Irradiated Patients Research Articles

Clinical dental management of the head and neck irradiated patient

To discuss important topics regarding the dental procedures performed in patients before, during and after the radiotherapy treatment. The biological effects of ionizing radiation on bone tissue focusing on clinical care will be described. The invasive and not invasive procedures after radiotherapy treatment in the head and neck region will be addressed using scientific evidences to determine the appropriate moment for tooth extractions, periodontal management, and preventive procedures for osteoradionecrosis. Methods: Thirty-three studies including original studies and reviews were selected in MEDLINE database (PubMed). No year of publication restriction was applied. Language was restricted to the English, and the following Medical Subject Heading terms were used: radiotherapy, osteoradionecrosis, dental management. Studies of osteoradionecrosis involving clinical management of irradiated patients, with an emphasis on updated guidelines and protocols were selected. Results: Care in dental procedures were related about restorative treatment, endodontic treatment, rehabilitation for edentulous regions using prostheses and implants and periodontal procedures before, during and after RTX treatment. Conclusions: The dental procedures should and can be performed before, during but also after radiotherapy. However, the clinical procedures should be less invasive as possible. A maintenance plan that reduces the necessity for major and more invasive treatments after radiotherapy is recommended.

THU215 Treatment Of Childhood-onset Craniopharyngioma Patients Using Proton Beam Therapy Versus Photon-based Radiation Therapy In The Prospective Kraniopharyngeom 2007 Trial

Abstract Disclosure: C. Friedrich: None. S. Boekhoff: None. P. Sowithayasakul: None. M. Eveslage: None. J. Beckhaus: None. B. Bison: None. B. Timmermann: None. H.L. Muller: None. Proton beam therapy (PBT) compared to photon-based radiotherapy (XRT) offers the benefit to administer lower radiation doses to critical organs thereby possibly minimizing the risk of sequelae in patients with residual craniopharyngiomas (CP) after hypothalamus-sparing surgery. The validation in large CP patient cohorts is still pending. Of 290 childhood-onset CP patients included 2007-2019 in the prospective multicenter trial KRANIOPHARYNGEOM 2007, 99 (34%) received external RT (65% PBT, 35% XRT). Outcome was compared between the different groups in terms of overall (OS) and event-free survival (EFS), quality of life (QoL using PEDQOL), functional capacity (FMH), and auxological data (BMI and height SDS) one, three and five years after irradiation/CP diagnosis. PBT became the predominant irradiation technique during the study period (used in 23% and 77% of all irradiated patients registered within the first and second half of the enrollment period, respectively). PBT as well as XRT were associated with high (p<0.001) EFS (PBT: 0.917 ± 0.040; XRT: 0.940 ± 0.041) compared to non-RT (EFS: 0.669 ± 0.044). OS was similar in all groups. No differences between PBT, XRT and non-RT CP patients concerning functional capacity and anthropometric parameters (height SDS, BMI SDS) have been obtained. Only in the PEDQOL domain “physical function”, proxy-assessed QoL was lower one year after PBT when compared to XRT treated and non-irradiated CP patients. PBT is similar efficient in preventing relapses in childhood-onset CP patients. During follow-up, clinically relevant differences between PBT and XRT in terms of QoL, functional capacity and degree of obesity as a marker of hypothalamic syndrome were not detectable. While PBT is increasingly applied, studies on larger CP cohorts with longer follow-up after RT are warranted to analyze, whether it can prevent sequelae such as hypothalamic syndrome and severe obesity compared to XRT. Presentation: Thursday, June 15, 2023

The Role of Coronary Artery Calcium Score to Assess Risk of Cardiovascular Disease in Irradiated Esophageal Cancer Patients

