Indications For Palliative Radiotherapy Research Articles

Tinjauan Pustaka: Sindrom Vena Kava Superior

Superior Vena Cava Syndrome (SVCS) includes various clinical signs and symptoms due to external compression and intrinsic obstruction of superior vena cava (SVC) itself or the superior cavo-atrial junction that cause reducing of blood flow. Infection becomes main etiology in previous decades but development in antibiotics treatment and improvement of socio-economyc condition made incidence of SVCS due to infection decreased. SVCS due to malignancy recently reach 60-90% of overall cases. 78-85% of SVC obstructions due to malignancy are caused by lung cancer and 80% of it is right lesion. Historically SVCS is considered as an oncology emergency condition and become one of a few indications for palliative radiotherapy. This literature review will explain the pathophysiology, etiology, diagnosis and management of SVCS with the aim of providing timely and effective intervention to treat the causes of this syndrome so that it can significantly relieve symptoms and improve the quality of life of patients with SVCS.

Palliative Appropriateness Criteria: A Pragmatic Method to Evaluate the Suitability of Palliative Radiotherapy Fractionation.

Purpose: To describe a novel metric to aid clinical decision making between shorter versus longer palliative radiotherapy (PRT) regimens using objective patient factors. Materials and Methods: Patients receiving PRT at a single institution between 2014 and 2018 were reviewed. The time between PRT start and finish was calculated and divided by overall survival (in days from start of PRT) to generate the percent of remaining life (PRL). This value was compared across various clinical factors using the Kruskal-Wallis test. Factors identified with a significance level p < 0.01 were included in a novel Palliative Appropriateness Criteria Score (PACS) and were included in an online risk assessment tool to assist clinicians in patient-specific fractionation decisions. Results: Totally 1027 courses of PRT were analyzed. Median age was 64 years; Eastern Cooperative Oncology Group (ECOG) performance status was 3-4 in 22%. Primary malignancies included were lung (38%), breast (13.8%), prostate (9.3%), and other (39%). The indication for PRT was pain (61%), neurological (21%), or other (18%). Palliative regimens included 199 (19.4%) receiving single fraction, 176 (17.1%) receiving 2-5 fractions, and 652 (63.5%) receiving 10 fractions. Median follow-up was 83 days overall and 437 days for patients alive at last follow-up. Factors significantly associated with increased PRL (and included in the PACS) were male gender, ECOG 3-4, lung or "other" primary diagnosis (vs. breast or prostate), PRT indication (neurological dysfunction vs. pain/other), inpatient status, and extraosseous sites treatment. Death within 30 days was significantly associated with high-risk PACS categorization, regardless of fractionation scheme (p < 0.001). Conclusions: The PACS is a novel metric for evaluating the utility of PRT regimens to improve clinical decision making. Single fraction is associated with low PRL. When considering multifraction PRT regimens, the PACS identifies patients who may benefit from shorter courses of PRT and alternatively, low-risk patients for whom a more protracted course is reasonable. Prospective external validation is warranted.

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial

BackgroundHypofractionated palliative radiotherapy for metastatic lung cancer patients is frequently used in order to ease pain, to increase bone stability, to treat local mass effects, or to prolong progression-free survival at critical sites. Recently introduced, immunotherapy for patients with non-squamous non-small cell lung carcinoma (NSCLC) has significantly improved outcome in this cohort. Preclinical and early clinical data suggest that the combination of photon radiation with programmed death-1 (PD-1) targeting immunotherapies may promote a strong and durable immune response against tumor manifestations both within and beyond radiation targets.Methods/designIn the present prospective, two-group, non-randomized, open-label phase II trial, 130 patients with stage IV non-squamous NSCLC in 2nd-line or 3rd-line treatment will be included. 65 patients with a clinical indication for palliative radiotherapy to non-cerebral/non-pulmonary metastatic sites will receive 240 mg nivolumab followed by palliative radiotherapy with 5 × 4 Gray (Gy) = 20 Gy photon radiation, which will be initiated within 72 h after first nivolumab administration (Group A). 65 patients without an indication for radiotherapy will only receive nivolumab (Group B). Nivolumab will be further administered every two weeks in both groups and will be continued until progression and loss of clinical benefit or until occurrence of limiting toxicities.The primary endpoint will be the objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints will be progression-free survival (PFS) according to RECIST 1.1, overall survival, descriptive subgroup analyses according to PD-L1 expression, toxicity and quality of life. Since response patterns following immunotherapies differ from those after conventional cytostatic agents, both objective response rate and progression-free survival will additionally be assessed according to immune-related RECIST (irRECIST) criteria.DiscussionThe FORCE study will prospectively investigate response rates, progression-free and overall survival (OS), and toxicity of nivolumab with and without hypofractionated palliative radiotherapy in a group of 130 patients with metastatic non-small cell lung cancer (non-squamous histology) in 2nd-line or 3rd-line treatment. This trial will contribute prospective data to the repeatedly published observation that the combination of hypofractionated photon radiotherapy and medical immunotherapy is not only safe but will also promote antitumoral immune responses.Trial registrationClinicaltrials.gov identifier: NCT03044626 (Date of initial registration: 05 January 2017).Eudra-CT Number: 2015–005741-31 (Date of initial registration: 18 December 2015).

A phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).

1047 Background: RT is frequently used for palliation in MBC. In animal models its use has been reported to induce distant (abscopal) tumor responses when combined with immune checkpoint inhibitors. Here, we report the safety and efficacy of palliative RT plus pembrolizumab in a phase II single-arm study in patients (pts) with HR+/HER2- MBC. Methods: Eligible pts had HR+/HER2- MBC, ECOG PS &lt;2, indication for palliative RT, and ≥1 measurable lesion outside of the RT field; there was no limit on prior lines of therapy. A total RT dose of 20 Gray was delivered over 5 daily fractions. Pembrolizumab was given at 200 mg IV 2-7 days before day 1 of RT, then every 3 weeks until disease progression. The primary endpoint was objective response rate (ORR) outside the field of radiation by RECIST v1.1. Using the Simons “optimal” method, if ≥ 1/8 pts responded during the first stage, 19 more would be enrolled. If ≥ 3/27 responded, the null hypothesis (ORR=3%) would be rejected in favor of a 20% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses associating PD-L1 expression, tumor-infiltrating lymphocytes (TIL), and neutrophil/lymphocyte ratio (NLR) with outcomes were exploratory. Results: Eight women were enrolled into the first stage of the trial; no objective responses were seen, and the study was closed to further accrual. The median age was 59y (37-68y), 6 (75%) had ECOG PS 1, all had bone and 5 (63%) had liver metastases. The median number of prior cytotoxic therapies for MBC was 2 (range 0 to 8). While one patient had a PR by RECIST criteria, this patient experienced concurrent clinical progression. Two pts had SD &lt; 16 weeks and 5 had PD as best response. The median PFS was 1.4 months (95% CI 0.4 – 2.1). All-cause adverse events occurred in 87.5% of pts (G3-4, 12.5%). TIL were available for 6 pts: 4 had ≤10%, and 2 &gt; 10%. Among 5 pts with PD-L1 status available, 2 were positive. Six pts had NLR &gt; 4. Conclusions: Pembrolizumab combined with RT was well-tolerated, and no unexpected adverse events were observed; however, clinical benefit of the combination was not demonstrated in this heavily pretreated HR+ population. Clinical trial information: NCT03051672.

Defining the role of palliative radiotherapy in bone metastasis from primary liver cancer: an analysis of survival and treatment efficacy.

Primary liver cancer is the fourth leading cause of cancer-related death worldwide and is still associated with a poor prognosis. Hepatocellular carcinoma and cholangiocarcinoma are known to cause bone metastasis resulting in pain, neurologic impairment and risk of fracture. Palliative radiotherapy is the treatment of choice in symptomatic bone lesions and is usually performed as percutaneous fractionated radiotherapy. From June 1987 to December 2009, 41 patients (median age, 64 years) with bone metastasis received radiotherapy in our department. The analyzed patients were treated for 67 sites of bone lesions. We analyzed the applied fractionation schedules and the preferred sites of metastasis and symptoms, evaluated the therapeutic outcome in terms of symptomatic improvement, and described the prognosis of these patients. Main indication for palliative radiotherapy was pain in 94% of all cases. Most frequent radiation protocols were 10 x 3 Gy (20 patients) and 20 x 2 Gy (19 patients). Median applied overall dose was 39 Gy (range, 4-48 Gy) and median single dose was 2.5 Gy (range, 1.8-4 Gy). The median duration of the radiotherapeutic treatment was 15 days (range, 2-24 days) and in 12 cases treatment was discontinuated. The overall response rate to palliative radiotherapy in bone metastasis was 77%. Median overall survival in both cholangiocarcinoma and hepatocellular carcinoma patients was 4.2 months after initiation of radiotherapy (range, 0.2-38.9). Considering the poor prognosis of patients with bone metastasis in hepatocellular carcinoma and cholangiocarcinoma, with a poor median survival of 3.7-5.0 months according to our study and existing literature, shorter radiotherapy schedules or even single-fraction irradiation can be considered.

