Novel Drugs and Radiotherapy in Relapsed Lymphomas. Abscopal Response and Beyond

Abstract: Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and intermediate-dose radiotherapy. More recently, several new agents, including immunotherapies, have reshaped the therapeutic panorama of some lymphomas. In parallel, radiotherapy techniques have witnessed substantial improvement, accompanied by a growing understanding that radiation itself comes with an immune-mediated effect. Six decades after a metastatic lesion regression outside the irradiated field was first described, there is increasing evidence that a combination of radiotherapy and immunotherapy could boost an abscopal effect. This review focuses on the mechanisms underlying this interaction in the setting of lymphomas, and on the results of pivotal prospective studies. Furthermore, the available evidence on the concomitant use of radiotherapy and small molecules (i.e., lenalidomide, venetoclax, and ibrutinib), as well as brentuximab vedotin, and chimeric antigen receptor (CAR) T-cell therapy, is summarized. Currently, combining radiotherapy with new agents in patients who are affected by lymphomas appears feasible, particularly as a bridge to anti-CD19 autologous CAR T-cell infusion. However, more studies are required to assess these combinations, and preliminary data suggest only a synergistic rather than a curative effec

Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Patients with Lymph Node Metastases from Gynecological Cancers

Background: To evaluate clinical outcomes of stereotactic body radiation therapy (SBRT) as a local treatment for lymph node metastases from gynecological cancers. Methods: Between November 2007 and October 2021, we retrospectively analyzed 29 lymph node metastases in 22 oligometastatic/oligoprogressive patients treated with SBRT. The Kaplan-Meier method was used to estimate the rates survival. Univariate analysis for prognostic factors were performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios (HR). Results: Median age was 62 years (IQR, 50-80 years). Median follow-up was 17 months (IQR 10.5-31 months). The median survival was 22 months (CI 95%: 4.2-39.7, IQR: 12.5-34.5 months). Six months, one year and two year overall survival (OS) were 96.6%, 85.2%, and 48.7%, respectively. Median local control (LC) was not reached. Six months, 1one year and 2 year were 93.1%, 87.9%, and 79.9%, respectively. Distant metastasis free survival (DMFS) at one year, and two year was 53% and 37.1%, respectively Four patients (18%) experienced acute G1-G2 toxicities. No G3-4 acute toxicity was reported, and no late toxicity was observed. Conclusions: SBRT for lymph node recurrence offers excellent in-field tumor control with safe profile and low toxicities. Size, number of oligometastases, and time primary tumor to RT seem to be significant prognostic factors

Stereotactic Body Radiation Therapy Boost in Patients With Cervical Cancer Ineligible for Brachytherapy

Background: Standard treatment for locally advanced cervical cancer is external beam radiotherapy followed by brachytherapy (BT). Stereotactic body radiation therapy (SBRT) is a possible option for treating patients ineligible for BT. Patients and methods: From October 2012 to July 2020, nine women with cervical cancer received SBRT to high-risk volumes. The Kaplan-Meier method was used to estimate the rates of overall and disease-free survival. Results: The median age was 52 years; 88% of patients had squamous carcinoma. Reasons for forgoing BT were cervical canal stenosis, treatment refusal and hematological disease. The median boost dose was 18 Gy and the median dose per fraction was 6 Gy. Median follow-up was 16 months. The median survival was 24 months, the actuarial 2-year OS rate was 70%, and median disease-free survival was 11 months. One grade 3 late vaginal toxicity was reported. No acute nor late grade 4 toxicities were observed. Conclusion: SBRT boost in patients with cervical cancer ineligible for BT led to acceptable survival outcomes and a safe toxicity profile

Mono-and Bi-weekly hypofractionated radiation therapy for the treatment of epithelial skin cancer in very elderly patients

urs in the elderly population, sometimes in an advanced stage, when intensive treatments are needed. Radiotherapy can achieve high response rates. We evaluated efficacy and tolerability of hypofractionated radiotherapy in a population of very elderly patients with locally advanced epithelial skin cancer. Patients and Methods: Two different hypofractionated schedules were administered (21 patients): 6 Gy in 10 bi-weekly fractions (13 lesions) and 5 Gy in 12 bi-weekly fractions (13 lesions). Median age at treatment was 88 years, life expectancy was ≤5 years in 90.5%. Results: The overall response rate was 96.1%, with 92.4% complete responses. All patients experienced an improvement of their symptoms and a reduction of pain and medication. The median overall survival time was 28 months (95% confidence interval=4.7-51.2 months). At the time of analysis, 52.3% of patients had died. Conclusion: Hypofractionated radiotherapy is an effective option of treatment, with low toxicity and optimal results, and can also be safely administered to these frail patients. Epithelial skin cancer is a common neoplasm. The m

Severe and prolonged myelosuppression during concomitant temozolomide and radiotherapy treatment in a patient with glioblastoma multiforme

