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Introduction As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN. Methods Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020. Results Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months. Conclusions Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor.

Introduction As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN. Methods Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020. Results Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months. Conclusions Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor.

INTRODUCTION: As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN. METHODS: Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020. RESULTS: Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months. CONCLUSIONS: Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor. ispartof: ADVANCES IN THERAPY vol:38 issue:1 pages:90-108 ispartof: location:United States status: published

Irradiation-induced sarcomas are well-known potential late sequelae of radiation therapy. These tumors are very aggressive and often elude early detection and timely intervention, rapidly leading to early demise of afflicted patients. Long-term patient follow-up and a high index of suspicion are crucial for timely intervention. In this report, we present a case of irradiation-induced osteosarcoma involving the mandible. Diagnostic and therapeutic considerations are subsequently discussed.

Purpose: Postradiation sarcoma, a sarcoma developing in a previously irradiated field, is a rare tumor. Surgery appears to be the only curative treatment option. In general the prognosis is poor, and new treatments options are needed. One study reported the expression of KIT receptor tyrosine kinase in two postradiation angiosarcomas. Success of inhibition of KIT in malignant gastrointestinal stromal tumors with imatinib mesylate seems mutation-dependent, with a favorable response in the presence of exon 11 mutations.Experimental Design: We performed a clinical, immunohistochemical, and genetic assessment of postradiation sarcomas, including angiosarcomas. Archival tumor tissue was available from 16 patients diagnosed with a postradiation sarcoma between 1978 and 2001. Data on the first and secondary tumor, treatment, and follow-up was documented. KIT expression was assessed by immunohistochemistry. For comparison, 23 spontaneous soft tissue sarcomas of similar histological types were analyzed. Exon 11 of the c-kit gene was analyzed by direct DNA sequencing.Results: Fifteen patients received initial irradiation for malignant disease and 1 patient for a benign condition. The median delivered dose was 50 Gy. The median latency period between irradiation and diagnosis of postradiation sarcomas was 222 months. Histological types included: angiosarcoma, fibrosarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and unspecified sarcoma. In concordance with the literature, patients had a poor outcome. Only 3 of 16 patients were disease-free 43, 60, and 161 months after being diagnosed of postradiation sarcoma, all 3 having favorable tumor and treatment characteristics. Fourteen of 16 tumor samples were KIT-positive (88%). In 8 cases >80% of tumor cells stained positively. Five of 23 (22%) spontaneous soft tissue sarcomas of comparable histological types, including 2 angiosarcomas, were KIT-positive. Molecular genetic analysis of exon 11 of the c-kit gene was attainable for 13 of the 16 postradiation sarcomas. No mutations were found.Conclusions: Postradiation sarcomas are aggressive malignancies, seldom amenable to curative treatment. A majority of the analyzed tumors showed extensive expression of the KIT protein, but no mutations in exon 11 of the c-kit gene were found. Still, without the availability of effective therapies, treatment with the KIT inhibitor imatinib mesylate might be considered for patients with postradiation sarcomas.

A 63-year-old man presented with malignant fibrous histiocytoma of the larynx occurring 16 years after radiation treatment for squamous cell carcinoma of the larynx. Postirradiation sarcoma of the larynx is an unusual tumor. The location, the histopathologic and immunohistochemical appearance of the tumor, and the time elapsed since the initial treatment make it probable that this tumor is associated with prior radiation treatment. The possibility of postirradiation sarcomas after radiation therapy should not be a major factor influencing treatment decisions in the patients with head and neck cancer. Wide surgical resection of the tumor seems to be an efficient means in the management of this tumor.

Postirradiation sarcomas of the head and neck are rare. When they do occur, most appear at least 10 years following radiation therapy. We report three cases of early-onset (1, 2, and 7 yr) postirradiation sarcoma. Physicians who care for previously irradiated patients should consider the possibility of a postirradiation sarcoma whenever they see a suspicious lesion, regardless of the amount of time that has passed since radiation therapy was administered. The original pathology should be reexamined to ensure that the original tumor was diagnosed correctly. Electron microscopy can be useful in differentiating sarcomatous-appearing epithelial lesions from true soft-tissue sarcomas, and thus can be helpful in guiding therapy.