Evaluation of systemic inflammation-based prognostic scores in patients with advanced colorectal cancer receiving palliative pelvic radiotherapy (RT).

558 Background: The presence of a systemic inflammatory response (SIR) in patients with advanced cancer is an increasingly recognised prognostic domain and is commonly assessed by the Glasgow Prognostic Score (GPS) and the Neutrophil Lymphocyte Ratio (NLR). However, little work has been carried out to evaluate their role in the field of palliative RT. The aim of the present study was to compare the prognostic value of the GPS and NLR in patients with advanced colorectal cancer receiving palliative pelvic RT. Methods: From a database of all patients undergoing RT in the West of Scotland (2010-2015) patients receiving palliative pelvic RT for colorectal cancer were examined (n = 175). Patients were excluded if they died within 30 days of treatment (n = 15). Demographic data, time from treatment to death/last clinic visit, medical comorbidities, tumour and RT location/dose, CRP, albumin, and differential blood counts were all recorded. GPS, mGPS and NLR were calculated and Cox regression analysis conducted in SPSS. Results: Of the remaining 160 analysed 85 (53%) were male and the median age was 77 (Range: 34-98). The most common clinical indications for palliative radiotherapy were pain (n = 78), bleeding (n = 71) and obstruction/tenesmus (n = 29). Medical comorbidities varied with the most common being hypertension (n- = 75), IHD (n = 36) and diabetes (n = 19). At the time of analysis 130 (81%) of the patients were dead with median survival of 9 months (Range: 1-62 months). On univariate survival analysis Male sex (p = 0.021), GPS (p = 0.015), mGPS (p = 0.028) and NLR ≥ 5 (p = 0.045) but not age &gt; 75 (p = 0.059), Tumour Site (p = 0.637), Performance Status (p = 0.747), ASA (p = 0.525), Delivered Fractions of Radiotherapy (p = 0.062), Dose of RT (p = 0.486) and low Haemoglobin (p = 0.383) were significantly associated with poor survival. On multivariate analysis of the significant variable only male sex (HR: 1.59, 95%CI 1.07-2.36, p = 0.021) and the GPS (HR: 1.47, 95%CI 1.09-1.98, p = 0.011) remained independently associated with survival. Conclusions: In the palliative RT setting systemic inflammation based scores (GPS, mGPS and NLR) had prognostic value and the GPS had independent prognostic value.

Relationships between family physicians' referral for palliative radiotherapy, knowledge of indications for radiotherapy, and prior training: a survey of rural and urban family physicians.

BackgroundThe primary objective of this research was to assess the relationship between FPs’ knowledge of palliative radiotherapy (RT) and referral for palliative RT.Methods1001 surveys were sent to FPs who work in urban, suburban, and rural practices. Respondents were tested on their knowledge of palliative radiotherapy effectiveness and asked to report their self-assessed knowledge.ResultsThe response rate was 33%. FPs mean score testing their knowledge of palliative radiotherapy effectiveness was 68% (SD = 26%). The majority of FPs correctly identified that painful bone metastases (91%), airway obstruction (77%), painful local disease (85%), brain metastases (76%) and spinal cord compression (79%) can be effectively treated with RT, though few were aware that hemoptysis (42%) and hematuria (31%) can be effectively treated. There was a linear relationship between increasing involvement in palliative care and both self-assessed (p < 0.001) and tested (p = 0.02) knowledge. FPs had higher mean knowledge scores if they received post-MD training in palliative care (12% higher; p < 0.001) or radiotherapy (15% higher; p = 0.002). There was a strong relationship between FPs referral for palliative radiotherapy and both self-assessed knowledge (p < 0.001) and tested knowledge (p = 0.01).ConclusionsSelf-assessed and tested knowledge of palliative RT is positively associated with referral for palliative RT. Since palliative RT is underutilized, further research is needed to assess whether family physician educational interventions improve palliative RT referrals. The current study suggests that studies could target family physicians already in practice, with educational interventions focusing on hemostatic and other less commonly known indications for palliative RT.

