High-dose Proton Beam Research Articles

Long-term survival after treatment of glioblastoma multiforme with hyperfractionated concomitant boost proton beam therapy

PurposeAlthough conventional x-ray therapy of 60 Gy in 30 fractions is generally used in our institute as well as others, the prognosis of patients with glioblastoma multiforme (GBM) is poor. The purpose of this study was to evaluate the characteristics of long-term GBM survivors after postoperative hyperfractionated concomitant boost x-ray radiation therapy and proton beam therapy. Methods and materialsTwenty-three of 81 GBM patients who met the eligible criteria and consented to the protocol were treated with x-ray radiation therapy (50.4 Gy in 28 fractions in T2-high areas) and proton beam therapy (46.2 GyE in 28 fractions in gadolinium-enhanced volumes >6 hours after x-ray radiation therapy) concurrent with nimustine hydrochloride or temozolomide. ResultsTreatment was completed in all patients within 38-50 days (median, 43 days). Six currently living patients (median follow-up period, 70.9 months) developed radiation necrosis without tumor recurrence. Of these, 5 underwent necrotomy and 2 received bevacizumab after necrotomy. Compared with the pretreatment status, the Karnofsky performance scale (KPS) for the 6 survivors decreased by 10%-30% at the last follow-up. However, radiation necrosis had been well controlled and 5 of 6 patients maintained a stable KPS without hospital care. ConclusionsThe results suggest that high-dose proton beam therapy could control GBM pathogenesis if the treatment area completely covers tumor infiltration. Although radiation necrosis was inevitable, the remaining brain volume was fairly well preserved in the long-term survivors.

Outcomes and Prognostic Factors for Recurrence After High-Dose Proton Beam Therapy for Centrally and Peripherally Located Stage I Non–Small-Cell Lung Cancer

IntroductionThis study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. Patients and MethodsSeventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. ResultsThe median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). ConclusionRadiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted.

Proton Beam Therapy for Inoperable Recurrence of Bronchial High-grade Mucoepidermoid Carcinoma

We report the case of a 17-year-old patient who received four courses of proton beam therapy for inoperable recurrent high-grade bronchial mucoepidermoid carcinoma of the chest wall and lymph nodes. The equivalent doses in conventional fractionation of 79.2-80.6 Gy were applied to the tumor from the first to third courses of proton beam therapy; the hemi-chest wall was also irradiated prophylactically in the third course. The irradiated tumor recurred marginally and liver metastasis developed, but tumor size within the irradiated field was suppressed. Proton beam therapy was also applied to the marginally recurrent tumor in the fourth course. The patient died of cancer about 5 years after the first course of proton beam therapy-about 9 years after the initial diagnosis and surgery. Repeated irradiation of the mediastinum and chest wall with photon radiotherapy is often limited by side-effects in the heart, esophagus and spinal cord. However, no severe late complications in critical organs were detected in this case. Only a Grade 2 skin reaction and lymphatic edema were observed. Therefore, high-dose proton beam therapy may be an option as a salvage therapy with less toxicity to normal tissues compared with photon radiotherapy and provide an alternative to repeated surgery.

The safety and efficacy of high‐dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial

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. 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. 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. 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. © 2011 American Cancer Society.

High-dose Proton Beam Therapy and Carbon-ion Radiotherapy for Stage I Non–small-cell Lung Cancer

High-dose Proton Beam Therapy and Carbon-ion Radiotherapy for Stage I Non–small-cell Lung Cancer

Hypofractionated High-Dose Proton Beam Therapy for Stage I Non–Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade > or =3 was observed. Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

Proton Beam Radiation Therapy for Skull Base Adenoid Cystic Carcinoma

To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. Retrospective analysis. Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. Locoregional control and disease-free survival and overall survival rates. Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P = .02) and involvement of sphenoid sinus and clivus (P = .01). High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors.

High-dose proton beam therapy for Stage I non–small-cell lung cancer

To evaluate retrospectively the safety and efficacy of high-dose proton beam therapy (PBT) for Stage I non-small-cell lung cancer (NSCLC). Between 1999 and 2003, 37 patients were treated in our institution. The indications for PBT were pathologically proven NSCLC, clinical Stage I, tumor size < or =5 cm, medically inoperable or refusal of surgery, and written informed consent. A total dose of 70-94 Gy(E) was delivered in 20 fractions (3.5-4.9 Gy(E) per fraction). Patient characteristics (number of patients) were as follows: Stage IA/IB, 17 of 20; medically inoperable/refusal of surgery, 23/14; total dose 70/80/88/94 Gy(E), 3/17/16/1. With a median follow-up period of 24 months, the 2-year local progression-free and overall survival rates were 80% and 84%, respectively. The 2-year locoregional relapse-free survival rates in Stage IA and Stage IB were 79% and 60%, respectively. No serious acute toxicity was observed. Late Grades 2 and 3 pulmonary toxicities were observed in 3 patients each. Of these 6 patients, 5 had Stage IB disease. Proton beam therapy is a promising treatment modality for Stage I NSCLC, though locoregional relapse and late pulmonary toxicities in Stage IB patients were substantial. Further investigation of PBT for Stage I NSCLC is warranted.

