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Purpose: To evaluate the histopathologic changes and potential correlations of tumor absorbed dose (TAD) after yttrium-90 transarterial radioembolization (TARE) for colorectal liver metastases (CLMs)., Materials and Methods: This prospective pilot study assessed 12 patients with 13 CLMs through positron emission tomography (PET)/computed tomography (CT)-guided biopsies before, immediately after TARE (T0), and 3 weeks after TARE (T3). Subsequent sampling from the same location was enabled by fiducial placement. Biopsy samples were evaluated with hematoxylin and eosin, TUNEL, Ki67, OxPhos, caspase-3 (CC3), and pH2AX antibodies. Proliferation changes (Ki67) and double-strand DNA breaks (DSBs) were evaluated quantitatively. TAD was calculated on post-TARE PET/CT scan of the biopsy needle location at T0 and T3., Results: Median TAD at 3 weeks after TARE was 162 Gy (interquartile range (IQR), 92-211 Gy). DSBs decreased significantly from T0 (median, 77%; IQR, 75%-100%) to T3 (median, 14%; IQR, 0%-54%; P = .028). A decrease in Ki67 was also documented (median, 73%; IQR, 70%-80% at T0 vs median, 41%; IQR, 0%-66% at T3; P = .046). There was a strong positive correlation between TAD and DSBs at T0 (r[9] = 0.68) and a strong negative correlation at T3 (r[10] = -0.855; P = .042 and P = .002, respectively). There was a strong negative correlation between TAD and Ki67 at both T0 (r[9] = -0.733; P = .025) and T3 (r[10] = -0.681; P = .030). Tumors that exhibited caspase-3 activation (8/13, 62%) at either T0 or T3 time point were more likely to develop progression (7/8 [88%] vs 1/5 [20%]; P = .015)., Conclusions: Post-TARE biopsy can be used to assess TAD and histopathologic changes. Significant decreases in DSBs and proliferation index were noted after TARE. Post-TARE CC3 activation deserves further exploration., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate safety and efficacy of radiation segmentectomy (RS) with 90 Y glass microspheres in patients with limited metastatic liver disease not amenable to resection or percutaneous ablation., Methods: Patients with ≤ 3 tumors treated with RS from 6/2015 to 12/2017 were included. Target tumor radiation dose was > 190 Gy based on medical internal radiation dose (MIRD) dosimetry. Tumor response, local tumor progression (LTP), LTP-free survival (LTPFS) and disease progression rate in the treated segment were defined using Choi and RECIST 1.1 criteria. Toxicities were evaluated using modified SIR criteria., Results: Ten patients with 14 tumors underwent 12 RS. Median tumor size was 3 cm (range 1.4-5.6). Median follow-up was 17.8 months (range 1.6-37.3). Response rates per Choi and RECIST 1.1 criteria were 8/8 (100%) and 4/9 (44%), respectively. Overall LTP rate was 3/14 (21%) during the study period. One-, two- and three-year LTPFS was 83%, 83% and 69%, respectively. Median LTPFS was not reached. Disease progression rate in the treated segment was 6/18 (33%). Median overall survival was 41.5 months (IQR 16.7-41.5). Median delivered tumor radiation dose was 293 Gy (range 163-1303). One major complication was recorded in a patient post-Whipple procedure who suffered anaphylactic reaction to prophylactic cefotetan and liver abscess in RS region 6.5 months post-RS. All patients were alive on last follow-up., Conclusion: RS of ≤ 3 hepatic segments can safely provide a 2-year local tumor control rate of 83% in selected patients with limited metastatic liver disease and limited treatment options. Optimal dosimetry methodology requires further investigation.

Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine. Controlling respiratory motion, the use of image guidance, and increasing the number of radiation fractions sometimes are necessary for the safe delivery of SABR in these situations., Competing Interests: Disclosure P.B. Romesser reports research funding from and is a consultant for EMD Serono and has received travel support from Elekta., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Definitive reirradiation using a stereotactic technique is an effective local treatment option for both recurrent liver metastases and recurrent primary liver cancers. The tolerance of the liver, bile ducts, and surrounding gastrointestinal luminal organs must be respected to ensure safe retreatment. The risks associated with retreatment to these organs must be carefully balanced with the probability of clinical benefit. We present 2 cases for consideration of repeat irradiation along with the opinions of 4 experts, along with conclusions about recommendations., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Ablative radiation therapy is increasingly being used for hepatocellular carcinoma (HCC) resulting in excellent local control rates; however, patients without evidence of disease progression often die from liver failure. The clinical benefit of proton- over photon-based radiation therapy is unclear. We therefore sought to compare clinical outcomes of proton versus photon ablative radiation therapy in patients with unresectable HCC., Methods and Materials: This is a single-institution retrospective study of patients treated during 2008 to 2017 with nonmetastatic, unresectable HCC not previously treated with liver-directed radiation therapy and who did not receive further liver-directed radiation therapy within 12 months after completion of index treatment. The primary outcome, overall survival (OS), was assessed using Cox regression. Secondary endpoints included incidence of non-classic radiation-induced liver disease (defined as increase in baseline Child-Pugh score by ≥2 points at 3 months posttreatment), assessed using logistic regression, and locoregional recurrence, assessed using Fine-Gray regression for competing risks. All outcomes were measured from radiation start date., Results: The median follow-up was 14 months. Of 133 patients with median age 68 years and 75% male, 49 (37%) were treated with proton radiation therapy. Proton radiation therapy was associated with improved OS (adjusted hazard ratio, 0.47; P = .008; 95% confidence interval [CI], 0.27-0.82). The median OS for proton and photon patients was 31 and 14 months, respectively, and the 24-month OS for proton and photon patients was 59.1% and 28.6%, respectively. Proton radiation therapy was also associated with a decreased risk of non-classic radiation-induced liver disease (odds ratio, 0.26; P = .03; 95% CI, 0.08-0.86). Development of nonclassic RILD at 3 months was associated with worse OS (adjusted hazard ratio, 3.83; P < .001; 95% CI, 2.12-6.92). There was no difference in locoregional recurrence, including local failure, between protons and photons., Conclusions: Proton radiation therapy was associated with improved survival, which may be driven by decreased incidence of posttreatment liver decompensation. Our findings support prospective investigations comparing proton versus photon ablative radiation therapy for HCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases., Methods and Materials: Nonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT., Results: A total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed., Conclusions: Treatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC)., Methods and Methods: Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0-2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT., Results: Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5-21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6-144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62% respectively; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED ≥90 GyE had a significantly better OS than those receiving BED <90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2-year LC improvement was observed in patients receiving BED ≥90 GyE compared with those receiving BED <90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity., Conclusions: High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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. All patients received 15 fractions of proton therapy to a median dose of 58 Gy (relative biological effectiveness). We used flow cytometry to measure the changes in the fractions of total CD3 + , CD4 + , and CD8 + T cells; CD4 + CD25 + T cells; CD4 + CD127 + T cells; CD3 + CD8 + CD25 + activated cytotoxic T lymphocytes (CTLs); and CD3 - CD56 + natural killer cells., Results: With a median follow-up period of 42 months, median overall survival (OS) in the study cohort was 30.6 months for HCC and 14.5 months for ICC patients. Longer OS was significantly correlated with greater CD4 + CD25 + T-cell (P = .003) and CD4 + CD127 + T-cell (P = .01) fractions at baseline only in ICC patients. In HCC patients, the fraction of activated CTLs mid treatment (at day 8) was significantly associated with OS (P = .007). These findings suggest a differential relevance of immunomodulation by HPT in these liver cancers., Conclusions: Antitumor immunity may depend on maintenance of a sufficiently high number of activated CTLs during HPT in HCC patients and CD4 + CD25 + T cells and CD4 + CD127 + T cells prior to treatment in ICC patients. These results could guide the design of future studies to determine the optimal treatment schedules when combining irradiation with specific immunotherapy approaches., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Bilobar colorectal liver metastases (CRLM), are now aggressively managed in a multidisciplinary fashion with a two-stage hepatectomy; however, up to 30% of patients are not candidates for second stage hepatectomy. In this report, we describe a novel technique of delivering ablative radiation to the entire right hemiliver by using proton therapy in a series of patients., Methods: A data base of patients undergoing entire right hemiliver ablative radiation was maintained prospectively. Clinical, pathologic and treatment characteristics were collected for these patients. Survival duration was calculated from end of radiation. Radiation was delivered with proton therapy using deep inspiratory breath hold (DIBH) and a phase contrast simulation CT scan., Results: All five patients tolerated radiation treatment well. All four patients treated with biologic equivalent dose (BED) >89.6 Gy achieved partial or complete radiographic response and in-field local control at last follow up. Two patients are alive and without evidence of disease. Two patients experienced disease progression outside of the liver., Conclusion: These results suggest that the use of stereotactic proton therapy as a salvage therapy for patients with CRLM not amenable to second stage hepatectomy may achieve good local control and permit an opportunity for long term survival., (Copyright © 2016. Published by Elsevier Inc.)

