Predictive Modeling of Survival and Toxicity in Patients With Hepatocellular Carcinoma After Radiotherapy.

Purpose: To stratify patients and aid clinical decision making, we developed machine learning models to predict treatment failure and radiation-induced toxicities after radiotherapy (RT) in patients with hepatocellular carcinoma across institutions.

Materials And Methods: The models were developed using linear and nonlinear algorithms, predicting survival, nonlocal failure, radiation-induced liver disease, and lymphopenia from baseline patient and treatment parameters. The models were trained on 207 patients from Massachusetts General Hospital.

Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors.

Magnetic resonance imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice cone-beam CT (CBCT)-guided PT, and other MR-guided methods, i.

Dosimetric Analysis and Normal-Tissue Complication Probability Modeling of Child-Pugh Score and Albumin-Bilirubin Grade Increase After Hepatic Irradiation.

Purpose: This study aimed to develop robust normal-tissue complication probability (NTCP) models for patients with hepatocellular carcinoma treated with radiation therapy (RT) using Child-Pugh (CP) score and albumin-bilirubin (ALBI) grade increase as endpoints for hepatic toxicity.

Methods And Materials: Data from 108 patients with hepatocellular carcinoma treated with RT between 2008 and 2017 were evaluated, of which 47 patients (44%) were treated with proton RT. Of these patients, 29 received stereotactic body RT and 79 moderately hypofractionated RT to median physical tumor doses of 43 Gy in 5 fractions and 59 Gy in 15 fractions, respectively.

Elective nodal irradiation with simultaneous integrated boost stereotactic body radiotherapy for pancreatic cancer: Analyses of planning feasibility and geometrically driven DVH prediction model.

Purpose: We evaluate the feasibility of the elective nodal irradiation strategy in stereotactic body radiotherapy (SBRT) for pancreatic cancer.

Methods: Three simultaneous integrated boost (SIB)-SBRT plans (Boost1, Boost2, and Boost3) were retrospectively generated for each of 20 different patients. Boost1 delivered 33 and 25 Gy to PTV1 and PTV2, respectively.

Liver reirradiation for patients with hepatocellular carcinoma and liver metastasis.

Purpose: This study aimed to assess the safety and efficacy of administering liver reirradiation to patients with primary liver tumors or liver metastasis.

Methods And Materials: A total of 49 patients (with 64 individual tumors) who received liver reirradiation at our institution between June 2008 and December 2016 were identified for retrospective review. Patients were treated to the same, different, or a combination of previously treated liver tumors for recurrent primary (53%) or metastatic (47%) disease using photons or protons.

Differential Association Between Circulating Lymphocyte Populations With Outcome After Radiation Therapy in Subtypes of Liver Cancer.

Purpose: Irradiation may have significant immunomodulatory effects that impact tumor response and could potentiate immunotherapeutic approaches. The purposes of this study were to prospectively investigate circulating lymphoid cell population fractions during hypofractionated proton therapy (HPT) in blood samples of liver cancer patients and to explore their association with survival.

Methods And Materials: We collected serial blood samples before treatment and at days 8 and 15 of HPT from 43 patients with liver cancer-22 with hepatocellular carcinoma (HCC) and 21 with intrahepatic cholangiocarcinoma (ICC)-enrolled in a phase 2 clinical trial.

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities.

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g.

Phase II Study of Proton-Based Stereotactic Body Radiation Therapy for Liver Metastases: Importance of Tumor Genotype.

Background: We evaluated the efficacy and safety of risk-adapted, proton-based stereotactic body radiation therapy (SBRT) for liver metastases from solid tumors.

Methods: This single-arm phase II single institutional study (NCT01239381) included patients with limited extrahepatic disease, 800 mL or greater of uninvolved liver, and no cirrhosis or Child-Pugh A, who had received proton-based SBRT to one to four liver metastases from solid tumors. Treatment comprised 30 to 50 Gray equivalent (GyE) in five fractions based on the effective volume of liver irradiated.

