Artificial intelligence applied to image-guided radiation therapy (IGRT): a systematic review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (yAIRO).

INTRODUCTION: The advent of image-guided radiation therapy (IGRT) has recently changed the workflow of radiation treatments by ensuring highly collimated treatments. Artificial intelligence (AI) and radiomics are tools that have shown promising results for diagnosis, treatment optimization and outcome prediction. This review aims to assess the impact of AI and radiomics on modern IGRT modalities in RT. METHODS: A PubMed/MEDLINE and Embase systematic review was conducted to investigate the impact of radiomics and AI to modern IGRT modalities. The search strategy was "Radiomics" AND "Cone Beam Computed Tomography"; "Radiomics" AND "Magnetic Resonance guided Radiotherapy"; "Radiomics" AND "on board Magnetic Resonance Radiotherapy"; "Artificial Intelligence" AND "Cone Beam Computed Tomography"; "Artificial Intelligence" AND "Magnetic Resonance guided Radiotherapy"; "Artificial Intelligence" AND "on board Magnetic Resonance Radiotherapy" and only original articles up to 01.11.2022 were considered. RESULTS: A total of 402 studies were obtained using the previously mentioned search strategy on PubMed and Embase. The analysis was performed on a total of 84 papers obtained following the complete selection process. Radiomics application to IGRT was analyzed in 23 papers, while a total 61 papers were focused on the impact of AI on IGRT techniques. DISCUSSION: AI and radiomics seem to significantly impact IGRT in all the phases of RT workflow, even if the evidence in the literature is based on retrospective data. Further studies are needed to confirm these tools' potential and provide a stronger correlation with clinical outcomes and gold-standard treatment strategies.

Management of radiation-induced oral mucositis in head and neck cancer patients: a real-life survey among 25 Italian radiation oncology centers.

AIM: Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian RT centers. METHODS: A 40-question survey was administered to 25 radiation oncologists working in 25 different RT centers across Italy. RESULTS: A total of 1554 HNC patients have been treated in the participating centers in 2021, the majority (median across the centers 91%) with curative intent. Median treatment time was 41 days, with a mean percentage of interruption due to toxicity of 14.5%. Eighty percent of responders provide written oral cavity hygiene recommendations. Regarding RIOM prevention, sodium bicarbonate mouthwashes, oral mucosa barrier agents, and hyaluronic acid-based mouthwashes were the most frequent topic agents used. Regarding RIOM treatment, 14 (56%) centers relied on literature evidence, while internal guidelines were available in 13 centers (44%). Grade (G)1 mucositis is mostly treated with sodium bicarbonate mouthwashes, oral mucosa barrier agents, and steroids, while hyaluronic acid-based agents, local anesthetics, and benzydamine were the most used in mucositis G2/G3. Steroids, painkillers, and anti-inflammatory drugs were the most frequent systemic agents used independently from the RIOM severity. CONCLUSION: Great variety of strategies exist among Italian centers in RIOM management for HNC patients. Whether different strategies could impact patients' compliance and overall treatment time of the radiation course is still unclear and needs further investigation.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Diverse Imaging Methods May Influence Long-Term Oncologic Outcomes in Oligorecurrent Prostate Cancer Patients Treated with Metastasis-Directed Therapy (the PRECISE-MDT Study).

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [18F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [68Ga]Ga-PSMA-11 versus [18F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.

Arthrogryposis multiplex congenita with maxillofacial involvement: a case report.

BACKGROUND: Arthrogryposis multiplex congenita is a rare condition that mainly involves the lower limbs, characterized by severe joint deformity and contracture, muscular atrophy, and functional impairment. Its clinical manifestations are heterogenous and may involve the maxillofacial district as well. CASE PRESENTATION: This case report describes a 20-year-old patient with arthrogryposis multiplex congenita with skeletal crossbite, facial asymmetry, reduced mouth opening and absence of lateral mandibular movement on the left side. After clinical evaluation, the following exams were required: postero-anterior cephalometric tracing, head and neck electromyography, computerized axiography, computed tomography scan, and maxillofacial magnetic resonance imaging. Orthognathodontic evaluation indicated skeletal asymmetry, reduced condylar movements on the left side and abnormally low electromyography activity of the masticatory muscles on the left side. Computed tomography and magnetic resonance imaging revealed unilateral left mandibular hypoplasia, hypotrophy, and fatty infiltration of masticatory muscles on the left side, as well as immobility of the left condyle during mouth opening, and hypoplasia of the left articular disk, which was however not displaced. Surgery was not indicated and conservative orthognathodontic treatment with function generating bite was suggested to balance the occlusal plane, as well as stretching exercises. CONCLUSIONS: A rare case of arthrogryposis multiplex congenita with maxillofacial involvement illustrates that a patient-centred, multidisciplinary approach with accurate diagnosis is required to formulate the best treatment plan. Because of the considerable damage to the masticatory muscles, conservative orthognathodontic therapy may be the best treatment option.

