treatment-related deaths were reported. INTERPRETATION:This pooled analysis from two clinical trials of SABR in patients with larger primary kidney tumours unsuitable for surgery supports evidence of long-term local control and low rate of severe adverse events. These results support further investigation through a randomised trial comparing SABR with surgery in select operable patients. FUNDING:None.

BACKGROUND:Stereotactic ablative body radiotherapy (SABR) is an emerging, non-invasive alternative for primary renal cell carcinoma. We aimed to provide the final long-term trial outcomes of TransTasman Radiation Oncology Group (TROG) 15.03 FASTRACK II, the first phase 2 trial investigating SABR for primary renal cell carcinoma to our knowledge. METHODS:FASTRACK II was a non-randomised, phase 2 study conducted in eight hospitals in Australia and the Netherlands by TROG and the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group. Here, we report the final pre-planned follow-up results. Adult patients (aged ≥18 years) with histologically confirmed primary renal cell carcinoma, who were medically inoperable, high risk, or declined surgery, had an Eastern Cooperative Oncology Group performance status of 2 or less, had tumours 10 cm or less in size, and had N0-N1 disease were included. Patients underwent either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions delivered 48 h apart for tumours more than 4 cm in maximum diameter. The primary outcome was freedom from local progression to assess local control after SABR evaluated with the Response Evaluation Criteria in Solid Tumours. The primary endpoint and safety were evaluated in the intention-to-treat population. A patient representative was involved in the study design and conduct. The trial was registered with ClinicalTrials.gov (NCT02613819) and is closed to enrolment. FINDINGS:Between July 28, 2016, and Feb 27, 2020, 71 patients were enrolled and one withdrew consent before treatment. Median follow-up was 62 months (IQR 60-72), median age was 77 years (70-82). 49 (70%) of 70 patients were male and 21 (30%) were female. Race and ethnicity data were not collected. The median tumour size was 46 mm (37-55), with 24 (34%) patients with T1a disease, 39 (56%) with T1b disease, six (9%) with T2a disease, and one (1%) with T3a disease. One patient (1%) had nodal involvement (N1). SABR resulted in 100% local control at 36 months, 60 months, and 84 months. Seven (10%) patients had at least one grade 3 adverse event within 9 months of SABR that was designated possibly, probably, or definitely related to treatment: nausea and vomiting (three [4%] events); abdominal, flank, or tumour pain (four [6%]); colonic obstruction (two [3%]); and diarrhoea (one [1%]). No new long-term safety signals, grade 4 events, or treatment-related deaths were noted. INTERPRETATION:Long-term follow-up supports the safety and local control of SABR for non-surgical patients with renal cell carcinoma, with no observed local recurrences or cancer-related deaths in this cohort, which had predominantly T1b disease or higher. FUNDING:The Cancer Australia Priority-driven Collaborative Cancer Research Scheme and Varian.

BACKGROUND:Single-fraction stereotactic ablative radiotherapy (SABR) is a curative treatment option for patients with early lung cancer. We undertook a feasibility study to assess whether simulation, planning and treatment could be undertaken within a single day and whether this expedited pathway was acceptable to patients. METHODS:A multidisciplinary team of radiation oncologists, radiation therapists and medical physicists developed a workflow to permit all aspects of planning and treatment to be conducted within a single working day. All aspects of the pathway were timed. Prescription dose was 30 Gray. Patients completed an Experience Survey within two weeks of treatment. The study would be deemed successful if it met both dual primary endpoints of feasibility (7/10 patients treated within 8 working hours) and patient satisfaction (7/10 expressing overall satisfaction). RESULTS:Ten patients were treated. These included 6 women and 4 men. Median age was 76.5 and 9 patients had been deemed to be medically inoperable. Median time from commencement of CT simulation to end of treatment was 6 h 50 min (IQR 6 h 42 m - 7 h 4 m); 9/10 patients were treated within the target 8-hour window. All 10 patients expressed overall satisfaction with the service. All 10 felt it was more convenient than our usual treatment pathway would have been. CONCLUSION:Same-day single-fraction SABR is feasible and acceptable to patients. This pathway should be considered for those who live a significant distance from treatment centres or who have other difficulties in attending for multiple visits.