Aims: We describe the case of a patient with glioblastoma (GBM) who developed severe and prolonged myelosuppression during concomitant daily temozolomide (TMZ) and radiotherapy (RT) treatment. Analysis of polymorphisms in genes correlated with TMZ-induced myelotoxicity was also performed. Presentation of the Case: A 67–year-old man with diagnosis of GBM undergoing concomitant RT-TMZ treatment developed severe and prolonged pancytopenia that led to discontinuation of TMZ and required frequent platelet and red cells transfusions. Analysis of single nucleotide polymorphisms (SNPs) in the genes NAD(P)H dehydrogenase, quinone 1 (NQO1) and glutathione S-transferase pi 1 (GSTP1) was carried out. Both SNPs were found to be wild-type. Discussion: TMZ is an oral alkylating agent used for the treatment of glioblastoma. TMZ is usually considered well tolerated and safe, with nausea and mild myelosuppression being the most common side effects. However, severe haematologic adverse events have been also reported. Recently, there has been growing interest in gene polymorphisms that might be associated with an increased risk of hematologic toxicity. Conclusion: Myelosuppression is a side effect that can occur relatively early during concomitant TMZ treatment and can negatively impact on patient’s quality of life. Further studies are warranted to find out a correlation between genetic factors and the occurrence of severe hematologic toxicity

Fondazione Italiana Linfomi (FIL) expert consensus on the use of intensity-modulated and image-guided radiotherapy for Hodgkin's lymphoma involving the mediastinum

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

Stereotactic body radiation therapy for the treatment of lymph node metastases: a retrospective mono-institutional study in a large cohort of patients

IntroductionLymph node metastases (NMs) are a common site of tumor spread that can occur at different times of the disease. Stereotactic body radiation therapy (SBRT) can be a therapeutic option for the treatment of NMs in the setting of oligometastatic disease (OMD). The aim of this study was to evaluate as primary end points the local control (LC) and secondary end points the locoregional nodal control (LRNC), distant nodal control (DNC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), and concurrently to assess the predictive factors of response.MethodsThis is a retrospective study that analyzes a group of patients treated with SBRT on NMs from different primary tumors, with a of maximum five metastasis. Treated lesions were divided into four groups: oligometastatics, oligorecurrents, oligoprogressives, and oligopersistents.ResultsFrom 2007 to 2021, 229 NMs were treated in 174 patients with different primary tumor. The schedule most represented was 30 Gy in five fractions. The LC was obtained in 90% of NMs treated by SBRT with rates at 1, 3, and 5 years of 93%, 86%, and 86%, respectively. The LRNC was reached in 84% of cases with rates at 1, 3, and 5 years of 88%, 83%, and 77%, respectively. The DNC was obtained in 87% of cases with rates at 1, 3, and 5 years of 92%, 82%, and 78%, respectively. The DMFS was obtained in 38% of cases with rates at 1, 3, and 5 years of 57%, 40%, and 30%, respectively. The rate of PFS were 44%, 23%, and 13% at 1, 3, and 5 years, respectively. The rates at 1, 3, and 5 years of OS were 78%, 48%, and 36%, respectively.ConclusionSBRT is an option for the treatment of NMS, with high rates of LC, improving survival, and with a good safety and tolerance. Tumor volume, tumor burden, lesion site, and doses can be predictive factors of response; however, multi-institutional studies with a greater number of patients could be helpful to better select patients and understand the right integrations between ablative treatment and systemic therapies

Efficacy of residual site radiation therapy (ISRT) in patients with primary mediastinal lymphoma with Deauville Score 4 following R-CHT: results of a retrospective mono institutional study

Background: In order to evaluate the efficacy of residual site radiation therapy (RSRT) in terms of progression-free survival (PFS) and overall survival (OS) in patients with primary mediastinal lymphoma (PMBCL) with Deauville Score 4 (DS 4) following rituximab and chemotherapy treatment (R-ICHT). Methods: Thirty-one patients with PMBCL were recruited. After completion of R-ICHT, patients were staged with 18F-fluorodeoxyglucose positron-emission tomography, showing DS 4, and were treated with adjuvant RSRT. The chosen techniques for RT delivery were intensity-modulated radiation therapy (IMRT) or three-dimensional conformal RT (3D-CRT). Most patients underwent the first one using cone-beam computed tomography (CBCT). All patients were evaluated every 3 months for the first 2 years and every 6 months afterwards for a period of at least 5 years, with clinical and radiological procedures as required. Results: All patients received RSRT with a dose of 30 Gy in 15 fractions. The median follow-up time of 52.7 months (IQR: 26–64.1 months). The 5-year OS rate was 100%. The 2-year and 5-year PFS rates were 96.7% and 92.5%, respectively. Patients with relapsed disease had been treated with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Conclusion: RSRT in patients with PMBCL treated with ICHT and DS 4 did not impact unfavorably on patient survival

Postoperative treatment of intermediate-risk early stage cervical cancer: results of a survey from the Gynecology Study Group in the AIRO Gyn and MITO Groups

This survey investigated prognostic factors, treatment modalities, references followed and radiation oncologists' opinions to prescribe adjuvant therapy in early intermediate-risk cervical cancer. All but one recommended pelvic radiotherapy ± vaginal boost (45%) with or without chemotherapy (20%). 88% believed other prognostic factors could integrate classic risk criteria. 66% considered chemo-radiation indicated in case of lymphovascular invasion and suboptimal node dissection, high grade, size ≥ 4cm, non squamous histology and risk factors combination. This wide heterogeneity of treatments reflects the different guideline options due to the lack of defined indications. The need of integrating the classic prognostic factors with others factors was unanimously expressed by radiation oncologists. The best local and systemic therapy should be established through new studies. These results highlighted the need of a position paper to standardize adjuvant treatment in Italy and to design collaborative studies to clarify the controversial aspects

Residual Site Radiotherapy After Immunochemotherapy in Primary Mediastinal B-Cell Lymphoma: A Monoinstitutional Retrospective Study

Aim: To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progressionfree (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT). Patients and Methods: The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with F-18-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed. Results: All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively. Conclusion: RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival