Radiation-induced Tumors Research Articles

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

Stereotactic radiosurgery for arteriovenous malformations in pediatric patients: an updated systematic review and meta-analysis.

Intracranial arteriovenous malformations are the most common cause of intracranial hemorrhages in pediatric patients. Stereotactic radiosurgery (SRS) has been used extensively to treat these lesions. The authors conducted a systematic review and meta-analysis to report treatment outcomes and long-term complications. This study follows the PRISMA and MOOSE guidelines, with the search spanning electronic databases up to February 6, 2024. The outcome measures included obliteration rate, hemorrhage in the latency period, symptomatic radiation-induced changes (RICs), cyst formation, and radiation-induced tumorigenesis. A total of 1493 patients across 24 studies were included. The pooled complete obliteration after single-fraction SRS was 64.7% (95% CI 58%-69%). The pooled post-SRS hemorrhage rate at the final follow-up was 6.2% (95% CI 5%-8%). The overall incidence rate of RIC was 31.3% (267/854 patients), and the incidence of symptomatic RIC was 8.8% (114/1289 patients). For permanent symptomatic RIC, the pooled incidence was 4.8% (62/1283 patients). At final follow-up, 17 cases of radiation-induced necrosis were documented among 654 patients (2.6%). Similarly, cyst formation was reported in 1.3% of cases (17/1265 patients) and radiation-induced tumors occurred in 0.15% of cases (2/1342 patients). SRS can be considered an effective intervention for appropriately selected pediatric patients with arteriovenous malformations. Long-term complication rates appear to be low but additional longitudinal studies are required to better define the long-term outcomes.

Current state of proton therapy for tumors of the central nervous system in Spain: physical bases, indications, controversies and perspectives.

The unique biophysical properties of proton therapy (PT), regarding the precise dose distribution, a remarkable better sparing of surrounding normal tissues, and the decreasing costs have promoted the spread of this technique worldwide. In Spain, eleven new PT centers, added to the currently two in function, are expected to be available in the near future. Indications for PT are currently evolving. The suitability of PT in central nervous system tumors of the adult population has been extrapolated from the favorable experience in children and adolescents. Given the lack of appropriate randomized trials, controversies remain regarding its use in lower grade tumors, re-irradiation, and other clinical scenarios in which an a priori dose distribution benefit is expected compared to photon-based radiotherapy. PT is a reasonable option in many brain and spinal tumors associating long life expectancy, in which cognitive decline, and the appearance of radiation-induced neoplasms can be minimized.Estado actual de la terapia con protones en los tumores del sistema nervioso central en España: bases físicas, indicaciones, controversias y perspectivas.

Stereotactic Radiosurgery Outcomes in Arteriovenous Malformations: A Pediatric-Adult Comparative Meta-Analysis

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs), but outcomes between pediatric and adult populations are not well compared. We conducted a systematic review and meta-analysis comparing SRS outcomes for pediatric versus adult AVMs. PubMed was searched for studies reporting SRS outcomes for pediatric or adult AVMs up to January 2024. Primary outcome was obliteration rate, with secondary outcomes including post-SRS hemorrhage, symptomatic radiation-induced changes (RICs), and permanent RICs. Pooled estimates were calculated using random effects models. Analysis included 22 studies with 3469 patients (1316 pediatric, 2153 adult). Pooled obliteration rate was 63% (95% confidence interval: 56%-70%) overall, with no significant difference between pediatric (61%) and adult (67%) cohorts (P= 0.38). Post-SRS hemorrhage rates were similar (5% pediatric, 6% adult, P= 0.60). Symptomatic RICs occurred in 9% (95% confidence interval: 6%-13%) overall, with 10% in both cohorts (P= 0.91). Permanent RIC rates were 4% in pediatric and 3% in adult cohorts (P= 0.43). Cyst formation (0.6%) and radiation-induced tumors (0.2%) were rare. All-cause mortality was significantly lower in the pediatric cohort (2.6% vs. 9.8%, P= 0.003). Hemorrhagic AVM presentation was inversely correlated with symptomatic RICs across both groups. SRS is a reasonable treatment option for appropriately selected AVM patients in both pediatric and adult populations, offering comparable obliteration rates and adverse event profiles. The lower mortality in pediatric patients underscores the importance of early intervention in this population given their high cumulative lifetime rupture risks.

Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: patient outcomes and lessons learned over a 3-decade single-center experience.

The role of stereotactic radiosurgery (SRS) in the management of intracranial dural arteriovenous fistula (dAVF) is unclear given the rarity of this lesion and the variability in treatment paradigms. This study describes a 3-decade experience with the SRS technique and its outcomes for patients with dAVF. The authors conducted a retrospective analysis of patients with dAVF who had undergone single-fraction SRS in the period from 1990 to 2021. The imaging modality initially used for targeting was angiography alone, then angiography plus MRI, and most recently MRI alone. Two hundred twenty-two patients underwent SRS alone (n = 56, 25%) or SRS plus embolization (n = 166, 75%), depending on the severity of symptoms or the presence of cortical venous drainage (CVD). Most patients were women (64%), and the median patient age was 60 years. Common presenting symptoms were pulsatile bruit (55%), visual change or chemosis (21%), headache (10%), and intracerebral hemorrhage (5%). The most frequent dAVF location was the transverse or sigmoid sinus (44%), followed by the cavernous sinus (24%), jugular bulb (9%), and torcula (5%). CVD was noted in 28% of cases, and venous ectasia in 5%. Borden dAVF types among the patients were I (72%), II (20%), and III (8%). Cognard dAVF types among the patients were I (44%), IIa (27%), IIb (5%), IIa+b (15%), III (4%), and IV (5%). The median SRS treatment volume was 7.6 cm3; the median margin and maximum doses were 18 and 36 Gy, respectively. Follow-up after SRS was available for 209 patients (median follow-up 31 months). Obliteration was noted in 75% of the patients (110/147) with follow-up vascular imaging; the median time to obliteration was 37 months. Multivariate analysis revealed that a cavernous sinus dAVF location was predictive of radiological obliteration (HR 1.86, 95% CI 1.08-3.18, p = 0.024). The absence of CVD was predictive of obliteration in subgroup analysis of non-cavernous sinus dAVF (HR 0.53, 95% CI 0.29-0.98, p = 0.04). Symptoms resolved in 86% of patients (160/185) with clinical follow-up. Twelve patients (5.4%) had complications related to angiography for SRS planning (n = 2, 0.9%), embolization (n = 3, 1.4%), post-SRS hemorrhage (n = 1, 0.5%), delayed sinus thrombosis (n = 1, 0.5%), radiation-induced tumors (n = 2, 0.9%), and chronic encapsulated expanding hematoma (n = 3, 1.4%). SRS alone or in conjunction with embolization provided obliteration and symptom relief for the majority of patients with dAVF, with a low rate of procedure-related morbidity. Patients are at risk for late radiation-related complications, which can require treatment many years after SRS.

Relative Biological Effectiveness of Carbon Ion Beams for Induction of Medulloblastoma with Radiation-specific Chromosome 13 Deletion in Ptch1+/- Mice.

Carbon ion radiotherapy (CIRT) for pediatric cancer is currently limited because of the unknown risk of induction of secondary cancers. Medulloblastoma of Ptch1+/- mice offers a unique experimental system for radiation-induced carcinogenesis, in which tumors are classified into spontaneous and radiation-induced subtypes based on their features of loss of heterozygosity (LOH) that affect the wild-type Ptch1 allele. The present study aims to investigate in young Ptch1+/- mice the carcinogenic effect, and its age dependence, of the low-linear energy transfer (LET, ∼13 keV/µm) carbon ions, to which normal tissues in front of the tumor are exposed during therapy. We irradiated Ptch1+/- mice at postnatal day (P) 1, 4, or 10 with 290 MeV/u carbon ions (0.05-0.5 Gy; LET, 13 keV/µm) and monitored them for medulloblastoma development. Loss of heterozygosity of seven genetic markers on chromosome 13 (where Ptch1 resides) was studied to classify the tumors. Carbon ion exposure induced medulloblastoma most effectively at P1. The LOH patterns of tumors were either telomeric or interstitial, the latter occurring almost exclusively in the irradiated groups, allowing the use of interstitial LOH as a biomarker of radiation-induced tumors. Radiation-induced tumors developed during a narrow age window (most strongly at P1 and only moderately at P4, with suppressed tumorigenesis at P10). Calculated using previous results using 137Cs gamma rays, the values for relative biological effectiveness (RBE) regarding radiation-induced tumors were 4.1 (3.4, 4.8) and 4.3 (3.3, 5.2) (mean and 95% confidence interval) for exposure at P1 and 4, respectively. Thus, the RBE of carbon ions for medulloblastoma induction in Ptch1+/- mice was higher than the generally recognized RBE of 1-2 for cell killing, chromosome aberrations, and skin reactions.

