PURPOSE:To determine whether a hypofractionated proton therapy regimen will control early-stage disease and maintain low rates of side effects similar to results obtained using standard-fraction proton therapy at our institution.MATERIALS AND METHODS:A cohort of 146 patients with low-risk prostate cancer according to National Comprehensive Cancer Network guidelines (Gleason score <7, prostate-specific antigen [PSA] <10, tumor stage of T1-T2a) received 60 Gy (cobalt Gy equivalent) of proton therapy (20 fractions of 3.0 Gy per fraction) in 4 weeks, a dose biologically equivalent to standard fractionation (44-45 fractions of 1.8 Gy to a total of 79.2 to 81 Gy in 0 weeks). Patients were evaluated at least weekly during treatment, at which time documentation of treatment tolerance and acute reactions was obtained. Follow-up visits were conducted every 3 months for the first 1 years, every 6 months for the next 3 years, then annually. Follow-up visits consisted of history and physical examination, PSA measurements, and evaluation of toxicity.RESULTS:The median follow-up time was 42 months (range, 3-96 months). Acute grade 2 urinary toxicity occurred in 16% (20/120) of the patients; acute grade 2 or higher gastrointestinal toxicity was seen in 1.7% (2/120). At 9 months, 1 patient had late grade 3 urinary toxicity, which resolved by 12 months; no grade 3 gastrointestinal toxicities occurred. The 3-year biochemical survival rate was 99.3% (144/145). The median time to PSA nadir was 30 months.CONCLUSION:Hypofractionated proton therapy of 60 Gy in 20 fractions was safe and effective for patients with low-risk prostate cancer.

Background Because early-stage breast cancer can be treated successfully by a variety of breast-conservation approaches, long-term quality of life (QoL) is an important consideration in assessing treatment outcomes for these patients. This study compares patient-reported QoL outcomes among women with stage 0-2 disease treated via lumpectomy followed by whole breast irradiation (WBI) or partial breast proton irradiation (PBPT). Methods In this cross-sectional study, 129 participants evaluated QoL several years post-treatment by responding to subjective instruments, including established scalar questionnaires and self-report measures. Responses were averaged between the two groups. Results At 6.5 years (median) postdiagnosis, participants' demographic, and clinical characteristics were similar. Patient-reported outcomes were reported as mean scale scores for the two groups, all displaying significant differences favoring PBPT, including: cosmetic breast cancer treatment outcome scale (BCTOS) (PBPT mean 1.45, WBI mean 1.88, P < 0.001); breast pain (PBPT mean 1.30, WBI mean 1.67, P < 0.05); breast texture (BPT mean 1.44, WBI mean 1.91, P < 0.001); clothing fit (PBPT mean 1.06, WBI 1.46, P < 0.001); fatigue (PBPT mean 2.24, WBI mean 3.77, P < 0.002); impact of daily life fatigue on personal relations (OBPT mean 0.83, WBI mean 2.15, P < 0.001); and self-consciousness (appearance dissatisfaction) (PBPT mean 1.38, WBI mean 1.77, P < 0.004). Conclusion Patients' responses suggest that PBPT is associated with improved overall QoL compared to standard whole breast treatment. These self-perceptions are reported by patients who are 5-10 years post-treatment, and that PBPT may enhance QoL in a multitude of interrelated ways.