High-Dose proton beam radiotherapy of hepatocellular carcinoma: Preliminary results of a phase II trial

This phase II trial was undertaken to determine the efficacy and toxicity of proton beam radiotherapy for patients with locally unresectable hepatocellular carcinoma. Cirrhotic patients were eligible if they had a Child-Pugh score of 10 or less. Eligible patients included those with T 1 -T 3 hepatocellular carcinoma; selected T 4 patients also were eligible. Patients with lymph node or distant metastases were ineligible. Daily proton beam radiotherapy was directed to the liver tumor with an additional 1-2 cm margin. The total dose was 63 cobalt Gray equivalents, administered in 15 divided fractions over 3 weeks. Thirty-four patients have completed treatment and have been followed up for a minimum of 6 months, with a median follow-up period of 20 months. The mean age was 65 years, and average tumor size was 5.7 cm. Posttreatment toxicity included a small but significant decline in albumin levels and increased total bilirubin; 3 experienced duodenal or colonic bleeding when bowel was immediately adjacent to the treated tumor. Two-year actuarial data showed a 75% local tumor control rate and an overall survival rate of 55%. Of patients with an elevated pretreatment alpha-fetoprotein, 85% were found to have declining alpha-fetoprotein levels from a pretreatment mean of 1405 to 35 at 6 months after treatment. Six patients underwent liver transplantation between 6 and 16 months after completion of radiotherapy with 2 showing no evidence of residual carcinoma within the explanted liver. Overall the majority of patients responded to treatment, and the therapy was well tolerated.

Hypofractionated Proton Beam Radiotherapy for Stage I Lung Cancer

To determine the efficacy and toxicity of high-dose hypofractionated proton beam radiotherapy for patients with clinical stage I lung cancer. A prospective phase 2 clinical trial. Loma Linda University Medical Center. Subjects with clinical stage I non-small cell lung cancer who were medically inoperable or refused surgery. All patients were treated with proton beam radiotherapy. The target included the gross tumor volume as seen on CT scan, with additional margin to allow for respiratory motion. A multibeam treatment plan was generated. Delivered treatment was 51 cobalt Gray equivalent (CGE) in 10 fractions over 2 weeks to the initial 22 patients; the subsequent 46 patients received 60 CGE in 10 fractions over 2 weeks. Sixty-eight patients were analyzed for this report, with a median follow-up time of 30 months. No cases of symptomatic radiation pneumonitis or late esophageal or cardiac toxicity were seen. The 3-year local control and disease-specific survival rates were 74%, and 72%, respectively. There was significant improvement in local tumor control in T1 vs T2 tumors (87% vs 49%), with a trend toward improved survival. Cox regression analysis revealed that patients with higher performance status, female gender, and smaller tumor sizes had significantly improved survival. High-dose hypofractionated proton beam radiotherapy can be administered safely, with minimal toxicity, to patients with stage I lung cancer. Local tumor control appears to be improved when compared to historical results utilizing conventional radiotherapy, with a good expectation of disease-specific survival 3 years following treatment.

High-energy proton beam radiation therapy for gynecologic malignancies. Potential of proton beam as an alternative to brachytherapy

Fifteen patients with advanced gynecologic malignancies were treated with high-energy proton beam radiation therapy (RT) at the Particle Radiation Medical Science Center (PARMS), Tsukuba University, Japan, from 1983 to 1987. The potential of proton beam RT as an alternative to conventional brachytherapy was evaluated. Except for one local recurrence, 14 of 15 patients were locoregionally controlled for 15 to 57 months. Two-year local control rate and 2-year survival rate were 92.3% and 93.3%, respectively. Two cases of transient, radiation-induced proctitis (neither of which required surgical treatment) were the only complications despite a target dose that exceeded 8000 cGy in most cases. The results suggest that sharply localized, high-dose proton beam RT can produce an antitumor effect equivalent to that of conventional brachytherapy.