NCMP-27. CHARACTERISTICS OF RADIATION-INDUCED BRAIN TUMORS AFTER CRANIAL IRRADIATION

Abstract INTRODUCTION The use of radiation therapy (RT) improves the outcome of cancer patients, while additionally increasing the risk of radiation-induced neoplasms in cancer survivors. The most common radiation-induced brain tumors (RIBT) are gliomas (RIG), meningiomas (RIM), and sarcomas (RIS). To investigate the characteristics of RIBT, we reviewed our case series and all relevant cases from the literature review. METHODS From our case series and literature review, we identified 920 RIBT patients who received cranial irradiation. We analyzed the age at irradiation for primary disease. The latency period from irradiation to the development of each RIBT and the median overall survival (OS) of RIBT were analyzed with Kaplan–Meier method. RESULTS Among RIBT patients, 23.2 % were irradiated less than 5 years, and 41.6% were irradiated in the first decade. The median age (interquartile range) at cranial irradiation were 9 (4.35 - 16) years in RIM patients, 9 (5 - 23) years in RIG patients, and 27 (13.7 - 40) years in RIS patients. The latency periods from irradiation to the development of RIM was significantly longer than RIG and RIS (RIM: 21 years, RIG: 9 years, RIS: 10 years; p < 0.0001). The median OS was significantly longer in patients with RIM than in those with RIG and RIS (RIM: not reached, RIG: 11 months, RIS 11 months; p < 0.0001). CONCLUSIONS RIG and RIS had a poor prognosis, while RIM had a relatively better prognosis. Because RIBTs develop more than a decade after cranial irradiation, long-term follow-up is crucial.

Newly discovered genomic mutation patterns in radiation-induced small intestinal tumors of ApcMin/+ mice.

Among the small intestinal tumors that occur in irradiated mice of the established mouse model B6/B6-Chr18MSM-F1 ApcMin/+, loss of heterozygosity analysis can be utilized to estimate whether a deletion in the wild-type allele containing the Adenomatous polyposis coli (Apc) region (hereafter referred to as Deletion), a duplication in the mutant allele with a nonsense mutation at codon 850 of Apc (Duplication), or no aberration (Unidentified) has occurred. Previous research has revealed that the number of Unidentified tumors tends to increase with the radiation dose. In the present study, we investigated the molecular mechanisms underlying the development of an Unidentified tumor type in response to radiation exposure. The mRNA expression levels of Apc were significantly lower in Unidentified tumors than in normal tissues. We focused on epigenetic suppression as the mechanism underlying this decreased expression; however, hypermethylation of the Apc promoter region was not observed. To investigate whether deletions occur that cannot be captured by loss of heterozygosity analysis, we analyzed chromosome 18 using a customized array comparative genomic hybridization approach designed to detect copy-number changes in chromosome 18. However, the copy number of the Apc region was not altered in Unidentified tumors. Finally, gene mutation analysis of the Apc region using next-generation sequencing suggested the existence of a small deletion (approximately 3.5 kbp) in an Unidentified tumor from a mouse in the irradiated group. Furthermore, nonsense and frameshift mutations in Apc were found in approximately 30% of the Unidentified tumors analyzed. These results suggest that radiation-induced Unidentified tumors arise mainly due to decreased Apc expression of an unknown regulatory mechanism that does not depend on promoter hypermethylation, and that some tumors may result from nonsense mutations which are as-yet undefined point mutations.

Secondary cancer risk assessments following the proton therapy of lung cancer as the functions of field characteristics and patient age

Introduction Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. Material and Methods A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. Results The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. Conclusion Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Expression of Stem Cell Markers in High-LET Space Radiation-Induced Intestinal Tumors in Apc1638N/+ Mouse Intestine.

