Late Toxicity Research Articles

Impact of neoadjuvant androgen deprivation therapy on toxicity in intensity-modulated radiation therapy for prostate cancer.

This study aimed to compare toxicities, prostate volume and dosimetry, between patients who underwent intensity-modulated radiation therapy (IMRT) combined with ≥3months of neoadjuvant androgen deprivation therapy (NADT) and those without NADT for prostate cancer. In total, 449 patients with intermediate- and high-risk prostate cancer received 78Gy IMRT in 39 fractions, of which 129 were treated without any ADT (non-ADT group) and 320 with NADT ≥3months (NADT group). Adverse events and dose-volume indices were compared between the two groups retrospectively. The NADT group had a lower rate of acute grade 2 gastrointestinal (GI) toxicities (17% vs 25%, P = 0.063) and late grade 2 GI toxicities (P = 0.055), including a significantly lower rate of late grade 2 rectal hemorrhage (P = 0.033), compared with the non-ADT group. There were no cases of late grade 3 or higher GI toxicities. The average volume of the prostate in the NADT group was 38% smaller than that in the non-ADT group (43.7 vs 27.0cm3, P < 0.001). Bladder V40Gy and V50Gy, and rectum V40Gy, V50Gy, V60Gy and V70Gy were significantly smaller in the NADT group. In the NADT group, no significant difference was observed in adverse events or dosimetry between the subgroups with NADT ≥12 and <12months. Acute and late rectal toxicities were reduced by NADT within ≥3months in accordance with reduced prostate volume and improved rectal dosimetry. This suggests a merit of administering neoadjuvant ADT ≥3months for reducing rectal toxicities.

Exploring Radiotherapy as a Promising Alternative for Managing Advanced Upper Tract Urothelial Carcinoma: Rescuing Chemotherapy-Intolerant Patients

PurposeTo investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy. MethodsData for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors. ResultsThe median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed. ConclusionFor patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

HYPCON trial: A phase II randomized study evaluating hypofractionated versus conventional adjuvant radiation therapy in head and neck malignancies.

143 Background: Hypofractionated RT has been established as standard of care at many cancer sites but there is limited data on use of hypofractionated RT for head and neck carcinomas (HNC). The HYPCON trial (CTRI/2023/02/049804) tested to reduce 10 fractions of PORT by delivery of hypofractionated PORT. Methods: Patients of HNC after radical surgery, with intermediate risk factors, were randomized based on site, T and N stage to either standard fractionation arm A (60Gy/30 fractions/6 weeks) or hypofractionated arm B (50Gy/20 fractions/4 weeks) in a 1:2 manner. The minimum sample size for the study was estimated based on a non-inferiority trial design as 120 considering a 10% clinical effectiveness margin and 5% attrition. Treatment allocation was done based on T stage, N stage &amp; HNC subsite. Target delineation included tumour bed with adequate margins (CTV_P) and microscopic lymph nodal (CTV_N) basin at risk. Organ delineation included all DARS. A double arc swallowing-sparing IMRT was used in both arms. The primary endpoint was locoregional control (LRC) at 1 year. Compliance, RT time (RTT), overall treatment time (OTT), progression-free survival (PFS) and overall survival (OS) were calculated in all patients. Acute &amp; late toxicities were recorded as per RTOG scale. Results: 135 patients were enrolled, 45 in Arm A &amp; 90 in Arm B. Majority of patients (96.9%) had oral cavity primary. Most of patients 74.8 % had early-stage disease. Compliance to PORT was 91.1% in Arm A versus 100% in Arm B. Median RTT for Arm A was 43 days (25-73 days) and 28 days (25-43 days) for Arm B (p&lt;0.0001). Median OTT in Arm A was 91 days (70-126 days) and 77 days (57-119 days) in Arm B (p&lt;0.0001). Median follow-up was 12.7 (2.73-23.87) months. One year, LRC was 72.9% vs 91.6% (p=0.007); PFS was 70.6% vs 90.5% (p=0.009) and OS was 88.7% vs 94.5% (p 0.02) Arm A versus Arm B respectively. Grade 3 or higher acute toxicity was seen in 39% in Arm A and 31.1% in Arm B (p=0.374). Grade 3 or higher late toxicity events were noted in 29.2% and 32.2% in arms A and B respectively (p= 0.671). Conclusions: Hypofractionated PORT reduced RTT &amp; OTT and was associated with improved treatment compliance, treatment outcomes (LRC, PFS, OS), and similar acute and late toxicity profile. This is the first study to demonstrate the superiority of hypofractionated compared to conventional PORT delivery for HNC. Clinical trial information: CTRI/2023/02/049804 .