Contains fulltext : 97908.pdf (Publisher’s version ) (Closed access) Ten years after chemoradiation for primary lymphoma of the left pelvic bone, a 38-year-old man presented with a 4-month history of gradually increasing pain in his left upper leg and thigh. Initial radiographs and contrast-enhanced magnetic resonance imaging were consistent with recurrent lymphoma, infection, or postirradiation sarcoma. Subsequent F-18 fluorodeoxyglucose positron emission tomography/computed tomography demonstrated a focal area of F-18 fluorodeoxyglucose-avidity within the previously irradiated bone consistent with tumor and the location was confirmed by advanced magnetic resonance imaging techniques and histopathology, thus optimizing treatment planning.

We present a 46-year-old female patient who is diagnosed with synchronous postirradiation sarcoma, cutaneous relapse of a previous soft tissue sarcoma, and lung adenocarcinoma. More than one malignant tumor at the same time with an accompanying relapse of a previous malignant tumor is a rare entity. A relatively young patient diagnosed with adenocarcinoma of the urethra before age 40, which is an unusual tumor for that age, later three more different malignant tumors being diagnosed, two of which are synchronous, causes the suspicion of Li-Fraumeni syndrome.

Background. With improvement in survival after cancer treatment, it is becoming increasingly important to examine treatment-related morbidity and mortality. Sarcomas can develop in the irradiated field after radiation therapy (RT). The authors undertook a study to estimate the risk, and compared the risk of postirradiation sarcoma (PIS) with other treatment modalities used against cancer. Me(hods. Since 1987 the authors have reviewed the records of 1089 patients with head and neck, gynecologic, gastrointestinal, and extremity sarcomas. Of these 1089 patients, 37 had a prior history of RT

Background. With improvement in survival after cancer treatment, it is becoming increasingly important to study treatment-related morbidity and mortality. Sarcoma can develop in the irradiated field after radiation therapy. The authors performed a study to estimate the risk, and compared the risk of sarcoma after radiation therapy with that of other treatment modalities used against cancer. Methods. Between 1955 and 1988, 229 patients with sarcoma of the head and neck were seen at the University of California, Los Angeles (UCLA), Medical Center. Of these, 13 (6%) had a previous history of radiation therapy to the head and neck. Results. Radiation doses were known in 10 of 13 patients and ranged from 30 to 124.4 Gy. The latency time from radiation therapy to the development of postirradiation sarcoma (PIS) ranged from 3 months to 50 years, with a median of 12 years. More than 2000 patients have received radiation therapy to the head and neck for various conditions at the UCLA Medical Center since 1955. Conclusions. The authors conclude that most head and neck sarcomas are not radiation related and that the risk of PIS after head and neck irradiation for other diseases is low. From a review of the literature comparing mortality risks of chemotherapy, general surgery, and anesthesia, the risk of PIS appears no worse. Given the large number of patients who can be cured or receive palliation with radiation therapy, concern about PIS should not be a major factor influencing treatment decisions in patients with cancer.

Purpose. An analysis of the clinicopathologic features and treatment of patients was performed to guide evaluation and management of postirradiation sarcoma.Patients and Methods. Between 1994 and 2001, 25 patients with postirradiation sarcoma were treated in one center with different chemotherapy, mainly in neoadjuvant setting (19). Tumors for which these patients received radiotherapy initially were mainly breast carcinoma (for 15 patients). The postirradiation sarcomas were of different histopathologic forms, most frequently osteosarcoma, leiomyosarcoma, and angiosarcoma.Results. Of the 25 patients, 19 were initially treated with chemotherapy. Nine of 19 pretreated patients achieved clinical partial response (RP 47%). Leiomyosarcomas were good responders (3/4) and undifferentiated sarcoma (3/5). Responders were more often treated with MAID (6/8). Eight of the 9 responders underwent surgery. Two patients achieved complete histological response. Seven of the 9 good responders are alive with a median follow up of 24 months. For all treated patients, median follow up 24 months (6–84 months), overall survival and disease free survival were, respectively, 17/25 (68%), and 14/25 (56%).Conclusion. From our data, postirradiation sarcoma should not be managed differently from primary sarcoma. Chemotherapy has to be included in the treatment plan of postirradiation sarcoma, in future studies.