PURPOSE:This prospective cohort evaluated patients with acoustic neuroma treated with proton irradiation at Loma Linda University Medical Center. A dose of 50.4 Gy in 28 fractions was given to improve hearing preservation while maintaining tumor control.PATIENTS AND METHODS:Ninety-five patients were treated from March 1991 to March 2008. Fractionated proton radiotherapy at daily doses of 1.8 Gy was employed. Patients were treated to 1 of 3 total doses: 59.4 Gy, used initially for patients without serviceable hearing; 54 Gy, used for patients with serviceable hearing through October 2000; and 50.4 Gy used since 2001 for patients with serviceable hearing. Survival and local control were calculated using the Kaplan-Meier method. Logistic regression analysis was preformed comparing dose, tumor size, and tumor location with hearing preservation.RESULTS:Ninety-four patients were assessable; the median follow-up was 64 months. Five-year local control rates for the 59.4 Gy, 54 Gy, and 50.4 Gy groups were 95%, 97%, and 92%, respectively (P = .80); the overall 10-year actuarial control rate was 90%. Cranial nerve injuries occurred in <5% in all groups. Four-year actuarial rates of hearing preservation were maintained in 44% of patients treated with 54 Gy and 64% treated with 50.4 Gy (P = .284). On multivariate analysis, initial tumor diameter (≤1.5 cm) was found to be a prognostic factor for maintaining serviceable hearing in both groups (P = .011).CONCLUSIONS:Fractionated proton therapy of 50.4 Gy offers excellent local control and minimal cranial nerve toxicities. Improved rates of hearing preservation that are comparable with radiosurgery were seen with 50.4 Gy compared with higher doses, although this did not reach significance. Maintaining hearing was found to be associated with smaller initial tumor size.

Long-term quality of life (QoL) is a salient factor in assessing outcomes of breast conservation therapy for patients with early-stage breast cancer. This study compares patient-reported QoL outcomes among women with stage 0-II disease treated with partial mastectomy followed by partial-breast proton irradiation (PBPI) or whole-breast photon (WBI). : PBPI subjects were recruited from previous participation in an institutional prospective clinical trial. WBI subjects were recruited from a registry maintained at the same institution. QoL tools completed included the Harvard Cosmesis Scale (HCS), Breast Cancer Treatment Outcome Scale (BCTOS), Brief Fatigue Inventory (BFI), Medical Outcomes Study (MOS) Short Form, and Body Image Scale (BIS). 180 subjects received surveys with 142 being completed and returned yielding a 79% participation rate. 13 were determined to be ineligible due to bilateral disease, disease recurrence, metastatic disease, or other serious medical co-morbidities. 129 participants completed QoL and were included for evaluation, 72 following PBPI and 57 following WBI. Median time from treatment was 7.4 years (PBPI) and 6.3 years (WBI). The two groups were well matched for age, weight, marital status, race, education, employment, recent health status, stage, tumor size, extent of surgery, and use of adjuvant systemic therapy. Significant differences favoring the proton group were seen for several domains. The HCS showed higher cosmetic mean scores for PBPI 3.4 vs WBI 2.4 (p<0.001). BCTOS results showed improved weighted BCTOS (5.5 vs 7.6, p<0.001), cosmetic BCTOS (11.6 vs 15.0, p<0.001), and BS pain (4.2 vs 5.3, p=0.005) for PBPI vs WBI respectively. BFI demonstrated reduced fatigue (2.2 vs 3.8, p=0.002) with less interference with daily general activities (1.7 vs 2.8, p=0.017) for PBPI vs WBI. MOS survey resulted in statistically significant improved perception of general health with improved emotional and social functioning for PBPI. BIS resulted in improved overall score favoring PBPI (12.1 vs 14.2, p=0.009). Patients' responses suggest that partial-breast proton radiotherapy is associated with higher long term overall QoL across multiple domains when compared to a comparable cohort of patients treated with whole breast radiotherapy.

To determine the maximum tolerated dose (MTD) of stereotactic body proton therapy (SBPT) for liver metastases in anticipation of a subsequent phase II study. Although phase I studies have shown safety with photon based treatments, similar clinical safety profile and tolerability with proton based therapy has not been reported. An IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5cm, and no CNS metastases, tense ascites requiring frequent paracentesis or metastases location within 2cm of the GI tract. The initial cohort received 36 GyE to the planning target volume (PTV) in 3 fractions. Subsequent cohorts received 48 GyE in 3 fractions and finally 60 GyE in 3 fractions, the final chosen maximum dose. At least 700mL of normal liver had to receive <15 GyE. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume 11.1 ml (range, 2.14-89.3 ml); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 GyE in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the first cohort had local recurrence and repeat SBPT was done to previously treated lesions without any reported toxicities. Biologically ablative SBPT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II SBPT study of 60 GyE over 3 fractions for liver metastases.

Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC).Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization.Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group.Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy. (C) 2016 Elsevier Inc. All rights reserved.

BACKGROUND Pancreatic cancer is a highly aggressive malignancy. Chemoradiotherapy (CRT) is utilized in many cases to improve locoregional control; however, toxicities associated with radiation can be significant given the location of the pancreas. RTOG 0848 seeks to evaluate chemoradiation using either intensity-modulated radiation therapy (IMRT) or 3D conformal photon radiotherapy (3DCRT) modalities as an adjuvant treatment. The purpose of this study is to quantify the dosimetric changes seen when using IMRT or 3D CRT photon modalities, as well as proton radiotherapy, in patients receiving CRT for cancer of the pancreas treated per RTOG 0848 guidelines. MATERIALS Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using IMRT and 3DCRT as well as proton radiotherapy were created for each patient. All planning volumes were created per RTOG 0848 protocol. Dose-volume histograms (DVH) were calculated and analyzed in order to compare plans between the three modalities. The organs at risk (OAR) evaluated in this study are the kidneys, liver, small bowel, and spinal cord. RESULTS There was no difference between the IMRT and 3DCRT plans in dose delivered to the kidneys, liver, or bowel. The proton radiotherapy plans were found to deliver lower mean total kidney doses, mean liver doses, and liver D1/3 compared to the IMRT plans. The proton plans also gave less mean liver dose, liver D1/3, bowel V15, and bowel V50 in comparison to the 3DCRT. CONCLUSIONS For patients receiving radiotherapy per ongoing RTOG 0848 for pancreatic cancer, there was no significant difference in normal tissue sparing between IMRT and 3DCRT treatment planning. Therefore, the choice between the two modalities should not be a confounding factor in this study. The proton plans also demonstrated improved OAR sparing compared to both IMRT and 3DCRT treatment plans.

validate this finding and will permit correlation with clinical outcome measures.

167 Background: Recent studies indicate that radiation exposure to heart may have a greater impact on perioperative cardiac morbidities than do other clinical factors. The purpose of this study is to investigate dose distributions of proton and photon treatment plans in patients (pts) with distal and esophagogastric junction (GEJ) carcinoma, focusing specifically on dose reduction to cardiac structures. Methods: Ten pts between 2010 and 2013 were included in this study. Three separate plans were generated for each patient: 3D proton plan, 3D photon plan, and Intensity modulated radiotherapy (IMRT) photon plan. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15mm. A dose of 50.4Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 90% isodose coverage of at least 95% of the PTV. Dose-volume histograms were calculated and analyzed in order to compare plans between the three modalities. ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The 3D proton plans showed decreased dose to partial volumes of the entire heart, arteries, valves, atria, and ventricles in comparison to both the IMRT and 3D photon plans (see Table). The IMRT plans showed decreased dose delivered to the LAD artery, pericardium, and atria in comparison to the 3D photon plans (see Table). Conclusions: For pts receiving radiation therapy for distal esophageal and GEJ cancer, proton plans are technically feasible with adequate coverage while resulting in lower dose to cardiac structures. This may result in decreased cardiac toxicity and less complications in a multimodality setting. [Table: see text]

