Candice Johnstone

External beam radiotherapy and bone metastases

Management of bone metastasis is a multi-disciplinary effort that involves coordination between several medical specialties. External beam radiation therapy (EBRT) remains a powerful and efficient method of palliating pain and preventing skeletal complications from osseous metastasis. The pain relief equivalence of various fractionation schemes, ranging from 8 Gy in a single dose to 30 Gy in 10 fractions, has been demonstrated in dozens of randomized clinical trials. Toxicity profiles are well established and the treatment is generally well tolerated. Radiopharmaceuticals and high-dose, stereotactic radiation therapy are adjuncts to EBRT whose role is being elucidated clinical trials. Multiple organizations have compiled guidelines and quality metrics to help refine the role of each modality in the management of painful osseous metastases.

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extracranial Irradiation for Extensive-Disease Small Cell Lung Cancer (ED SCLC): NRG Oncology RTOG 0937

Introduction: NRG Oncology RTOG 0937 is a randomized phase II trial evaluating 1‐year overall survival (OS) with prophylactic cranial irradiation (PCI) or PCI plus consolidative radiation therapy (PCI+cRT) to intrathoracic disease and extracranial metastases for extensive‐disease SCLC. Methods: Patients with one to four extracranial metastases were eligible after a complete response or partial response to chemotherapy. Randomization was to PCI or PCI+cRT to the thorax and metastases. Original stratification included partial response versus complete response after chemotherapy and one versus two to four metastases; age younger than 65 years versus 65 years or older was added after an observed imbalance. PCI consisted of 25 Gy in 10 fractions. cRT consisted of 45 Gy in 15 fractions. To detect an improvement in OS from 30% to 45% with a 34% hazard reduction (hazard ratio = 0.66) under a 0.1 type 1 error (one sided) and 80% power, 154 patients were required. Results: A total of 97 patients were randomized between March 2010 and February 2015. Eleven patients were ineligible (nine in the PCI group and two in the PCI+cRT group), leaving 42 randomized to receive PCI and 44 to receive PCI+cRT. At planned interim analysis, the study crossed the futility boundary for OS and was closed before meeting the accrual target. Median follow‐up was 9 months. The 1‐year OS was not different between the groups: 60.1% (95% confidence interval [CI]: 41.2–74.7) for PCI and 50.8% (95% CI: 34.0–65.3) for PCI+cRT (p = 0.21). The 3‐ and 12‐month rates of progression were 53.3% and 79.6% for PCI and 14.5% and 75% for PCI+cRT, respectively. Time to progression favored PCI+cRT (hazard ratio = 0.53, 95% CI: 0.32–0.87, p = 0.01). One patient in each arm had grade 4 therapy‐related toxicity and one had grade 5 therapy‐related pneumonitis with PCI+cRT. Conclusions: OS exceeded predictions for both arms. cRT delayed progression but did not improve 1‐year OS.

Negative predictive value (NPV) of FDG PET-CT for nodal disease in clinically node-negative early stage lung cancer (AJCC 7 th ed T1-2aN0) and identification of risk factors for occult nodal (pN1-N2) metastasis: implications for SBRT

Non-surgical methods are increasingly employed in the management of early stage lung cancer, but do not afford histological confirmation of nodal status. We sought to assess the incidence, pattern, and predictors of occult nodal involvement (pN1-pN2) in non-small cell lung cancer (NSCLC) patients with negative nodal uptake on fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in early stage lung cancer (clinical stage I AJCC 7 th edition). All patients treated surgically over a 3-year period at Dartmouth Hitchcock Medical Center who were AJCC 7th ed. clinical stage I by pre-operative PET-CT were included in this analysis. The agreement between the clinical stage based on PET-CT and true stage based on pathologic dissection was assessed. Multivariate logistic regression was used to analyze predictors of occult nodal metastasis. Of 144 clinically node-negative patients, 125 were pathologically nodenegative. For all 144 patients, the negative predictive values (NPVs) of PET-CT were 92% for mediastinal disease, 90% for N1 disease, and 87% for overall nodal metastases. The NPVs for mediastinal metastases were 95% in T1 disease and 87% in T2 disease. In multivariate analysis, tumor size (adjusted OR: 3.28, 95% CI: 1.41-7.57), central tumor location (adjusted OR: 7.3, 95% CI: 2.22-24.3), and age at surgery (adjusted OR: 0.95, 95% CI: 0.92-0.98) were significant predictors of occult nodal metastasis. The NPV of PET-CT in nodal staging has implications for the non-surgical treatment of lung cancer, such as stereotactic body radiotherapy, where routine pathologic nodal staging is not performed. Our data suggest PET-CT more accurately rules out the presence of nodal disease in smaller, peripherally located primary tumors.