Coronary artery calcium (CAC) score is an important predictive imaging marker of cardiovascular disease (CVD). While studies have found positive association between CAC score and cardiac toxicity in irradiated lung and breast cancer patients, there are no studies assessing CAC scores in esophageal cancer (EC). While a cardiac-gated CT is required for standard Agatston CAC score, visual assessment of CAC via ordinal scoring on non-gated CT has shown good concordance with Agatston score. In this study, we sought to examine whether visual assessment of CAC, measured on standard of care, non-contrast chest CT, predicts the development of adverse cardiovascular events (ACVE) in irradiated EC patients. This is a single institution retrospective study of EC patients treated with RT from 2010-2021. We included patients with available PET/CT at diagnosis or chest CT simulation scan without contrast, and excluded those with history of percutaneous coronary intervention, coronary bypass surgery, or prior thoracic RT. Pre-treatment characteristics, clinical factors, and grade ≥ 3 (G3+) adverse cardiovascular events (ACVE) (CTCAEv5.0) were evaluated. Visual assessment of CAC was performed using ordinal method (CAC scored from 0 to 12), by a thoracic radiologist. Fine and Gray regression was used to compute hazard ratios for time to first ACVE. Univariate analyses using Cox proportional hazards were used for overall survival (OS). ACVEs were recorded from start of oncologic treatment and OS calculated after completion of RT. A total of 118 patients were analyzed with a median follow-up of 16 months. Median age was 67 years, 65% male, 43% white, 59% with EC of distal esophagus, and 59% had squamous cell carcinoma. Median mean heart dose was 21.93 Gy (range 0.15-36.94). 24% developed G3+ ACVEs: atrial fibrillation 9%, stroke 6%, heart failure 4%, pulmonary embolism 4%, pericardial effusion 3%, myocardial infarction 2%, heart block 2%, and cardiac death 1%. On univariate analyses, CAC >1 vs. CAC ≤ 1 trended towards increased risk of ACVE (HR = 1.95, 95% CI = 0.89-4.26; p = 0.094), however it is not predictive of OS (HR = 1.31, 95% CI = 0.75-2.30; p = 0.343). Proportion of patients with ACVEs was greater in CAC>1 group (Table). When compared to patients with CAC ≤ 1, those with CAC >1 were older (median age 62 vs 72 years, p = 0.0015), less likely to be never smokers (38% vs 30%, p = 0.0437), and more likely to have hypertension (43% vs 64%, p = 0.0197), and hyperlipidemia (30% vs 47%, p = 0.0557). This is the first study to investigate the relationship between CAC score and ACVEs in EC. While the study was underpowered (likely due to low rates of recorded ACVEs), to detect a significant association between CAC score and ACVEs, there was a trend towards increased risk of ACVEs in patients with a CAC score >1 by visual ordinal scoring. Further prospective evaluation with a larger cohort is warranted.

Radiotherapy Utilization and Outcomes on a Contemporary Trial for Pediatric High-Risk Hodgkin Lymphoma Study

Contemporary trials in pediatric Hodgkin lymphoma (cHL) evaluate strategies to reduce radiotherapy (RT) utilization while maintaining excellent progression-free survival (PFS). An alternative strategy is to irradiate selective sites at higher risk of relapse, and/or use proton therapy (PT) to minimize exposure to healthy tissue. We investigated the use of PT and photon therapy (XRT) and associated early outcomes among patients receiving involved site RT (ISRT) to high-risk sites on the Children's Oncology Group (COG) trial AHOD1331 (NCT021664643). This multicenter randomized, open-label phase 3 study enrolled patients 2-21 years (yrs) with previously untreated cHL: stages IIB + bulk, IIIB, IVA, IVB. Patients were randomized to 5 cycles of either ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) or the brentuximab vedotin (BV) containing regimen BV-AVE-PC given every 21 days. ISRT to 21 Gy was given to bulky mediastinal adenopathy and slow responding lesions (SRL) defined by 5-point score 4 or 5 on PET-CT after 2 cycles. ISRT could be delivered as 3D conformal XRT (3D), intensity modulated XRT (IMRT), or proton therapy (PT). Utilization of RT was compared by mode and by study enrollment midpoint among irradiated patients. Severe acute toxicity assessment included any incident grade 3 or higher toxicity during the ISRT period, except for neuropathy. Among 587 eligible patients who were enrolled across 153 institutions between March 2015 and August 2019 with a median follow up of 43.1 months, the 3-yr PFS was 82.5% (90% CI, 78.3%-85.9%) with ABVE-PC and 92.5% (90% CI 89.5%-94.6%) with BV-AVE-PC (p = 0.0002). There was no difference in ISRT receipt or modality by study arm (p = 0.33). Among those who received RT 69.7% received it due to bulky mediastinal adenopathy, 6.6% due to SRL, and 23.7% for both. Overall, 317 (54.0%) patients received protocol RT of which 28.7% received 3D, 44.8% received IMRT, and 26.5% received PT. PT utilization increased over the course of the study from 21.5% among the first 50% of irradiated patients to 31.5% in the second half of irradiated patients (p = 0.045). The 3-yr progression-free survival rates overall by RT were comparable: PT (88.0%, 90% CI 80.6% - 92.7%%); XRT (87.1%, 90% CI 82.9%-90.4%) (p = 0.85). No difference in PFS was observed between 3D versus IMRT (p = 0.65). No differences were observed in severe acute toxicities (8.33% vs. 8.15%, p = 0.96) between PT and XRT. Selective use of RT results in excellent outcomes for pediatric patients with high-risk HL and combination chemotherapy inclusive of the novel agent BV. Over the course of the study, PT utilization increased as an RT modality. Early results suggest that PT does not compromise disease control and has similar acute toxicity as XRT. Long term follow-up (>10 years) is needed to evaluate for secondary malignancies and cardiac toxicity among the different RT modalities.