Estimation of cancer risk among astronauts planning to undertake future deep-space missions requires understanding the quantitative and qualitative differences in radiogenic cancers after low- and high-LET radiation exposures. Previously, we reported a multifold higher RBE for high-LET radiation-induced gastrointestinal (GI) tumorigenesis in Apc1638N/+ mice. Using the same model system, i.e., Apc1638N/+ mice, here, we report qualitative differences in the cellular phenotype of low- and high-LET radiation-induced GI tumors. Stem cell (SC) phenotypes were identified using BMI1, ALDH1, CD133, DCLK1, MSI1, and LGR5 markers in low (γ-rays)- and high (56Fe)-LET radiation-induced and spontaneous tumors. We also assessed the expression of these markers in the adjacent normal mucosa. All six of these putative SC markers were shown to be overexpressed in tumors compared to the adjacent normal intestinal tissue. A differential SC phenotype for spontaneous and radiogenic intestinal tumors in Apc1638N/+ mice was observed, where the ALDH1, BMI1, CD133, MSI1, and DCLK1 expressing cells were increased, while LGR5 expressing cells were decreased in 56Fe-induced tumors compared to γ-ray-induced and spontaneous tumors. Furthermore, higher β-catenin activation (marked by nuclear localization) was observed in 56Fe-induced tumors compared to γ and spontaneous tumors. Since differential tumor cell phenotype along with activated β-catenin may very well affect malignant progression, our findings are relevant to understanding the higher carcinogenic risk of high-LET radiation. This study has implications for the assessment of GI-cancer risk among astronauts, as well as for the estimation of secondary cancer risk among patients receiving hadron therapy, considering that our results indicate increased stemness properties after radiation.

Long-term outcomes of symptomatic optic pathway glioma: 32-year experience at a single Western Australian tertiary pediatric oncology center.

Optic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse. This study reviews the clinical course, disease progression, survival outcomes and long-term sequelae in pediatric patients with symptomatic OPGs in our institution over three decades. Retrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016. A total of 37 patients were diagnosed with symptomatic OPG. Decreased visual acuity was the commonest presenting symptom (75.7%). Surgical intervention was performed in 62.2%; 56.5% underwent biopsy, 26.1% surgical debulking and 17.4% had orbital decompression with cystic fenestration and cosmetic optic nerve excision at different treatment intervals. CSF diversion was performed in 47.8% patients. Histopathologic examination confirmed 86% to be pilocytic astrocytoma and 1 ganglioglioma. 46% received chemotherapy and 48% had radiotherapy, at different intervals. Median follow-up was 13.74 years. In NF1 patients, overall survival (OS) was 100% at 5 years and 55.6 ± 24.8% at 25 years while progression-free-survival (PFS) was 50 ± 15.8% at 5 and 20 years. In non-NF1 patients, OS was 96.2 ± 3.8% at 5 years and 87.4 ± 9% at 25-years. 5-year PFS was 53.8 ± 9.8% and 25-year PFS was 49.0 ± 10%. Cumulative PFS was 53 ± 8.3% at 5 years and 49.7 ± 8.4% at 20 years while cumulative OS was 97.2 ± 2.7% at 5 years and 77.5 ± 10.8% at 25 years. 59.5% patients developed post-operative endocrinopathy. Long-term vision was normal in 8.1%, improved in 13.5%, stabilized in 40.5% but worsened in 37.8% patients. Three patients treated with radiotherapy developed second brain tumors. 25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.

Secondary tumors following radiation therapy and chemotherapy : Incidence of cavernous hemangiomas

There is arisk of developing secondary central nervous system (CNS) tumors after cranial radiation therapy. Meningiomas and pituitary tumors are also increasingly treated with radiation therapy, which means that the risk of secondary tumors from radiation in children and adults must be communicated. Studies in children show that radiation causes a7- to 10-fold increase in subsequent CNS tumors with acumulative incidence over 20years ranging from 1.03 to 28.9. The latency period for the occurrence of secondary tumors ranged from 5.5 to 30years, with gliomas developing after 5-10years and meningiomas around 15years after irradiation. The latency period for secondary CNS tumors in adults ranged from 5to 34years. After radiation treatment, tumors can rarely occur as secondary sequelae, mostly meningiomas and gliomas, but also cavernomas. The treatment and long-term results of radiation-induced CNS tumors showed no worse results than primary CNS tumors over the course of time.