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience

ObjectivesImage-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. Materials and MethodsData of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. ResultsOverall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3–4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3–4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. ConclusionsCT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

Three-Dimensional Conformal Radiotherapy Versus Image-Guided Intensity Modulated External Beam Radiotherapy in Locally Advanced Cervical Cancer: A Phase III Randomized Control Study

AimsThe standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities. Materials and MethodsThis was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II–IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging. ResultsTwo hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms. ConclusionBased on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control.

Impact of Vaginal Dilator Use and 68 Gy EQD2(α/β=3) Dose Constraint on Vaginal Complications in External Beam Irradiation Followed by Brachytherapy in Post-Operative Endometrial Cancer.

This study evaluated the clinical outcomes of applying a 68 Gy EQD2(α/β=3) dose constraint to the most exposed 2 cm3 area of the vagina in post-operative endometrial cancer patients treated with vaginal-cuff brachytherapy after external beam irradiation and the impact of vaginal dilator use on late vaginal complications. We analyzed 131 patients treated with vaginal-cuff brachytherapy after external beam irradiation. Group-1 (65 patients) received one fraction of 7 Gy, and Group-2 (66 patients) received one fraction of between 5.5 and 7.0 Gy after applying a 68 Gy EQD2(α/β=3) dose constraint. Vaginal-cuff relapse, late toxicity, clinical target volume, vaginal dilator use, D90, and EQD2(α/β=3) at 2 cm3 of the most exposed part of the clinical target volume were evaluated. Descriptive analysis, the chi-squared test, Student's t-test, and the Cox proportional and Kaplan-Meier models were used for the statistical analysis. With a median follow-up of 60 months, the vaginal-cuff relapse rate was 1/131 (0.8%). Late vaginal complications appeared in 36/65 (55.4%) Group-1 patients and 17/66 (25.8%) Group-2 patients (p = 0.003). Multivariate analysis showed that belonging to Group-1 and vaginal dilator use of <9 months were independent prognostic factors of late vaginal complications with hazard ratios of 1.99 (p = 0.021) and 3.07 (p = 0.010), respectively. A 68 Gy EQD2(α/β=3) constraint at 2 cm3 of clinical target volume and vaginal dilator use of ≥9 months were independent prognostic factors, having protective effects on late vaginal complications.

Early exposure to glyphosate during larval development induces late behavioural effects on adult honey bees

As the most abundant pollinator insect in crops, Apis mellifera is a sentinel species of the pollinator communities. In these ecosystems, honey bees of different ages and developmental stages are exposed to diverse agrochemicals. However, most toxicological studies analyse the immediate effects during exposure. Late effects during adulthood after early exposure to pollutants during larval development are poorly studied in bees. The herbicide glyphosate (GLY) is the most applied pesticide worldwide. GLY has been detected in honey and beebread from hives near treated crops. Alterations in growth, morphogenesis or organogenesis during pre-imaginal development could induce late adverse effects after the emergence. Previous studies have demonstrated that GLY alters honey bee development, immediately affecting survival, growth and metabolism, followed by late teratogenic effects. The present study aims to determine the late impact on the behaviour and physiology of adult bees after pre-imaginal exposure to GLY. For that, we reared brood in vitro or in the hive with sub-chronic exposure to the herbicide with the average detected concentration in hives. Then, all newly emerged bees were reared in an incubator until maturity and tested when they became nurse-aged bees. Three behavioural responses were assessed as markers of cognitive and physiological impairment. Our results show i) decreased sensitivity to sucrose regardless of the rearing procedure, ii) increased choice latency and locomotor alterations during chemotaxis and iii) impaired associative learning. These late toxicity signs could indicate adverse effects on task performance and colony efficiency.