Comparison of Estimated Late Toxicities between IMRT and IMPT when Treating Retroperitoneal Sarcoma Preoperatively with Ultra-Hypofractionation

While preoperative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. The risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. Thus, finding methods to mitigate the issues of delaying surgery and irradiating normal tissue may provide a path towards affording the benefits of radiation while limiting its downside. One potential solution involves the use of hypofractionation to limit delay from radiation initiation to surgery, and proton therapy to limit dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of preoperative ultra-hypofractionated intensity-modulated photon radiotherapy (IMRT) and proton therapy (IMPT) for RPS, comparing estimated rates of late toxicity using published normal tissue complication probability (NTCP) models. Volumetric modulated arc therapy IMRT and IMPT plans were generated on 10 RPS patients previously treated with preoperative radiation. The prescription was 25 Gy radiobiological equivalent (GyE) to the clinical target volume (CTV) and 30 GyE to the margin-at-risk, all in five fractions. Proton doses were calculated using a radiobiological effective dose of 1.1. NTCPs were calculated for each OAR as a function of equivalent uniform dose. The ΔNTCP (difference in absolute NTCP between IMRT and IMPT plans) for each of the toxicity domains was calculated. Student T-tests were used to compare differences in dosimetric and NTCP outcomes. CTV coverage was met for all IMRT and IMPT plans with >99% of CTVs receiving ≥100% of prescription doses. The following endpoints were significantly lower with IMPT than IMRT: mean doses to liver, bone, and all analyzed genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. No OAR endpoint was significantly higher with IMPT. The average ΔNTCP for grade 3 bowel ulceration/perforation and renal toxicity was 1.9% (p = .037) and 43.0% (p = .023), respectively, favoring IMPT. Using a model-based selection threshold of any ΔNTCP >10%, 50% (n = 5) of patients would be eligible for IMPT. IMPT maintained target coverage while significantly reducing dose to adjacent OARs and integral dose compared to IMRT. This translated to significantly lower risks of estimated late gastrointestinal and renal toxicities with IMPT. Further investigation is warranted to validate these findings and potential clinical benefit in the management of RPS. A prospective trial treating RPS with preoperative ultra-hypofractionated IMPT at our institution is currently being pursued (NCT05302570).

Pancreatic Cancer Outcome: Local Treatment with Radiation Using MRI-Linac

Stereotactic MR-guided on-table adaptive radiotherapy (SMART) is a surging modality in radiotherapy, delivering high dose radiation to the tumor in great proximity to susceptible organs. The aim of this study is to evaluate the clinical outcome in locally advanced or recurrent pancreatic tumors with or without prior irradiation. All consecutive patients were treated in our center for pancreatic cancer (PC) using SMART technology to a prescription of 50Gy (BED10 100 Gy1o) in 5 fractions, with daily on-table adaptation of treatment plan. Endpoints for this retrospective, single center, IRB approved study were local control, overall survival, local disease-free period, acute and late toxicities. Fifty-four PC patients were treated between 8.2019-9.2022, with median follow-up of 8.9 months from SMART (0.8-34 months). Forty patients had upfront inoperable PC (45% were metastatic at RT, five treated to liver metastatic lesions concomitantly) and fourteen patients had local recurrence following prior pancreatectomy, six of them had prior adjuvant RT. 87% received at least one round of chemotherapy (Oxaliplatin based- 72%), 25% received ≥2 regimens. Mean age was 68.9 (45-86) years. There was no significant difference in baseline parameters between prior pancreatectomy and inoperable groups. On-table adaptive replanning was performed for 100% of all (269) fractions (one patient received 4 fractions). No patient reported grade ≥2 acute GI toxicity. Six patients reported fatigue at the end of RT, four of them had prior radiation. Forty-eight patients were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for median of 9 months (2.8-28.8 months), three had later local progression. Eight patients had regional or marginal recurrence following treatment. 6-months and 12-months OS was 75% and 52%, respectively. There was no significant difference in toxicity and outcome between post-pancreatectomy and inoperable groups. Pancreatic cancer local ablative SMART is safe, with minimal treatment-related toxicity, even in previously irradiated patients. Local control with complete response was achieved by 20% of patients. Further studies are needed to evaluate long-term outcome and late toxicity.