Breast cancer after thoracic radiotherapy in young patients: what does the radiologist need to know?

Radiation-induced secondary tumors constitute a rare complication of radiation therapy and typically occur in or near the irradiated area. Women who undergo thoracic radiotherapy before 30 years of age have a significantly greater lifetime risk of developing breast cancer than do those in the general population. It is recommended that a patient who has previously received thoracic radiotherapy with a radiation dose ≥ 10 Gy subsequently undergo annual screening with mammography and magnetic resonance imaging, beginning eight years after the initial treatment or when the patient has reached 25 years of age (whichever comes later). The treatment of secondary breast cancer in this population should be individualized and should be discussed with a multidisciplinary team to avoid toxicity related to the treatment of the primary cancer.

Interstitial deletion of the Apc locus in β-catenin-overexpressing cells is a signature of radiation-induced intestinal tumors in C3B6F1 ApcMin/+ mice†.

Recent studies have identified interstitial deletions in the cancer genome as a radiation-related mutational signature, although most of them do not fall on cancer driver genes. Pioneering studies in the field have indicated the presence of loss of heterozygosity (LOH) spanning Apc in a subset of sporadic and radiation-induced intestinal tumors of ApcMin/+ mice, albeit with a substantial subset in which LOH was not detected; whether copy number losses accompany such LOH has also been unclear. Herein, we analyzed intestinal tumors of C3B6F1 ApcMin/+ mice that were either left untreated or irradiated with 2Gy of γ-rays. We observed intratumor mosaicism with respect to the nuclear/cytoplasmic accumulation of immunohistochemically detectable β-catenin, which is a hallmark of Apc+ allele loss. An immunoguided laser microdissection approach enabled the detection of LOH involving the Apc+ allele in β-catenin-overexpressing cells; in contrast, the LOH was not observed in the non-overexpressing cells. With this improvement, LOH involving Apc+ was detected in all 22 tumors analyzed, in contrast to what has been reported previously. The use of a formalin-free fixative facilitated the LOH and microarray-based DNA copy number analyses, enabling the classification of the aberrations as nondisjunction/mitotic recombination type or interstitial deletion type. Of note, the latter was observed only in radiation-induced tumors (nonirradiated, 0 of 8; irradiated, 11 of 14). Thus, an analysis considering intratumor heterogeneity identifies interstitial deletion involving the Apc+ allele as a causative radiation-related event in intestinal tumors of ApcMin/+ mice, providing an accurate approach for attributing individual tumors to radiation exposure.

Radio Induced Temporal Meningioma: A Rare Case Report and Literature Review

We report the case of a 37 year old female patient who had got high-dose irradiation after subtotal removal of an ependymoma in posterior cerebral fossa. 16 years later a temporal meningioma is diagnosed and removed surgically. In this case the following meningioma fulfills the criteria for a radiation-induced tumor. There exist many reports about tumors of the central nervous system which have developed after radiotherapy in the irradiated field after a latency period. But after a thorough review of the international literature about radiation-induced tumors of the CNS is this the five cases in which a benign meningioma has followed a radiotherapy for an ependymoma.

Pediatric Brain Tumor Risk Associated with Head Computed Tomography: Systematic Literature Review