Preoperative Magnetic Resonance Guided Single-Dose Partial Breast Irradiation: 5-Year Results of the Prospective Single-Arm ABLATIVE Trial

Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15/36 patients achieved pathologic complete response (pCR) 6-8 months after preoperative PBI and breast conserving surgery (BCS). We now present the 5-year results. The ABLATIVE trial is a Dutch prospective cohort study in four hospitals. Women aged ≥ 50 years with unifocal, non-lobular breast cancer, ER-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015-2018 with preoperative single-dose PBI followed by BCS after six or eight months. The primary endpoint was pCR. Secondary endpoints were yearly evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians) and quality of life. Thirty-six patients were treated with BCS six (n=15) and eight (n=21) months following PBI. Median tumor size was 13 mm (IQR 9-16). After a median follow-up of 5.5 years (IQR 5.1-6.0 years), two (6%) patients had ipsilateral breast events and two (6%) distant metastases. The 5-years overall survival was 94% [95% CI 87-100%]. The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR 67-92), similar to baseline (83 (IQR 75-83), p=0.42). Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity, and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice.

Dosimetric predictors of acute and late gastrointestinal toxicities in stereotactic online adaptive magnetic resonance-guided radiotherapy (SMART) for locally advanced pancreatic adenocarcinoma

Background and purposeA retrospective evaluation of dosimetric predictors and leveraged dose-volume data for gastrointestinal (GI) toxicities for locally-advanced pancreatic cancer (LAPC) treated with daily stereotactic MRI-guided online-adaptive radiotherapy (SMART). Materials and methods147 patients with LAPC were treated with SMART at our institution between 2018 and 2021. Patients were evaluated using CTCAE V5.0 for RT-related acute (≤3 months) and late (>3 months) toxicities. Each organ at risk (OAR) was matched to a ≥ grade 2 (Gr2+) toxicity endpoint composite group. A least absolute shrinkage selector operator regression model was constructed by dose-volumes per OAR to account for OAR multicollinearity. A receiver operator curve (ROC) analysis was performed for the combined averages of significant toxicity groups to identify critical volumes per dose levels. Results18 of 147 patients experienced Gr2+ GI toxicity. 17 Gr2+ duodenal toxicities were seen; the most significant predictor was a V33Gy odds ratio (OR) of 1.69 per cc (95 % CI 1.14–2.88). 17 Gr2+ small bowel (SB) toxicities were seen; the most significant predictor was a V33Gy OR of 1.60 per cc (95 % CI 1.01–2.53). The AUC was 0.72 for duodenum and SB. The optimal duodenal cut-point was 1.00 cc (true positive (TP): 17.8 %; true negative (TN); 94.9 %). The SB cut-point was 1.75 cc (TP: 16.7 %; TN: 94.3 %). No stomach or large bowel dose toxicity predictors were identified. ConclusionsFor LAPC treated with SMART, the dose-volume threshold of V33Gy for duodenum and SB was associated with Gr2+ toxicities. These metrics can be utilized to guide future dose-volume constraints for patients undergoing upper abdominal SBRT.