Bone marrow sparing in prostate cancer patients treated with Post-operative pelvic nodal radiotherapy - A proton versus photon comparison.

PURPOSE: Extending salvage radiotherapy to treat the pelvic lymph nodes (PLNRT) improves oncologic outcomes in prostate cancer (PCa). However, a larger treatment volume increases the extent of bone marrow (BM) exposure, which is associated with hematologic toxicity (HT). Given the potential long-term impact of BM dose in PCa, clinical studies on BM sparing (BMS) are warranted. Herein, we dosimetrically compared photon and proton plans for BMS. MATERIALS AND METHODS: Treatment plans of 20 post-operative PCa patients treated with volumetric-modulated arc photon therapy (VMAT) PLNRT were retrospectively identified. Contours were added for the whole pelvis BM (WPBM) and BM sub-volumes: lumbar-sacral (LSBM), iliac (ILBM), and lower pelvis (LPBM). Three additional plans were created: VMAT_BMS, intensity-modulated proton therapy (IMPT), and IMPT_BMS. Normal tissue complication probabilities (NTCP) for grade >3 hematologic toxicity (HT3+) were calculated for the WPBM volumes. RESULTS: Compared to the original VMAT plan, mean doses to all BM sub-volumes were statistically significantly lower for VMAT_BMS, IMPT, and IMPT_BMS resulting in average NTCP percentages of 20.5 ± 5.9, 10.7 ± 4.2, 6.1 ± 2.0, and 2.5 ± 0.6, respectively. IMPT_BMS had significantly lower low dose metrics (V300cGy-V2000cGy) for WPBM and sub-volumes except for LPBM V2000cGy compared to VMAT_BMS and ILBM V20Gy compared to IMPT. In most cases, V4000cGy and V5000cGy within ILBM and LSBM were significantly higher for IMPT plans compared to VMAT plans. CONCLUSIONS: BMS plans are achievable with VMAT and IMPT without compromising target coverage or OARs constraints. IMPT plans were overall better at reducing mean and NTCP for HT3+ as well as low dose volumes to BM. However, IMPT had larger high dose volumes within LSBM and ILBM. Further studies are warranted to evaluate the clinical implications of these findings.

The oligometastatic setting in HNSCC: A critical review by the Rete Oncologica Piemonte e Valle d'Aosta multidisciplinary team.

INTRODUCTION: The oligometastatic disease is a low burden metastatic disease that might still benefit from curable treatment. Squamous cell carcinoma of the head and neck (HNSCC) is a complex group of malignancies, with high rates of loco-regional recurrences. Distant metastases are less frequent, and a single or few deposits are often observed (oligometastatic disease). The optimal management of oligometastatic HNSCC remains to be defined. MATERIALS AND METHODS: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. RESULTS: This paper contains a narrative report and a critical discussion of the available evidence on the management of oligometastatic HNSCC patients, with a focus on metastasis-directed therapy (MDT), particularly stereotactic ablative radiotherapy (SABR). CONCLUSIONS: in line with literature data, the multidisciplinary evaluation emerged as the key element in the management of oligometastatic HNSCC patients.

Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort.

Introduction: Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. Methods: The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study's prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. Results: The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. Discussion: This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.

Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review.

Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life.

Predictors of Bone Metastases at 68Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer (HSPC) Patients with Early Biochemical Recurrence or Persistence.