Computed tomography (CT) of the brain has changed diagnostic neuroradiology significantly over the past 50 years since it was firstly used back in 1971 to visualize suspected frontal lobe tumour. The safety of head CT is determined by the small amount of radiation and the low sensibility of brain tissue to cytotoxic damage due to ionizing radiation compared to other organs. However, some population groups may be at increased risk. Thus, children are more susceptible to radiation cancer than adults and lifelong attributive risk (LAR) can be more than 10 times higher for an infant than for a middle-aged adult. The authors have reviewed published studies that examined the prevalence and mortality of intracranial tumors in children undergoing head CT in comparison to unaffected individuals. Electronic search of publications in the PubMed database from 1966 to date was carried out. We have carried out intersectoral search for documents containing keywords or medical subject headings (MeSH) related to three wide categories: 1) computed tomography, 2) radiation-induced tumors, 3) risk, morbidity or epidemiology. Further search was performed in manual mode. Available epidemiological data generally confirmed correlation between head CT and tumor growth induction. Thus, current epidemiological data accept the opinion that the risk of tumor induction associated with head CT in children is very small (one tumor per 3,000–10,000 studies). The minimal estimated risk of tumor induction due to head CT in children is mostly offset by its diagnostic imaging benefits considering the clinical indications to minimize radiation dose. Understanding and quantitative risk assessment of carcinogenesis associated with CT imaging led to dose reduction in pediatric CT protocols. This trend should continue and should be implemented in all age groups. Although the decision to perform head CT is often undeniable (injury or hemorrhage), careful assessment of studies frequency is required, especially in patients who need disease monitoring. Cumulative effect in such cases may increase the minimal risk of carcinogenesis. Larger and advanced epidemiological studies are required to better understand these risks.

Case series report: radiation-induced oropharyngeal carcinoma.

The incidence of radiation-induced secondary primary tumors (SPTs) is estimated to be between 1 and 20%. The oropharynx is not a common site for postradiotherapy head and neck SPTs. We describe the cases of eight patients, each with an SPT of the oropharynx. These developed after a long median latency of 17.7 years with each receiving two-dimensional radiation therapy and delivery of at least 5000 cGy per pharynx, except for one who was treated with IMRT. Tumor histological commonalities revealed squamous cell carcinoma p16 negative staining, local invasion, and limited lymphatic spread, with posterior wall of the oropharynx and the base of the tongue being the most common locations. Limited and challenging treatment options have been reported such as surgery, reirradiation, or clinical trials. Radiation-induced SP oropharyngeal carcinoma has unique clinical and pathological features. Patients with this disease have limited treatment options, which should be discussed in a multidisciplinary tumor board meeting. For this population, lifelong follow-up may help in early diagnosis and improve outcomes.

Second Neoplasms in Children Following Radiotherapy in the Modern Era: A Bicentric Report from the University of Florida and Memorial Sloan Kettering Cancer Center

<h3>Purpose/Objective(s)</h3> Over the past two decades, eliminating secondary radiation-induced neoplasms has been a primary aim of our field. This study quantifies the results of that effort with a focus on children who received intensity-modulated radiotherapy (IMRT) and proton therapy (PT). <h3>Materials/Methods</h3> A total of 1880 pediatric patients with > 2 years follow-up received radiotherapy between 1999 and 2019, including 348 treated with IMRT and 1532 treated with PT (97% passive-scatter). The median age was 9.2 years old, including 623 patients ≤5 years old. Overall, 31 patients had a known genetic tumor predisposition syndrome, most commonly neurofibromatosis (n=15); 1044 had central nervous system tumors; 191 patients were treated with large volume-radiation, including craniospinal irradiation (CSI) in 135; and 988 patients received alkylating chemotherapy. Patients treated with IMRT were more likely to receive alkylating chemotherapy (76.4% vs 47.1%, p <0.001), but received a lower median radiation dose (50.4 vs 54 Gy, p <0.001) and were marginally less likely to have a tumor predisposition syndrome (0.6% vs 1.9%, p = 0.10). Cumulative incidence method provided estimates of secondary neoplasms including benign and malignant solid tumors as well as leukemia. Multiple variables were assessed using proportional hazard regression for competing risks. The median follow-up duration was 6.5 years (range, 2-21.9) and included 296 and 773 patients with >5 years follow-up in the IMRT and proton cohorts, respectively. <h3>Results</h3> The 5-year local control rate was similar between the 2 cohorts at 90.7% following PT vs 91.4% following IMRT. For all patients, the 5- and 10-year rates of developing a second neoplasm were 1.2% and 3.3%, respectively. On multivariate analysis, the presence of a tumor predisposition syndrome (10.1% vs 1.1%), the use of alkylating chemotherapy (2.1% vs 0.3%), and the use of IMRT (2% vs 1%) were significantly associated with the development of a second neoplasm 5 years after treatment (all p < 0.05). When patients with tumor predisposition syndromes were excluded from the analysis, the use of alkylating chemotherapy (1.9% vs 0.2%) and the use of IMRT (2.0% vs 0.8%) independently retained a significant association with second neoplasms (both p < 0.05). The difference in secondary malignant solid tumors was non-significant; however, 4/14 (29%) malignant solid tumors occurred outside the target region in the patients treated with PT compared to 5/10 (50%) in patients treated with IMRT. <h3>Conclusion</h3> Compared to IMRT, early data reveal a significant reduction in second neoplasms among children treated with PT, most pronounced in those who do not have underlying tumor predisposition syndromes. This could be due to a reduction in leukemia and malignant solid tumors developing in tissue exposed to low-dose radiation outside the target region.

