Search

Background: To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer., Material and Methods: We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n  = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed., Results: Median follow-up was 8.0 years (0.9-12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up., Conclusion: Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

Background: The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT)., Material and Methods: Between 2009 and 2018, 23 patients with T1-T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58-88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks., Results: Median follow-up for all patients was 3.2 years (range, 0.2-9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27-79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46-92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18-61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement., Conclusion: Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Objective: Thymic malignancies (TM) are rare tumors with long-term survivorship, causing concerns for radiotherapy-related late side effects. Proton therapy (PT) reduces the radiation dose to organs at risk, potentially decreasing long-term toxicities while preserving disease control. We report patterns-of-care and early clinical outcomes after PT for thymoma and thymic carcinoma. Methods: Between January 2008 and March 2017, 30 patients with TMs enrolled on one of two IRB-approved prospective protocols and received postoperative or definitive PT. Clinical outcomes, pathology, treatment dose, toxicities, and follow-up information were analyzed. Results: Twenty-two thymoma patients with a median age of 52.1 years (range, 23-72) received a median RT dose of 54 Gy (RBE) (range, 45-70) either postoperatively (91%) or definitively (9%); 23% received adjuvant chemotherapy. Among eight thymic carcinoma patients, the median age was 65.5 years (range, 38-88) and median RT dose was 60 Gy (RBE) (range, 42-70) delivered postoperatively (75%) or definitively (25%); 50% received chemotherapy. Median follow-up for all patients was 13 months (range, 2-59 months). Five patients relapsed, one locally (3%). Three patients died of disease progression, including two thymomas and one thymic carcinoma patient; a fourth died of intercurrent disease. One patient with thymic carcinoma and 1 with thymoma are alive with disease. No patients treated with PT for their initial disease (de novo) experienced grade ≥3 toxicities. The most common grade 2 toxicities were dermatitis (37%), cough (13%), and esophagitis (10%). Conclusion: Adjuvant and definitive PT are being used in the treatment of TMs. Early results of the largest such cohort reported to date demonstrates an acceptable rate of recurrence with a favorable toxicity profile. Longer follow-up and a larger patient cohort are needed to confirm these findings.

Purpose: To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT)., Material and Methods: From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1 < 1.0 or O 2 dependency, prior lung cancer, prior lung surgery, prior 2nd cancer in the past 3 years, and prior chest irradiation were evaluated. All patients received standard fractionation of 1.8-2 Gy(RBE) (median dose, 70 Gy[RBE]). Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. The impact of unfavorable factors was analyzed in Cox regression models., Results: Twenty-six percent were favorable-risk, while 42%, 22%, and 10% had 1-, 2-, or ≥3 unfavorable factors. The 2-year OS was 52% and 45% (p = .8522), and 2-year PFS was 21% and 44% (p = .0207), for favorable and unfavorable risk patients, respectively. Among patients with stage III-IV, only PS ≥2 adversely impacted OS (p = .0015)., Conclusion: Most patients treated with PT for LA-NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients. Enrollment in future clinical trials may improve if eligibility is less restrictive.

Background: We investigated long-term outcomes for men ≤60 years old treated with proton therapy (PT)., Methods: Of 254 men ≤60 years old were treated with proton therapy alone for prostate cancer. Risk stratification included 56% with low-, 42% with intermediate- and 2% with high-risk disease. Patients received 76-82 Gy at 2 Gy/fraction or 70-72.5 Gy at 2.5 Gy/fraction. Before treatment and every 6-12 months for 5 years, patients were evaluated by a physician, answered health-related quality of life surveys, including the EPIC, IIEF and IPSS, and had PSA evaluated., Results: Median follow-up for the cohort was 7.1 years; 7-year biochemical-free survival was 97.8%. Eight men (one high-risk; five intermediate-risk and two low-risk) experienced biochemical progression, including one who died of disease 9 years after treatment. Potency (erections firm enough for sexual intercourse) was 90% at baseline and declined to 72% at the first-year follow-up, but declined to only 67% at 5 years. Only 2% of patients developed urinary incontinence requiring pads. The bowel habits mean score declined from a baseline of 96 to 88 at 1 year, which improved over the following years to 93 at 5 years., Conclusions: Young men with prostate cancer continue to have excellent results with respect to 7-year biochemical control and 5-year erectile function, without clinically significant urinary incontinence 5 years after proton therapy. Comparative effectiveness studies of proton therapy with surgery and IMRT are needed.

