Salvage Radiotherapy Strategy and Its Prognostic Significance for Patients With Locally Recurrent Cervical Cancer After Radical Resection: a Retrospective 10-year Analysis

Background: Salvage radiotherapy modes for treating patients with local cervical cancer recurrence after radical surgery are controversial. Therefore, we aimed to evaluate the clinical efficacy and prognostic significance of two radiotherapy modes—involved-field radiotherapy combined with regional lymph nodes (regional radiotherapy) and involved-field radiotherapy alone (local radiotherapy)—in these patients.Methods: We retrospectively enrolled patients with local recurrence who underwent radical surgery without radiotherapy for early-stage cervical cancer from January 2010 to January 2020. Clinical outcomes were analyzed using the Kaplan–Meier method and a Cox proportional hazards model.Results: Forty-four patients underwent intensity-modulated radiotherapy (IMRT)-based salvage treatment. The 5-year overall survival and progression-free survival rates were 64% and 60.2%, respectively. Sixteen of 18 patients with stump recurrence and 15 of 26 patients with pelvic and abdominal cavity recurrence received regional radiotherapy, while others received local radiotherapy. Univariate analysis showed that patients with stump recurrence, who underwent regional radiotherapy, and with a lower systemic inflammation response index (SIRI) had better prognosis than their counterparts. Patients aged < 51 years, with stump recurrence, recurrence time ≤ 24 months, recurrence site=1, and a lower SIRI who received regional radiotherapy had a better prognosis than patients who received local radiotherapy. SIRI correlated with the recurrence site and radiotherapy mode.Conclusion: Locally recurrent cervical cancer treated with IMRT-based salvage therapy has a good prognosis. Recurrence site, SIRI, and the radiotherapy mode significantly influenced prognosis. Regional radiotherapy may be suitable for patients with stump recurrence, recurrence time ≤ 24 months, and one recurrence site.

Predicted Risks of Cardiovascular Disease Following Chemotherapy and Radiotherapy in the UK NCRI RAPID Trial of Positron Emission Tomography–Directed Therapy for Early-Stage Hodgkin Lymphoma

PURPOSE The contemporary management of early-stage Hodgkin lymphoma (ES-HL) involves balancing the risk of late adverse effects of radiotherapy against the increased risk of relapse if radiotherapy is omitted. This study provides information on the risk of radiation-related cardiovascular disease to help personalize the delivery of radiotherapy in ES-HL. METHODS We predicted 30-year absolute cardiovascular risk from chemotherapy and involved field radiotherapy in patients who were positron emission tomography (PET)–negative following three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy within a UK randomized trial of PET-directed therapy for ES-HL. Cardiac and carotid radiation doses and chemotherapy exposure were combined with established dose-response relationships and population-based mortality and incidence rates. RESULTS Average mean heart dose was 4.0 Gy (range 0.1-24.0 Gy) and average bilateral common carotid artery dose was 21.5 Gy (range 0.6-38.1 Gy), based on individualized cardiovascular dosimetry for 144 PET-negative patients receiving involved field radiotherapy. The average predicted 30-year radiation-related absolute excess overall cardiovascular mortality was 0.56% (range 0.01%-6.79%; < 0.5% in 67% of patients and > 1% in 15%), whereas average predicted 30-year excess incidence was 6.24% (range 0.31%-31.09%; < 5% in 58% of patients and > 10% in 24%). For cardiac disease, the average predicted 30-year radiation-related absolute excess mortality was 0.42% (0.79% with mediastinal involvement and 0.05% without) and for stroke, it was 0.14%. CONCLUSION Predicted excess cardiovascular risk is small for most patients, so radiotherapy may provide net benefit. However, for a minority of patients receiving high doses of radiation to cardiovascular structures, it may be preferable to consider advanced radiotherapy techniques to reduce doses or to omit radiotherapy and accept the increased relapse risk. Individual assessment of cardiovascular and other risks before treatment would allow personalized decision making about radiotherapy in ES-HL.

RARE-50. TREATMENT RESPONSE OF CNS HIGH-GRADE NEUROEPITHELIAL TUMORS WITH MN1 ALTERATION

BACKGROUND CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) are a rare entity recently described as a high-grade tumor containing a mixture of solid and pseudopapillary patterns with MN1 rearrangement. METHODS CNS HGNET-MN1 patients were identified using genome wide methylation arrays across 5 institutions (the Hospital JP Garrahan, Hospital for Sick Children, the University Hospital Motol, Royal Children`s Hospital and Christchurch Hospital) and was correlated with treatment and outcome. Central imaging review with radiological features analysis was performed. RESULTS We identified 9 patients harboring CNS HGNET-MN1 tumors through application of the Heidelberg brain tumor classifier. Seven tumors were T supratentorial and two in the spinal cord. Median age was 5 (range 3.6–14.6). All patients had surgery (6 GTR and 3 STR) as initial management followed by radiotherapy (focal 5/CSI 1) and systemic chemotherapy in 2 patients. Four of the 9 patients relapsed by 3 years post diagnosis, with 2 local and 2 metastatic failures despite complete surgical resections and radiotherapy. Three patients died due to tumor relapse after 24 months despite upfront radiotherapy. Seven of 9 patients had an initial diagnosis of ependymoma. CONCLUSION Treatment of CNS HGNET-MN1 remains a major challenge with multiple failures, despite aggressive surgical resections and upfront involved field radiotherapy. Further multicenter, international prospective studies are required to determine the optimal treatment strategy for this group of tumors.

