Inconsistent Associations Between Risk Factor Profiles and Adjuvant Radiation Therapy (ART) Treatment in Patients with Cutaneous Squamous Cell Carcinoma and Utility of the 40-Gene Expression Profile to Refine ART Guidance.

INTRODUCTION: National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. METHODS: A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3 years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. RESULTS: Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. CONCLUSIONS: ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.

Unraveling Skin Carcinoma: A Comprehensive Examination of Diagnosis, Treatment Strategies, and Emerging Therapeutic Avenues in Skin Cancer Management.

Cancer that begins in the skin is by far the most common kind of skin cancer found everywhere in the globe. It is further subdivided into groups, such as basal cell carcinoma and cutaneous squamous cell carcinoma, in addition to other, less common types of skin cancer. In this article, the diagnostic aspects that need to be taken into consideration when utilizing these new guidelines, go over the essential features of cutaneous SCC, conduct an analysis of recent changes in the category of cutaneous SCC, and speak about recent advancements in the categorization of cutaneous SCC. Over the course of the past decade, photodynamic therapy has developed into a potentially effective treatment for a variety of solid tumors that may be found in people. The combination of metallic nanoparticles and phytoconstituents as a therapy for skin cancer has the potential to be more successful than each treatment used independently. In this article, the various treatment modalities for skin cancer were examined. This included excision surgery, Mohs surgery, radiation therapy, and immunotherapy. These were then followed by targeted therapy or immunotherapy, in addition to surgery, radiation, or photodynamic therapy. Since excision surgery is the most typical procedure used to eradicate skin cancer, we concentrate on it in particular.

The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases.

Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 ×10-13 cm3 molecules-1s-1 for adenine, 1.02 ×10-11 cm3 molecules-1s-1 for guanine, 5.52 ×10-13 cm3 molecules-1s-1 for thymine, 1.47 ×10-13 cm3 molecules-1s-1 for cytosine and 7.59 ×10-14 cm3 molecules-1s-1 for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics.

Integrating 40-GEP Testing to Improve Clinical Recommendations for Adjuvant Radiation for Cutaneous Squamous Cell Carcinoma: Multidisciplinary Consensus Guidelines.

Early identification and intervention in patients with cutaneous squamous cell carcinoma (cSCC) who are at high risk for metastasis is important for optimal outcomes. Prognostic tools (e.g., American Joint Committee on Cancer, 8th edition [AJCC-8]) and management guidelines (National Comprehensive Cancer Network® [NCCN]) are useful in helping to identify high-risk patients with cSCC who might benefit from adjuvant therapies, such as radiation and/or immunotherapies; however, traditional staging and management guidelines rely on clinicopathologic risk factors to predict risk, which limits their prognostic accuracy. Gene expression profiling (GEP) is a clinically available, objective metric that can be used in conjunction with traditional clinicopathological staging to help clinicians stratify risk in patients with cSCC. The validated 40-GEP test can accurately classify patients with at least one high-risk feature as being at low (Class 1), higher (Class 2A), or highest (Class 2B) biological risk of nodal or distant metastasis within three years of diagnosis. A multidisciplinary panel comprising radiation oncologists and dermatologists/Mohs micrographic surgeons with expertise in cSCC management convened in June 2023 to discuss the utility of 40-GEP testing in cSCC clinical decision-making in regard to adjuvant radiation therapy (ART). The panel identified gaps in clinical practice in which 40-GEP testing has particular utility: in escalation of care for lower-stage patients with high-risk tumors; in de-escalation of care for patients for whom the risks of ART may outweigh the benefits; and in decision-making regarding elective radiation to the nodal basin. The expert panel developed a risk-based clinical workflow for ART in patients with cSCC, utilizing 40-GEP testing within NCCN management guidelines and AJCC-8 staging.

PET/SPECT/Spectral-CT/CBCT imaging in a small-animal radiation therapy platform: A Monte Carlo study-Part II: Biologically guided radiotherapy.

