Diagnosis Of Radiation-induced Sarcoma Research Articles

Radiation-induced sarcomas following childhood cancer - A Canadian Sarcoma Research and Clinical Collaboration Study (CanSaRCC).

Radiation-induced sarcoma (RIS) is a late toxicity of radiation therapy (RT) usually associated with poor prognosis. Due to ongoing improvements in childhood cancer treatment and patient outcomes, RIS may become more prevalent notwithstanding evolving indications for RT. Due to limited reported studies, we sought to review our experience with RIS in survivors of pediatric cancer. Data were collected on RIS patients following treatment for childhood cancer (initial diagnosis <18 years) identified in the CanSaRCC database. Additionally, details on the protocol guidance at time of treatment were compared with current guidelines for the same disease. Among 12 RIS identified, median age at initial diagnosis was 3.5 years (range 0.16-14) and the latency from RT to RIS diagnosis was 24.5 (range 5.4-46.2) years. Initial diagnoses included neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, retinoblastoma and Hodgkin's Lymphoma. RIS histologies included osteosarcoma and soft tissue sarcomas. In comparison to protocols followed at time of diagnosis to current ones (2022), 7/12 (58%) patients would have required RT. RIS treatment included chemotherapy, radiation and surgery in 3/11 (27%), 10/11 (90%), and 7/11 (63%) patients, respectively. With a median follow-up time of 4.7 years from diagnosis of RIS, 8 (66%) patients were alive and 4 (33%) had died of progressive RIS. RIS is a serious late effect of radiotherapy in childhood cancer; however, radiation remains an integral component of primary tumor management and requires participation from a specialized multi-disciplinary team, aiming to mitigate RIS and other potential late effects.

Radiation-Induced Sarcomas of the Breast: A Review of a 20-Year Single-Center Experience.

Background Radiation-induced sarcomas (RISs) are histologically proven sarcomas within or around a previously irradiated site, per Cahan's criteria. RIS incidence is higher in breast cancer compared to other solid cancers and the prognosis remains poor given limited treatment options. This study aimed to review 20-year experience with RISs at a large tertiary care center. Methodology Using our institutional cancer registry database, we included patients meeting Cahan's criteria diagnosed between 2000 and 2020. Patient demographics, oncologic treatment, and oncologic outcomes data were collected. Descriptive statistics were used to describe demographic data. Oncologic outcomes were assessed using the Kaplan-Meier method. Results A total of 19 patients were identified. The median age at RIS diagnosis was 72 years (range = 39-82 months), and the median latency period for the development of RIS was 112 months (range = 53-300 months). All patients underwent surgery, three patients received systemic therapy, and six patients received re-irradiation as salvage treatment. The median follow-up time was 31 months (range = 6-172 months) from the diagnosis of RIS. Overall, five patients had local recurrence, and one patient developed distant metastases. The median time to progression was seven months (range = 4-14 months). The progression-free survival (95% confidence interval (CI)) at two years was 56.1% (37.4-84.4%). At follow-up two years after the diagnosis of sarcoma, the overall survival (95% CI) was 88.9% (75.5-100%). Conclusions While breast RIS remains rare, when managed in a large tertiary care center, overall survival outcomes appear favorable. A significant proportion of patients recur locally after maximal treatment and require salvage therapy to improve outcomes. These patients should be managed in high-volume centers where multidisciplinary expertise is available.

Treatment related factors associated with the risk of breast radio-induced-sarcoma

Background and purposeThe Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. Materials and methodsPatient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. ResultsThe mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2–32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. ConclusionsThis study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years.

Abstract P3-19-23: Radiation-induced sarcomas of the breast: A 20-year single-centre experience

