The incidence of malignant gastrointestinal (GI) tumors is increasing, and advancements in medical care have significantly improved patient survival rates. As a result, the number of cases involving multiple primary cancers (MPC) has also increased. The rarity of MPC and the absence of sensitive and specific diagnostic markers often lead to missed or incorrect diagnoses. It is, therefore, of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease. Patients with GI malignancies face a higher relative risk of developing additional primary malignant tumors compared to those with other systemic tumors. Vigilant monitoring and follow-up are crucial, especially for high-risk groups, which include older adults, men, those with addictions to alcohol and tobacco, those with a family history of tumors, and those who have undergone radiotherapy.

In this article, we report three cases of MPC, each involving malignant tumors of the GI tract as the initial primary carcinoma, offering insights that may aid in effectively managing similar cases.

Patients with GI malignancies face a higher MPC risk. Developing screening and follow-up protocols may enhance detection and treatment outcomes.

• Multiple primary cancer
• Gastrointestinal tract
• Synchronous
• Metachronous
• Case report

• GASTROENTEROLOGY
• Prognosis
• RADIOTHERAPY

• Humans
• Neoplasms, Second Primary/epidemiology
• Neoplasms, Second Primary/etiology
• Stomach Neoplasms/epidemiology
• Stomach Neoplasms/radiotherapy
• Female
• Retrospective Studies
• Male
• SEER Program
• Middle Aged
• Radiotherapy, Adjuvant/adverse effects
• Radiotherapy, Adjuvant/statistics & numerical data
• Aged
• Incidence
• Adult
• Risk Factors
• United States/epidemiology

• cancer
• oncology

• Humans
• Carcinoma, Non-Small-Cell Lung/pathology
• Lung Neoplasms/pathology
• Radiosurgery
• Dose Fractionation, Radiation
• Radiotherapy Dosage
• Retrospective Studies

The improvement of the efficacy of intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC) has prolonged the survival of patients, and the incidence of the second tumor has gradually increased. Among them, second primary lung adenocarcinoma (SPLAC) attributes the highest incidence. This study aimed to determine the long-term risk of SPLAC in NPC patients after IMRT.

From May 2005 to May 2018, a total of 1,102 non-metastatic NPC patients who received IMRT in our hospital were enrolled, and the incidence and efficacy of SPLAC were followed up in the long term.

Over a median follow-up period of 66 months, a total of 22 cases of SPLAC were observed, with an incidence of 2.0%. The 1-, 2-, 3-, 4-, and 5-year cumulative risks of SPLAC were 0.4%, 0.7%, 0.8%, 1.1%, and 1.7%, respectively. During follow-up, 90.9% (20/22) of the SPLAC detected was in early stage, and the recurrence rate of surgery alone was 5.3% (1/19).

In NPC patients, the proportion of SPLAC after IMRT was similar to that of the normal population, and most of them were found in early stage during follow-up, with good surgical efficacy.

• cumulative incidence risk
• intensity-modulated radiotherapy
• nasopharyngeal carcinoma
• second primary lung adenocarcinoma
• survival

• Brachytherapy
• Curiethérapie
• French society for radiation oncology
• Guidelines
• Image-guided radiotherapy
• Oncologie radiothérapie
• Radiation therapy
• Radiothérapie guidée par l’imagerie
• Recommandations
• Société française de radiothérapie oncologique

• Age Factors
• Humans
• Neoplasms, Radiation-Induced/prevention & control
• Organs at Risk/radiation effects
• Radiotherapy, Intensity-Modulated/adverse effects
• Radiotherapy, Intensity-Modulated/methods
• Risk Factors