CANTO: Skin Toxicities Evaluation of a Multicenter Large Prospective Cohort of Irradiated Patients for Early-Stage Breast Cancer

Skin damage is a common toxicity during oncology management. Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients treated for an early breast cancer (BC). CANTO (NCT01993498) is a prospective, multicentric, clinical cohort study of 11 400 patients with stage I-III BC, treated in 26 French cancer centers. In this study, we will evaluate the 8561 patients during their overall management for a BC. We are focus on specifical skin toxicities: Erythema, fibrosis, telangiectasia and skin color (CTCAE v4.0). These toxicities were assessed at 3-6 (M0), 12 (M12), 36 (M36), 60 (M60) months. The prevalence of toxicities of interest varied over time, so at M0, 30.4% of patients had erythema while 17.7% of patients had fibrosis. At M12, M36 and M60, the prevalence of erythema decreased from 5.5 % to 2.5 % then to 2 %, respectively, while fibrosis remained stable at about 19 %. The prevalence of telangiectasia increased from 0.8 % to 7 % from M0 to M60. While the modification of skin color was 51.1 % at M0, and 10.6 % at M60. After adjustments, at M0, there was a statistically significant association between the onset of cutaneous erythema and obesity, the presence of axillary dissection, the type of surgery the age of the patient as well as the tumor phenotype RH+/HER2+ [OR: 0.79 [0.67; 0.93]]. Concerning fibrosis, a statistically significant association was found, at M12, with the age of the patient, obesity, tumor grade, Charlson score, type of surgery and mitotic index. Obesity and the age of the patient represent at M12 and M36 a risk significantly associated with the onset of telangiectasia. Concerning the modification of skin color at M12, we find a link between the age of the patient, obesity, tobacco consumption, tumor grade, Charlson score, type of surgery, and alcohol consumption [OR: 0.69 [0.51; 0.91]]. In this study we identified several risk factors for acute and late skin toxicity. The knowledge of its predictive factors allows a personalized management of the patient by adapting our treatments and our monitoring according to these different factors.

Which Patients With Rhabdomyosarcoma Need Radiotherapy? Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry.

To analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5). The 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT. RT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Comparison of patient-reported achievements of goals and core outcomes with delayed breast reconstruction in irradiated patients: latissimus dorsi with an implant versus DIEP.

Different women's individual goals with a breast reconstruction vary, and few studies compare techniques in light of the different goals. This study aimed to compare patient-reported core outcomes in patients reconstructed with deep inferior epigastric artery perforator (DIEP) flaps and latissimus dorsi (LD) flaps. Second, breast-related factors that the patients were particularly satisfied/dissatisfied with were analyzed. This was a retrospective cross-sectional study, which includes women who had undergone mastectomy and radiation, followed by delayed breast reconstructions with either LD flap and implant or DIEP flap during 2007-2017. The patient-reported core outcomes of overall breast-specific quality of life, normality, women's cosmetic satisfaction, self-esteem, emotional well-being, and physical well-being were analyzed using BREAST-Q. The patients were divided into LD and implant (n = 135 patients) and DIEP (n = 118 patients) groups, and both were demographically similar. The median follow-up was 8 years. The DIEP group scored significantly higher than the LD and implant group in five out of six domains. A high satisfaction was reported in questions regarding the feeling or appearance when having clothes on, whereas the greatest dissatisfaction was reported regarding questions entailing symmetry and the appearance without clothes. After 7 years, patients' breast-specific quality of life, normality, women's cosmetic satisfaction, self-esteem, emotional well-being, and physical well-being seem to be higher in irradiated patients who have been reconstructed with DIEP flap as compared to patients reconstructed with LD flap and implant. In both groups, patient satisfaction is high regarding their appearance when clothed, whereas the lowest satisfaction scores were reported in situations without clothing.