Purpose: Fifteen fraction treatment schedules are increasingly used to deliver high doses of radiation therapy (RT) to both lung and hepatobiliary malignancies. The purpose of our study was to examine the incidence and predictors of chest wall (CW) toxicity in patients treated with this regimen., Methods and Materials: We evaluated 135 patients treated with RT to doses ≥52.5 Gy in 15 fractions for thoracic and hepatobiliary malignancies between January 2009 and December 2012. We documented patient characteristics and CW dosimetric parameters for each case. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 4.0, criteria for radiation dermatitis and CW pain. Patient characteristics and CW dosimetric parameters were evaluated for their association with CW toxicity using proportional hazards regression., Results: Median follow-up was 9 months from the start of RT. Forty-eight patients (36%) developed dermatitis at a median time of 18 days. In multivariable analysis, the absolute volume of CW (in cm 3 ) receiving 40 Gy (V40) ≥120 cm 3 was associated with the occurrence of dermatitis (hazard ratio, 3.12; 95% confidence interval, 1.74-5.60; P < .001). Twenty-one patients (16%) developed CW pain (20 grade 1, 1 grade 2) at a median time of 3 months. In multivariable analysis, CW V40 ≥150 cm 3 was associated with the occurrence of CW pain (hazard ratio, 2.65; 95% confidence interval, 1.12-6.24; P = .03). The absolute rate of CW pain in patients with V40 <150 cm 3 was 11% versus 26% in patients with V40 ≥150 cm 3 (P = .03)., Conclusions: Hypofractionated RT with 15 fraction regimens results in an acceptable incidence of CW toxicity, specifically CW pain. We recommend a dose constraint of V40 <150 cm 3 to minimize this adverse event., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: Patients with unresectable liver tumors who fail initial treatment modalities have a poor prognosis (<1 yr). Although effective, delivery of high dose radiation therapy to these tumors is limited by proximity of radiosensitive bowel. We have previously reported that placement of a biologic mesh spacer (BMS) can effectively displace the bowel allowing for dose-intense radiation to be delivered with low short-term toxicity. The purpose of this study was to assess and report the long-term safety and oncologic outcomes of this cohort., Methods: From 2012 to 2014 seven patients with unresectable hepatic malignancy (6 IHCC, 1 CRLM) underwent BMS (acellular human dermis) placement (2 open, 5 MIS) prior to radiation therapy. Prospective registry data were reviewed for tumor and treatment details, progression, metastasis and survival. RTOG guidelines were used to define radiation toxicities., Results: Mean patient age was 50.4 years (30-62 years) and 4 patients were male (57.1%). Prior to surgery, all patients had been treated for an average of 12.5 months with surgery, chemotherapy, radiation and/or TACE. After surgery, all patients recovered well and received a mean radiation dose of 76.1 Gy (58.1-100 Gy) over 13-25 fractions. 1 patient received SBRT; 4 fractions, 10 Gy each. Maximum dose delivered was 100 Gy (Biologic Equivalent Dose of 140 Gy, α/β = 10). Mean time to initiation of radiation therapy was 24 days (12-48 days) from surgery. No significant GI toxicity was recorded, and no GI bleeding or ulcers were observed. Mean follow-up after XRT was 18.2 months (5.5-31 months). Three patients had no loco-regional progression of disease. 2 patients had infield progression of liver disease and another had progressive lymphadenopathy. 3 patients developed pulmonary metastasis, at a mean time to distant failure of 3 months. There are 4 survivors over 2-years from surgery., Conclusion: For patients with unresectable liver tumors, placement of a BMS enhances the safety and efficacy of high-dose radiotherapy, providing a survival benefit via delay in time to progression compared to traditional treatments with no significant short or long term GI toxicity., (Copyright © 2016 Elsevier Ltd and British Association of Surgical Oncology/European Society of Surgical Oncology. All rights reserved.)