Gallbladder toxicity and high-dose ablative-intent radiation for liver tumors: Should we constrain the dose?

Purpose: Little is known about the risk of gallbladder toxicity from hypofractionated (HFXRT) and stereotactic body radiation therapy (SBRT). We report on gallbladder toxicity and attribution to treatment in a prospective series of patients with primary and metastatic liver tumors receiving ablative-intent HFXRT and SBRT with protons.

Methods And Materials: We evaluated 93 patients with intact gallbladders enrolled in either of 2 trials investigating proton HFXRT and SBRT for primary and metastatic liver tumors from 2009 to 2014.

Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Purpose: To evaluate the efficacy and safety of high-dose, hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Materials And Methods: In this single-arm, phase II, multi-institutional study, 92 patients with biopsy-confirmed HCC or ICC, determined to be unresectable by multidisciplinary review, with a Child-Turcotte-Pugh score (CTP) of A or B, ECOG performance status of 0 to 2, no extrahepatic disease, and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent.

Impact of intravenous contrast enhancement phase on target definition for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC): Observations from patients enrolled on a prospective phase 2 trial.

Background: The safety and efficacy of radiation therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC) depend on accurate definition of gross tumor volume (GTV), but GTV often varies between phases of multiphasic computed tomography (CT) imaging.

Methods: We contoured GTVs on arterial, portal venous, and delayed phases of multiphasic CT scans for 32 patients treated on an institutional review board-approved prospective trial of proton therapy for primary liver tumors and determined which phase provided optimal GTV visualization. We assessed agreement between individual phase GTVs to determine if GTV for each phase was encompassed in a 5-mm expansion of either the smallest or the best-visualized GTV.

Clinical and treatment factors associated with vaginal stenosis after definitive chemoradiation for anal canal cancer.

Purpose: We sought to evaluate the incidence of vaginal stenosis (VS) and identify clinical and treatment factors that predict for VS in female patients with anal cancer treated with definitive chemoradiation.

Methods And Materials: The cohort included 95 consecutive women receiving definitive chemoradiation between 2003 and 2012. All but 1 received intensity modulated radiation therapy; median primary tumor dose 50.

Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection.

Purpose: The purpose of this study was to evaluate the efficacy of voluntary deep inspiration breath-hold (DIBH) over a free-breathing (FB) technique to minimize cardiac radiation exposure in radiation therapy of left-sided breast cancer. Also, to better select patients for DIBH, the correlation between cardiac contact distance (CCD) and cardiac dose was assessed.

Methods And Materials: Thirty-five patients with left-sided breast cancer underwent DIBH and FB planning computed tomography scans, and the 2 plans were compared.

A prospective feasibility study of respiratory-gated proton beam therapy for liver tumors.

Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors.

Methods And Materials: Fifteen patients were enrolled in a prospective institutional review board-approved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectable biopsy- proven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤6 cm.

Exploiting tumor shrinkage through temporal optimization of radiotherapy.

In multi-stage radiotherapy, a patient is treated in several stages separated by weeks or months. This regimen has been motivated mostly by radiobiological considerations, but also provides an approach to reduce normal tissue dose by exploiting tumor shrinkage. The paper considers the optimal design of multi-stage treatments, motivated by the clinical management of large liver tumors for which normal liver dose constraints prohibit the administration of an ablative radiation dose in a single treatment.

Gastric lymph node contouring atlas: A tool to aid in clinical target volume definition in 3-dimensional treatment planning for gastric cancer.

Purpose: To develop a contouring atlas of the gastric lymph node stations to be used in defining and planning clinical target volumes in 3-dimensional treatment planning for gastric cancers.

Methods And Materials: Four physicians, including 2 radiation oncologists, a diagnostic radiologist, and a surgical oncologist specialized in gastric cancer, convened over the course of multiple meetings. Four patients were identified as representative cases, including 3 gastric cancer patients treated with differing surgical approaches (total gastrectomy, Ivor-Lewis esophagogastrectomy, and distal gastrectomy) and 1 patient with intact gastric anatomy.

