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Normal tissue reactions vary significantly among patients receiving the same radiation treatment regimen, reflecting the multifactorial etiology of late radiation toxicity. Predicting late radiation toxicity is crucial, as it aids in the initial decision-making process regarding the treatment modalities. For patients undergoing radiotherapy, anticipating late toxicity allows for planning adjustments to optimize individualized care. Various dosimetric parameters have been shown to influence the incidence of late toxicity, and the literature available on this topic is extensive. This narrative review examines patient-related determinants of late toxicity following external beam radiotherapy for pelvic tumors, with a focus on prostate and cervical cancer patients. In Part I, we address various methods for quantifying radiation toxicity, providing context for interpreting toxicity data. Part II examines the current insights into the clinical risk factors for late toxicity. While certain factors—such as previous abdominal surgery, smoking behavior, and severe acute toxicity—have consistently been reported, most of the others show inconsistent associations. In Part III, we explore the influence of genetic factors and discuss promising predictive assays. Single-nucleotide polymorphisms (SNPs) likely elevate the risk in specific combinations. Advances in artificial intelligence now allow for the identification of SNP patterns from large datasets, supporting the development of polygenic risk scores. These innovations hold promise for improving personalized treatment strategies and reducing the burden of late toxicity in cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction: Temporo-insular gliomas, rare brain tumors originating from glial cells, comprise about 30% of brain tumors and vary in aggressiveness from grade I to IV. Despite advancements in neuroimaging and surgical techniques, their management remains complex due to their location near critical cognitive areas. Techniques like awake craniotomy have improved outcomes, but tumor heterogeneity and proximity to vital structures pose challenges. Radiotherapy and chemotherapy offer benefits post-surgery, though issues like resistance and side effects persist. This article discusses a case report and literature review to deepen understanding of temporo-insular gliomas, focusing on advanced diagnostic and treatment approaches. Materials and Methods: A systematic review was conducted using PubMed, Embase, and Google Scholar, covering studies from 2019 to July 2024. Keywords included 'brain tumor', 'neurosurgery', and 'treatment'. Articles on glioma diagnosis, management, and outcomes were selected, excluding non-English studies, irrelevant reports, non-glioma research, and inaccessible texts. Results: From 156 studies, 11 met inclusion criteria, highlighting advanced diagnostics, surgical strategies, and adjunct therapies for temporo-insular gliomas (TIGs). Gross total resection (GTR) was achieved in 39% of cases. Awake craniotomy enhanced functional outcomes, while temozolomide and radiotherapy improved survival. Challenges included ischemic complications and treatment resistance. Two patient cases underscored the complexity of TIG management and the importance of individualized approaches, achieving satisfactory resection with minimal deficits. Conclusions: Temporo-insular gliomas (TIGs) necessitate a multidisciplinary strategy that integrates advanced imaging, meticulous surgical methods, and cutting-edge adjuvant therapies. Despite progress with techniques like awake craniotomy and the use of temozolomide improving patient outcomes, significant challenges persist in maintaining functional integrity and addressing treatment resistance. Ongoing research into targeted therapies, immunotherapies, and innovative technologies remains critical to advancing patient care and improving long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population. [ABSTRACT FROM AUTHOR]