The evolution of SARS-CoV-2 pneumonia to acute respiratory distress syndrome is linked to a virus-induced “cytokine storm”, associated with systemic inflammation, coagulopathies, endothelial damage, thrombo-inflammation, immune system deregulation and disruption of angiotensin converting enzyme signaling pathways. To date, the most promising therapeutic approaches in COVID-19 pandemic are linked to the development of vaccines. However, the fight against COVID-19 pandemic in the short and mid-term cannot only rely on vaccines strategies, in particular given the growing proportion of more contagious and more lethal variants among exposed population (the English, South African and Brazilian variants). As long as collective immunity is still not acquired, some patients will have severe forms of the disease. Therapeutic perspectives also rely on the implementation of strategies for the prevention of secondary complications resulting from vascular endothelial damage and from immune system deregulation, which contributes to acute respiratory distress and potentially to long term irreversible tissue damage. While the anti-inflammatory effects of low dose irradiation have been exploited for a long time in the clinics, few recent physiopathological and experimental data suggested the possibility to modulate the inflammatory storm related to COVID-19 pulmonary infection by exposing patients to ionizing radiation at very low doses. Despite level of evidence is only preliminary, these preclinical findings open therapeutic perspectives and are discussed in this article.

• SARS-CoV-2 pneumonia
• immune system
• radiation therapy
• radiation-induced cancers
• radiobiology

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Recently, flank target volumes adjusted for organ shift/motion have been defined.

For decades, Anterior-Posterior/Posterior-Anterior (AP/PA) photon beams were standard-of-care for flank irradiation in children with renal cancer. Recently, highly conformal flank target volumes were defined correcting for postoperative organ shift and intra-fraction motion.

By radiotherapy treatment plan comparison, this study aims to estimate the clinical benefits and potential risks of combining highly conformal target volumes with Volumetric-Modulated Arc Therapy (VMAT) versus conventional target volumes with AP/PA beams for flank irradiation.

Twenty consecutive renal tumor cases (left/right-sided:10/10; median age:3.2 years) were selected. Highly conformal flank target volumes were generated for VMAT, while conventional target volumes were used for AP/PA. For each case, the dose to the organs at risk (OARs) and Total Body Volume (TBV) was calculated to compare VMAT with AP/PA treatment plans for a prescribed dose (PD) of 14.4/1.8 Gy. Dose constraint violation of the tail of the pancreas and spleen (D_mean < 10 Gy), heart (D₅₀ < 5 Gy) or mammary buds (D_mean < 10 Gy) were prioritized as potentially beneficial for clinics.

Highly conformal Planning Target Volumes (PTV) were smaller than conventional volumes (mean ΔPTV_AP/PA-PTV_VMAT: 555 mL, Δ60%, p=<0.01). A mean dose reduction favoring VMAT was observed for almost all OARs. Dose constraints to the tail of the pancreas, spleen, heart and mammary buds were fulfilled in 8/20, 12/20, 16/20 and 19/20 cases with AP/PA, versus 14/20, 17/20, 20/20 and 20/20 cases with VMAT, respectively. In 12/20 cases, VMAT prevented the dose constraint violation of one or more OARs otherwise exceeded by AP/PA. VMAT increased the TBV receiving 10% of the PD, but reduced the amount of irradiated TBV for all higher doses.

Compared to 14.4 Gy flank irradiation using conventional AP/PA photon beams, an estimated clinical benefit by dose reduction to the OARs can be expected in 60% of the pediatric renal tumor cases using highly conformal flank target volumes combined with VMAT.

• 95% CI, 95% Confidence Interval
• AP/PA, Anterior-Posterior/Posterior-Anterior
• CT, Computed Tomography
• CTV, Clinical Target Volume
• Conformal radiotherapy
• GTV, Gross Tumor Volume
• ID, integral dose
• IMRT, Intensity-Modulated Radiotherapy
• ITV, Internal Target Volume
• MRI, Magnetic Resonance Imaging
• OARs, organs at risk
• Organs at risk
• PD, Prescribed Dose
• PTV, Planning Target Volume
• Pediatric renal tumors
• RT, radiotherapy
• SIOP-RTSG, International Society of Pediatric Oncology – Renal Tumor Study Group
• Side-effects
• TBV, Total Body Volume
• VMAT
• VMAT, Volumetric-Modulated Arc Therapy
• Wilms tumor
• vs, versus