Background Definitive concurrent chemoradiotherapy (CRT) is the primary curative-intent treatment option for unresectable locally advanced nonsmall-cell lung cancer (NSCLC). Completion of CRT is generally required for eligibility for consolidation durvalumab, which significantly improves survival. We sought to establish CRT completion rates at a comprehensive cancer center. Patients and Methods 265 patients were treated with concurrent CRT over the decade 2012-2022, during which durvalumab became available. 63% were male, median age was 67, and 91% had performance status 0-1. All patients were recruited into the AURORA prospective cohort study which captured baseline demographics and comorbidities, and prospectively updated treatment and outcome data at subsequent hospital visits. Data were analyzed retrospectively to evaluate CRT completion rates, reasons for noncompletion, and survival outcomes. Survival was also analyzed based on durvalumab availability and administration. Results CRT was completed as planned by 246/265 (93%) patients. Reasons for noncompletion included treatment related toxicity (n = 6/19), unrelated illnesses (n = 7/19), local disease progression (n = 2/19), and distant progression (n = 4/19). Median overall survival (OS) was 2.2 years (95% CI, 1.7-2.8) for the entire cohort and 1.0 years (95% CI, 0.2-1.5) for those who ceased CRT early. No specific baseline characteristics predicted noncompletion of CRT. Consolidation durvalumab was associated with improved OS (HR 0.39; 95% CI, 0.21-0.72, P = .002). Conclusion With appropriate supportive care, most patients initially considered suitable for CRT could complete it and access consolidation durvalumab. Consolidation durvalumab was associated with improved survival in this “real-world” stage III NSCLC cohort.

PURPOSE:To utilize 68Gallium (Ga) Ventilation-Perfusion (V/Q) 4-dimensional (4D) PET/CT to establish the impact of curative radiotherapy (RT) doses on lung ventilation and perfusion, and to evaluate associations with clinical outcomes. METHODS AND MATERIALS:This prospective non-randomized observational clinical trial included 67 patients undergoing definitive RT +/-chemotherapy for NSCLC. Patients underwent 68Ga 4D V/Q PET/CT at baseline, mid-treatment, and at 3- and 12-months post-treatment. Pulmonary Function Tests (PFTs) and toxicities were assessed at baseline and 3 monthly after treatment. Linear mixed models were used to assess for associations between radiotherapy dose-volume, applied to ventilated and perfused lung at 5 %, 30 % and 70 % thresholds as defined by 68Ga 4D V/Q PET/CT, and toxicity. RESULTS:Sixty-seven patients were evaluable, of whom 44 (66 %) were male, mean age was 68, and 61 (91 %) were ECOG 0-1. Sixty-three patients completed treatment and grade ≥2 pneumonitis occurred in 20 (32 %). Lung ventilation and perfusion, and FEV1 and DLCO, fell slightly from baseline to 3-months post treatment. V54 Gy of perfused lung at the 30 % threshold was higher in those with grade ≥2 pneumonitis (median 12.9 % (IQR 8.7-14.8 %) vs 6.3 % (IQR 3.7-8.5 %), p = 0.003). No association between grade ≥2 pneumonitis and the absolute change in ventilated (p = 0.12) or perfused (p = 0.14) lung was observed. CONCLUSIONS:We observed a decrease in lung ventilation and perfusion on 68Ga 4D V/Q PET/CT from baseline to 3 months after RT. The association between the volume of well-perfused lung receiving near-therapeutic RT doses and the development of grade ≥2 pneumonitis warrants future investigation.

Metastasis-directed therapy (MDT) in oligometastatic renal cell carcinoma (RCC) is typically based on conventional imaging. Prostate-specific membrane antigen (PSMA) PET/CT has shown superiority over conventional imaging. Our objective was to perform a proof-of-concept study to evaluate the efficacy of PSMA-guided MDT in oligometastatic RCC. Methods: A PSMA PET/CT database was queried for oligometastatic RCC patients undergoing MDT from 2014 to 2020. The primary endpoint was progression-free survival. Secondary endpoints included freedom from local progression, freedom from change in systemic therapy strategy, and overall survival. Results: A search of 3,095 PSMA PET/CT scans identified 83 RCC patients and 34 receiving MDT to 60 sites. The median follow-up was 4.1 y. Six patients (18%) had synchronous metastatic disease. The median number of metastases was 1 (interquartile range, 1-2). Common sites included bone (19, 32%) and lung (19, 32%). Radiation therapy was delivered to 56 metastases (93%), including stereotactic ablative body and conventional radiotherapy (38 and 18 metastases, respectively), and 4 (7%) underwent surgery. One-, 3-, and 5-y freedom from local progression was 94% (95% CI, 85%-98%), 85% (95% CI, 69%-94%), and 85% (95% CI, 69%-94%), respectively. One-, 3-, and 5-y overall survival was 88% (95% CI, 71%-95%), 71% (95% CI, 52%-84%), and 64% (95% CI, 45%-79%), respectively. One-, 3-, and 5-y progression-free survival was 47% (95% CI, 30%-63%), 26% (95% CI, 13%-42%), and 8% (95% CI, 2%-22%), respectively. One-, 3-, and 5-y freedom from change in systemic therapy strategy was 76% (95% CI, 57%-87%), 65% (95% CI, 45%-79%), and 43% (95% CI, 19%-65%), respectively. Conclusion: In this proof-of-concept study, PSMA-guided MDT provided durable oncologic outcomes for oligometastatic RCC, even at 5 y. To our knowledge, this study had the first cohort uniformly undergoing PSMA-guided MDT and one of the longest follow-ups of MDT for oligometastatic RCC. With increasing availability, PSMA PET/CT can be rapidly instituted to select patients for MDT and improve outcomes for patients with oligometastatic RCC.