Rapid palliative radiotherapy: comparing IG-IMRT with more conventional approaches

AbstractPurpose: To assess the efficiency of an integrated imaging, planning, and treatment delivery system to provide image-guided intensity-modulated radiotherapy (IG-IMRT) for patients requiring palliative radiotherapy (PRT).Methods: Between December 2006 and May 2008, 28 patients requiring urgent PRT were selected to undergo single-session megavoltage computed tomography (MV-CT) simulation, IMRT treatment planning, position verification and delivery of the first faction of radiotherapy on a helical Tomotherapy® unit. The time required to complete each step was recorded and compared to our standard approach of using either fluoroscopic or CT-based simulation, simplified treatment planning and delivery on a megavoltage unit.Results: Twenty-eight patients were treated with our integrated IG-IMRT protocol. The median age was 72 years, with 61% men and 39% women. The indications for PRT were: painful bone and soft tissue metastasis (75%); bleeding lesions (14%); and other reasons (11%). The areas treated included the following: hip and/or pelvis (42%); spine (36%); and other areas (21%). The most commonly used dose prescription was 20 Gy in five fractions. Average times for the integrated IG-IMRT processes were as follows: image acquisition, 15 minutes; target delineation, 16 minutes; IMRT treatment planning, 9 minutes; treatment position verification, 10 minutes; and treatment delivery, 12 minutes. The average total time was 62 minutes compared to 66 minutes and 81 minutes for fluoroscopic and CT-simulation-based approaches, respectively. The IMRT dose distributions were also superior to simpler plans.Conclusions: PRT with an integrated IG-IMRT approach is efficient and convenient for patients, and has potential for future applications such as single-fraction radiotherapy.

Knowledge and Utilization of Palliative Radiotherapy by Pediatric Oncologists

Palliative radiotherapy (PRT) is a routine part of oncology care in adult patients, but it is used much less frequently among children with incurable cancer. We surveyed Canadian pediatric oncologists to learn about their knowledge and use of PRT and to identify potential barriers to referral. A 13-item questionnaire assessing PRT knowledge and utilization was sent to 80 Canadian pediatric oncologists. The survey completion rate was 80%, with most respondents being providers of palliative care for children and making referrals for PRT. Although 62% had received training in radiation oncology, only 28% had received formal palliative care training. Respondents with palliative care training were found to be significantly more knowledgeable about PRT and were more likely to refer children for PRT (p < 0.01). Only 59% of respondents thought that they had adequate knowledge about the indications for PRT. A positive correlation was found between knowledge about the indications for PRT and referral for treatment (p < 0.01). Among survey respondents, 51% believed that PRT was underutilized, and the perceived barriers to PRT referral included patient or family reluctance, distance to the cancer centre, belief that PRT has little impact on quality of life, and concerns about toxicity. Palliative radiotherapy is considered to be underutilized among children. This situation appears to be related, in part, to inadequate knowledge and training among pediatric oncologists, suggesting that more emphasis needs to be placed on pediatric palliative care education.

Factors Influencing Referral for Palliative Radiotherapy

In Canada, patients with incurable or metastatic cancer are commonly followed by Medical Oncologists (MO) or Palliative Care physicians, or discharged to the care of their General Practitioners (GP). Relying on other physicians to refer symptomatic patients for palliative radiotherapy (PRT) presumes a familiarity with the efficacy of PRT. Our objectives were to assess patterns in referral and knowledge about the indications for PRT.

Palliative Strahlentherapie – Notfallindikation und schonende Therapie zur Symptomlinderung

Even if cure of a malignant disease cannot be achieved, palliative radiotherapy often alleviates or resolves symptoms and prevents complications thus facilitating a good quality of life. Palliative radiotherapy differs in some principal matters from curative radiotherapy. First, there is a different treatment goal. Second, total dose, fractionation, treatment time, and tolerable side effects vary substantially. Tumor or metastases related pain is the main field for palliative radiotherapy. Especially for metastatic bone disease, radiotherapy is the most effective treatment modality in reducing pain, preventing pathological fractures, and allowing re-stabilization of the bone. Another sphere for palliative radiotherapy are tumor caused compressionsyndromes. These include intracerebral pressure due to cerebral metastases, spinal cord compression, vena cava superior syndrome, compression of the esophagus, the tracheal-bronchial system, ureter or bile ducts causing dysphagia, dyspnea, urinary or bile retention and others. The most frequent indications for palliative radiotherapy are bone and cerebral metastases. The most common emergency indications are spinal cord compression and vena cava superior syndrome.