The purpose of this study is to investigate methods of minimizing radiation induced perioperative cardiopulmonary complications. Ten patients with esophageal cancer treated with radiation therapy between 2010 and 2013 were included in this study. Three separate plans were generated for each patient: 3D proton plan, 3D photon plan, and IMRT plan. A dose of 50.4Gy given in 28 fractions was delivered to the PTV allowing 90% isodose coverage of at least 95% of the PTV. Dose distributions of proton, 3D conformal photon, and intensity modulated radiation therapy (IMRT) treatment plans in patients with esophageal carcinoma were examined, focusing specifically on dose reduction to cardiac and pulmonary structures. Dose-volume histograms were calculated and analyzed in order to compare plans. The 3D proton plans showed decreased dose to partial volumes of the entire heart, arteries, and left ventricle in comparison to both the IMRT and 3D photon plans. The IMRT plans showed decreased dose delivered to the LAD artery, pericardium, and left atrium in comparison to the 3D photon plans (See Table). For patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible with adequate coverage and may results in lower dose to cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.Scientific Abstract 2308; TableProtonIMRT3D PhotonProton vs IMRTProton vs 3D photonIMRT vs 3D photonHeart V30 (%)20.85±7.1242.28±15.332.72±9.390.0010.0050.109 V40 (%)16.21±6.3525.45±10.9725.78±8.760.0360.0120.942 Mean (Gy)12.56±3.8628.5±5.5427.53±5.180.0010.0010.692 Mean (Gy)0.99±1.1121.23±9.1419.90±9.060.0010.0010.747Left Main Coronary Artery Max (Gy)11.86±12.8935.25±11.433.51±11.690.0010.0010.740 Mean (Gy)0.36±0.5917.57±5.7615.08±8.180.0010.0010.441Left Anterior Descending Artery Max (Gy)5.37±8.6531.4±3.6326.86±4.780.0010.0010.028Pericardium Mean (Gy)13.49±1.7826.03±5.1224.76±4.220.0010.0010.552 Max (Gy)52.64±1.3153.38±0.4555.3±2.020.1180.0030.015Left Ventricle Mean (Gy)13.86±6.6130.28±5.5827.31±5.560.0010.0010.250 Max (Gy)51.43±0.8852.33±0.8250.6±10.590.0290.8080.613Lung V5 (Gy)21.4±10.3246.93±17.6134.12±13.860.0010.0320.087 V20 (Gy)15.46±6.5416.19±5.7822.1±10.80.7940.1140.144 Mean (Gy)6.03±2.589.45±3.179.38±4.040.0160.0400.966 Open table in a new tab

Abstract Purpose: Pancreatic cancer is a highly aggressive malignancy. Chemoradiation therapy (CRT) is used in many cases to improve local-regional control; however, toxicities associated with radiation can be significant given the location of the pancreas. The purpose of this study is to quantify the dosimetric changes seen when using photons or protons in patients receiving CRT for cancer of the pancreas. Patients and Methods: Ten patients with pancreatic head adenocarcinoma treated between 2010 and 2013 were evaluated in this study. All patients underwent simulation with contrast-enhanced computed tomography imaging. Separate treatment plans using proton radiation therapy, intensity-modulated radiation therapy, and 3-dimensional photon radiation therapy modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the 3 modalities. The organs at risk evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statis...

Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

369 Background: The purpose of this study is to investigate dose distributions of proton and intensity-modulated radiation therapy (IMRT) photon treatment plans in patients with resected pancreatic adenocarcinoma, focusing specifically on dose reduction to the kidney, liver, and small bowel as organs at risk. Methods: Ten patients with pancreatic head adenocarcinoma underwent Whipple procedure between 2010 and 2013 were included in this study. Most of the patients had locally advanced disease (T3-4N1). All patients were simulated with contrast-enhanced CT imaging. The clinical target volume (CTV) consisted of the pre-operative extent of tumor plus a 10 mm manual expansion in all directions. The planning target volume (PTV) was generated by a further expansion on the CTV ranging from 10-15 mm. A dose of 50.4 Gy given in 28 fractions was delivered to the PTV. All plans were optimized to allow 95% isodose coverage of at least 95% of the PTV. Dose-volume histograms, conformity index (CI), uniformity index (UI), homogeneity index (HI), were calculated and analyzed in order to compare plans between the two modalities. The OAR being evaluated in this study are the kidneys, liver, small bowel, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results: The proton plans resulted in a lower mean kidney dose (3.17 Gy vs. 9.59 Gy, p=0.039), a lower dose delivered to 1/3 of the liver, D1/3, (0.25 Gy vs. 4.56 Gy, p=0.003), and a lower mean liver dose (1.83 Gy vs. 5.24 Gy, p=0.021). See table for a summary of the results. Conclusions: For patients receiving postoperative radiotherapy for pancreatic cancer, the proton plans are technically feasible and dosimetrically appealing with superior organ at risk sparing compared to IMRT photon treatment plans.[Table: see text]