OBJECTIVE:To evaluate the predictive value of the R.E.N.A.L. ([R]adius, [E]xophytic/endophytic properties, [N]earness of tumour to the collecting system or sinus, [A]nterior/posterior descriptor, and [L]ocation relative to polar lines) nephrometry score (RNS) for outcomes following stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC), as the impact of tumour complexity on outcomes following nephron-sparing SABR treatment is unclear. PATIENTS AND METHODS:This was a single institutional retrospective analysis of patients with primary RCC receiving SABR between 2012 and 2020. The primary outcome was the change in renal function post-SABR, measured by estimated glomerular filtration rate (eGFR), and the effect of baseline RNS on it was assessed using linear mixed models (LMMs). RESULTS:A total of 90 patients with a median (interquartile range [IQR]) age of 77 (71-82) years and a median (IQR) follow-up of 4.8 (2.8-7.8) years were included. In all, 52 patients (58%) had T1b disease, nine (10%) had T2 disease, and three (3%) had T3 disease. The median (IQR) maximum tumour size was 4.6 (2.1-8.4) cm. Most patients had moderate-complex renal tumours with a median (IQR) RNS of 9 (7-10). The baseline median eGFR was 53.6 mL/min/1.73 m2 (95% confidence interval [CI] 49.7-57.5 mL/min/1.73 m2). The eGFR declined by -8.1 mL/min/1.73 m2 (95% CI -6.5 to -9.6 mL/min/1.73 m2) at 1 year. The P value for the post-SABR eGFR trajectory according to baseline RNS was P = 0.06. Two patients (2.2%) underwent dialysis. Three patients (3.3%) experienced local progression. The 3- and 5-year estimates for freedom from local failure were 97% (95% CI 89-99%), and 91% (95% CI 68-98%), respectively. Four (4.4%) patients experienced Grade 3 toxicities. CONCLUSION:Stereotactic ablative body radiotherapy is an effective treatment option, with acceptable decline in renal function and toxicity for medically inoperable patients with complex primary kidney tumours. The association between baseline RNS and renal function trajectories is worthy of further investigation.

Introduction: Smoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). Methods: All patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database. A detailed smoking history was routinely obtained at baseline. Kaplan-Meier statistics were used to assess overall survival and progression-free survival in never versus former versus current smokers. Results: Median overall survival for 265 eligible patients was 2.21 years (95 % Confidence Interval 1.78, 2.84). It was 5.5 years (95 % CI 2.1, not reached) for 25 never-smokers versus 1.9 years (95 % CI 1.5, 2.7) for 182 former smokers and 2.2 years (95 % CI 1.3, 2.7) for 58 current smokers. Hazard ratio for death was 2.43 (95 % CI 1.32-4.50) for former smokers and 2.75 (95 % CI 1.40, 5.40) for current smokers, p = 0.006. Actionable tumour mutations (EGFR, ALK, ROS1) were present in more never smokers (14/25) than former (9/182) or current (3/ 58) smokers. TKI use was also higher in never smokers but this was not significantly associated with superior survival (Hazard ratio 0.71, 95 % CI 0.41, 1.26). Conclusions: Never smokers have substantially better overall survival than former or current smokers after undergoing CRT for NSCLC.

BACKGROUND:Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS:This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS:Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION:To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING:Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Abstract Background Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC. Methods and materials This was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012–2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan–Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models. Results Seventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70–83), tumor size of 4.5 cm (IQR 3.9–5.8) and follow-up of 42.2 months (IQR 23–60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1–2. By last follow-up, 1/35 (2.8%) of baseline CKD 1–2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4–5. The estimated probability of freedom from CKD stage 4–5 at 1 and 5 years was 89.6% (CI 83.0–97.6) and 65% (CI 51.4–81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4–5 CKD though only the former remained significant in multivariable model. Conclusion In this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.