BACKGROUND: This study addresses the technical gap between clinical radiation therapy (RT) and preclinical small-animal RT, hindering the comprehensive validation of innovative clinical RT approaches in small-animal models of cancer and the translation of preclinical RT studies into clinical practices. PURPOSE: The main aim was to explore the feasibility of biologically guided RT implemented within a small-animal radiation therapy (SART) platform, with integrated quad-modal on-board positron emission tomography (PET), single-photon emission computed tomography, photon-counting spectral CT, and cone-beam CT (CBCT) imaging, in a Monte Carlo model as a proof-of-concept. METHODS: We developed a SART workflow employing quad-modal imaging guidance, integrating multimodal image-guided RT and emission-guided RT (EGRT). The EGRT algorithm was outlined using positron signals from a PET radiotracer, enabling near real-time adjustments to radiation treatment beams for precise targeting in the presence of a 2-mm setup error. Molecular image-guided RT, incorporating a dose escalation/de-escalation scheme, was demonstrated using a simulated phantom with a dose painting plan. The plan involved delivering a low dose to the CBCT-delineated planning target volume (PTV) and a high dose boosted to the highly active biological target volume (hBTV) identified by the 18F-PET image. Additionally, the Bayesian eigentissue decomposition method illustrated the quantitative decomposition of radiotherapy-related parameters, specifically iodine uptake fraction and virtual noncontrast (VNC) electron density, using a simulated phantom with Kidney1 and Liver2 inserts mixed with an iodine contrast agent at electron fractions of 0.01-0.02. RESULTS: EGRT simulations generated over 4,000 beamlet responses in dose slice deliveries and illustrated superior dose coverage and distribution with significantly lower doses delivered to normal tissues, even with a 2-mm setup error introduced, demonstrating the robustness of the novel EGRT scheme compared to conventional image-guided RT. In the dose-painting plan, doubling the dose to the hBTV while maintaining a low dose for the PTV resulted in an organ-at-risk (OAR) dose comparable to the low-dose treatment for the PTV alone. Furthermore, the decomposition of radiotherapy-related parameters in Kidney1 and Liver2 inserts, including iodine uptake fractions and VNC electron densities, exhibited average relative errors of less than 1.0% and 2.5%, respectively. CONCLUSIONS: The results demonstrated the successful implementation of biologically guided RT within the proposed quad-model image-guided SART platform, with potential applications in preclinical RT and adaptive RT studies.

Pre- and Postoperative Antioxidant Use, Aryl Hydrocarbon Receptor (AhR) Activation and Clinical Outcome in Different Treatment Groups of Breast Cancer Patients.

BACKGROUND: Cancer patients often use antioxidants that may interact with adjuvant treatments. The purpose was to investigate pre- and postoperative antioxidant use in relation to clinicopathological characteristics and prognosis in different breast cancer treatment groups. METHODS AND PATIENTS: Pre- and postoperative antioxidant (vitamin A, C, E, carotenoids, or Q10) or multivitamin use was self-reported by patients from Lund (n = 1855) and Helsingborg (n=478), Sweden. Patients were followed for up to 15 years. Clinical data were obtained from patient charts. The aryl hydrocarbon receptor (AhR) was evaluated in tumor tissue arrays from 915 patients from Lund and with Western blot in MCF-7 and MDA-MB-231 cells. RESULTS: About 10% of patients used antioxidants. Nuclear AhR (AhRnuc) positivity was twice as common in preoperative antioxidant users compared to non-users. In mechanistic studies vitamin C increased AhR levels and its downstream target CYP1B1, indicating AhR activation. There were significant interactions between tumor AhRnuc status and preoperative antioxidant use in relation to clinical outcome. In all patients, antioxidant use (other than multivitamins) at both visits was associated with poorer prognosis, while use only at the follow-up visit was associated with better prognosis, compared with no use at either visit. CONCLUSION: The clinical impact of antioxidants depended on antioxidant type, timing of use, and tumor AhR activation. Antioxidants may influence clinical outcome by activation of the master regulator AhR in addition to interference with free radicals. Further studies are needed to identify breast patients that might improve or worsen their prognosis when using antioxidants postoperatively.

A Longitudinal Metagenomic Comparative Analysis of Oral Microbiome Shifts in Patients Receiving Proton Radiation versus Photon Radiation for Head and Neck Cancer.

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation, with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n = 4) were compared to photon radiation (n = 4). Additional control groups included healthy age- and sex-matched controls (n = 5), head and neck cancer patients who never received radiation therapy (n = 8), and patients with oral inflammatory disease (n = 3). Results: Photon therapy patients presented with lower microbial alpha diversity at all timepoints, and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy, in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. The bacterial de novo pyrimidine biosynthesis pathway and the nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for the proliferation of pathogenic bacteria. Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status.