PURPOSE:We updated our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation (PBI) in patients with early stage breast cancer.METHODS AND MATERIALS:Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm. Patients underwent partial mastectomy with negative margins; axillary lymph nodes were negative on sampling. Subjects received postoperative proton beam radiation therapy to the surgical bed. The dose delivered was 40 Gy in 10 fractions, once daily over 2 weeks. Multiple fields were treated daily, and skin-sparing techniques were used. Following treatment, patients were evaluated with clinical assessments and annual mammograms to monitor toxicity, tumor recurrence, and cosmesis.RESULTS:One hundred subjects were enrolled and treated. All patients completed the assigned treatment and were available for post-treatment analysis. The median follow-up was 60 months. Patients had a mean age of 63 years; 90% had ductal histology; the average tumor size was 1.3 cm. Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97% (95% confidence interval: 100%-93%); disease-free survival of 94%; and overall survival of 95%. There were no cases of grade 3 or higher acute skin reactions, and late skin reactions included 7 cases of grade 1 telangiectasia. Patient- and physician-reported cosmesis was good to excellent in 90% of responses, was not changed from baseline measurements, and was well maintained throughout the entire 5-year follow-up period.CONCLUSIONS:Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity. The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations. Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment. Cosmetic results may be improved over those reported with photon-based techniques due to reduced breast tissue exposure with proton beam, skin-sparing techniques, and the dose fractionation schedule used in this trial.