Palliative Radiotherapy Knowledge Among Community Family Physicians and Nurses

Primary care physicians and nurses care for patients with advanced cancer and need to be aware of the role for palliative radiotherapy (PR). We surveyed 250 family physicians, family medicine residents, and nurses attending oncology educational symposia to determine their knowledge of PR. The survey response rate was 59%, and most respondents (77%) were involved with the care of cancer patients. Many (58%) thought that their knowledge of PR was insufficient for their needs. Although bone metastasis and spinal cord compression were frequently recognized indications for PR, only 50% of other assessed indications for PR were correctly identified. Almost all respondents stated that they wanted to learn more about PR. More education regarding PR is required for primary care physicians and nurses caring for cancer patients.

Palliative Radiation Therapy in the Management of Brain Metastases, Spinal Cord Compression, and Bone Metastases

Radiation therapy plays an important role in both curative and palliative cancer treatment. Palliative radiation therapy is given to alleviate symptoms, restore function, relieve suffering caused by cancer, and improve quality of life. Pain relief, control of bleeding or ulceration, prevention of impending compression or obstruction from tumor, and shrinkage of tumor masses causing symptoms are indications for palliative radiotherapy. Palliative radiotherapy is a very effective tool in alleviating pain symptoms and generally well tolerated. Common fractionation schemes are 8 Gy delivered in one fraction and 30 Gy delivered in 10 fractions. This article discusses general principles of administering palliative radiation therapy. Site-specific treatment is addressed, divided into palliative radiotherapy for brain metastases, spinal cord compression, and bone metastases. In each of these areas, we discuss presentation, management, and therapeutic strategies.

A Phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics

Purpose: Preclinical studies indicate that RSR13 oxygenates and radiosensitizes hypoxic solid tumors by decreasing the oxygen (O 2)-binding affinity of hemoglobin (Hb). A Phase I open-label, multicenter dose and frequency escalation study was conducted to assess the safety, tolerance, pharmacokinetics, and pharmacodynamic effect of daily RSR13 administration to cancer patients receiving concurrent palliative radiotherapy (RT). Methods and Materials: Eligibility criteria included the following: ECOG performance status ≤2; resting and exercise arterial oxygen saturation (SaO 2) ≥90%; an indication for palliative RT, 20–40 Gy in 10–15 fractions. RSR13 was administered i.v. via central vein over 60 min immediately before RT. Patients received supplemental O 2 via nasal cannula at 4 L/min during RSR13 infusion and RT. Plasma, red blood cell (RBC), and urine RSR13 concentrations were assayed. The pharmacodynamic effect of RSR13 on Hb-O 2 binding affinity was quantified by multipoint tonometry and expressed as an increase in p50, defined as the partial pressure of O 2 that results in 50% SaO 2. The RSR13 dose in the first cohort was 75 mg/kg once a week for two doses; successive cohorts received higher, more frequent doses up to 100 mg/kg/day for 10 days during RT. Results: Twenty patients were enrolled in the study. Repeated daily doses of RSR13 were generally well tolerated. Two adverse events of note occurred: ( 1) A patient with pre-existing restrictive lung disease had transient persistent hypoxemia after the sixth RSR13 dose; ( 2) a patient with a recurrent glioma receiving high-dose corticosteroids had edema after the seventh RSR13 dose, likely due to the daily high-volume fluid infusions. Both patients recovered to baseline status with conservative management. Maximum pharmacodynamic effect occurred at the end of RSR13 infusion and was proportional to the RBC RSR13 concentration. After an RSR13 dose of 100 mg/kg, the peak increase in p50 averaged 8.1 mm Hg, consistent with the targeted physiologic effect, and then diminished with a half-life of approximately 5 h. Conclusions: RSR13 was well tolerated in daily doses up to 100 mg/kg administered for 10 days during RT. The combined administration of RSR13 with 4 L/min supplemental O 2 yielded pharmacodynamic conditions in which hypoxic tumor radiosensitization can occur. Ongoing Phase II and Phase III studies are evaluating the combination of RT and RSR13 for selected indications, including primary brain tumors, brain metastases, and non–small-cell lung cancer.