Variations in tumor size and position due to irregular breathing in 4D-CT: a simulation study.

Purpose: To estimate the position and volume errors in 4D-CT caused by irregular breathing.

Methods: A virtual 4D-CT scanner was designed to reproduce axial mode scans with retrospective resorting. This virtual scanner creates an artificial spherical tumor based on the specifications of the user, and recreates images that might be produced by a 4D-CT scanner using a patient breathing waveform.

Extension of the NCAT phantom for the investigation of intra-fraction respiratory motion in IMRT using 4D Monte Carlo.

The purpose of this work was to create a computational platform for studying motion in intensity modulated radiotherapy (IMRT). Specifically, the non-uniform rational B-spline (NURB) cardiac and torso (NCAT) phantom was modified for use in a four-dimensional Monte Carlo (4D-MC) simulation system to investigate the effect of respiratory-induced intra-fraction organ motion on IMRT dose distributions as a function of diaphragm motion, lesion size and lung density. Treatment plans for four clinical scenarios were designed: diaphragm peak-to-peak amplitude of 1 cm and 3 cm, and two lesion sizes--2 cm and 4 cm diameter placed in the lower lobe of the right lung.

An effective preoperative three-dimensional radiotherapy target volume for extremity soft tissue sarcoma and the effect of margin width on local control.

Purpose: There is little information on the appropriate three-dimensional (3D) preoperative radiotherapy (XRT) volume for extremity soft-tissue sarcomas (STS). We retrospectively analyzed the pattern of local failure (LF) to help elucidate optimal field design.

Methods And Materials: We analyzed the 56 patients who underwent computed tomography-planned XRT for Stage I to III extremity STS between June 2000 and December 2006.

Effects of interfractional anatomical changes on water-equivalent pathlength in charged-particle radiotherapy of lung cancer.

Intrafractional motion and interfractional changes affect the accuracy of the delivered dose in radiotherapy, particularly in charged-particle radiotherapy. Most recent studies are focused on intrafractional motion (respiratory motion). Here, we report a quantitative simulation analysis of the effects of interfractional changes on water-equivalent pathlength (WEL) in charged-particle lung therapy.

Nanoparticle-enhanced MRI to evaluate radiation delivery to the regional lymphatics for patients with breast cancer.

Purpose: At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes.

Implications of respiratory motion as measured by four-dimensional computed tomography for radiation treatment planning of esophageal cancer.

Purpose: To evaluate the respiratory motion of primary esophageal cancers and pathologic celiac-region lymph nodes using time-resolved four-dimensional computed tomography (4D CT).

Methods And Materials: Respiration-synchronized 4D CT scans were obtained to quantify the motion of primary tumors located in the proximal, mid-, or distal thoracic esophagus, as well as any involved celiac-region lymph nodes. Respiratory motion was measured in the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions and was analyzed for correlation with anatomic location.

Quality assurance challenges for motion-adaptive radiation therapy: gating, breath holding, and four-dimensional computed tomography.

Compared with conventional three-dimensional (3D) conformal radiation therapy and intensity-modulated radiation therapy treatments, quality assurance (QA) for motion-adaptive radiation therapy involves various challenges because of the added temporal dimension. Here we discuss those challenges for three specific techniques related to motion-adaptive therapy: namely respiratory gating, breath holding, and four-dimensional computed tomography. Similar to the introduction of any other new technologies in clinical practice, typical QA measures should be taken for these techniques also, including initial testing of equipment and clinical procedures, as well as frequent QA examinations during the early stage of implementation.

Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons.

Purpose: To report preliminary clinical outcomes for pediatric patients treated with proton beam radiation for intracranial ependymoma and compare the dose distributions of intensity-modulated radiation therapy with photons (IMRT), three-dimensional conformal proton radiation, and intensity-modulated proton radiation therapy (IMPT) for representative patients.

Methods And Materials: All children with intracranial ependymoma confined to the supratentorial or infratentorial brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron between November 2000 and March 2006 were included in this study.