Efficacy of an aloe vera, chamomile, and thyme cosmetic cream for the prophylaxis and treatment of mild dermatitis induced by radiation therapy in breast cancer patients: a controlled clinical trial (Alantel Trials).

BACKGROUND: Dermatitis is a skin condition caused by multiple causes, including radiotherapy treatment. Pharmacological treatments can become chronic and are not exempt from side effects. The latest recommendations of the American Academy of Dermatology establish the use of natural, nourishing, and moisturizing cosmetic products as prevention and the first therapeutic step for dermatitis. Alantel® is a cream developed to reduce redness and irritation, promote the local immune system, combat immunosenescence, and promote the healing of epidermal lesions. The objective was to evaluate the effect of a cream (Alantel) based on natural products at high concentrations for the preventive and curative treatment (at early stages) of radiation-induced dermatitis in patients with breast cancer. METHODS: Our protocol is an experimental, prospective, triple-blind, multicenter, controlled clinical trial with two parallel arms. The experimental group will be treated with Alantel, while the control group will receive another moisturizing cream. Radiotherapy oncology professionals will recruit a total of 88 patients (44 per comparison group) with breast cancer who will receive radiotherapy oncology treatment for 15 days, and they will be randomly allocated to the experimental or control group. Selected patients will be followed up for four visits by primary care physicians for up to 1 week after completion of radiotherapy. The main study variable will be the incidence rate of mild post-radiation dermatitis. An intention-to-treat analysis will be performed, applying a comparison test for independent means and proportions. A bivariate and multivariate analysis will also be developed to check the treatment effect, adjusting for predictive sociodemographic and clinical variables. DISCUSSION: By carrying out this clinical trial, it is expected to verify that Alantel cream, based on natural products at high concentrations, has advantages over a moisturizing cream for the preventive and curative treatment of RD in patients with breast cancer. The COVID-19 pandemic has been influenced by delaying the start of the study. One of the main limitations of this study will be the time required to recruit the patients from the planned sample, given that the selection criteria are restrictive and, although the study is multicenter, recruitment will be coordinated through a single service on radiotherapy oncology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04116151 . Registered on 4 October 2019.

[Radiation-induced morphea-an overview]. / Postradiogene Morphea ­ eine Übersicht.

BACKGROUND: Radiation-induced morphea is a fibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose a significant problem in the care of those patients. OBJECTIVES: The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. RESULTS AND CONCLUSIONS: Radiation-induced morphea is a rare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Intraoperative Radiation Therapy as a Safe Alternative to Whole Breast Radiation for Treatment of Minimally Invasive Breast Cancers: A Retrospective Cohort Study.

BACKGROUND: Intraoperative radiation therapy (IORT) in select populations is a viable alternative to whole breast radiation therapy (WBRT) in the treatment of biopsy-proven localized invasive and non-invasive breast cancer. We aim to assess recurrence and complication rates following IORT in lumpectomy patients at a community hospital in Baltimore City. METHODS: An IRB-approved retrospective cohort study was conducted on consecutive cases of lumpectomy with IORT from 2013 through 2020 by a single surgeon. Patient demographics, tumor and operative characteristics, and complications were retrieved from electronic medical records. Primary outcomes were postoperative complications and local recurrence rates. RESULTS: The final cohort included 117 patients with mean follow-up time of 2.60 + 1.78 years. Mean age was 69.84 + 8.77 years. Thirty-three (28.21%) of patients developed a seroma. Odds of seroma formation were mildly significant for skin spacing [OR: 1.18, 95% CI: (1.02-1.37)] and balloon fill volume [1.04 (1.00-1.08)], but not for age, BMI, diabetes, former or current smoking status, history of WBRT, tumor size, or balloon size. Three (2.6%) patients had local recurrence. Odds of local recurrence were mildly significant for increased tumor size [1.14 (1.04-1.24)] and not significant for any other covariates. CONCLUSIONS: IORT exposure did not confer higher rates of complications and the local recurrence rate mirrored that of the general population undergoing lumpectomy and WBRT. This study demonstrates the need for equitable treatment options based on individual needs: IORT is a safe alternative to WBRT in certain subpopulations, especially those with physical, social, or personal limitations preventing participation in a 3- to 7-week time commitment of WBRT.