Prostate-specific-membrane-antigen/positron-emission-tomography (PSMA-PET) can accurately detect disease localizations in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP), allowing for more personalized image-guided treatments in oligometastatic patients with major impact in the case of bone metastases (BM). Therefore, this study aimed to identify predictors of BM at PSMA-PET in early-BCR/BCP hormone-sensitive PCa (HSPC) patients, previously treated with radical intent (radiotherapy or radical prostatectomy ± salvage-radiotherapy (SRT)). A retrospective analysis was performed on 443 68Ga-PSMA-11-PET/CT scans. The cohort median PSA at PET-scan was 0.60 (IQR: 0.38-1.04) ng/mL. PSMA-PET detection rate was 42.0% (186/443), and distant lesions (M1a/b/c) were found in 17.6% (78/443) of cases. BM (M1b) were present in 9.9% (44/443) of cases, with 70.5% (31/44) showing oligometastatic spread (≤3 PSMA-positive lesions). In the multivariate binary logistic regression model (accuracy: 71.2%, Nagelkerke-R2: 13%), T stage ≥ 3a (OR: 2.52; 95% CI: 1.13-5.60; p = 0.024), clinical setting (previous SRT vs. first-time BCR OR: 2.90; 95% CI: 1.32-6.35; p = 0.008), and PSAdt (OR: 0.93; 95% CI: 0.88-0.99; p = 0.026) were proven to be significant predictors of bone metastases, with a 7% risk increment for each single-unit decrement of PSAdt. These predictors could be used to further refine the indication for PSMA-PET in early BCR/BCP HSPC patients, leading to higher detection rates of bone disease and more personalized treatments.

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC.

Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

The Impact of the COVID-19 Pandemic on Head and Neck Cancer Diagnosis in the Piedmont Region, Italy: Interrupted Time-Series Analysis.

Background: The COVID-19 pandemic has likely affected the most vulnerable groups of patients and those requiring time-critical access to healthcare services, such as patients with cancer. The aim of this study was to use time trend data to assess the impact of COVID-19 on timely diagnosis and treatment of head and neck cancer (HNC) in the Italian Piedmont region. Methods: This study was based on two different data sources. First, regional hospital discharge register data were used to identify incident HNC in patients ≥18 years old during the period from January 1, 2015, to December 31, 2020. Interrupted time-series analysis was used to model the long-time trends in monthly incident HNC before COVID-19 while accounting for holiday-related seasonal fluctuations in the HNC admissions. Second, in a population of incident HNC patients eligible for recruitment in an ongoing clinical cohort study (HEADSpAcE) that started before the COVID-19 pandemic, we compared the distribution of early-stage and late-stage diagnoses between the pre-COVID-19 and the COVID-19 period. Results: There were 4,811 incident HNC admissions in the 5-year period before the COVID-19 outbreak and 832 admissions in 2020, of which 689 occurred after the COVID-19 outbreak in Italy. An initial reduction of 28% in admissions during the first wave of the COVID-19 pandemic (RR 0.72, 95% CI 0.62-0.84) was largely addressed by the end of 2020 (RR 0.96, 95% CI 0.89-1.03) when considering the whole population, although there were some heterogeneities. The gap between observed and expected admissions was particularly evident and had not completely recovered by the end of the year in older (≥75 years) patients (RR: 0.88, 0.76-1.01), patients with a Romano-Charlson comorbidity index below 2 (RR 0.91, 95% CI: 0.84-1.00), and primary surgically treated patients (RR 0.88, 95% CI 0.80-0.97). In the subgroup of patients eligible for the ongoing active recruitment, we observed no evidence of a shift toward a more advanced stage at diagnosis in the periods following the first pandemic wave. Conclusions: The COVID-19 pandemic has affected differentially the management of certain groups of incident HNC patients, with more pronounced impact on older patients, those treated primarily surgically, and those with less comorbidities. The missed and delayed diagnoses may translate into worser oncological outcomes in these patients.

The Impact of Pelvic Nodal Radiotherapy on Hematologic Toxicity: A Systematic Review with Focus on Leukopenia, Lymphopenia and Future Perspectives in Prostate Cancer Treatment.

INTRODUCTION: Hematologic toxicity (HT), particularly leukopenia, is a common side-effect of oncologic treatments for pelvic malignancies. Pelvic nodal radiotherapy (PNRT) has been associated with HT development mainly through incidental bone marrow (BM) irradiation; however, several questions remain about the clinical impact of radiotherapy-related HT. Herein, we perform a systematic review of the available evidence on PNRT and HT. MATERIALS AND METHODS: A comprehensive systematic literature search was performed through EMBASE. Hand searching and clinicaltrials.gov were also used. RESULTS: While BM-related dose-volume parameters and BM-sparing techniques have been more thoroughly investigated in pelvic malignancies such as cervical, anal, and rectal cancers, the importance of BM as an organ-at-risk has received less attention in prostate cancer treatment. CONCLUSIONS: We examined the available evidence regarding the impact of PNRT on HT, with a focus on prostate cancer treatment. We suggest that BM should be regarded as an organ-at-risk for patients undergoing PNRT.

Decreasing treatment burden in HPV-related OPSCC: A systematic review of clinical trials.