The educational objectives of this self-assessment module on the imaging of postirradiation osteosarcoma are for the participant to exercise, self-assess, and improve his or her understanding of the features used to establish the diagnosis of postirradiation sarcoma.

Background: Treatment of radiation-induced sarcoma (RIS) remains an unsolved problem. To provide more insight into the disease process, its characteristics, outcome, and potential outcome determinants were defined.Methods: From 1978 to 2003, 27 patients-20 females (74%) and 7 males (26%) with a median age 44 years (range, 1-73 years) at the time of diagnosis of the primary tumor-developed an RIS after a median interval of 8 years (range, 3-41 years). The histology of the RIS was 10 (37%) undifferentiated high-grade pleomorphic sarcomas, 7 (26%) angiosarcomas, 6 (22%) fibrosarcomas, 2 (7%) osteosarcomas, 1 (4%) pleomorphic rhabdomyosarcoma, and 1 (4%) pleomorphic leiomyosarcoma. Surgical resection was performed in 21 patients: 13 (62%) R0 (microscopically radical), 4 (19%) R1 (microscopically irradical), 2 (9.5%) R2 ( macroscopically irradical), and 2 (9.5%) RX (unknown radicality). Six (22%) patients underwent no resection.Results: The 5-year disease-free and overall survival rates were 27% and 30%, respectively. The local failure rate after R0 resection was 54%. The distant failure rate for the entire group was 41%. Patients with an R0 resection had a significantly better survival rate (PConclusions: RISs are aggressive malignancies with a high tendency for local recurrence and distant metastases. Previously applied treatment often hampers adequate resection. Therefore, radical surgical resection is the only chance to improve disease-free and overall survival, but it may also have a palliative role. Still, the overall prognosis remains poor.

Purpose: Postradiation sarcoma, a sarcoma developing in a previously irradiated field, is a rare tumor. Surgery appears to be the only curative treatment option. In general the prognosis is poor, and new treatments options are needed. One study reported the expression of KIT receptor tyrosine kinase in two postradiation angiosarcomas. Success of inhibition of KIT in malignant gastrointestinal stromal tumors with imatinib mesylate seems mutation-dependent, with a favorable response in the presence of exon 11 mutations. Experimental Design: We performed a clinical, immunohistochemical, and genetic assessment of postradiation sarcomas, including angiosarcomas. Archival tumor tissue was available from 16 patients diagnosed with a postradiation sarcoma between 1978 and 2001. Data on the first and secondary tumor, treatment, and follow-up was documented. KIT expression was assessed by immunohistochemistry. For comparison, 23 spontaneous soft tissue sarcomas of similar histological types were analyzed. Exon 11 of the c-kit gene was analyzed by direct DNA sequencing. Results: Fifteen patients received initial irradiation for malignant disease and 1 patient for a benign condition. The median delivered dose was 50 Gy. The median latency period between irradiation and diagnosis of postradiation sarcomas was 222 months. Histological types included: angiosarcoma, fibrosarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and unspecified sarcoma. In concordance with the literature, patients had a poor outcome. Only 3 of 16 patients were disease-free 43, 60, and 161 months after being diagnosed of postradiation sarcoma, all 3 having favorable tumor and treatment characteristics. Fourteen of 16 tumor samples were KIT-positive (88%). In 8 cases >80% of tumor cells stained positively. Five of 23 (22%) spontaneous soft tissue sarcomas of comparable histological types, including 2 angiosarcomas, were KIT-positive. Molecular genetic analysis of exon 11 of the c-kit gene was attainable for 13 of the 16 postradiation sarcomas. No mutations were found. Conclusions: Postradiation sarcomas are aggressive malignancies, seldom amenable to curative treatment. A majority of the analyzed tumors showed extensive expression of the KIT protein, but no mutations in exon 11 of the c-kit gene were found. Still, without the availability of effective therapies, treatment with the KIT inhibitor imatinib mesylate might be considered for patients with postradiation sarcomas.