Radio-induced malignancies of the scalp in adult after depilatory radiotherapy for tinea capitis in childhood: 137 cases

Abstract Introduction: Radiation-induced malignancies are the most feared complications of radiotherapy. Depilatory radiotherapy for ringworm of the scalp in childhood was the cause of an increase in the incidence of skin tumours of the scalp in adults. The aim of our study was to describe the epidemiological, clinical and therapeutic characteristics of radiation-induced skin tumours of the scalp in order to highlight the characteristics of these tumours compared to non-radiation-induced tumours. Methods: This is a bi-centric retrospective study, extending over a period of 41 years, which collected 137 patients with 200 tumours of the scalp. These patients were selected after noting a history of depilatory radiotherapy for ringworm in childhood in the clinical records of all patients with scalp tumours. We studied the epidemiological, clinical, therapeutic and evolving characteristics of this population. Results: The average age of consultation was 56·6 years. The sex ratio M/F was 3. Radiation dermatitis was found in 33% of cases. The average latency between depilatory radiotherapy and the appearance of radiation-induced tumours was 42·6 years. Multiple carcinomas (&gt;2 tumours) were observed in 23·3% of cases. In 73% of cases, ulceration was the most frequent macroscopic aspect. The predominant histological type was basal cell carcinoma in 82% of cases. Radiation therapy has been the main treatment modality in 77·3% of cases, followed by surgery in 43% of cases. The appearance of new tumours on the scalp was observed in six patients. Conclusion: Radiation-induced tumours of the scalp are comparable in epidemiological and clinical characteristics to non-radiation-induced tumours. However, they may represent a challenge in therapeutic care and require regular monitoring.

Lung-Cancer Risk in Mice after Exposure to Gamma Rays, Carbon Ions or Neutrons: Egfr Pathway Activation and Frequent Nuclear Abnormality

Lung is one of the high-risk organs for radiation-induced carcinogenesis, but the risk of secondary lung-cancer development after particle-beam therapy and the underlying mechanism(s) remain to be elucidated. To investigate the effects of particle-beam radiation on adjacent normal tissues during cancer therapy, 7-week-old male and female B6C3F1 mice were irradiated with 0.2-4 Gy of gamma rays (for comparison), carbon ions (290 MeV/u, linear energy transfer 13 keV/µm), or fast neutrons (0.05-1 Gy, mean energy, ∼2 MeV), and lung-tumor development was assessed by histopathology. Mice irradiated with ≥2 Gy of carbon ions or ≥0.2 Gy of neutrons developed lung adenocarcinoma (AC) significantly sooner than did non-irradiated mice. The relative biological effectiveness values for carbon ions for lung AC development were 1.07 for male mice and 2.59 for females, and the corresponding values for neutrons were 4.63 and 4.57. Genomic analysis of lung ACs revealed alterations in genes involved in Egfr signaling. Hyperphosphorylation of Erk and a frequent nuclear abnormality (i.e., nuclear groove) were observed in lung ACs of mice irradiated with carbon ions or neutrons compared with ACs from non-irradiated or gamma-ray-irradiated groups. Our data indicate that the induction of lung AC by carbon ions occurred at a rate similar to that for gamma rays in males and approximately 2-to 3-fold greater than that for gamma rays in females. In contrast, the effect of neutrons on lung AC development was approximately 4- to 5-fold greater than that of gamma rays. Our results provide valuable information concerning risk assessment of radiation-induced lung tumors after particle-beam therapy and increase our understanding of the molecular basis of tumor development.