Purpose/Objective(s)The purpose of this study was to investigate dose distributions of proton and IMRT treatment plans in patients with HCC, focusing specifically on dose reduction to the liver, kidney, spinal cord, and bowel as organs at risk (OAR).Materials/MethodsSeven patients treated for HCC were subjects of this study. Their treatment planning CT scans were utilized. Separate proton therapy and IMRT plans delivering 70 Gy in 15 fractions were created for each patient. The gross tumor volume (GTV) was defined on CT imaging with contrast. The clinical target volume (CTV) was defined as the GTV plus a 1 cm expansion, which was edited based on anatomical organ boundaries. Using the treatment planning system, proton and IMRT plans were created and several liver dose parameters, including mean liver dose, and OAR dose measurements were calculated and compared. The Mann-Whitney test for non-parametric variables was used.ResultsEight liver lesions were present among the seven patients. The proton therapy plans delivered a lower mean liver dose [9.9 Gy (4.90-16.90) vs 16 Gy (8.57-21); p = 0.026], a lower mean body dose [1.36 Gy (0.51-2.55) vs 2.95 Gy (1.31-4.30); p = 0.017], and a lower dose to the spinal cord [0.20 Gy (0.10-0.80) vs 7.16 Gy (2.00-14.70); p = 0.001]. The V10, V20, and V30 parameters were also measured. In the proton and IMRT plans, respectively, V10 was [20.91% (10.60-34.10) vs 33.01% (8.20-46.80); p = 0.128]; V20 was [17.94% (9.10-30.00) vs 25.29% (5.50-36.80); p = 0.165]; and V30 was [15.27% (7.40-26.60) vs 18.36% (3.60-31.50); p = 0.383]. The mean doses delivered by the proton and IMRT plans, respectively, to bowel were [2.68 Gy (0.05-11.85) vs 9.04 Gy (0.92-26.78); p = 0.053] and to kidney were [4.24 Gy (0.05-13.90) vs 11.27 Gy (0.05-24.42); p = 0.128].ConclusionsThis study demonstrated improved protection of hepatic tissues with the use of proton beam radiation compared to IMRT. Purpose/Objective(s)The purpose of this study was to investigate dose distributions of proton and IMRT treatment plans in patients with HCC, focusing specifically on dose reduction to the liver, kidney, spinal cord, and bowel as organs at risk (OAR). The purpose of this study was to investigate dose distributions of proton and IMRT treatment plans in patients with HCC, focusing specifically on dose reduction to the liver, kidney, spinal cord, and bowel as organs at risk (OAR). Materials/MethodsSeven patients treated for HCC were subjects of this study. Their treatment planning CT scans were utilized. Separate proton therapy and IMRT plans delivering 70 Gy in 15 fractions were created for each patient. The gross tumor volume (GTV) was defined on CT imaging with contrast. The clinical target volume (CTV) was defined as the GTV plus a 1 cm expansion, which was edited based on anatomical organ boundaries. Using the treatment planning system, proton and IMRT plans were created and several liver dose parameters, including mean liver dose, and OAR dose measurements were calculated and compared. The Mann-Whitney test for non-parametric variables was used. Seven patients treated for HCC were subjects of this study. Their treatment planning CT scans were utilized. Separate proton therapy and IMRT plans delivering 70 Gy in 15 fractions were created for each patient. The gross tumor volume (GTV) was defined on CT imaging with contrast. The clinical target volume (CTV) was defined as the GTV plus a 1 cm expansion, which was edited based on anatomical organ boundaries. Using the treatment planning system, proton and IMRT plans were created and several liver dose parameters, including mean liver dose, and OAR dose measurements were calculated and compared. The Mann-Whitney test for non-parametric variables was used. ResultsEight liver lesions were present among the seven patients. The proton therapy plans delivered a lower mean liver dose [9.9 Gy (4.90-16.90) vs 16 Gy (8.57-21); p = 0.026], a lower mean body dose [1.36 Gy (0.51-2.55) vs 2.95 Gy (1.31-4.30); p = 0.017], and a lower dose to the spinal cord [0.20 Gy (0.10-0.80) vs 7.16 Gy (2.00-14.70); p = 0.001]. The V10, V20, and V30 parameters were also measured. In the proton and IMRT plans, respectively, V10 was [20.91% (10.60-34.10) vs 33.01% (8.20-46.80); p = 0.128]; V20 was [17.94% (9.10-30.00) vs 25.29% (5.50-36.80); p = 0.165]; and V30 was [15.27% (7.40-26.60) vs 18.36% (3.60-31.50); p = 0.383]. The mean doses delivered by the proton and IMRT plans, respectively, to bowel were [2.68 Gy (0.05-11.85) vs 9.04 Gy (0.92-26.78); p = 0.053] and to kidney were [4.24 Gy (0.05-13.90) vs 11.27 Gy (0.05-24.42); p = 0.128]. Eight liver lesions were present among the seven patients. The proton therapy plans delivered a lower mean liver dose [9.9 Gy (4.90-16.90) vs 16 Gy (8.57-21); p = 0.026], a lower mean body dose [1.36 Gy (0.51-2.55) vs 2.95 Gy (1.31-4.30); p = 0.017], and a lower dose to the spinal cord [0.20 Gy (0.10-0.80) vs 7.16 Gy (2.00-14.70); p = 0.001]. The V10, V20, and V30 parameters were also measured. In the proton and IMRT plans, respectively, V10 was [20.91% (10.60-34.10) vs 33.01% (8.20-46.80); p = 0.128]; V20 was [17.94% (9.10-30.00) vs 25.29% (5.50-36.80); p = 0.165]; and V30 was [15.27% (7.40-26.60) vs 18.36% (3.60-31.50); p = 0.383]. The mean doses delivered by the proton and IMRT plans, respectively, to bowel were [2.68 Gy (0.05-11.85) vs 9.04 Gy (0.92-26.78); p = 0.053] and to kidney were [4.24 Gy (0.05-13.90) vs 11.27 Gy (0.05-24.42); p = 0.128]. ConclusionsThis study demonstrated improved protection of hepatic tissues with the use of proton beam radiation compared to IMRT. This study demonstrated improved protection of hepatic tissues with the use of proton beam radiation compared to IMRT.