• Flank irradiation
• Highly conformal radiotherapy
• Locoregional
• Pediatric renal tumors
• Tumor recurrences
• VMAT

The purpose of the in silico study was to compare free breathing volumetric modulated arc therapy (VMAT) to standard deep inspiration breath‐hold (DIBH) three‐dimensional conformal radiotherapy (3DCRT) and determine whether the former is a viable option for elderly patients with left‐sided early stage breast cancer. Data from 22 patients with early‐stage left breast carcinoma requiring breast‐only radiation therapy were used for this planning study. The robustness of VMAT plans when using the free breathing method was compared to that of standard 3DCRT plans using the DIBH method. The endpoints for evaluation were the target dose coverage as well as doses to the organs‐at‐risk. The free breathing VMAT plans produced a significantly higher mean dose to the heart and right breast than the DIBH‐3DCRT plans. Free breathing VMAT plans resulted in significantly better target coverage than did 3DCRT using DIBH. The external volume that received more than 40 Gy was significantly smaller in the VMAT plans. Free breathing VMAT is a viable alternative to DIBH 3DCRT in elderly patients with a limited life expectancy and in subjects who are unable to perform DIBH. The choice of treatment should be individualized, and all relevant risks ought to be considered.

• VMAT
• deep inspiration breath-hold
• free breathing
• volumetric modulated arc therapy

• Intensity-modulated radiotherapy
• Nasopharyngeal carcinoma
• Second primary cancer
• Survival
• Survivorship

• neoplasms
• proton therapy
• radiotherapy
• radiotherapy, conformal
• radiotherapy, intensity-modulated
• second primary

Advances in therapy have resulted in improved cure rates and an increasing number of long-term Hodgkin's lymphoma (HL) survivors. However, radiotherapy (RT)-related late effects are still a significant issue, particularly for younger patients with mediastinal disease (secondary cancers, heart diseases). In many Centers, technological evolution has substantially changed RT planning and delivery. This consensus document aims to analyze the current knowledge of Intensity-Modulated Radiation Therapy (IMRT) and Image-Guided Radiation Therapy (IGRT) for mediastinal HL and formulate practical recommendations based on scientific evidence and expert opinions.

A dedicated working group was set up within the Fondazione Italiana Linfomi (FIL) Radiotherapy Committee in May 2018. After a first meeting, the group adopted a dedicated platform to share retrieved articles and other material. Two group coordinators redacted a first document draft, that was further discussed and finalized in two subsequent meetings. Topics of interest were: 1) Published data comparing 3D-conformal radiotherapy (3D-CRT) and IMRT 2) dose objectives for the organs at risk 3) IGRT protocols and motion management.

Data review showed that IMRT might allow for an essential reduction in the high-dose regions for all different thoracic OAR. As very few studies included specific dose constraints for lungs and breasts, the low-dose component for these OAR resulted slightly higher with IMRT vs. 3D-CRT, depending on the technique used. We propose a set of dose objectives for the heart, breasts, lungs, and thyroid. The use of IGRT is advised for margin reduction without specific indications, such as the use of breath-holding techniques. An individual approach, including comparative planning and considering different risk factors for late morbidity, is recommended for each patient.

As HL therapy continues to evolve, with an emphasis on treatment reduction, radiation oncologists should use at best all the available tools to minimize the dose to organs at risk and optimize treatment plans. This document provides indications on the use of IMRT/IGRT based on expert consensus, providing a basis for clinical implementation and future development.