Reduction of post-radiotherapy urinary toxicity via intrafractional MV-kV prostate location monitoring

We hypothesized that an in-house developed system using MV and kV image guidance (MKIG) to ensure correct prostate positioning during SBRT could potentially avoid unwanted doses to non-target tissues, leading to reduced toxicities. We built a 3D MKIG platform that accurately tracks prostate implanted fiducials in real-time and clinically translated the system to replace a commercial approach, intrafraction motion review (IMR), which only tracks fiducials in the 2D kV views. From 2017 to 2019, 150 prostate cancer patients were treated with SBRT and monitored by MKIG. The motion trace of the fiducials alerts therapists to interrupt and reposition the prostate when displacement exceeds a 1.5 mm threshold. A comparison cohort of 121 patients was treated with the same dose regimen and treatment technique but managed by IMR. Statistics of intrafractional patient shifts and delivery time were collected to evaluate the workflow efficacy. The incidence of grade ≥2 urinary toxicities was analyzed to assess clinical complications. The median follow-up time was 3.7 years (0.2 to 8.2 years). MKIG treatments had more treatment shifts (1.09 vs. 0.28) and a longer average delivery time per fraction (579±205s vs. 357±117s) than IMR treatments. Three-quarters (75%) of shifts resulting from MKIG were ≤3mm, vs. 51% in IMR, indicating that MKIG detected and corrected smaller deviations. The incidence of grade ≥2 urinary toxicity was lower in the MKIG than IMR cohort: 10.7% vs. 19.8% (p=0.047). On multivariate analysis of late urinary toxicity, only high (>7) pre-RT IPSS (p<0.043) and the use of MKIG were selected (p< 0.029). Automated and quantitative MKIG introduced minimal workflow impact and was superior to IMR in localizing the prostate during SBRT, which correlated with a clinically significant reduction in late urinary toxicity. Further clinical testing via randomized trial will be required to validate the impact on outcomes.

Escalade de dose en radiothérapie modérément hypofractionnée pour les cancers de la prostate localisés, ESHYPRO : résultats d’une série monocentrique rétrospective évaluant la toxicité et l’efficacité

PurposeProstate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. Material and methodsThe study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75Gy in 30 fractions of 2.5Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46Gy in 23 fractions with simultaneous integrated boost. ResultsA total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4years and 3.96years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6months, 1year and 5years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6months, 1year and 5years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P=0.0028 for both). ConclusionExternal radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses.

Long-Term Results of Bladder Preservation With Twice-Daily Radiation Plus 5-Fluorouracil/Cisplatin or Daily Radiation Plus Gemcitabine for Muscle-Invasive Bladder Cancer—Updated Report of NRG/RTOG 0712: A Randomized Phase 2 Trial

Purpose5-FU/cisplatin and twice-daily radiation (FCT) or gemcitabine and once daily radiation (GD) are effective chemoradiation (CRT) regimens for bladder sparing treatment of muscle-invasive bladder cancer (MIBC). This trial evaluated these regimens and demonstrated efficacy with either regimen at 3 years. With further follow-up, longer term results are reported here. Methods and MaterialsPatients with cT2-4a MIBC were randomized to FCT or GD. Patients had a transurethral resection and induction CRT to 40 Gy. Patients with a complete response (CR) received consolidation CRT to 64 Gy. Others had cystectomy. Adjuvant gemcitabine/cisplatin chemotherapy was administered. The primary endpoint was freedom from distant metastasis (FDM). This updated analysis reports 7-year data. Toxicity and efficacy endpoints, including bladder intact distant metastasis free survival (BI-DMFS) were also assessed. ResultsFrom 12/2008 to 4/2014, 70 patients were enrolled; 66 eligible for analysis, 33 per arm. Median follow-up was 9.1 years for eligible living patients. At 7 years, FDM was 65% and 73% for FCT and GD, respectively. BI-DMFS was 58% (95% CI: 41 – 76) and 68% (95% CI: 51-84), respectively. The post-hoc hazard ratio of 0.75 (95% CI: 0.37-1.55) showed no difference between treatments (p=0.44). Overall survival at 7 years was 48% and 59%. There were 4 and 5 cystectomies performed for FCT and GD, respectively. In the FCT arm, there were 5 (16%), 1 (3%) and 0 grade 3, 4 and 5 late toxicities reported. In the GD arm, there were 7 (23%), 0 and 0. ConclusionsBoth regimens maintained high FDM rates at 7 years. Cystectomy rates were low and overall survival rates high on both arms. Late toxicity rates were low. Either gemcitabine and daily radiation or a cisplatin-based regimen are effective bladder sparing therapies.