Pelvic Extirpative Surgery for the "End-Stage Irradiated Bladder".

Men with prostate cancer have the daunting task of selecting from multiple modalities of treatment. The long-term effects of radiation therapy are only now being recognized. For both patients and surgeons, the end-stage irradiated bladder poses numerous problems and challenges. Specifically, irradiated bladders with urosymphyseal fistula, radiation cystitis, and rectourethral fistula are challenging to manage and treat. This review outlines the presentation, workup, and management including cystectomy for these three devastating late complications of radiation therapy. There are special considerations when performing benign cystectomy that are not typically considered during oncologic cystectomy. We discuss an overview of the current literature regarding the "end-stage bladder" resulting from radiation therapy and the important considerations that must be acknowledged when managing these patients. It is shown that many of the less invasive and conservative options ultimately lead to cystectomy. Indeed, our review concludes that cystectomy with urinary diversion is a safe and viable option in select irradiated patients with the goal to improve quality of life.

Evaluation of changes in thyroid volume and selected parameters on Doppler ultrasound examination in radically irradiated patients with primary cancers of the head and neck region – preliminary report

Introduction: Implementation of even the most advanced radiotherapy techniques is still associated with a risk of damaging healthy tissues and organs by ionizing radiation. Structural and functional abnormalities of the thyroid gland have been reported in patients after radiotherapy administered for head and neck cancers (HNC). Aim: Ultrasound evaluation of changes in thyroid volume, characteristics of blood flow in the right inferior thyroid artery (ITA) and vascular invasion (VI) of the thyroid gland in patients radically irradiated due to primary HNC. Material and methods: The study group consisted of 20 patients who underwent ultrasound examinations at three time points: prior to commencing radiotherapy (I), in the first week after completion of radiotherapy (II) and after another 3–6 months (III). Results: The mean radiation dose absorbed by the thyroid gland was 54.95 6.95 Gy. The mean thyroid volume measured at the first time point was 17.14 (13.74–23.43) cm3 and this result turned out to be higher as compared to measurements obtained in the second and third examinations: 15.92 (12.51–20.35) cm3 with p<0.001; 15.01 (11.16–18.92) cm3 with p<0.001, respectively. Thyroid volume from the second examination was also greater than in the third examination (p<0.001). Evaluation conducted at time point II showed an increase in the following vascular flow parameters: peak systolic velocity (PSV), pulsatility index (PI) and resistivity index (RI) measured in the ITA, as well as an increase in thyroid VI in comparison to results from time point I. Furthermore, a decrease of the above-mentioned values was observed at time point III as compared to time point II. However, the ultrasound vascular characteristics measured in the ITA and VI of the thyroid gland were still higher on examination III when compared to the initial values. Conclusions: We have observed that radiotherapy leads to a decrease in thyroid volume, which is found to be progressing for at least 3–6 months after treatment completion. Post-radiotherapy changes in vascular parameters of the ITA and VI value measured on Doppler ultrasound partially resolve within 3–6 months after the end of radiation treatment.

Ankle fracture internal fixation performed by cadaveric simulation-trained versus standard-trained orthopaedic trainees: a preliminary, multicentre randomized controlled trial.

Ankle fracture fixation is commonly performed by junior trainees. Simulation training using cadavers may shorten the learning curve and result in a technically superior surgical performance. We undertook a preliminary, pragmatic, single-blinded, multicentre, randomized controlled trial of cadaveric simulation versus standard training. Primary outcome was fracture reduction on postoperative radiographs. Overall, 139 ankle fractures were fixed by 28 postgraduate year three to five trainee surgeons (mean age 29.4 years; 71% males) during ten months' follow-up. Under the intention-to-treat principle, a technically superior fixation was performed by the cadaveric-trained group compared to the standard-trained group, as measured on the first postoperative radiograph against predefined acceptability thresholds. The cadaveric-trained group used a lower intraoperative dose of radiation than the standard-trained group (mean difference 0.011 Gym2, 95% confidence interval 0.003 to 0.019; p = 0.009). There was no difference in procedure time. Trainees randomized to cadaveric training performed better ankle fracture fixations and irradiated patients less during surgery compared to standard-trained trainees. This effect, which was previously unknown, is likely to be a consequence of the intervention. Further study is required.