Purpose: To report 5-year outcomes of a prospective trial of image-guided accelerated hypofractionated proton therapy (AHPT) for prostate cancer., Patients and Methods: 215 prostate cancer patients accrued to a prospective institutional review board-approved trial of 70Gy(RBE) in 28 fractions for low-risk disease (n = 120) and 72.5Gy(RBE) in 29 fractions for intermediate-risk disease (n = 95). This trial excluded patients with prostate volumes of ≥60 cm 3 or International Prostate Symptom Scores (IPSS) of ≥15, patients on anticoagulants or alpha-blockers, and patients in whom dose-constraint goals for organs at risk (OAR) could not be met. Toxicities were graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. This trial can be found on ClinicalTrials.gov (NCT00693238)., Results: Median follow-up was 5.2 years. Five-year rates of freedom from biochemical and clinical disease progression were 95.9%, 98.3%, and 92.7% in the overall group and the low- and intermediate-risk subsets, respectively. Actuarial 5-year rates of late radiation-related CTCAE v3.0 grade 3 or higher gastrointestinal and urologic toxicities were 0.5% and 1.7%, respectively. Median IPSS before treatment and at 4+ years after treatment were 6 and 5 for low-risk patients and 4 and 6 for intermediate-risk patients., Conclusions: Image-guided AHPT 5-year outcomes show high efficacy and minimal physician-assessed toxicity in selected patients. These results are comparable to the 5-year results of our prospective trials of standard fractionated proton therapy for patients with low-risk and intermediate-risk prostate cancer. Longer follow-up and a larger cohort are necessary to confirm these findings.

Background: The present study investigates the impact of scatter dose radiation to the testis on ejaculate and sperm counts from treatment of prostate cancer with passive-scatter proton therapy., Material and Methods: From March 2010 to November 2014, 20 men with low- or intermediate-risk prostate cancer enrolled in an IRB-approved protocol and provided a semen sample prior to passive-scatter proton therapy and 6-12 months following treatment. Men were excluded if they had high-risk prostate cancer, received androgen deprivation therapy, were on alpha blockers (due to retrograde ejaculation) prior to treatment, had baseline sperm count <1 million, or were unable to produce a pre-treatment sample or could not provide a follow-up specimen. Sperm counts of 0 were considered azoospermia and <15 million/ml were classified as oligospermia., Results: Four patients were unable to provide a sufficient quantity of semen for analysis. Among the 16 remaining patients, only one was found to have oligospermia (7 million/ml). There was a statistically significant reduction in semen volume (median, 0.5 ml) and increase in pH (median 0.5). Although not statistically significant, there appeared to be a decline in sperm concentration (median, 16 million/ml), total sperm count (median, 98.5 million), normal morphology (median, 9%), and rapid progressive motility (median, 9.5%)., Discussion: Men did not have azoospermia 6-12 months following passive-scatter proton therapy indicating minimal scatter radiation to the testis during treatment. Changes in semen quantity and consistency may occur due to prostate irradiation, which could impact future fertility and/or sexual activity.

Background: Proton therapy (PT) for prostate cancer reduces rectal and bladder dose, but increases dose to the femoral necks. We assessed the risk of hip fracture and pain in men treated with PT for prostate cancer., Material and Methods: From 2006 to 2008, 382 men were treated for prostate cancer and evaluated at six-month intervals after PT for toxicities at University of Florida Proton Therapy Institute (UFPTI). The WHO Fracture Risk Assessment Tool (FRAX) generated annual hip-fracture risk for the cohort. The WHO FRAX tool was utilized to generate the expected number of patients with hip fractures and the observed-to-expected ratio; confidence intervals and p-value were generated with the mid-P exact test. Univariate analysis of hip pain as a function of several prognostic factors was accomplished with Fisher's exact test., Results: Median follow-up was four years (range, 0.1-5.5 years). Per FRAX, 3.02 patients were expected to develop a hip fracture without PT. Three PT patients actually developed fractures for a rate of 0.21 fractures per 100 person-years of follow-up. There was an observed-expected ratio of 0.99 (p-value not significant). Forty-eight patients (13%) reported new pain in the hip during follow-up; three required prescription analgesics., Conclusion: PT for prostate cancer did not increase hip-fractures in the first four years after PT compared to expected rates in untreated men.