• Image-guided radiotherapy
• Intensity-modulated radiotherapy
• Lymphoma

• Filtration/instrumentation
• Filtration/methods
• Humans
• Incidence
• Neoplasms/classification
• Neoplasms/pathology
• Neoplasms/surgery
• Neoplasms, Second Primary/diagnosis
• Neoplasms, Second Primary/epidemiology
• Organs at Risk/radiation effects
• Prognosis
• Radiosurgery/methods
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods
• Spain/epidemiology

• brachytherapy
• cervical cancer
• evidence-based medicine
• image-guided adaptive brachytherapy
• overall survival
• precision medicine
• prostate cancer
• quality of life
• radiation oncology
• therapeutic index

• Antineoplastic Agents/therapeutic use
• Brachytherapy/methods
• Chemoradiotherapy/methods
• Disease Progression
• Dose Fractionation, Radiation
• Education, Medical, Continuing
• Evidence-Based Medicine/methods
• Humans
• Neoadjuvant Therapy/methods
• Neoplasms/complications
• Neoplasms/mortality
• Neoplasms/therapy
• Patient Selection
• Physicians
• Quality of Life
• Randomized Controlled Trials as Topic

• Cosmetovigilance
• Cosmétovigilance
• Materialovigilance
• Matériovigilance
• Pharmacovigilance
• Radiovigilance

• Dosimetry
• Scattered radiation
• TLD 100
• TomoLINAC
• Tomotherapy

• Image-guided radiotherapy
• Imaging dose in pediatric patients
• Radiotherapy for Hodgkin lymphoma
• Secondary cancer risk

• Adolescent
• Child
• Child, Preschool
• Cone-Beam Computed Tomography/adverse effects
• Female
• Germany
• Hodgkin Disease/radiotherapy
• Humans
• Male
• Neoplasms, Radiation-Induced/etiology
• Neoplasms, Second Primary/etiology
• Phantoms, Imaging
• Radiation Dosage
• Radiation Exposure/adverse effects
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/adverse effects
• Radiotherapy, Image-Guided/adverse effects
• Retrospective Studies
• Risk Assessment

• Animals
• Bystander Effect/physiology
• Bystander Effect/radiation effects
• Dose-Response Relationship, Radiation
• Humans
• Models, Biological
• Radiation Protection
• Radiation, Ionizing

• DNA repair
• apoptosis
• bone
• irradiation
• osteoblast

• DNA REPAIR
• MESENCHYMAL PROGENITORS
• OSTEOBLASTS
• RADIOTHERAPY
• SCL-AB

Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers. ROS have been shown to play important roles in mediating the biological effects of IR. ROS have been implicated in IR-induced EMT, via activation of several EMT transcription factors—including Snail, HIF-1, ZEB1, and STAT3—that are activated by signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, G-CSF, EGFR/PI3K/Akt, and MAPK. Cancer cells that undergo EMT have been shown to acquire stemness and undergo metabolic changes, although these points are debated. IR is known to induce cancer stem cell (CSC) properties, including dedifferentiation and self-renewal, and to promote oncogenic metabolism by activating these EMT-inducing pathways. Much accumulated evidence has shown that metabolic alterations in cancer cells are closely associated with the EMT and CSC phenotypes; specifically, the IR-induced oncogenic metabolism seems to be required for acquisition of the EMT and CSC phenotypes. IR can also elicit various changes in the tumour microenvironment (TME) that may affect invasion and metastasis. EMT, CSC, and oncogenic metabolism are involved in radioresistance; targeting them may improve the efficacy of radiotherapy, preventing tumour recurrence and metastasis. This study focuses on the molecular mechanisms of IR-induced EMT, CSCs, oncogenic metabolism, and alterations in the TME. We discuss how IR-induced EMT/CSC/oncogenic metabolism may promote resistance to radiotherapy; we also review efforts to develop therapeutic approaches to eliminate these IR-induced adverse effects.

• Cancer stem cells
• Epithelial-mesenchymal transition
• Metastasis
• Oncogenic metabolism
• Radioresistance
• Radiotherapy
• Reactive oxygen species
• Snail
• Tumour microenvironment