Abstract Background: Radiation-induced sarcomas (RIS) are rare malignancies comprising only 2.5-5.5% of all sarcomas. As per the Cahan criteria, diagnosis requires histologically proven sarcoma within or around a previously irradiated site. Breast cancer patients are known to have a higher incidence of RIS compared to other primary solid cancers. Following breast irradiation, RIS typically occur after a prolonged latency up to 20 years, although this is often shorter for angiosarcomas. A clear mechanism for RIS development has not yet been elucidated, and prognosis remains poor given limited treatment options. This study aimed to review incidence, risk factors, management, and subsequent oncologic outcomes of breast RIS using 20-year experience at the McGill University Health Centre (MUHC), a large tertiary care centre. Methods: Using our institutional cancer registry database, we identified patients with histologically proven sarcomas of the breast diagnosed between the years 2000 to 2020. We then identified and included patients meeting the Cahan criteria as described above. Patient data including demographics, oncologic treatment of primary breast cancer as well as subsequent sarcoma, and oncologic outcomes were collected from our electronic medical record systems. Descriptive statistics were used to describe patient demographic data. Oncologic outcomes were assessed using the Kaplan Meier method. Results: From 2000 to 2020, we identified 19 patients with breast RIS: 11 angiosarcomas (57.9%), 3 osteosarcomas (15.8%), 2 carcinosarcomas (10.5%), 2 undifferentiated pleomorphic sarcomas (10.5%) and 1 high-grade leiomyosarcoma (5.3%). The median age at RIS diagnosis was 72 years (range 39-82, mean 67) and median latency period for development of RIS was 112 months (range 53-300, mean 120). In terms of secondary treatment, all patients underwent surgery, either total or partial mastectomy (n=14 and n=5, respectively), 3 patients received systemic therapy, and 6 patients received re-irradiation. The median follow-up time was 31 months (range 6-172, mean 48) from diagnosis of RIS. Overall, 5 patients had recurrence at the site of sarcoma and 1 patient developed distant metastases through the study follow-up. The median time to progression was 7 months (range 4-14). The progression-free survival (95% CI) at two years was 56.1 % (37.4-84.4%). At two years follow-up after sarcoma diagnosis, 2 patients were deceased, resulting in an overall survival (95% CI) of 88.9% (75.5-100%). Conclusion: Our 20-year institutional experience confirms that while RIS of the breast remains rare, when managed in a high patient-volume centre, overall survival outcomes appear favorable when salvage is possible. However, a significant proportion of patients still recur locally after maximal treatment, confirming the aggressive nature of this disease and suggesting further follow-up is needed for survival data maturation. Given the rarity of this disease in the context of limited treatment options, patients with RIS should be ideally managed in high-volume centres where multidisciplinary management is available. Citation Format: Vanessa Di Lalla, Marwan Tolba, Farzin Khosrow-Khavar, Ayesha Baig, Carolyn Freeman, Valerie Panet-Raymond. Radiation-induced sarcomas of the breast: A 20-year single-centre experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-23.

Radiation-induced sarcomas of the head and neck.

With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stage-matched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure.

Radiation-induced malignant fibrous histiocytoma of the occipital: a case report

Malignant fibrous histiocytoma (MFH) is a rare neoplasm exhibiting a propensity for aggressive clinical behavior. Effective treatment modality is surgical resection with wide margins, but its rate of recurrence and metastasis is still high. Early detection and complete excision of the tumor is necessary. A MFH of the occipital developed in a 51-year-old woman eight years after surgery and radiation for medulloblastoma of the cerebellar vermis. The secondary neoplasm arose at the site of tumor resection within the irradiated field, and was resected. The development of sarcomas is a recognized complication of radiation therapy. The final diagnosis after the operation was MFH. Radiation-induced sarcoma (RIS) is well known, but radiation-induced MFH is relatively rare in the head and neck region, especially in the occipital. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by computerized tomography (CT) and magnetic resonance imaging (MRI) and appreciation of the expected latency period may help in providing the diagnosis of RIS.

Role of Surgery in the Treatment of Radiation-Induced Sarcomas of the Head and Neck