Background: To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT., Material and Methods: Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78-82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively., Results: Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15-25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months., Conclusion: Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15-25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15-25).

Background: To review treatment toxicity for patients with pancreatic and ampullary cancer treated with proton therapy at our institution., Material and Methods: From March 2009 through April 2012, 22 patients were treated with proton therapy and concomitant capecitabine (1000 mg PO twice daily) for resected (n = 5); marginally resectable (n = 5); and unresectable/inoperable (n = 12) biopsy-proven pancreatic and ampullary adenocarcinoma. Two patients with unresectable disease were excluded from the analysis for reasons unrelated to treatment. Proton doses ranged from 50.40 cobalt gray equivalent (CGE) to 59.40 CGE., Results: Median follow-up for all patients was 11 (range 5-36) months. No patient demonstrated any grade 3 toxicity during treatment or during the follow-up period. Grade 2 gastrointestinal toxicities occurred in three patients, consisting of vomiting (n = 3); and diarrhea (n = 2). Median weight loss during treatment was 1.3 kg (1.75% of body weight). Chemotherapy was well-tolerated with a median 99% of the prescribed doses delivered. Percentage weight loss was reduced (p = 0.0390) and grade 2 gastrointestinal toxicity was eliminated (p = 0.0009) in patients treated with plans that avoided anterior and left lateral fields which were associated with reduced small bowel and gastric exposure., Discussion: Proton therapy may allow for significant sparing of the small bowel and stomach and is associated with a low rate of gastrointestinal toxicity. Although long-term follow-up will be needed to assess efficacy, we believe that the favorable toxicity profile associated with proton therapy may allow for radiotherapy dose escalation, chemotherapy intensification, and possibly increased acceptance of preoperative radiotherapy for patients with resectable or marginally resectable disease.

Large prostate size is associated with higher rates of genitourinary and gastrointestinal toxicities after definitive treatment for prostate cancer, and because of this many men will undergo cytoreduction with androgen deprivation therapy (ADT) before definitive therapy, which results in its own unique toxicities and worsens quality of life. This series investigates genitourinary and gastrointestinal toxicity in men with large prostates (> 60 cm(3)) undergoing definitive proton therapy (PT) for prostate cancer. Material and methods. From 2006 to 2010, 186 men with prostates ≥ 60 cm(3) were treated with definitive PT (median dose, 78 CGE) for low- (47%), intermediate- (37%) and high-risk (16%) prostate cancer. Median prostate size was 76 cm(3) (range, 60-143 cm(3)) and pretreatment IPSS was > 15 in 27%. At baseline, 51% were managed for obstructive symptoms with transurethral resection of the prostate (TURP) (9.7%) or medical management with α blockers (32%), 5 α-reductase inhibitors (15%), and/or saw palmetto (11%). Fourteen men received ADT for cytoreduction. Results. Median follow-up was two years. Grade 3 genitourinary toxicities occurred in 14 men, including temporary catheterization (n = 7), TURP (n = 6), and balloon dilation for urethral stricture (n = 1). Multivariate analysis demonstrated pretreatment medical management (p = 0.0065) and pretreatment TURP (p = 0.0002) were significantly associated with grade 3 genitourinary toxicity. One man experienced grade 3 gastrointestinal toxicity and 15 men had grade 2 gastrointestinal toxicities. On multivariate analysis, dose > 78 CGE was associated with increased grade 2 + gastrointestinal toxicity (p = 0.0142). Conclusion. Definitive management of men with large prostates without ADT was associated with low rates of genitourinary and gastrointestinal toxicity.

Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT)., Material and Methods: Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans., Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points., Conclusion: In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

Background: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy., Material and Methods: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs., Results: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant., Conclusion: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.