We present a case of concurrent metastatic thymic carcinoma and postirradiation sarcoma in the same lobe of the lung in a woman who had received partial resection of thymic carcinoma with chemoradiotherapy 11 years ago. One tumor showed similar histology to the previous carcinoma. The other tumor was a pleomorphic sarcoma, suggestive of a postirradiation sarcoma. Irradiation-induced sarcomas are rare and have not been reported in patients with thymic carcinoma. This case may serve as a model in considering the possibility of postirradiation sarcoma for patients encountering recurrent masses with the history of radiotherapy for thymic carcinoma several years ago.

A patient with a sarcoma of the left groin at a site where a prior seminoma had been irradiated is presented. Very few postirradiation sarcomas are described in patients treated with radiation therapy for testicular cancers, even if an increased risk of second malignancies has been reported. In contrast with the highly aggressive clinical course of postirradiation sarcomas, an early discovery of the lesion allowed a radical surgical approach with a presumable cure of the patient. A continuous and precise follow-up of patients irradiated for seminoma is suggested.

We report 3 cases of postirradiation sarcoma that arose in the pelvis 8, 15, and 16 years after completion of external beam radiation therapy (RT) for localized adenocarcinoma of the prostate. Although such cases must be regarded as extremely rare, postirradiation sarcoma should be considered as a potential cause of pelvic pain developing after RT.

A case of postirradiation sarcoma is described. The tumor, a malignant fibrous histiocytoma, occurred in the radiation field 11 years following postoperative external beam radiation therapy (7000 rad) for carcinoma of the cervix. Reports of postirradiation malignant fibrous histiocytoma are rare, and the occurrence of this neoplasm following treatment of cervix cancer has not previously been described. The literature concerning postirradiation bone and soft tissue sarcomas is briefly reviewed, with special attention to malignant fibrous histiocytomas.

Ten cases of irradiation induced sarcoma of bone which fulfilled Cahan's criteria were seen in a twenty year period at the Princess Margaret Hospital. The overall incidence of this complication is 0.035% of all irradiated five year survivors. Combining our data with three other large series presented in the literature, a dose complication curve could be deduced. On the basis of the human and animal data reviewed, it was concluded that the risk of radiation induced sarcoma is so low in the dose range of modern radiotherapeutic practise that it does not represent a contraindication to the use of radiation therapy.

1948年Cahanが放射線照射後一定の潜伏期をおき, その照射野に一致して発生した腫瘍で組織学的に肉腫であるものをPostirradiation sarcomaと定義したが, 今回われわれは68歳の症例で子宮頸部角化型扁平上皮癌にて外照射60Co 5,000 Rad, Radium 5,090mghにて治療後8年目に, 照射野磐部に生じたそれらの肉腫でも, まれなmalignant fibrous histiocytornaの1例を若干の文献的考察を加え報告する.腫瘍の穿刺・捺印細胞診とも線維形の細胞質で, 小型の短楕円形の核をもつ線維芽細胞様細胞と, 類円形～不正形の細胞質と核を示す組織球様細胞, さらに両者の移行型細胞・大型多核巨細胞が存在した. 組織像は線維芽様細胞が密な束状配列でいわゆるstoriform patternを示し, そのなかに多形性の組織球性細胞と大型多核巨細胞が存在していた. 電顕的にもelectron-dense materialを認めるrough ER, lysosome, 空胞, 脂肪滴などを有する上記の細胞を確認した.

A case is reported of a patient who developed a histologically unusual sarcoma in the axilla and chest wall 8 years after receiving radiation therapy (6500 rad) for carcinoma of the breast. This sarcoma showed light- and electron-microscopic features of a malignant fibrous histiocytoma, a tumor not documented among 24 previously reported cases of postirradiation sarcoma following the diagnosis of breast carcinoma. In addition, the literature is reviewed and discussed regarding postirradiation sarcoma in general following breast carcinoma.

A fatal case of postirradiation malignant fibrous histiocytoma was reported, with a review of postirradiation sarcoma in the Japanese literature.

Leiomyosarcoma rarely occurs in the orbit and is seldom encountered as a postirradiation sarcoma in any anatomic location. Three patients with bilateral retinoblastoma who had received radiation therapy are known to have orbital leiomyosarcoma develop in their third decade of life. The clinical and pathological data pertaining to two of these patients are given and discussed herein.

• An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods. (Arch Otolaryngol Head Neck Surg1988;114:640-644)

This paper reports a sarcoma of the chest wall following postoperative radiation therapy for breast carcinoma. A total of 9346 rads was delivered at a 2-cm tissue depth from two treatment courses separated by a five-year interval. The sarcoma appeared 16 years following the initial radiation course. The existence of two mesenchymal elements in the lesion led to the final diagnosis of malignant mesenchymoma. Criteria for evaluating a possible radiation-induced malignancy are discussed.

Four patients with postirradiation sarcoma occurring in the bony pelvis following primary irradiation therapy for squamous cell carcinoma of the cervix are reported. All of the cases occurred following orthovoltage therapy with a lag period of 9 to 23 years. The incidence of sarcoma in this series is approximately 650 times the rate of spontaneous osteogenic sarcoma of the bony pelvis in women. Pain antedated radiologic evidence of the tumor by 3 to 12 months in all patients.

StreszczenieNowotwory indukowane napromienianiem są rzadkim powikłaniem odległym radioterapii. Histologicznie są to w ogromnej większości mięsaki tkanek miękkich lub kości. Przypadki zlokalizowane w miednicy mniejszej są zwykle późno rozpoznawane i rokują źle. Opisujemy przypadek popromiennego mięsaka trzonu macicy u chorej leczonej 7 lat wcześniej napromienianiem z powodu raka szyjki macicy, która pomimo przeprowadzonego chirurgicznego leczenia radykalnego zmarła wkrótce z powodu gwałtownej progresji. Przedstawiamy krótki przegląd aktualnego piśmiennictwa o częstości występowania, najczęstszych typach histologicznych, a także możliwych mechanizmach powstania wtómych nowotworów popromiennych. Kontrola chorych po skutecznym leczeniu napromienianiem powinna być prowadzona przez wiele lat. Wiedza o możliwości rozwoju wtórnych nowotworów upowszechniona wśród lekarzy pierwszego kontaktu może pozwolić na wcześniejsze rozpoznanie i skuteczniejsze leczenie tych nowotworów.SummaryPostirradiation tumors are rare kind of late complication of radiation therapy. The most of them are histologicaly confirmed sarcomas of bones or soft tissues. The pelvic location of malignance are usualy recognised late and has poor prognosis. We report a case of the postirradiation sarcoma developing in uterus 7 years after radiation therapy for cervical cancer. The rapid progresion was cause of death of observed patient, nevertheless radical surgery treatment. A short references review, concerning frequency, the most common histological types and possible mechanisms of secondary postirradiation malignancies has been presented. According to reccurence, dissemination and secondary malignancies risks the follow-up after radiation therapy should last for many years. Acknowledgement of the nature of postirradiation malignancies among primary care doctors may result in earlier diagnosis and better treatmant efficacy.

A fatal nasopharyngeal malignant fibrous histiocytoma developed in a young male after irradiation of juvenile nasopharyngeal angiofibroma diagnosed 5 years earlier. The sarcoma extended from the nasopharynx into the floor of the pituitary fossa and into both parasellar regions. There was no clinical evidence of any distant spread. Many of the malignant cells contained cytoplasmic granular and globular PAS-positive inclusions shown to be alpha-1-antitrypsin immuno-histochemically. Ultrastructurally, this probably corresponded to electron-dense material with distinctive patterns and which had accumulated within distended ergastoplasmic cisternae of the neoplastic cells. Three previously reported cases of postirradiation sarcomas arising in nasopharyngeal angiofibroma were said to be fibrosarcomas and none produced alpha-1-antitrypsin.

Sarcoma of the chest wall following postoperative radiation therapy (2500 rads) for breast carcinoma is presented; it appeared 16 years after the initial radiation, and had light and electron microscopic features of malignant fibrous histiocytoma (MFH). Unique ultrastructural finding was the presence of Langerhans cell granules in some of the tumor cells. This appears to be the first documented instance of a soft tissue MFH containing such granules in the tumor cells.