Evidence for the use of curcumin in radioprotection and radiosensitization.

Curcumin has antineoplastic properties and is considered a chemotherapeutic and chemopreventive agent. Curcumin may be associated with radiation therapy (RT) as a radiosensitizer for cancer cells and a radioprotector for normal cells. In principle, it may result in a reduction of RT dosage for the same therapeutic effect on cancer cells, and further reduced damage to normal cells. Though the overall level of evidence is modest, limited to in vivo and in vitro experiences and practically no clinical trials, as the risks of adverse effects are extremely low, it is reasonable to promote the general supplementation with curcumin during RT targeting the reduction of side effects through anti-inflammatory mechanisms.

Nutrition outcomes and treatment toxicities in patients with head and neck cancer receiving helical intensity-modulated radiotherapy.

BACKGROUND: Helical intensity-modulated radiotherapy (H-IMRT) provides excellent limitation of dose to tissues not requiring treatment, although acute toxicity still occurs. The present study aimed to determine how treatment-related acute toxicities affect nutrition outcomes in patients with head and neck cancer. METHODS: A prospective observational study was conducted in 194 patients undergoing curative intent H-IMRT with or without other treatment modalities. Weight outcomes (kg) and acute toxicity and dysphagia data were collected during treatment using Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0. RESULTS: Significant weight loss (> 10%) was observed in 30% of high nutritional risk patients and 7% of low nutritional risk patients. Nausea, adjusted for baseline dysphagia, in high nutritional risk patients and nausea, dysphagia and pharyngeal mucositis in low nutritional risk patients were significant factors in explaining the percentage loss in baseline weight to treatment completion. CONCLUSIONS: Significant weight loss remains an issue during treatment, despite improvements in radiotherapy technology and high-level multidisciplinary care.

[Photobiomodulation in the prevention and the management of side effects of cancer treatments: Bases, results and perspectives]. / Photobiomodulation dans la prévention et la prise en charge des effets secondaires des traitements anticancéreux : bases, bilan et perspectives.

BACKGROUND: Assess the current and potential indications of photobiomodulation (PBM) therapy and their level of evidence in the prevention or treatment of side effects related to oncology treatments (radiation therapy, and to a minimal extent favored and hematopoietic stem cell transplants). And report on the recommended modalities (parameters and doses) of PBM therapy. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that evaluated PBM in the prevention or management side effects related to cancer treatments. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "dysgeusia"; "hyposalivation"; "lockjaw"; "bone necrosis"; "osteoradionecrosis"; "radiation induced fibrosis"; "voice and speech alterations"; "palmar-plantar erythrodysesthesia"; "graft versus host disease"; "peripheral neuropathy"; "chemotherapy induced alopecia". Prospective studies were included, while retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has been shown to be effective in randomized controlled trials in the prevention and management of certain complications related to radiotherapy, in particular acute mucositis, epitheliitis and upper limb lymphedema. The level of evidence associated with PBM was heterogeneous, but overall remained moderate. The main limitations were the diversity and the lack of precision of the treatment protocols which could compromise the efficiency and the reproducibility of the results of the PBM. For other effects related to chemo/radiation therapy (dysgeusia, osteonecrosis, peripheral neuropathy, alopecia, palmar-plantar erythrodysaesthesia) and haematopoietic stem cell transplantation (graft versus host disease), treatment with PBM suffers from a lack of studies or limited studies at the origin of a weakened level of proof. However, based on these results, it was possible to establish safe practice parameters and doses of PBM. CONCLUSION: Published data suggest that PBM could therefore be considered as supportive care in its own right for patients treated with radiation, chemotherapy, immunotherapy, hormone therapy or targeted therapies, whether in clinical practice or clinical trials. therapies. However, until solid data have been published on its long-term safety, the use of PBM should be considered with caution and within the recommended parameters and doses, particularly when practiced in areas of known or possible tumours. In this case, the patient should be informed of the theoretical benefits and risks of PBM in order to obtain informed consent before treatment.

Developing a novel quasi-3D movable water phantom for radiation therapy workable in the magnetic resonance environment.

