Abscopal Effects in Radio-Immunotherapy—Response Analysis of Metastatic Cancer Patients With Progressive Disease Under Anti-PD-1 Immune Checkpoint Inhibition

Immune checkpoint inhibition (ICI) targeting the programmed death receptor 1 (PD-1) has shown promising results in the fight against cancer. Systemic anti-tumor reactions due to radiation therapy (RT) can lead to regression of non-irradiated lesions (NiLs), termed “abscopal effect” (AbE). Combination of both treatments can enhance this effect. The aim of this study was to evaluate AbEs during anti-PD-1 therapy and irradiation. We screened 168 patients receiving pembrolizumab or nivolumab at our center. Inclusion criteria were start of RT within 1 month after the first or last application of pembrolizumab (2 mg/kg every 3 weeks) or nivolumab (3 mg/kg every 2 weeks) and at least one metastasis outside the irradiation field. We estimated the total dose during ICI for each patient using the linear quadratic (LQ) model expressed as 2 Gy equivalent dose (EQD2) using α/β of 10 Gy. Radiological images were required showing progression or no change in NiLs before and regression after completion of RT(s). Images must have been acquired at least 4 weeks after the onset of ICI or RT. The surface areas of the longest diameters of the short- and long-axes of NiLs were measured. One hundred twenty-six out of 168 (75%) patients received ICI and RT. Fifty-three percent (67/126) were treated simultaneously, and 24 of these (36%) were eligible for lesion analysis. AbE was observed in 29% (7/24). One to six lesions (mean = 3 ± 2) in each AbE patient were analyzed. Patients were diagnosed with malignant melanoma (MM) (n = 3), non-small cell lung cancer (NSCLC) (n = 3), and renal cell carcinoma (RCC) (n = 1). They were irradiated once (n = 1), twice (n = 2), or three times (n = 4) with an average total EQD2 of 120.0 ± 37.7 Gy. Eighty-two percent of RTs of AbE patients were applied with high single doses. MM patients received pembrolizumab, NSCLC, and RCC patients received nivolumab for an average duration of 45 ± 35 weeks. We demonstrate that 29% of the analyzed patients showed AbE. Strict inclusion criteria were applied to distinguish the effects of AbE from the systemic effect of ICI. Our data suggest the clinical existence of systemic effects of irradiation under ICI and could contribute to the development of a broader range of cancer treatments

Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment

Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest. We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty-six patients treated with SRS alone (n = 13;20 lesions) or in combination with anti-PD-1 therapy (n = 13;28 lesions) were analyzed. Lesion size was evaluated three and six months after SRS using a volumetric assessment based on cranial magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE). Local control after six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities reported were less than or equal to grade 2. One metastasis (5%) in the SRS group and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas four (14%) of the six regressed during further follow-ups. This was rated as pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be combined safely in melanoma patients with cerebral metastases. Early volumetric progression of lesions under simultaneous treatment may be related to PsP;thus, the evaluation of combined radioimmunotherapy remains challenging and requires experienced teams

Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma.

The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result

Positron emission tomography in Hodgkin's lymphoma

The FDG-PET method is a standard procedure in staging and response assessment of Hodgkin's lymphoma patients. An accurate staging allows the bone marrow biopsy to be omitted if PET is negative concerning bone marrow involvement. An FDG-PET after induction therapy provides additional relevant prognostic information. The FDG-PET adapted therapy regimens have been introduced making use of the high predictive value of FDG PET early in the treatment course, e.aEurog. after two cycles of chemotherapy. Success rates of treatment could be improved for both intensification and de-escalation of treatment on the basis of PET performed after two cycles of chemotherapy. In the case of a negative PET after two cycles of effective chemotherapy for advanced stages, chemotherapy can be restricted to a total of 4 cycles instead of 6 cycles. Furthermore, radiotherapy in advanced stages can be safely omitted in PET negative patients after effective chemotherapy. The reliability of end of treatment PET as a basis for omitting radiotherapy in early and intermediate stages of Hodgkin's lymphoma is probably given, but remains to be documented. Robust and reproducible interpretation criteria are being used both in ongoing clinical trials and in the daily routine. The recommended five-point Deauville scale has become the standard in assessment of the response to PET treatment, with the caveat that the consequences of a PET scan may be influenced by previous and subsequent treatment