In the first multicenter prospective trial of a non-surgical primary RCC cohort, enrolling mostly T1b+ disease, SBRT was an effective treatment strategy with no observed local failures. We observed an acceptable side effect profile and renal function after SBRT. These outcomes support the design of a future randomized clinical trial of SBRT versus surgery for primary RCC. The trial was registered with ID: NCT02613819.

There was no evidence of a concerning safety signal from either SABR before or after start of pembrolizumab. The combination demonstrated activity with promising PFS and OS and is worthy of evaluation in larger randomized trials.

BACKGROUND:The Victorian prison population is growing and ageing. Little has been documented about this group's cancer incidence, presentation or treatment. AIMS:To conduct a retrospective review of Victorian prisoners with cancer, including assessment of change over 15 years and adequacy of treatment delivery. METHODS:Detailed demographic, cancer and treatment data were collected for all prisoners with malignancy treated at St Vincent's Hospital Melbourne from 2002 to 2017. Detailed analysis of adherence to Optimal Care Guidelines was undertaken for a subset. Descriptive statistics were used. RESULTS:We identified 200 cancers in 191 prisoners. The population was predominantly male (185 of 191, 93%), with a median age of 54 years. Rates of cigarette smoking (118 of 191, 59%), mental illness (92 of 191, 46%) and intravenous drug use (59 of 191, 29.5%) were high. Exposure-related cancers predominated (nonmelanoma skin cancer, lung cancer and hepatoma). Most were symptomatic (154 of 191, 77%) and almost one-third had incurable disease at diagnosis (64 of 191, 32%). The number of prisoners with cancer increased over time (2002-2006 [T1], n = 31 vs 2012-2016 [T3], n = 101), as did the median age (45 years in T1 vs 55 years in T3) and rates of mental illness (10 of 31 [32%] in T1 vs 55 of 101 [54%] in T3). Delayed treatment initiation occurred in eight of 12 (66%) assessable patients, largely because of nonattendance. CONCLUSIONS:Victorian prisoners with cancer are at risk of poor outcomes because of late presentation, delayed treatment initiation and medical comorbidities. Tailored interventions are urgently required to improve the provision of timely, comprehensive cancer care to this vulnerable and growing population.

Tobacco causes most non-small cell lung cancers (NSCLC), but it is unclear how smoking history influences survival once a NSCLC is diagnosed. Retrospective studies have suggested better survival for former or never smokers compared with current smokers after cancer treatment. We used a prospective database, with systematically collected tobacco use history, to ascertain if smoking status was correlated with outcomes after treatment with chemoradiotherapy in patients with loco-regionally advanced NSCLC.

Background: The kinetics of circulating tumor DNA (ctDNA) release following commencement of radiotherapy or chemoradiotherapy may reflect early tumour cell killing. We hypothesised that an increase in ctDNA may be observed after the first fraction of radiotherapy and that this could have clinical significance.Materials and methods: ctDNA analysis was performed as part of a prospective, observational clinical biomarker study of non-small cell lung cancer (NSCLC) patients, treated with curative-intent radiotherapy or chemoradiotherapy. Blood was collected at predefined intervals before, during (including 24 h after fraction 1 of radiotherapy) and after radiotherapy/chemoradiotherapy. Mutation-specific droplet digital PCR assays used to track ctDNA levels during and after treatment.Results: Sequential ctDNA results are available for 14 patients with known tumor-based mutations, including in EGFR, KRAS and TP53, with a median follow-up of 723 days (range 152 to 1110). Treatments delivered were fractionated radiotherapy/chemoradiotherapy, in 2-2.75 Gy fractions (n = 12), or stereotactic ablative body radiotherapy (SABR, n = 2). An increase in ctDNA was observed after fraction 1 in 3/12 patients treated with fractionated radiotherapy with a complete set of results, including in 2 cases where ctDNA was initially undetectable. Neither SABR patient had detectable ctDNA immediately before or after radiotherapy, but one of these later relapsed systemically with a high detected ctDNA concentration. Conclusions: A rapid increase in ctDNA levels was observed after one fraction of fractionated radiotherapy in three cases. Further molecular characterization will be required to understand if a "spike" in ctDNA levels could represent rapid initial tumor cell destruction and could have clinical value as a surrogate for early treatment response and/or as a means of enriching ctDNA for mutational profiling.