Purpose: We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients.Methods and Materials: Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC).Results: One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P = .006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment.Conclusions: High-dose hypofractionated proton therapy achieves excellent outcomes for lung carcinomas that are peripherally or centrally located. The 70-Gy regimen has been adopted as standard therapy for T1 tumors at our institution. Larger T2 tumors show a trend toward improved outcomes with higher doses, suggesting that better results could be seen with intensified treatment. (C) 2013 Elsevier Inc.

The purpose of the study is to compare the prognostic value of percentage of positive biopsy cores (PPBC), percentage of cancer volume (PCV), and maximum involvement of biopsy cores (MIBC) as a prognostic factor in low- and intermediate-risk patients with clinically localized prostate cancer who received proton or photon beam therapy. Four hundred and fifty-nine patients with clinically localized prostate carcinoma who were treated with proton or photon beam therapy at Loma Linda University Medical Center were used for this analysis. Patients were treated with a median dose of 74.0 Gy (range 70.2–79.2) proton or combined proton/photon beam radiotherapy. Pathology reports were reviewed and PPBC, PCV, and MIBC were recorded. Analysis of biochemical no evidence of disease (bNED) outcome was assessed using Kaplan-Meier analyses. Cox regression multivariate analyses were performed to assess the impact of the biopsy factors on survival. Results: 285, 291, and 291 patients had biopsy information available for analysis, respectively. Survival analysis showed that a higher PPBC, PCV, and MIBC were each individually associated with an increased risk of biochemical failure on univariate analysis (p < 0.01). Only PPBC and PCV were associated with an increased risk of biochemical failure on multivariate analysis, adjusting for age, NCCN risk group, and dose (p < 0.01). When isolating the intermediate-risk group, only PPBC and PCV were statistically significant on multivariate analysis. Multivariate analysis of the intermediate-risk group comparing PPBC and PCV showed that PPBC was not a significant predictor of biochemical failure, while PCV was a significant predictor of biochemical failure (p = 0.37 and p = 0.03, respectively). Conclusion: PPBC and PCV can potentially be used for additional risk stratification of intermediate-risk patients with PCV potentially being the most clinically relevant predictor bNED survival. MIBC was not found to have utility in the prognosis of low- and intermediate-risk patients.

Proton therapy has been shown to be very effective for low-risk prostate cancer, with 10-year bRFS over 90%. A Phase I/II study was undertaken to use hypofractionation in an attempt to significantly reduce the cost of proton treatment for low-risk prostate cancer, while still retaining excellent control with minimal toxicity. In 2009, an IRB-approved trial was initiated, utilizing protons delivered in a hypofractionated schedule. Patients with low-risk prostate cancer (cT1-T2bN0M0 and PSA < 10 and Gleason Score ≤6) received protons to the prostate only, treating all fields per day, to a total dose of 60 Gy in 20 fractions over 4 weeks. Sixty-three patients entered the trial through November 2009; two ultimately decided not to start protocol therapy, for a total of 61 completing treatment. Toxicity was followed using NCI CTCAE for adverse events at three-month intervals. Biochemical control was evaluated using the Phoenix definition (PSA nadir + 2 ng/mL). All patients but four, one who died of MI six months after treatment and three who refused or were lost to follow-up, were eligible for the minimum 36-month follow-up. At the time of analysis, median follow-up was 36 months, ranging from 3 to 42 months. GI toxicity at 24 months was seen in 6%, 2% and 0% for grade 1, 2, and 3 toxicity, respectively. At 36 months, GI toxicity by grade was 5.4%, 0%, and 0%, respectively. Grade 1 GU toxicity was 24% at both 24 and 36 months; grade 2 toxicity was 0% at 24 months and 3% at 36 months. Overall, no grade 3 or greater toxicities have been seen. No biochemical failures have been seen to date. Post-treatment PSA values continued to decrease with time. At 24 months, 68% and 32% of patients had post-treatment PSA nadirs below 1.0 and 0.5, respectively; by 36 months, the same respective PSA nadirs were 78% and 33%. Preliminary analysis shows that hypofractionated proton therapy for low-risk prostate cancer, as delivered in this protocol, yields minimal toxicity and severe (≥ grade 3) GI or GU toxicity has not been seen. PSA reductions are consistent with previous reports at this time, albeit longer follow-up is necessary to fully define the role of hypofractionated protons in low-risk prostate cancer.