Breast cancer is diagnosed in nearly 3 million people worldwide. Radiation therapy is an integral component of disease management for patients with breast cancer, and is used after breast-conserving surgery or a mastectomy to reduce the risk of a local recurrence. The following review describes the methods used to personalize radiation therapy by optimizing patient selection, using advanced treatment techniques to lessen the radiation dose to normal organs, and using hypofractionation in order to shorten the duration of radiation treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is often utilized for symptom control at the end of life. Palliative RT (pRT) may not be taken to completion by patients, thus decreasing clinical benefits and adversely impacting resource allocation. We determined rates of incomplete pRT and examined predictors of non-completion using an electronic questionnaire. Methods: A questionnaire was embedded within the RT electronic prescribing system for all five cancer centers of Alberta, Canada, between 2017 and 2020. Prescribing radiation oncologists (ROs) were tasked with completing the questionnaire. Treatment variables were collected for 2040 patients prescribed pRT. Details on pRT courses delivered and completed were used to determine rates of incomplete RT. Electronic medical records of a subset of 367 patients randomly selected from the 2040 patients were then analyzed to examine for association of non-completion of RT with patient, disease, and therapy-related factors. Results: Overall, 10% of patients did not complete pRT. The rate of single fractions prescribed as a proportion of all RT fractions increased from 18% (pre-2017: pre-study era) to 29% (2017–2020: study era) (p < 0.0001). After conducting multivariate analysis on the overall group, multiple lifetime malignancies (OR:0.64) or increasing the number of pRT fractions (OR:0.08–0.17) were associated with non-completion. Being selected for stereotactic RT (OR:3.75) or survival > 30 days post-RT prescription (OR:2.20–5.02) were associated with greater rates of RT completion. The ROs' estimates of life expectancy at the time of RT prescription were not predictive of RT completion. In the multivariate analysis of the 367-patient subset, the presence of hepatic metastases (OR 2.59), survival 30–59 days (OR 6.61) and survival 90+ days (OR 8.18) post-RT prescription were associated with pRT completion. Only increasing pRT fractionation (OR:0.05–0.2) was associated with non-completion. Conclusion: One in ten patients prescribed pRT did not complete their treatment course. Decreasing pRT fractionation and improving prognostication in patients near the end of life may decrease rates of incomplete RT courses. [ABSTRACT FROM AUTHOR]

Background: We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. Methods: An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1–2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). Results: A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1–2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre–South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. Conclusions: Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations. [ABSTRACT FROM AUTHOR]

Uveal melanoma represents the most prevalent form of primary malignant intraocular tumor in adults. Historically, enucleation was considered the gold-standard approach in the treatment of uveal melanoma. Currently, radiotherapy is the most commonly used therapy, aiming at a better quality of life. However, radiotherapy can result in several ocular complications, some of which may be vision-threatening. Radiation-induced dry eye, scleral necrosis, cataract, rubeosis iridis, neovascular glaucoma, radiation retinopathy, maculopathy, and optic neuropathy are the most common complications. This article aims to summarize the current literature regarding the ocular complications after radiotherapy, as well as their clinical features, risk factors, and management strategies. A thorough understanding of these issues is crucial for ophthalmologists and oncologists to provide optimal patient care, improve visual outcomes, and minimize long-term complications. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors significantly improve progression-free survival and overall survival among metastatic breast cancer patients. However, given the effects on cell cycle arrest, there is potential for CDK4/6 inhibitors and radiotherapy (RT) to work synergistically, enhancing the effect and toxicities of RT. A comprehensive review of the literature on the combination of RT and CDK4/6 inhibitors was performed with 19 eligible studies included in the final analysis. A total of 373 patients who received radiotherapy combined with CDK4/6 inhibitors were evaluated across 9 retrospective studies, 4 case reports, 3 case series, and 3 letters to the editor. The CDK4/6 inhibitor used, RT target, and RT technique were assessed in terms of toxicities. This literature review demonstrates generally limited toxicities with the combination of CDK4/6 inhibitors and palliative radiotherapy to metastatic breast cancer patients. The current evidence is nonetheless limited, and further results of ongoing prospective clinical trials will help clarify whether these treatments can be safely combined. [ABSTRACT FROM AUTHOR]

AIM: In our radiation departments, all patients received psycho-oncological support during RT and during follow-up. Based on the latter, the aim of this retrospective analysis was to evaluate the role of tele-visits and in-person psychological support for cancer patients after RT, and to report a descriptive analysis pointing out the needs of psychosocial intervention in a radiation department during radiation treatment. METHODS: According to our institutional care management, all patients receiving RT were prospectively enrolled to receive charge-free assessment of their cognitive, emotional and physical states and psycho-oncological support during treatment. For the whole population who accepted the psychological support during RT, a descriptive analysis was reported. For all patients who agreed to be followed up by a psycho-oncologist, at the end of RT, a retrospective analysis was conducted to evaluate the differences between tele-consultations (video-call or telephone) and on-site psychological visits. Patients were followed up by on-site psychological visit (Group-OS) or tele-consult (Group-TC) visit. For each group, to evaluate anxiety, depression and distress, the Hospital Anxiety Depression Scale (HADS), Distress Thermometer and Brief COPE (BC) were used. RESULTS: From July 2019 to June 2022, 1145 cases were evaluated during RT with structured psycho-oncological interviews for a median of 3 sessions (range 2–5). During their first psycho-oncological interview, all the 1145 patients experienced the assessment of anxiety, depression and distress levels with the following results: concerning the HADS-A scale, 50% of cases (574 patients) reported a pathological score ≥8; concerning the HADS-D scale, 30% of cases (340 patients) reported a pathological score ≥8, concerning the DT scale, 60% (687 patients) reported a pathological score ≥4. Eighty-two patients were evaluated after RT: 30 in the Group-OS and 52 in the Group-TC. During follow-up, a median of 8 meetings (range 4–28) were performed. Comparing psychological data at baseline (beginning of RT) and at the last follow-up, in the entire population, a significant improvement in terms of HADS-A, global HADS and BC was shown (p 0.04; p 0.05; and p 0.0008, respectively). Compared to baseline, statistically significant differences were observed between the two groups in terms of anxiety in favor of on-site visit: Group-OS reported a better anxiety score compared with Group-TC. In each group, a statistical improvement was observed in BC (p 0.01). CONCLUSION: The study revealed optimal compliance to tele-visit psychological support, even if the anxiety could be better controlled when patients were followed up on-site. However, rigorous research on this topic is needed. [ABSTRACT FROM AUTHOR]

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor. [ABSTRACT FROM AUTHOR]

Patients with oligometastatic breast cancer (BC) are candidates of choice for metastasis-directed therapy (MDT). This paper summarizes the opinions of an expert committee about the management of oligometastatic BC. The experts could complete the questionnaire from 13 September 2021, to 10 October 2021, followed by a discussion. The experts were physicians working in the Province of Quebec (Canada) and specialized in BC care, including surgical oncologists, medical oncologists, and radiation oncologists. The experts provided their opinions about the context of the disease and therapeutic approach, local and systemic therapies, and the prognosis of oligometastatic BC. In addition to the expert panel's opinions about the management of oligometastatic disease per se, the experts stated that a prospective data registry should be implemented to collect data about oligometastatic BC to improve knowledge about oligometastatic BC and implement data-driven MDT. These data could also allow for the design of treatment algorithms. In conclusion, this paper presents the expert panel's opinions about the management of oligometastatic BC and highlights the needs to be met to improve the care of this condition. [ABSTRACT FROM AUTHOR]

Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is also limited data on efficacy and safety of external beam hypofractionation and accelerated partial-breast irradiation (APBI) regimens. This paper reviews existing retrospective and prospective data for breast reRT after BCS, APBI reRT outcomes and delivery at our institution and the need for a randomized controlled trial using shorter courses of radiation to better define patient selection for different reRT fractionation regimens. [ABSTRACT FROM AUTHOR]

Omission of radiotherapy among older women taking 5 years of adjuvant endocrine therapy following breast conserving surgery for early-stage, hormone sensitive breast cancers is well-studied. However, endocrine therapy toxicities are significant, and many women have difficulty tolerating endocrine therapy, particularly elderly patients with comorbidities. Omission of endocrine therapy among women receiving adjuvant radiation is less well-studied, but available randomized and non-randomized data suggest that this approach may confer equivalent local control and survival for select patients. Herein we review available randomized and non-randomized outcome data for women treated with radiation monotherapy and emphasize the need for future prospective, randomized studies of endocrine therapy omission. [ABSTRACT FROM AUTHOR]

Background: breast cancer (BC) is the world's most prevalent cancer in the female population, with 2.3 million new cases diagnosed worldwide in 2020. The great efforts made to set screening campaigns, early detection programs, and increasingly targeted treatments led to significant improvement in patients' survival. The Full-Field Digital Mammograph (FFDM) is considered the gold standard method for the early diagnosis of BC. From several previous studies, it has emerged that breast density (BD) is a risk factor in the development of BC, affecting the periodicity of screening plans present today at an international level. Objective: in this study, the focus is the development of mammographic image processing techniques that allow the extraction of indicators derived from textural patterns of the mammary parenchyma indicative of BD risk factors. Methods: a total of 168 patients were enrolled in the internal training and test set while a total of 51 patients were enrolled to compose the external validation cohort. Different Machine Learning (ML) techniques have been employed to classify breasts based on the values of the tissue density. Textural features were extracted only from breast parenchyma with which to train classifiers, thanks to the aid of ML algorithms. Results: the accuracy of different tested classifiers varied between 74.15% and 93.55%. The best results were reached by a Support Vector Machine (accuracy of 93.55% and a percentage of true positives and negatives equal to TPP = 94.44% and TNP = 92.31%). The best accuracy was not influenced by the choice of the features selection approach. Considering the external validation cohort, the SVM, as the best classifier with the 7 features selected by a wrapper method, showed an accuracy of 0.95, a sensitivity of 0.96, and a specificity of 0.90. Conclusions: our preliminary results showed that the Radiomics analysis and ML approach allow us to objectively identify BD. [ABSTRACT FROM AUTHOR]

Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens' decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions. [ABSTRACT FROM AUTHOR]

Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin's lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrhythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative body radiotherapy (SABR) is one of the treatment options for oligometastatic renal cell carcinoma (RCC) but is limited by a lack of data to evaluate high-dose SABR to all/multiple sites. Objective: This study retrospectively investigated the efficacy and prognostic factors of high-dose SABR for oligometastatic RCC patients. Design, setting, and participants: Patients with oligometastatic RCC on systemic therapy were retrospectively collected. Intervention(s): All patients were treated with SABR (40–50 Gy/5 fractions) for small tumors or partial-SABR (tumor center boosted with 6–8 Gy/3–5 fractions with 50–60 Gy/20–25 fractions to the whole tumor volume) for bulky tumors or tumors adjacent to critical organs. Outcome measurements and statistical analysis: Progression-free survival (PFS) and overall survival (OS) were calculated. Results and limitations: In total, 35 patients were enrolled, of which 88.5% had intermediate- or high-risk disease, with 60% on second- to fourth-line systemic therapy. The median follow-up time was 17 months. The median PFS and OS times were 11.3 and 29.7 months, respectively. Univariate analysis showed that an OS benefit was found in patients who received radiation before tyrosine kinase inhibitor (TKI) failure (p = 0.006) and where there was a short time interval (

Locoregional management of breast cancer is founded on evidence generated over a vast time period, much longer than the career span of many practicing physicians. Oncologists rely on specific patient and tumour characteristics to recommend modern-day treatments. However, some of this information may not have been available during prior periods in which the evidence was generated. For example, the comprehensive Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analyses published in the 2000s typically included older trials accruing patients between the 1960s and 1980s. This raises some uncertainty about whether conclusions from studies conducted in prior eras are as relevant or applicable to modern-day patients and treatments. Reviewing the chronological order and details of the evidence can be beneficial to understanding these nuances. This review discusses the evolution of locoregional management through some key clinical trials. We aim to highlight the time period in which the evidence was generated and emphasize the 10-year outcomes for the comparability of results. Evidence supporting surgical management of the breast and axilla, as well as details of radiotherapy are discussed briefly for all stages of breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. Methods: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle–Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). Results: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34–0.44). Conclusions: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has shifted oncology practices to prioritize patient safety while maintaining necessary treatment delivery. We obtained patient feedback on pandemic-based practices in our radiotherapy department to improve quality of patient care and amend policies as needed. We developed a piloted questionnaire which quantitatively and qualitatively assessed patients’ pandemic-related concerns and satisfaction with specific elements of their care. Adult patients who were treated at our Centre between 23 March and 31 May 2020, had initial consultation via telemedicine, and received at least five outpatient fractions of radiotherapy were invited to complete the survey by telephone or online. Relative frequencies of categorical and ordinal responses were then calculated. Fifty-three (48%) out of 110 eligible patients responded: 32 patients by phone and 21 patients online. Eighteen participants (34%) admitted to feeling anxious about hospital appointments, and only five (9%) reported treatment delays. Forty-eight patients (91%) reported satisfaction with their initial telemedicine appointment. The majority of patients indicated that healthcare workers took appropriate precautions, making them feel safe. Overall, all 53 patients (100%) reported being satisfied with their treatment experience during the pandemic. Patient feedback is needed to provide the highest quality of patient care as we adapt to the current reality. [ABSTRACT FROM AUTHOR]

Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient's cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion. [ABSTRACT FROM AUTHOR]