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA. Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift. Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity. Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism.

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8-167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1-110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003-0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001-0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

Tracheoesophageal fistula development following radiotherapy and tyrosine kinase inhibitors in a patient with advanced follicular thyroid carcinoma: a case-based review.

INTRODUCTION: Tracheoesophageal fistulas (TEF) are a rare complication that can occur in patients with radioactive iodine refractory metastatic follicular thyroid carcinoma (FTC) following treatment with radiotherapy (RT) and tyrosine kinase inhibitors (TKI). METHODS: We describe the case of a TEF development in a 69-year-old male who underwent targeted therapy TKIs and adjuvant RT for radioactive iodine refractory FTC. RESULTS: In the case, staging investigations revealed a metastatic, poorly differentiated FTC refractory to radioactive iodine. After 2 years of disease control on Lenvatinib, the patient's condition progressed, necessitating a switch to Cabozantinib. Soon after, they presented with haemoptysis secondary to invasion of the primary thyroid tumour into the trachea. Radical radiotherapy (45 Gy/30 fractions) was also administered to the thyroid gland, ultimately complicated by radiation necrosis. Four months post-completion of RT and recommencing TKI, the patient presented with haemoptysis and hoarseness secondary to recurrent laryngeal nerve compression and tracheal invasion, as well as dysphagia secondary to oesophageal compression. Following an acute presentation with intractable throat pain, investigations revealed a TEF. Surgical and endoscopic management was deemed inappropriate given the patient's rapid deterioration and anatomical position of the TEF, and therefore a palliative approach was taken. CONCLUSION: This case report highlights a rare cause of TEF development in a patient having TKI therapy post-RT for advanced FTC. It highlights the importance of monitoring TEF development in this cohort of patients. It demonstrates the importance of patient counselling and education regarding treatment options and the rare side effects of treatments.

Advances in radiation therapy for testicular seminoma.

PURPOSE: Novel techniques and advances in radiation therapy (RT) have been explored to treat testicular seminoma, a highly radiosensitive and curable histology. We evaluated the historical and current indications for radiation therapy (RT) in testicular seminoma. METHODS: A narrative literature review was performed. Studies of RT for testicular seminoma were included. Additionally, recent trials testing the use of combination or surgical therapies for clinical stage (CS) II were included. Search parameters included radiation therapy, testicular seminoma, surgery, and chemoradiation. Parameters and outcomes assessed were progression-free survival (PFS), overall survival (OS), acute toxicities, long-term sequelae, and rates of secondary malignancies. RESULTS: Practice defining and changing studies in the use or omission of radiation therapy for testicular seminoma were identified along with resultant changes in National Comprehensive Cancer Network (NCCN) and European guidelines. Recent trials in combined chemoradiation and upfront surgical approaches to CS II disease were reviewed. CONCLUSION: RT has historically been used as adjuvant treatment for CS I disease and is highly effective at treating CS II (A/B) testicular seminoma. The drive to maintain therapeutic efficacy and reduce acute and long-term side effects, namely secondary malignancies, is being tested using new radiation technologies, combined modality therapy in the form of chemoradiation and with upfront surgical approaches. Also, as guidelines now "strongly prefer" surveillance instead of adjuvant RT for CS I disease, the current CS II population comprises patients presenting with CS II disease ("de novo") and those who present with CSII after relapsing post orchiectomy for CS I ("relapsed"). Emerging evidence suggests that these two groups have different outcomes with respect to RT and chemoradiation. Consequently, future trials may need to sub-stratify according to these groups.

Neoadjuvant photodynamic therapy as a therapeutic alternative in multiple basal cell carcinoma induced by radiotherapy.