Antibacterial, antibiofilm and anticaries effect of BioXtra® mouthrinse for head and neck cancer (HNC) patients under a microcosm biofilm model

Background and purposeConsidering the lack of studies investigating salivary substitutes to control post-radiation caries for patients with head and neck cancer (HNC), this study aimed to evaluate the antibacterial, antibiofilm, and anticaries effects of BioXtra® on the microcosm biofilm formed on different enamel types (non-irradiated and irradiated) and from distinct saliva sources (control and HNC patients). Materials and methodsNon-irradiated and irradiated enamel specimens were treated with BioXtra®, phosphate-buffered-saline (PBS; negative control), or 0.12% chlorhexidine (CHX; positive control) for 1 min. Biofilm was produced from human saliva (healthy participants with normal salivary flow for the control group or irradiated HNC patients with hyposalivation for the HNC group), mixed with McBain saliva, under 0.2% sucrose exposure, daily submitted to the treatments (1 min), for 5 days. Bacterial metabolic activity, biofilm viability, CFU counting, and enamel demineralization were determined. ResultsBioXtra® significantly reduced the bacterial metabolic activity for both enamel types and the inoculum sources, being more effective for the irradiated enamel or for the saliva from the control group. Similarly, BioXtra® significantly reduced the biofilm viability, the CFU for total microorganisms, mutans streptococci, and lactobacilli, and was able to significantly reduce the mineral loss and the lesion depth compared to PBS. CHX was an effective treatment to significantly reduce all parameters, performing better than BioXtra® and reinforcing its reliable efficiency as a positive control. ConclusionRegardless of the enamel type and the inoculum source, BioXtra® presented antibacterial, antibiofilm, and anticaries effects under this experimental model, which should be confirmed in further clinical studies.

Urethral Slings for Irradiated Patients With Male Stress Urinary Incontinence: A Meta-analysis

To systematically compare success, cure and complication rates of urethral sling surgeries in stress urinary incontinence patients with and without a history of pelvic radiotherapy (RT). We searched PUBMED, EMBASE, and Web of Science to identify relevant articles. The primary outcomes were the success and cure rates. The secondary outcomes included the rates of infection, urethral erosion, total complications, explantation, and satisfaction. Outcomes were analyzed using a random-effects model to calculate the unadjusted odds ratio (OR) in patients with a history of RT compared with those without prior RT. On pooled analysis, we found significantly lower odds of success (OR 0.68; 95% confidence interval [CI] 0.53-0.87, P<.001) and cure (OR 0.67; 95% CI 0.55-0.82, P<.001) in radiated patients than in nonirradiated patients. Subgroup analysis by type of sling showed significantly lower odds of success in Advance subgroup (OR 0.66; 95% CI 0.45-0.95, P<.001) and significantly lower odds of cure in Advance (OR 0.59; 95% CI 0.36-0.95, P<.001) and Atoms subgroups (OR 0.70; 95% CI 0.54-0.93, P<.001). We also found significantly greater odds of sling explantation (OR 2.93; 95% CI 1.62-5.29, P<.001) and infection (OR 3.06, 95% CI 1.03-9.07, P<.001) in radiated patients than in nonradiated patients. Patients with a history of pelvic RT have lower odds of success and cure and higher odds of infection and sling explantation than those without a history of pelvic RT.

Effects on the Hypothalamo-Pituitary Axis in Patients with CNS or Head and Neck Tumors following Radiotherapy.

Knowledge about the precise effects of radiotherapy on hypothalamo-pituitary functions is limited. Reduction of side effects is a major goal of advanced radiotherapy modalities. We assessed strategies for monitoring and replacement of hormone deficiencies in irradiated patients. A search strategy was systematically conducted on PubMed®. Additional articles were retrieved to describe endocrine mechanisms. 45 studies were evaluated from 2000 to 2022. They were predominantly retrospective and highly heterogeneous concerning patient numbers, tumor types, radiotherapy technique and follow-up. Endocrine deficiencies occurred in about 40% of patients within a median follow-up of 5.6 years without a clear difference between radiotherapy modalities. Somatotropic and thyrotropic axes were, respectively, the most and least radiosensitive. Current pituitary gland dose constraints may underestimate radiation-induced endocrine deficiencies, thus impairing quality of life. Little difference might be expected between radiation techniques for PG tumors. For non-PG tumors, dose constraints should be applied more systematically.

Checkpoint Inhibitors in Combination With Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors

Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors. This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non-small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023. Patients were randomized (1:1) to receive anti-PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions). The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population. Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred. This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS. ClinicalTrials.gov Identifier: NCT03511391.