INTRODUCTION: Favorable outcomes are observed after treatment with standard chemoradiotherapy (CRT) for Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) patients. The consistent growing interest on treatment-related toxicity burden, potentially jeopardizing survivors' quality of life, led clinicians to investigate possible de-escalation strategies. MATERIALS AND METHODS: A comprehensive systematic literature search of clinical trials was performed through the EMBASE database to provide an overview of the de-escalation strategies spectrum. Additionally, hand searching and clinicaltrials.gov were also used. RESULTS: Herein, we report and discuss different approaches to de-escalation of therapy, with respect to both local and systemic strategies. CONCLUSIONS: Several promising de-escalation experiences have been published. However, while further evidence is awaited, no changes in the management nor deviation from the standard of care should be made outside of clinical trials.

A bond between rheumatic diseases and cancer in the elderly: The interleukin-6 pathway.

Interleukin (IL)-6 is a soluble factor secreted by T lymphocytes, involved in antibody generation by B lymphocytes. The IL-6 pathway has risen as a pivotal pathway implicated in immune regulation and dysregulation in various rheumatic diseases. Nonetheless, elevated IL-6 levels can also play a role in cancer. Targeting the IL-6 pathway has led to innovative therapeutic approaches for rheumatic diseases and for COVID-19, particularly in the elderly. Indeed, tocilizumab, an agent targeting IL-6, has recently amassed significant attention as a promising univocal agent for different conditions. In this viewpoint, we sought to recall and describe the common pathway among osteoarthritis, rheumatoid arthritis, and cancer, suggesting that anti-IL-6 may be considered a jack-of-all-trades against inflammaging in the elderly.

Role of Radiotherapy in Post-transplant Lymphoproliferative Disorders: Three Case Reports and Review of the Literature.

Post-transplant lymphoproliferative disorder (PTLD) is an aggressive malignancy that occurs in patients who have undergone solid organ transplantation or hematopoietic stem cell transplantation. It develops as the result of uncontrolled cell proliferations owing to reduced immunological surveillance. PTLD may occur with a various spectrum of clinical presentations, including both localized and extensive disease. Management can be significantly variable according both to the clinical presentation and to the histologic features. The most important systemic treatment strategies are reduction of immunosuppressive therapy, chemotherapy, anti B-cell antibodies, especially rituximab and cytokine-based therapies. The localized form of PTLD could be efficiently treated, and potentially cured, with surgery or radiotherapy (RT). Involved site RT may be a feasible effective option for the treatment of patients with PTLD, given the excellent radio-sensitivity of lymphoid disorders. In this report, we describe 3 adult patients with PTLD treated with moderate-dose RT (24-36 Gy) having a good local control with negligible toxicity. We also review the literature data on the role of radiation therapy in this particular setting.

The impact of modern radiotherapy on radiation-induced late sequelae: Focus on early-stage mediastinal classical Hodgkin Lymphoma. A critical review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

INTRODUCTION: The historically feared radiation-induced secondary cancers and cardiac toxicities observed among mediastinal classical Hodgkin Lymphoma (cHL) patients may still negatively burden the benefit of radiotherapy among long-term survivors. Modern radiotherapy (RT) delivery techniques, including intensity-modulated RT (IMRT) and deep inspiration breath-hold (DIBH) solutions, are drastically changing this scenario. Results of a literature overview are reported and discussed in this paper. MATERIALS AND METHODS: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. RESULTS: This paper contains a narrative report and a critical discussion of organs-at-risk dose-volume metrics linked with radiation-induced toxicities in cHL patients. CONCLUSIONS: The scenario of early-stage cHL presents long-life expectancies, thus the goal of treatment should aim at maintaining high cure rates and limiting the onset of late complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring.

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients.

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.

The role of radiotherapy in epithelial ovarian cancer: a literature overview.

Ovarian cancer (OC) accounts for 3% of all cancer in women and for 5% of all cancer-related deaths. Epithelial Ovarian Cancer (EOC) is a radiosensitive malignancy with a poor prognosis. In the pre-chemotherapy era, radiation therapy (RT) delivered to the abdominopelvic region (whole abdominal irradiation, WAI) has historically played a role in the adjuvant and consolidation setting. Specific cluster of patients with early-stage disease and definite histologies may take advantage of RT. Platinum-based chemotherapy (CT) has replaced RT and plays a major role in most of the clinical settings. Radiation Therapy for palliation is recommended in patients with localized symptoms. Nevertheless, modern RT represents a reliable treatment option, with a mild toxicity profile, particularly effective for oligo-recurrent or progressive disease. The present literature review aims to highlight the historical role of RT in EOC, the actual lines of evidence, and the future perspectives.