Managing patient flows in radiation oncology during the COVID-19 pandemic Reworking existing treatment designs to prevent infections at a German hot spot area University Hospital

Purpose The described work aimed to avoid cancellations of indispensable treatments by implementing active patient flow management practices and optimizing infrastructure utilization in the radiation oncology department of a large university hospital and regional COVID-19 treatment center close to the first German SARS-CoV-2 hotspot region Heinsberg in order to prevent nosocomial infections in patients and personnel during the pandemic. Patients and methods The study comprised year-to-date intervention analyses of in- and outpatient key procedures, machine occupancy, and no-show rates in calendar weeks 12 to 19 of 2019 and 2020 to evaluate effects of active patient flow management while monitoring nosocomial COVID-19 infections. Results Active patient flow management helped to maintain first-visit appointment compliance above 85.5%. A slight appointment reduction of 10.3% daily (p = 0.004) could still significantly increase downstream planning CT scheduling (p = 0.00001) and performance (p = 0.0001), resulting in an absolute 20.1% (p = 0.009) increment of CT performance while avoiding overbooking practices. Daily treatment start was significantly increased by an absolute value of 18.5% (p = 0.026). Hypofractionation and acceleration were significantly increased (p = 0.0043). Integrating strict testing guidelines, a distancing regimen for staff and patients, hygiene regulations, and precise appointment scheduling, no SARS-CoV-2 infection in 164 tested radiation oncology service inpatients was observed. Conclusion In times of reduced medical infrastructure capacities and resources, controlling infrastructural time per patient as well as optimizing facility utilization and personnel workload during treatment evaluation, planning, and irradiation can help to improve appointment compliance and quality management. Avoiding recurrent and preventable exposure to healthcare infrastructure has potential health benefits and might avert cross infections during the pandemic. Active patient flow management in high-risk COVID-19 regions can help Radiation Oncologists to continue and initiate treatments safely, instead of cancelling and deferring indicated therapies

Robot-assisted Extracranial Stereotactic Radiotherapy of Adrenal Metastases in Oligometastatic Non-small Cell Lung Cancer

Aim: The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with adrenal metastases in oligometastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Between November 2012 and May 2015, fifteen patients with oligometastatic non-small cell lung cancer and adrenal metastases were treated with the Cyberknife (R) system. The primary endpoint was local control. Results: The 1-year and 2-year local control rates were 60% and 46.6%, respectively. The differences in local control for patients with metachronous and synchronous metastases reached statistical significance (p= 0.00028). Two-year overall survival of 91.2% for patients with metachronous metastases was also more favourable compared to patients with synchronous adrenal metastases with 42.8%. Conclusion: Extracranial stereotactic radiotherapy with the Cyberknife (R) is a safe and non-invasive technique that extends the therapeutic spectrum in the treatment of patients with adrenal metastases in oligometastatic NSCLC

Role of radiotherapy in Hodgkin lymphoma

Background The role of radiotherapy (RT) in the treatment of Hodgkin lymphoma (HL) has changed considerably over time. Nevertheless, it remains an integral part of combined-modality therapy; however, the increasing use of immunotherapeutics means that the role of RT will be re-evaluated. This article provides an up-to-date review of RT in HL covering indications, target volume concepts, side effects, and a look to the future. Materials and methods A review of RT in HL was performed using a literature search and current guidelines. Results According to current studies, modern RT in HL continues to be the standard of care in the early stages with 20 Gy involved site RT (IS-RT). In the intermediate stages, based on the HD17 study, positron emission tomography (PET)-guided 30 Gy IS-RT has become the standard of care, so that all PET-negative patients are no longer irradiated after chemotherapy. In advanced stages, local RT continues to be given in patients with positive PET after chemotherapy with 30 Gy. In addition, new target volume concepts, such as IS-RT, have led to a further reduction in RT fields, aiming for a reduction in late side effects and secondary malignancies. Looking ahead, the emergence of checkpoint immunotherapy has significantly changed the treatment of HL. The role and benefits of RT must now be explored in this environment as well, and initial results appear promising. Conclusion Although the role of RT in the treatment of HL has changed significantly over the decades, it appears that it will also remain an important part of combined-modality therapy for HL in the future