BACKGROUND: Proton beam therapy (PBT) may provide useful local-regional treatment for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of PBT for HCC. METHODS: Patients with cirrhosis who had radiological features or biopsy-proven HCC were included in the study. Patients without cirrhosis and patients with extrahepatic metastasis were excluded. The mean age was 62.7 years. The mean tumor size was 5.5 cm. Eleven patients had multiple tumors, and 46% were within the Milan criteria. Patients received 63 Gy delivered over a 3-week period with PBT. RESULTS: Seventy-six patients were treated and followed prospectively for treatment outcomes at Loma Linda University Medical Center. Acute toxicity was minimal; all patients completed the full course of treatment. Radiation-induced liver disease was evaluated using liver enzyme, bilirubin, and albumin levels; no significant change supervened 6 months posttreatment. Median progression-free survival for the entire group was 36 months, with a 60% 3-year progression-free survival rate for patients within the Milan criteria. Eighteen patients subsequently underwent liver transplantation; 6 (33%) explants showed pathological complete response and 7 (39%) showed only microscopic residual. CONCLUSIONS: PBT was found to be a safe and effective local-regional therapy for inoperable HCC. A randomized controlled trial to compare its efficacy to a standard therapy has been initiated. Cancer 2011;117:3053-9. (c) 2011 American Cancer Society

The purpose of this study was to evaluate the uncertainty of prostate position relative to CT-planned position during proton therapy. Twenty-five patients enrolled in a clinical proton therapy study had 3 or 4 gold markers implanted into the prostate one week prior to radiation planning CT study. To minimize prostate motion, a water-filled endorectal balloon was placed; patients were instructed to comfortably fill the bladder by controlling water intake prior to CT and treatment. During the first five treatment days, orthogonal posterior-anterior and lateral x-ray films were taken immediately before and after treatment. The 3-D location of the centroid of the seeds was determined in reference to pelvic anatomical axes, defined during CT-based treatment planning. SDs of the prostate intrafractional motion about the daily mean and interfractional motion about the global mean position over five days were calculated. The mean and SD of the deviation of the global mean prostate position relative to the CT-planned position also were determined. From these SDs, the overall composite SD and a 99.7% confidence interval of the prostate position relative to the planned position were derived. The SD of intrafractional motion about the daily mean was 0.3 mm left-right (LR), 1.1 mm anterior-posterior (AP), and 1.1 mm inferior-superior (IS). The SDs of the interfractional motion were 0.4 mm LR, 1.6 mm AP, and 1.4 mm IS. The difference between the global mean and the CT-planned reference position for each patient was -0.2 ± 0.6 mm LR, 1.5 ± 3.2 mm AP, and -1.8 ± 2.4 mm (mean ± SD). Composite SDs for the uncertainty of prostate position relative to the CT-planned position were 0.8 mm LR, 3.8 mm AP, and 3.0 mm IS; the 99.7% confidence (3 SDs) margins were 2.4 mm LR, 11.3 mm AP, and 8.9 mm IS. Intra- and interfractional motion, and deviation of mean prostate position from CT reference position contribute to the uncertainty of prostate position with increasing magnitude. Required confidence margins including the prostate within field boundaries match current practice but can be reduced by using implanted gold markers.