Ewing Sarcoma Family Tumors: Past, Present and Future Prospect

Ewing’s sarcoma (ES), also known as mesenchymal primitive neuroectodermal tumor (PNET), is a malignant round blue cell tumour (MRBCT) with a varying degree of neuronal differentiation. PNET arise from the primitive nerve cells of the central nervous system (CNS) but they may occur in the bones of the extremities, pelvis, vertebral column and chest wall. Extraskeletal ES/PNET may affect the various soft tissues including those of the pelvis, paraspinal region and the thoraco - pulmonary regions Histopathological differentiation between ES, PNET and other related sarcomas is often difficult. On light microscopy, the same histopathological appearance of ES, has been termed PNET, Askin – Rosay (A – R) tumor and malignant neuropeithelioma by various other authors. Immunohistochemical distinction is also difficult due to poor tissue differentiation and poor intake of the various specific immunohistochemical markers. The most frequent translocation is t (11; 22) (q24; q12) resulting in the EWSR1-FLI1 fusion gene detected in nearly 90% of cases and is considered the whole mark of the diagnosis ES, PNET, atypical ES and A – R tumor. Therefore, ES, atypical ES, PNET and A – R tumor are currently regarded as one entity grouped together under the Ewing Family Tumors (EFT) and are treated in an identical way. EFT represent only about 3% of all pediatric malignancies. The annual incidence is between 2 and 5 cases per million children per year. The peak prevalence of the tumor is between the ages of 10 and 15 years. The incidence is higher in males than in females with a ratio of 1.3: 1. Newer groups of MRBCT are with great similarities to EFT are being recently described. These tumors; atypical EFT and Ewing’s like Sarcomas (ELS) bear similarities to EFT but has basic morphological and molecular differences. Optimal treatment requires the use of adjuvant and new-adjuvant chemotherapy (CTR), radical surgical resection and/or involved field radiotherapy (RT). The reported disease free survival (DFS) and overall survival (OS) ranges between 45 – 80% and 36 - 71% respectively. The overall prognosis for metastatic and recurrent disease remains poor. Use of newer conventional and targeted medications, improved RT delivery and surgical techniques may further improve the outcomes. The past few years has seen advances in genomics-based sarcoma diagnosis and targeted therapies. In this wide review article we provide comprehensive report of EFT and discuss the various clinical aspects and the recent advances used in the diagnosis and treatment.

Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study

Purpose: A phase I/II study of intrathecal pemetrexed (IP) combined with involved-field radiotherapy (IFRT) was performed to determine feasibility, safety, and antitumor activity for leptomeningeal metastases (LM) from solid tumors. Methods: Participants first received induction IP administration, followed by concomitant radiotherapy within 3 days. The concomitant regimen consisted of IP (pemetrexed 10 mg, dexamethasone 5 mg, once per week, 4 times in 4 weeks) and IFRT (40 Gy in 20 fractions). Six participants were recruited to assess feasibility in phase I, and then 28 patients were recruited further. All patients were assessed to investigate safety, efficacy, and outcomes. Results: Between April 2018 and December 2018, 34 patients (male: 15; female: 19; median age: 56 years) were enrolled, including non-small-cell lung cancer (21), small-cell lung cancer (5), breast cancer (4), and others (4). Thirty-two patients received concurrent therapy and 25 (74%) patients completed the treatment. Major adverse events (AEs) consisted of myelosuppression, the elevation of hepatic aminotransferases, and radiculitis. Total AEs rate was 53% (18/34), including 6 (18%) patients with grade 3 and 1 (3%) with grade 4 AEs. The response rate was 68% (23/34). The median overall survival was 5.5 (0.3–16.6) months. Median neurological progression-free survival (NPFS) was 3.5 (0.3–15.2) months. Six-month NPFS rate was 47%. One-year survival rate was 21.6%. Conclusion: IP at a 10 mg dose on a schedule of 1–2 times per week presented good efficacy and safety in CSF. The concomitant regimen is an efficacious therapeutic option for LM patients with solid tumors. Trial Registration: This study (IPLM) was registered at https://register.clinicaltrials.gov [ClinicalTrials.gov identifier: NCT03507244].