Background: Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1 % of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported., Methods: We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases., Results: Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67 % was 24.2 and 10 %, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity., Conclusions: RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC., Competing Interests: The authors report no conflicts of interest.

The emergence and success of stereotactic body radiation therapy (SBRT) for the treatment of lung cancer have led to its rapid adoption for liver cancers. SBRT can achieve excellent results for small liver tumors. However, the vast majority of physicians interpret SBRT as meaning doses of radiation (range, 4-20 Gray [Gy]) that may not be ablative but are delivered within about 1 week (ie, in 3-6 fractions). Adherence to this approach has limited the effectiveness of SBRT for large liver tumors (>7 cm) because of the need to reduce doses to meet organ constraints. The prognosis for patients who present with large liver tumors is poor, with a median survival ≤12 months, and most of these patients die from tumor-related liver failure. Herein, the authors present a comprehensive solution to achieve ablative SBRT doses for patients with large liver tumors by using a combination of classic, modern, and novel concepts of radiotherapy: fractionation, dose painting, motion management, image guidance, and simultaneous integrated protection. The authors discuss these concepts in the context of large, inoperable liver tumors and review how this approach can substantially prolong survival for patients, most of whom otherwise have a very poor prognosis and few effective treatment options. Cancer 2016;122:1974-86. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

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. Sample size was calculated to demonstrate > 80% local control (LC) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria at 2 years for HCC patients, with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC., Results: Eighty-three patients were evaluable: 44 with HCC, 37 with ICC, and two with mixed HCC/ICC. The CTP score was A for 79.5% of patients and B for 15.7%; 4.8% of patients had no cirrhosis. Prior treatment had been given to 31.8% of HCC patients and 61.5% of ICC patients. The median maximum dimension was 5.0 cm (range, 1.9 to 12.0 cm) for HCC patients and 6.0 cm (range, 2.2 to 10.9 cm) for ICC patients. Multiple tumors were present in 27.3% of HCC patients and in 12.8% of ICC patients. Tumor vascular thrombosis was present in 29.5% of HCC patients and in 28.2% of ICC patients. The median dose delivered to both HCC and ICC patients was 58.0 Gy. With a median follow-up among survivors of 19.5 months, the LC rate at 2 years was 94.8% for HCC and 94.1% for ICC. The overall survival rate at 2 years was 63.2% for HCC and 46.5% ICC., Conclusion: High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely, supporting ongoing phase III trials of radiation in HCC and ICC., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Background: Hepatocellular carcinoma is one of the most common cancers worldwide. Data regarding the use of radiotherapy is limited in patients from populations without endemic viral hepatitis. We examine the outcomes for patients treated with radiotherapy in the modern era at a single institution., Material and Methods: A total of 29 patients with localized hepatocellular carcinoma treated from 2000-2010 were reviewed. Patients with metastatic disease at the time of radiation were excluded. Median radiation dose was 50 Gy (range 30 to 75 Gy) with a median biologically effective dose of 80.6 (range 60 to 138.6). Median tumor size at the time of radiation was 5.2 cm (range 2 to 25 cm)., Results: Eighty three percent of all patients had either stable disease or a partial response to radiation, based on RECIST criteria. Median change in tumor size following radiation was -17% (range -73.5 to 177.8%). Estimated one-year overall survival and in-field progression-free survival rates for the study population were 56% and 79%, respectively. One-year overall survival in patients treated to a biologically effective dose <75 was significantly lower than in patients treated to a biologically effective dose ≥75 (18% vs. 69%). One-year in-field progression-free survival rate (60% vs. 88%) and biochemical progression-free survival duration (median 6.5 vs. 1.6 months) were also significantly improved in patients treated to a biologically effective dose ≥75. Grade 3 toxicity was seen in 13.8% of patients., Discussion: In a population without endemic viral hepatitis, unresectable hepatocellular carcinoma demonstrates significant response to radiotherapy with minimal toxicity. Furthermore, our findings suggest that increased biologically effective dose is associated with improved survival and local tumor control.