Introduction: Radiation-induced sarcoma (RIS) is a well-known complication of radiotherapy. It is an aggressive tumour and the prognosis is often poor, despite radical treatment. We aim to investigate the role of surgery in the treatment of patients with RIS of the head and neck region. Method: We conducted a retrospective review of records of patients whom were treated for radiation-induced sarcoma at Queen Mary Hospital, Hong Kong, between the period 1999 to 2010. Data collected included patient age, gender, latency period for the development of RIS, site of RIS, symptoms, treatment given, pathology and survival. Results: Nineteen patients were included, (M=11, F=8). Eighteen received radiotherapy for treatment of primary nasopharyngeal carcinoma. One received radiotherapy for carcinoma of the parotid. The medial latency period for the development of sarcoma was 11.1 years (range 5.3-25.1). The most common site for development of RIS was the neck (n=8), followed by the oropharynx/oral cavity (n=4), nasopharynx (n=3) nasal cavity (n=2), maxilla (n=1) and mandible (n=1). The most common histology was undifferentiated sarcoma (n=6). Nine patients underwent surgical resection of the RIS with curative intent, three and six patients achieved R0 and R1 resection respectively. Chemotherapy was used in eleven instances after surgery. Radiotherapy was used in seven instances, three through brachytherapy, four through external beam irradiation. Overall medial survival from diagnosis of RIS was 1.74 years (95% CI 0.60-2.87), which improves to 2.47 years (95% CI 0.97-3.97) when only calculating those whom surgery was performed. Conclusions: Patients suffering from radiation-induced sarcomas have a poor prognosis, in keeping with existing literature. Treatment is mainly by surgery aiming at resection with a curative intent. If curative resection is impossible, surgery may still have a role in palliating the patients’ symptoms such as bleeding, fungation, or pain.

"Very Late" isolated para-aortic nodal recurrence of carcinoma cervix mimicking radiation-induced sarcoma

Only a minority of the patients who develop recurrence after definitive treatment for cervical cancer are detected after 5 years (late recurrence); the numbers are lesser still after 10 years (very late recurrence). Among the infrequent cases that do develop "late" and "very late" recurrence, the commonest site is the pelvis. We report an unusually rare recurrence of treated cervical cancer confined to the para-aortic nodal group after a protracted disease-free interval of 13 years. On the basis of the long disease-free interval, location of the mass at the periphery of the radiation field, and aggressive imaging appearance, a diagnosis of radiation-induced sarcoma was considered. However, the final diagnosis of isolated para-aortic nodal recurrence of cervical cancer was rendered based on the histopathological and immunohistochemistry findings, supported by the absence of disease elsewhere on whole-body imaging.

Radiation‐induced sarcoma in patients with nasopharyngeal carcinoma

The increasing incidence of radiation-induced sarcoma (RIS) has become a significant problem that can limit long-term survival. The objective of the current study was to analyze the clinicopathologic characteristics, treatment outcomes, and prognostic factors of RIS after radiotherapy for nasopharyngeal carcinoma (NPC). Institutional electronic medical records of patients with NPC who received definitive radiotherapy between February 1964 and 2003 were reviewed. Fifty-three patients who developed RIS and fulfilled the study criteria were included. The median follow-up after a diagnosis of RIS was 15.5 months (range, 0.4-90.3 months), and the median latency between radiotherapy for NPC and an RIS diagnosis was 9.3 years (range, 3.2-26.6 years). Fibrosarcoma was the most frequent histologic type observed, followed by osteosarcoma, and malignant fibrous histiocytoma. The 3-year overall survival (OS) rate for 49 patients who received treatment was 32.4%, and the median survival was 21.2 months (95% confidence interval, 8.7-33.8 months). The median OS was 41.3 months, 8.4 months, and 11 months for the complete resection group, the incomplete resection group, and the chemotherapy group, respectively (P<.0001). The only independent predictive factor that was associated with better OS was complete surgical resection. This retrospective study confirmed the rarity and poor prognosis of RIS in patients with NPC. Complete surgical resection was a significant prognostic factor for survival. The authors concluded that long-term follow-up is necessary for the early detection of RIS in patients with NPC.

Radiation-induced sarcoma: 25-year experience from The Norwegian Radium Hospital

Background. The aim of this study was to determine the prevalence and outcome of radiation-induced sarcomas (RISs) among sarcoma patients referred to the Norwegian Radium Hospital (NRH). Material and Methods. Ninety patients were identified from the institutional sarcoma data base. Medical records and histological and cytological material from both primary and secondary tumours were reviewed. Results. RIS represented 3.0 % of the sarcomas in the data base. The median latency time from radiotherapy of the primary tumour to the diagnosis of RIS was 13.6 years (range 2.5-57.8 years). Gynaecological, breast and testicular cancers were the most common primary diagnoses. For the RISs 13 different histological types were identified including 25 malignant fibrous histiocytomas (28% of all) and 22 osteosarcomas (24%). The sarcoma-related 5-year crude survival was 33% (95 % CI 23-43 %). Unfavourable prognostic factors were metastases at presentation, incomplete surgery and presence of tumour necrosis. Conclusion. Radiation-induced sarcoma is rare and harbours an aggressive clinical behaviour. Complete surgical resection is mandatory for cure.