Treatment outcome of localized prostate cancer using transperineal ultrasound image-guided radiotherapy

BackgroundWe report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT).MethodsA total of 124 patients (median age: 74 y, 46–84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5–7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76–78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2–3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation.ResultsA total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups.ConclusionThese results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

Proton therapy toxicity outcomes for localized prostate cancer: Long-term results at a comprehensive cancer center

BackgroundProton therapy (PT) has unique biologic properties with excellent clinical outcomes for the management of localized prostate cancer. Here, we aim to characterize the toxicity of PT for patients with localized prostate cancer and propose mitigation strategies using a large institutional database. MethodsWe reviewed medical records of 2772 patients with localized prostate cancer treated with definitive PT between May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 849]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 117]. Descriptive statistics and Kaplan-Meier estimates assessed toxicity and freedom from biochemical relapse (FFBR). ResultsMedian follow-up was 7.0 years. The median dose was 78 Gy(RBE)(range: 72–79.2 Gy) in 2.0 Gy(RBE) fractions; 63 % of patients received 78 Gy(RBE) in 39 fractions, and 29 % received 76 Gy(RBE) in 38 fractions. Overall rates of late grade ≥3 GU and GI toxicity were 0.87 % and 1.01 %, respectively. Two patients developed grade 4 late GU toxicity and seven patients with grade 4 late GI toxicity. All patients experiencing severe late grade 4 toxicities were treated to 78 Gy(RBE) in 39 fractions with 80 Gy(RBE) dose to the anterior rectal wall and/or bladder neck. The 10-year FFBR rates for patients with LR to U-IR disease were compared between those treated with 76 and 78 Gy(RBE); the rates were 94.5 % (95 % confidence interval [CI] 92.4–96.0 %) and 93.2 % (95 % CI 91.3–95.7 %), respectively (log-rank p = 0.22). ConclusionsProton therapy is associated with low rates of late grade ≥3 GU and GI toxicity. While rare, late grade 4 toxicities occurred in nine (0.3 %) patients. De-escalation to a total dose of 76 Gy(RBE) yields excellent clinical outcomes for patients with LR to U-IR disease with the potential for significant reductions in grade ≥3 late toxicity.

Evaluating a hypofractionated radiotherapy schedule for prostate cancer at an institution in South Africa

Background: Hypofractionated radiotherapy (HFRT) in the treatment of prostate cancer (PCa) has logistical and cost advantages, especially in a resource constrained setting. Studies have demonstrated equivalent efficacy with HFRT schedules using Intensity Modulated Radiation Therapy (IMRT) as treatment modality. However, higher rates of acute and late gastrointestinal (GI) and genitourinary (GU) toxicity have been reported when compared to conventionally fractionated radiotherapy (CFRT). In this study, we evaluate the efficacy and toxicity rates of a HFRT schedule using 3D conformal radiotherapy (RT) as treatment modality.Aim: With this study, we aim to describe the safety and outcomes of a definitive HFRT schedule used for localised PCa. We hypothesise that there is no difference in the biochemical relapse rate and incidence rates of normal tissue toxicities between patients receiving CFRT and HFRT schedules.Setting: This RT schedule was used at Tygerberg Academic Hospital in South Africa for the treatment of localised prostate cancer.Methods: This is a retrospective study in which the records of patients diagnosed with localised PCa were reviewed. Patients were treated with either CFRT regimen to a total of 74Gy in 37 daily fractions for 5 days a week or a HFRT regimen to a total of 65Gy in 26 daily fractions for 4 days per week.Results: In all, 116 patients were included in the study with a median follow-up of 57.2 months from the start of RT. No statistically significant differences in overall survival (OS) and biochemical relapse-free survival were found between the two schedules. A significant difference in acute GI toxicity was observed, with a higher incidence noted in the HFRT schedule. No significant differences were observed in late GI toxicity or in early and late GU toxicities.Conclusion: This study observes a hypofractionated regimen using three-dimensional conformal radiation therapy (3DCRT) with similar efficacy and RT-related toxicities to CFRT.Contribution: The HFRT schedule used in this study could be useful in hospitals with limited access to resources.

Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer

ObjectivesLocally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer. MethodsPatients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates. Results19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed. ConclusionsLattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.

A randomised trial of short- vs long-term androgen deprivation with salvage radiotherapy for biochemical failure following radical prostatectomy: URONCOR 06-24.

Salvage radiotherapy (SRT) and androgen-deprivation therapy (ADT) are widely used in routine clinical practice to treat patients with prostate cancer who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, there is no standard-of-care consensus on optimal duration ADT. Investigators propose three distinct risk groups in patients with prostate cancer treated with SRT in order to better define the indications and duration of ADT combined with SRT. The URONCOR 06-24 trial (ClinicalTrials.gov identifier NCT05781217) is a prospective, multicentre, randomised, open-label, phase III, clinical trial. The aim of the trial is to determine the impact of short-term (6 months) vs long-term (24 months) ADT in combination with SRT on distant metastasis-free survival (MFS) in patients with prostate cancer with BCR after RP (intermediate and high risk). The primary endpoint is 5-year MFS rates in patients with prostate cancer treated with long- vs short-term ADT in combination with SRT. Secondary objectives are biochemical-relapse free interval, pelvic progression-free survival, time to start of systemic treatment, time to castration resistance, cancer-specific survival, overall survival, acute and late toxicity, and quality of life. Total of 534 patients will be randomised 1:1 to ADT 6 months or ADT 24 months with a luteinizing hormone-releasing hormone analogue in combination with SRT, stratified by risk group and pathological lymph node status. The study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals. EudraCT number 2021-006975-41.

Salvage radiotherapy for locally recurrent cervical and endometrial carcinoma: clinical outcomes and toxicities

BackgroundThe management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma.MethodsThe study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan–Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5.ResultsDuring a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1–2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1–2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients.Conclusions3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Stereotactic Magnetic Resonance–Guided Daily Adaptive Radiation Therapy for Localized Prostate Cancer: Acute and Late Patient-Reported Toxicity Outcomes

ObjectiveTo report acute and late bowel, urinary and sexual dysfunction patient reported outcome measures (PROMS), amongst localised prostate cancer patients who underwent Stereotactic MRI-guided daily adaptive radiotherapy (SMART). MethodsAll patients who completed a baseline 12 item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), before undergoing 36.25 Gy in 5 fractions by SMART, were subsequently followed up with the same graded questionnaire at set time points. Latest PSA levels were recorded. The percentage of patients who reported no change from their baseline AE or reported a new ≥ ‘frequent’ or’ severe’ AE grade during follow up was calculated. The maximum PRO-CTCAE grade for each item was recorded for each patient. The percentage of toxicity levels for each separate AE item at set time points were calculated. ResultsThe total number of patients was 69 with a median follow-up of 27 months. Median age of cohort 73 (range 54-85). The median pre-treatment PSA, T stage and Gleason score was 7.5 mmol/l (4.5-32 mmol/l), T2b (T2-T3b) and Gleason Score of 7 (3+4, range: 6-9) respectively. No patient had biochemical failure during follow up. Regarding bowel symptoms, >80% of men reported no change from baseline toxicity during follow up. New ≥ frequent diarrhoea was reported in 9% of patients. ‘Almost constant’ diarrhoea peaked at 1 month but was absent at >33 months. Regarding urinary symptoms, increased urinary urgency was the most common complaint (39%). 20% of men reported new ≥ frequent urinary urgency incidence peaking at 1 month but absent at >33 months. New “severe” sexual dysfunction was seen in 26% of patients and was persistent at >33 months. ConclusionOur study is one the largest patient reported outcomes study post prostate SMART. It shows acceptable levels of toxicity even up to 2 years post treatment.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.