Objective: To study the behavior of hypoattenuating liver lesions, deemed too small to characterize at baseline scanning with multidetector computed tomography (CT), in patients with rectal cancer., Methods: Retrospective review of locally advanced rectal cancer patients from a radiation oncology therapy database was conducted. Patients who presented before neoadjuvant chemoradiation without metastases at baseline CT and with follow-up scans for at least 1 year after therapy were evaluated. CT studies were reviewed for the presence and change in size of hypoattenuating liver lesions (<15 mm) at baseline and follow-up., Results: A total of 616 consecutive patients from the radiotherapy database were reviewed. Of these, 70 patients with a total of 163 hepatic lesions met the selection criteria. The mean patient age was 62.4 years (range, 26-85 years). All patients subsequently underwent surgery and adjuvant chemotherapy. The mean time of radiographic imaging from baseline CT to most recent surveillance CT was 3.3 years (range, 1.1-7.4 years). Two radiologists independently reviewed the CTs. The lesions were stable in 56 of 70 (80.0%, 95% confidence interval: 69%, 89%) patients. Of 163 lesions, 148 (90.8%) were stable, 8 (4.9%) regressed, and 7 (4.3%) progressed in size. No significant difference in results was found for patients stratified according to T-stage (P = 0.41) and N-stage (P > 0.99)., Conclusion: In patients with rectal cancer, majority of small hypoattenuating liver lesions remain stable and are treated as benign lesions, at multidetector CT follow-up of more than a year. Nevertheless, hepatic lesion stability during systemic therapy should still be interpreted with caution and closely followed for at least 1 year after completion of therapy.

The purpose of the study is to dosimetrically investigate the advantages of proton radiotherapy over photon radiotherapy for liver tumors. The proton plan and the photon plan were designed using commercial treatment planning systems. The treatment target dose conformity and heterogeneity and dose-volume analyses of normal structures were compared between proton and photon radiotherapy for 9 patients with liver tumors. Proton radiotherapy delivered a more conformal target dose with slightly less homogeneity when compared with photon radiotherapy. Protons significantly reduced the fractional volume of liver receiving dose greater or equal to 30 Gy (V(30)) and the mean liver dose. The stomach and duodenal V(45) were significantly lower with the use of proton radiotherapy. The V(40) and V(50) of the heart and the maximum spinal cord dose were also significantly lower with the use of proton radiotherapy. Protons were better able to spare one kidney completely and deliver less dose to one (generally the left) kidney than photons. The mean dose to the total body and most critical structures was significantly decreased using protons when compared to corresponding photon plans. In conclusion, our study suggests the dosimetric benefits of proton radiotherapy over photon radiotherapy. These dosimetric advantages of proton plans may permit further dose escalation with lower risk of complications.

Purpose: To investigate a deformable image registration method to improve soft-tissue contrast in four-dimensional (4D) computed tomography (CT) images of the liver., Methods and Materials: Ten patients with hepatocellular carcinoma underwent 4D CT scan for radiotherapy treatment planning on a positron emission tomography/CT scanner. Four-dimensional CT images were binned into 10 equispaced phases. The exhale phase served as the reference phase, and images from the other nine phases were coregistered to the reference phase image using an intensity-based, automatic deformable image registration method. Then the coregistered images were combined to create a single, high-quality reconstructed CT image at exhale phase as the new reference for target delineation. The extent of image quality enhancement was quantified relative to the original CT by calculating the signal-to-noise ratio and the contrast-to-noise ratio., Results: The soft tissue image contrast was noticeably better after deformable image registration than in the original scans. Signal-to-noise ratios inside the liver region of interest increased for all patients by a factor of 3.0 (range, 2.3-3.7). The improvement in image quality was not linearly proportionate to the number of images averaged. Using only 6 phases can achieve at least 85% of the contrast enhancement that can be achieved using all 10 phases. We also found that contrast enhancement was inversely proportional to the original image quality (p = 0.006), and the contrast enhancement is attained with little loss of spatial resolution., Conclusions: This deformable image registration method is feasible to improve soft-tissue image quality in 4D CT images.