Major outcomes of dental implants in oncological patients: a concise systematic review

Introduction: The etiology of oral cancer is multifactorial resulting from several factors that predispose to the development of this pathology. The rehabilitation of oral functions after jaw surgery in patients with oral cancer is a goal that is often difficult to achieve. Dental implants offer a mechanism to provide stability to prostheses. Objective: This study aimed to present the main outcomes of dental implants in cancer patients. Methods: The systematic review rules of the PRISMA Platform were followed. The search was carried out from February to May 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using articles from 2013 to 2023. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 118 articles were found, 34 articles were evaluated in full and 14 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 32 studies with a high risk of bias and 32 studies that did not meet GRADE. It was concluded that implants inserted into irradiated bone showed significantly lower survival. Head and neck radiotherapy has always been considered a risk factor for rehabilitation with dental implants. However, recent data suggest that the overall 5-year implant survival in irradiated patients may be greater than 90%.

Vestibuloplasty and its impact on the long-term survival and success of dental implants in irradiated and non-irradiated patients after head and neck tumor therapy: a retrospective study

ObjectivesThis study aimed to evaluate the influence of vestibuloplasty on the clinical success and survival of dental implants in head and neck tumor patients.Materials and methodsA retrospective single-center study was conducted. All patients received surgical therapy of a tumor in the head or neck and underwent surgical therapy and, if necessary, radiotherapy/radiochemotherapy. Patients with compromised soft tissue conditions received vestibuloplasty using a split thickness skin graft and an implant-retained splint. Implant survival and success and the influence of vestibuloplasty, gender, radiotherapy, and localizations were evaluated.ResultsA total of 247 dental implants in 49 patients (18 women and 31 men; mean age of 63.6 years) were evaluated. During the observation period, 6 implants were lost. The cumulative survival rate was 99.1% after 1 year and 3 years and 93.1% after 5 years for patients without vestibuloplasty, compared to a survival and success rate of 100% after 5 years in patients with vestibuloplasty. Additionally, patients with vestibuloplasty showed significantly lower peri-implant bone resorption rates after 5 years (mesial: p = 0.003; distal: p = 0.001).ConclusionThis study demonstrates a high cumulative survival and success rate of dental implants after 5 years in head and neck tumor patients, irrespective of irradiation. Patients with vestibuloplasty showed a significantly higher rate of implant survival and significantly lower peri-implant bone resorption after 5 years.Clinical relevanceVestibuloplasty should always be considered and applied if required by the anatomical situations to achieve high implant survival/success rates in head and neck tumor patients.

Is the Standard Artificial Urinary Sphincter AMS 800 Still a Treatment Option for the Irradiated Male Patient Presenting with a Devastated Bladder Outlet?

Circular urethral compression with an artificial sphincter allows control of voiding, even in patients with severe stress urinary incontinence, but it heightens the risk of urethral atrophy and erosion. This study of one of the largest populations of patients treated with radiotherapy investigates the additive effect of the post-radiogenic stricture of the membranous urethra/bladder neck on AMS 800 artificial urinary sphincter outcomes. In a retrospective multicenter cohort study, we analyzed patients fitted with an AMS 800, comparing those who had received radiotherapy with patients presenting a devastated bladder outlet (stricture of the membranous urethra/bladder neck). We determined the correlation between these groups of patients using both univariate and stepwise adjusted multivariate regression. The revision-free interval was estimated by a Kaplan-Meier plot and compared by applying the log-rank test. A p value below 0.05 was considered statistically significant. Of the 123 irradiated patients we identified, 62 (50.4%) had undergone at least one prior desobstruction for bladder-neck/urethra stenosis. After a mean follow-up of 21 months, the latter tended to achieve social continence less frequently (25.7% vs. 35%; p = 0.08). Revision was required significantly more often for this group (43.1% vs. 26.3%; p = 0.05) due to urethral erosion in 18 of 25 cases. A stenosis recurred in five cases; desobstruction was performed in two cases, leading to erosion in both. Multivariate analysis revealed a significantly higher risk of revision when recurrent stenosis necessitated at least two prior desobstructions (HR 2.8; p = 0.003). A devastated bladder outlet is associated with a lower proportion of men with social continence and a significantly higher need for revision compared with irradiated patients without a history of urethral stenosis. Alternative surgical procedures should be discussed beforehand, especially in cases of recurrent urethral stenosis.