Determination of Internal Target Volume for Radiation Treatment Planning of Esophageal Cancer by Using 4-Dimensional Computed Tomography (4DCT)

PURPOSE To determine an efficient strategy for the generation of the internal target volume (ITV) for radiation treatment planning for esophageal cancer using 4-dimensional computed tomography (4DCT). METHODS AND MATERIALS 4DCT sets acquired for 20 patients with esophageal carcinoma were analyzed. Each of the 4DCT sets was binned into 10 respiratory phases. For each patient, the gross tumor volume (GTV) was delineated on the 4DCT set at each phase. Various strategies to derive ITV were explored, including the volume from the maximum intensity projection (MIP; ITV_MIP), unions of the GTVs from selected multiple phases ITV2 (0% and 50% phases), ITV3 (ITV2 plus 80%), and ITV4 (ITV3 plus 60%), as well as the volumes expanded from ITV2 and ITV3 with a uniform margin. These ITVs were compared to ITV10 (the union of the GTVs for all 10 phases) and the differences were measured with the overlap ratio (OR) and relative volume ratio (RVR) relative to ITV10 (ITVx/ITV10). RESULTS For all patients studied, the average GTV from a single phase was 84.9% of ITV10. The average ORs were 91.2%, 91.3%, 94.5%, and 96.4% for ITV_MIP, ITV2, ITV3, and ITV4, respectively. Low ORs were associated with irregular breathing patterns. ITV3s plus 1 mm uniform margins (ITV3+1) led to an average OR of 98.1% and an average RVR of 106.4%. CONCLUSIONS The ITV generated directly from MIP underestimates the range of the respiration motion for esophageal cancer. The ITV generated from 3 phases (ITV3) may be used for regular breathers, whereas the ITV generated from 4 phases (ITV4) or ITV3 plus a 1-mm uniform margin may be applied for irregular breathers.

Samarium-153-ethylene diamine tetramethylene phosphonate, a beta-emitting bone-targeted radiopharmaceutical, useful for patients with osteoblastic bone metastases

Bone metastases are prevalent among cancer patients and frequently cause significant morbidity. Oncology providers must mitigate complications associated with bone metastases while limiting therapy-related adverse effects and their impact on quality of life. Multiple treatment modalities, including chemotherapy, surgery, external beam radiation therapy, and radioisotopes, among others, have been recommended and utilized for palliative treatment of bone metastases. Radioisotopes such as samarium-153 are commonly used in the setting of multifocal bone metastases due to their systemic distribution, affinity for osteoblastic lesions, acceptable toxicity profile, and convenience of administration. This review focuses on samarium-153, first defining its radiobiologic and pharmacokinetic properties before describing many clinical trials that support its use as a safe and effective tool in the palliation of patients with bone metastases.

Bleeding in cancer patients and its treatment: a review

Bleeding is a common problem in cancer patients, related to local tumor invasion, tumor angiogenesis, systemic effects of the cancer, or anti-cancer treatments. Existing bleeds can also be exacerbated by medications such as bevacizumab, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants. Patients may develop acute catastrophic bleeding, episodic major bleeding, or low-volume oozing. Bleeding may present as bruising, petechiae, epistaxis, hemoptysis, hematemesis, hematochezia, melena, hematuria, or vaginal bleeding. Therapeutic intervention for bleeding should start by establishing goals of care, and treatment choice should be guided by life expectancy and quality of life. Careful thought should be given to discontinuation of medications and reversal of anticoagulation. Interventions to stop or slow bleeding may include systemic agents or transfusion of blood products. Noninvasive local treatment options include applied pressure, dressings, packing, and radiation therapy. Invasive local treatments include percutaneous embolization, endoscopic procedures, and surgical treatment.

Palliative Care Specialist Series: Top 10 Tips Palliative Care Clinicians Should Know About Radiation Oncology

Abstract As palliative care (PC) moves upstream in the course of advanced illness, it is critical that PC providers have a broad understanding of curative and palliative treatments for serious diseases. Possessing a working knowledge of radiation therapy (RT), one of the three pillars of cancer care, is crucial to PC providers given RTs role in both the curative and palliative settings. This article provides PC providers with a primer on the vocabulary of RT; the team of people involved in the planning of RT; and common indications, benefits, and side effects of treatment.As palliative care (PC) moves upstream in the course of advanced illness, it is critical that PC providers have a broad understanding of curative and palliative treatments for serious diseases. Possessing a working knowledge of radiation therapy (RT), one of the three pillars of cancer care, is crucial to PC providers given RTs role in both the curative and palliative settings. This article provides PC providers with a primer on the vocabulary of RT; the team of people involved in the planning of RT; and common indications, benefits, and side effects of treatment.