Radiation‐induced sarcomas after radiotherapy for breast carcinoma

Sarcomas are a rare complication of radiotherapy for breast carcinoma and patients have a poor prognosis. The incidence, histology, and management of patients with sarcomas were reviewed in the current study. The authors reviewed the records of 16,705 patients with breast carcinoma. Of these, 13,472 (81%) were treated with megavoltage radiotherapy and 3233 were treated without at the Institute Curie (Paris, France) between 1981 and 1997. Median doses of 50-55 grays (Gy) in 25-27 fractions were delivered to the whole breast over a period of 5-5.5 weeks (2 Gy/day, 5 weekly fractions) followed, when indicated, by a 16-26-Gy boost to the tumor or tumor bed. Treatment of radiation-induced sarcomas (RIS) consisted mostly of radical surgery and chemotherapy. Overall, 35 patients developed sarcomas. Of these, 27 fulfilled the Cahan criteria. The median follow-up was 9.3 years (range, 1-22.4 years). The latency period ranged from 3 years to 20.3 years. Thirteen sarcomas were located in the breast, 5- in the chest wall, 3 in the sternum, 2 in the supraclavicle, 1 in the scapula, and 3 in the axilla. Histologic evaluation identified 13 angiosarcomas, 3 osteosarcomas, 5 undifferentiated sarcomas, 1 malignant fibrous histiocytoma, 2 leiomyosarcomas, 1 fibrosarcoma, 1 rhabdomyosarcoma, and 1 myosarcoma. The cumulative RIS incidence was 0.07% (+/- 0.02) at 5 years, 0.27% (+/- 0.05) at 10 years, and 0.48% (+/- 0.11) at 15 years. Standardized incidence ratios were 10.2 (95% confidence interval, 9.03-11.59) for irradiated patients and 1.3 (0.3-3.6) for nonirradiated patients. Of the 27 patients, 15 died of sarcoma within 1 month to 14.5 years (mean, 34.2 +/- 0.7 months). The 5-year actuarial survival rate after diagnosis of RIS was 36% (+/- 0.11). The current study confirmed the rarity of RIS. However, it showed that the risk increased with time. Therefore, careful, long-term follow-up of patients treated with radiotherapy is needed for early detection and efficacious treatment of these malignancies.

Radiation-induced sarcomas following radiotherapy for breast cancer: six case reports and a review of the literature

Seven patients with radiation-induced sarcomas (RIS) following radiotherapy (RT) for breast cancer were treated between 1983 and 1994 at the ‘Henri Mondor’ University Hospital (France). All patients underwent surgery and RT for breast cancer. Only one patient received chemotherapy (CT). All patients at the time of diagnosis of RIS were free of disease. Radiation-induced sarcoma appeared with a latency period varying from 5 years to 18 years (median, 11 years). The age of the patients ranged from 39 years to 88 years (median, 58.1 years) at the time of diagnosis of the sarcoma. The sarcomas occurred as follows: two in the treated breast, two in the chest wall, one in the preclavicular area and one in the axillary region. The histological types of sarcomas were: angiosarcoma (1), fibrosarcoma (2), osteosarcoma (1), malignant fibrous histiocytoma (MFH) (1), and highly malignant undifferentiated sarcoma (1). All six patients received treatment for their sarcoma: all underwent surgery, one had combined therapy of RT and CT, two patients in combination with CT, and one with immunotherapy also. Three patients are still alive. Two patients who died had local recurrence and metastatic disease. One had locally recurrent sarcoma only. Among the patients who are still alive, one has ovarian metastasis of breast cancer, one has local recurrence of sarcoma, and one is free of disease. The overall survival ranges from 14 months to 91 months (median, 32.6 months). Radiation therapy can induce malignancies after a latent period of several years. Radiation-induced sarcomas are associated with poor overall prognosis. The treatment in most cases is late and ineffective, and careful follow-up is needed. There are still many uncertainties and questions concerning RIS.