Objectives: To evaluate the safety and efficacy of conformal radiotherapy (RT) of the dominant liver metastasis as palliative treatment of patients with unresectable colorectal cancer liver metastases., Methods: We retrospectively reviewed the hospital and RT records of 17 patients with unresectable colorectal liver metastases who had been treated with palliative RT to the dominant liver metastasis at our institution., Results: The median size of the dominant liver metastasis was 10 cm (range, 3-19 cm). Twelve patients (71%) had evidence of extrahepatic disease. A median of 2 (range, 0-4) prior chemotherapy regimens had been administered. Median radiation dose was 42 Gy (range, 7.5-72 Gy). Concurrent chemotherapy included celecoxib in 1 (6%), capecitabine in 6 (35%), and both agents in 9 (53%) patients. Frequencies of acute diarrhea, nausea, vomiting, fatigue, hand-foot syndrome, and neutropenia were 29%, 47%, 6%, 29%, 7%, and 0%, respectively (all grade 2 or lower; no grade 3 toxicities). No late toxicities were noted. With a median follow-up time of 9.2 months, the median actuarial overall survival time from RT was 12.6 months (95% confidence interval [CI]: 3.3-40.9 months). The actuarial in-field local control rate was 62% at 6 months. The median actuarial time to in-field, out-of-field hepatic and distant progression were 6.8, 3.9, and 4.1 month, respectively (95% CIs, 3.9-15.8, 1.8-6.3, and 1.8-11.5 months, respectively)., Conclusions: Conformal RT to the dominant liver metastasis as palliative therapy for unresectable colorectal cancer liver metastases has an acceptable toxicity profile and may improve survival. This approach merits further exploration.

Purpose: To assess pelvic chemoradiotherapy (CXRT) without colostomy as a component of the multidisciplinary management of patients presenting with metastatic rectal cancer., Methods and Materials: Eighty patients with synchronous distant metastases from rectal cancer were treated with initial CXRT. Hypofractionated radiotherapy was administered usually with concurrent 5-FU (92%, 300 mg/m(2)/day, M-F). Three-field belly-board technique was used in 89%. Group 1 had CXRT alone (n = 55). Group 2 (n = 25) patients were selected for primary disease resection, and sometimes HAI chemotherapy (n = 10) or hepatic resection (n = 5). Subsequently, 78% received systemic chemotherapy., Results: Symptoms from primary tumor resolved in 94%. Endoscopic complete clinical response rate was 36%. Two-year survival (11% vs. 46%, p < 0.0001) and symptomatic pelvic control (PC, 81% vs. 91%, p = 0.111) were higher in Group 2, but colostomy-free rate (CFR) was lower (79% vs. 51% p = 0.02). CFR was 87% in Group 1 patients managed initially without fecal diversion (n = 50). Examining all patients using multivariate analysis, pelvic pain at presentation (p < 0.00001), BED (biologic equivalent dose at 2 Gy/fraction) < 35 Gy (p = 0.077), and poor differentiation (0.079) predicted worse PC. Poor differentiation (p = 0.017) and selection for CXRT alone (p < 0.0001) predicted worse survival. There were 4 RTOG of Grade 3 or greater acute complications, 5 severe perioperative complications, and no significant late treatment-related complications., Conclusion: Durable PC can be safely achieved without colostomy in most patients presenting with primary rectal cancer and synchronous systemic metastases using hypofractionated pelvic chemoradiation. A BED greater than 35 Gy is recommended. Selected patients appear to benefit from resection of primary disease. Higher doses should be investigated in patients with pelvic pain.