Management of independent motion between multiple targets in lung cancer radiation therapy

PURPOSE To quantify interfractional independent motions between multiple primary targets in radiation therapy (RT) of lung cancer and to study the dosimetric benefits of an online adaptive replanning method to account for these variations. METHODS AND MATERIALS Ninety-five on-treatment diagnostic-quality computed tomography (CT) scans acquired for 9 lung cancer patients treated with image-guided RT (IGRT) using a CT-on-rails (CTVision, Siemens) were analyzed. On each on-treatment CT set, contours of the targets (gross tumor volume, clinical target volume, or involved nodes), and organs at risk were generated by populating the planning contours using an autosegmentation tool (ABAS, Elekta) with manual editing. For each patient, an intensity modulated RT plan was generated based on the planning CT with a prescription dose of 60 Gy in 2 Gy per fraction. Three plans were generated and compared for each on-treatment CT set: an IGRT (repositioning) plan by copying the original plan with the required shifts, an online adaptive plan by rapidly modifying the aperture shapes, and segment weights of the original plan to conform to the on-treatment anatomy and a new fully reoptimized plan based on the on-treatment CT. RESULTS The interfractional deviations of the distance between centers of masses of the targets from the planning CTs varied from -1.0 to 0.8 cm with an average -0.09 ± 0.41 cm (1 standard deviation). The average combined CTV receiving at least 100% of the prescribed dose (V100) were 99.0 ± 0.7%, 97.8 ± 2.8%, 99.0 ± 0.6%, and 99.1 ± 0.6%, and the lung V20Gy 928 ± 332 cm3, 944 ± 315 cm3, 917 ± 300 cm3, and 891 ± 295 cm3 for the original, repositioning, adaptive, and reoptimized plans, respectively. Wilcoxon signed-rank tests showed that the adaptive plans were statistically significantly better than the repositioning plans and comparable with the reoptimized plans. CONCLUSION Interfractional, relative volume changes and independent motions between multiple primary targets during lung cancer RT, which cannot be accounted for by the current IGRT repositioning exist, but can be corrected by the online adaptive replanning method.

Technical Note: Is bulk electron density assignment appropriate for MRI‐only based treatment planning for lung cancer?

Purpose MRI‐based treatment planning in radiation therapy (RT) is prohibitive, in part, due to the lack of electron density (ED) information within the image. The dosimetric differences between MRI‐ and CT‐based planning for intensity modulated RT (IMRT) of lung cancer were investigated to assess the appropriateness of bulk ED assignment. Methods Planning CTs acquired for six representative lung cancer patients were used to generate bulk ED IMRT plans. To avoid the effect of anatomic differences between CT and MRI, “simulated MRI‐based plans” were generated by forcing the relative ED (rED) to water on CT‐delineated structures using organ specific values from the ICRU Report 46 and using the mean rED value of the internal target volume (ITV) from the planning CT. The “simulated MRI‐based plans” were generated using a research planning system (Monaco v5.09.07a, Elekta, AB) and employing Monte Carlo dose calculation. The following dose‐volume‐parameters (DVPs) were collected from both the “simulated MRI‐based plans” and the original planning CT: D95, the dose delivered to 95% of the ITV & planning target volume (PTV), D5 and V5, the volume of normal lung irradiated ≥5 Gy. The percent point difference and relative dose difference were used for comparison with the CT based plan for V5 and D95 respectively. A total of five plans per patient were generated; three with the ITV rED (rEDITV) = 1.06, 1.0 and the mean value from the planning CT while the lung rED (rEDlung) was fixed at the ICRU value of 0.26 and two with rEDlung = 0.1 and 0.5 while the rEDITV was fixed to the mean value from the planning CT. Results Noticeable differences in the ITV and PTV DVPs were observed. Variations of the normal lung V5 can be as large as 9.6%. In some instances, varying the rEDITV between rEDmean and 1.06 resulted in D95 increases ranging from 3.9% to 6.3%. Bulk rED assignment on normal lung affected the DVPs of the ITV and PTV by 4.0–9.8% and 0.3–19.6% respectively. Dose volume histograms were presented for representative cases where the variations in the DVPs were found to be very large or very small. Conclusions The commonly used bulk rED assignment in MRI‐only based planning may not be appropriate for lung cancer. A voxel based method, e.g., synthetic CT generated from MRI data, is likely required for dosimetrically accurate MR‐based planning for lung cancer.

Preoperative Radiation Therapy Followed by Reexcision May Improve Local Control and Progression-Free Survival in Unplanned Excisions of Soft Tissue Sarcomas of the Extremity and Chest-Wall

Background. The management for unplanned excision (UE) of soft tissue sarcomas (STS) has not been established. In this study, we compare outcomes of UE versus planned excision (PE) and determine an optimal treatment for UE in STS. Methods. From 2000 to 2014 a review was performed on all patients treated with localized STS. Clinical outcomes including local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) were evaluated using the Kaplan-Meier estimate. Univariate (UVA) and multivariate (MVA) analyses were performed to determine prognostic variables. For MVA, Cox proportional hazards model was used. Results. 245 patients were included in the analysis. 14% underwent UE. Median follow-up was 2.8 years. The LR rate was 8.6%. The LR rate in UE was 35% versus 4.2% in PE patients (p < 0.0001). 2-year PFS in UE versus PE patients was 4.2 years and 9.3 years, respectively (p = 0.08). Preoperative radiation (RT) (p = 0.01) and use of any RT for UE (p = 0.003) led to improved PFS. On MVA, preoperative RT (p = 0.04) and performance status (p = 0.01) led to improved PFS. Conclusions. UEs led to decreased LC and PFS versus PE in patients with STS. The use of preoperative RT followed by reexcision improved LC and PFS in patients who had UE of their STS.