INTRODUCTION: Non-melanoma skin cancer within previously irradiated areas presents a common challenge, requiring innovative therapies. Complex scenarios, like XRT-induced basal cell carcinoma (BCC) or Gorlin's syndrome, often involve multiple synchronous tumor lesions where photodynamic therapy (PDT) offers a viable therapeutic alternative. CLINICAL CASE: We present the case of a 49-year-old male with a history of XRT for brain tumors. The patient was undergoing treatment for recurrent basal cell carcinomas (BCCs) in the right temporal irradiated area, unresponsive to conventional treatments. In the latest evaluation, the patient presented a nodular tumor and several peripheral superficial foci. Photodynamic therapy (PDT) was administered using methyl aminolevulinate 160 mg/g in cream (Metvix®) in two sessions spaced 7 days apart before surgery. The photosensitizer was applied 3 h before initiating PDT, and red light exposure was performed with the Aktilite© lamp (wavelength 630 nm, 100 mm distance, voltage 100 to 240 V, frequency 50 Hz, power 180 W) for 7 min. CONCLUSIóN: PDT with methyl aminolevulinate demonstrated efficacy as a neoadjuvant treatment in a case of multiple XRT-induced BCCs before surgery. PDT emerges as a valuable therapeutic alternative for multiple BCCs, particularly in non-responsive cases.

Case-Matched Outcomes of Proton Beam and Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

Purpose: Although both intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT) offer effective long-term disease control for localized prostate cancer (PCa), there are limited data directly comparing the 2 modalities. Methods: The data from 334 patients treated with conventionally fractionated (79.2 GyRBE in 44 fractions) PBT or IMRT were retrospectively analyzed. Propensity score matching was used to balance factors associated with biochemical failure-free survival (BFFS). Age, race, and comorbidities (not BFFS associates) remained imbalanced after matching. Univariable and covariate-adjusted multivariable (MVA) Cox regression models were used to determine if modality affected BFFS. Results: Of 334 patients, 176 (52.7%) were included in the matched cohort with exact matching to National Comprehensive Cancer Network (NCCN) risk group. With a median follow-up time of 9.0 years (interquartile range [IQR]: 7.8-10.2 years), long-term BFFS was similar between the IMRT and PBT matched arms with 8-year estimates of 85% (95% CI: 76%-91%) and 91% (95% CI: 82%-96%, P = .39), respectively. On MVA, modality was not significantly associated with BFFS in both the unmatched (hazard ratio [HR] = 0.75, 95% CI: 0.35-1.63, P = .47) and matched (HR = 0.87, 95% CI: 0.33-2.33, P = .78) cohorts. Prostate cancer-specific survival (PCSS) and overall survival (OS) were also similar (P > .05). However, in an unmatched analysis, the PBT arm had significantly fewer incidences of secondary cancers within the irradiated field (0.6%, 95% CI: 0.0%-3.1% versus 4.5%, 95% CI: 1.8%-9.0%, P = .028). Conclusions: Both PBT and IMRT offer excellent long-term disease control for PCa, with no significant differences between the 2 modalities in BFFS, PCSS, and OS in matched patients. In the unmatched cohort, fewer incidences of secondary malignancy were noted in the PBT group; however, owing to overall low incidence of secondary cancer and imbalanced patient characteristics between the 2 groups, these data are strictly hypothesis generating and require further investigation.

Therapeutic cannabis use by patients with cancer in Canada: A national survey of the experiences, opinions and information needs of Radiation Therapists.

PURPOSE: To understand the experiences, opinions and information needs of Canadian Radiation Therapists when caring for cancer patients who are taking cannabis for therapeutic purposes (CTP). METHODS: The study employed prospective data collection, via a single cross-sectional web-based questionnaire. After REB approval, the questionnaire was distributed electronically to all Radiation Therapists across Canada. The questionnaire was open for a one month accrual, with reminders sent at two and four weeks. The raw data was aggregated using standard descriptive statistics. The response differences between naturally occurring demographic cohorts was determined using inferential statistics. RESULTS: Two hundred and eighty two Therapists completed the questionnaire (25.6%), of which 19.1% reported being approached by patients to talk about cannabis more than once per month and 4.4% reported initiating a conversation with patients about cannabis. There were no differences between the provinces or catchment areas regarding how common or socially acceptable cannabis use by patients was. Confidence in discussing cannabis was strongly positively correlated with ratings of current knowledge (r² 0.77). Of the respondents, 99.9% believed that their radiation therapy training did not prepare them to support patients using cannabis. CONCLUSIONS: The data revealed that patients more frequently seek out guidance for CTP than Therapists initiate those discussions. This lack of Therapist willingness to begin cannabis conversations was associated with the low levels of knowledge. Almost all Therapists recognized the limitations of their knowledge and expressed interest in receiving further information about cannabis. The findings of this study strongly advocate for the development of educational tools to meet Therapists clinical needs.