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.

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.

Approximately 20% of patients with subfoveal choroidal neovascularization qualify for laser photocoagulation, a treatment associated with both disease control and reduced visual acuity. No proved treatment exists for other patients. Single-fraction proton therapy was investigated as an alternative for two groups of patients: 21 patients received 8 GyE; 27 received 14 GyE. Follow-up by fluorescein angiography, visual acuity, contrast sensitivity, and reading speed were done (mean duration: 16 months). Actuarial lesion control at 21 months was 36% for 8-GyE patients and 89% for 14-GyE patients; 77% of patients with controlled lesions achieved improved/stable visual acuity, compared to 44% with uncontrolled lesions. Actuarial mean visual loss for proton-treated maculas was zero at 24 months. No treatment-related morbidity supervened, based on Radiation Therapy Oncology Group criteria. Proton therapy of 14 GyE in one fraction appears to be more effective in controlling neovascular macular degeneration than 8 GyE in one fraction, for both laser-ineligible and -eligible patients.

It appears that patients treated with conformal protons have 5-year biochemical disease-free survival rates comparable to those who undergo radical prostatectomy, and display no significant toxicity. A Phase III randomized dose-escalation trial is underway to define the optimum radiation dose for early-stage prostate cancer.

PURPOSE:To analyze control, survival, and complication rates of conformal proton radiation for recurrent nasopharyngeal carcinoma.MATERIALS AND METHODS:Sixteen patients with nasopharyngeal carcinoma initially treated with 50.0-88.2 Gy photons were re-treated with protons to additional doses of 59.4-70.2 CGE. Local-regional control and survival were correlated with extent of relapse, recurrence versus persistence, and prescribed dose and were subjected to dose-volume histogram analysis. Mean follow-up was 23.7 months (range, 4-47 months).RESULTS:Twenty-four-month actuarial overall and local-regional progression-free survival rates were both 50%. The 24-month actuarial overall survival rates for patients with "optimal" dose-volume histogram coverage versus "suboptimal" coverage were 83% and 17%, respectively (P = .006). Doses to critical structures were low (0-22.0 Gy); no central nervous system side effects supervened.CONCLUSION:Adequate tumor coverage, as evaluated by using dose-volume histogram analysis, was found to be the most important variable influencing local-regional control and survival. No central nervous system complications were observed; increases in the dose to adjacent critical structures are being evaluated.

Objectives. To assess the effect of proton radiation on clinical and biochemical outcomes for early prostate cancer.Methods. Three hundred nineteen patients with T1-T2b prostate cancer and initial prostate-specific antigen (PSA) levels 15.0 ng/mL or less received conformal radiation doses of 74 to 75 cobalt gray equivalent with protons alone or combined with photons. No patient had pre- or post-treatment hormonal therapy until disease progression was documented. Patients were evaluated for biochemical disease-free survival, PSA nadir, and toxicity; the mean and median follow-up period was 43 months.Results. Overall 5-year clinical and biochemical disease-free survival rates were 97% and 88%, respectively. Initial PSA level, stage, and post-treatment PSA nadir were independent prognostic variables for biochemical disease-free survival: a PSA nadir 0.5 ng/mL or less was associated with a 5-year biochemical disease-free survival rate of 98%, versus 88% and 42% for nadirs 0.51 to 1.0 and greater than 1.0 ng/mL, respectively. No severe treatment-related morbidity was seen.Conclusions. It appears that patients treated with conformal protons have 5-year biochemical disease-free survival rates comparable to those who undergo radical prostatectomy, and display no significant toxicity. A Phase III randomized dose-escalation trial is underway to define the optimum radiation dose for early-stage prostate cancer. UROLOGY 53: 978-984, 1999. (C) 1999, Elsevier Science Inc. All rights reserved.

BACKGROUND:The role and optimum dose of radiation to eradicate prostate cancer continues to be evaluated. Protons offer an opportunity to increase the radiation dose to the prostate while minimizing treatment toxicity. METHODS:Six hundred forty-three patients with localized prostate cancer were treated with protons, with or without photons. Treatments were planned with a 3D planning system; patients received 74-75 CGE (Cobalt Gray Equivalent) at 1.8-2.0 CGE per fraction. Patients were evaluated for response to therapy and treatment-related toxicity. RESULTS:The overall clinical disease-free survival rate was 89% at 5 years. When post-treatment prostate-specific antigen (PSA) was used as an endpoint for disease control, the 4.5-year disease-free survival rate was 100% for patients with an initial PSA of < 4.0 ng/ml, and 89%, 72%, and 53% for patients with initial PSA levels of 4.1-10.0, 10.1-20.0, and > 20.0, respectively. Patients in whom the post-treatment PSA nadir was below 0.5 ng/ml did significantly better than those whose nadir values were between 0.51-1.0 or > 1.0 ng/ml: the corresponding 5-year disease-free survival rates were 91%, 79%, and 40%, respectively. Minimal radiation proctitis was seen in 21% of patients; toxicity of greater severity was seen in less than 1%. CONCLUSION:Proton therapy to 74-75 CGE produced minimal treatment-related toxicity and excellent PSA normalization and disease-free survival in patients with low initial PSA levels. A prospective randomized dose-escalation trial is now underway to help define the optimum dose of radiation for patients with early stage prostate cancer.

Background: Single-dose-fraction conformal proton beam and multiple-fraction X ray dose schedules have been used to treat subfoveal neovascular membranes. All schedules successfully controlled membrane progression, stabilized vision in most patients, and increased visual acuity in some. Conformal protons also decreased the radiation dose to healthy tissues outside the designated volume (16 mm in diameter). It appears that radiation therapy could be useful and cost-effective, but neither the optimal time-dose schedule single or multiple dose fractions nor the type of radiation proton conformal beam or x-ray therapy are defined.Methods: By means of an extensive literature survey, we reviewed the rationale for using radiation to treat subfoveal neovascularization, examined a paradigm of radiation interaction with tissue, reviewed the histopathology of neovascular membranes, and documented the role of growth factors in the pathophysiology of the disease. Accepting that the eye is an extracranial brain extension, and that its microvasculature has properties similar to brain microvessels, we reviewed the radiobiologic response of brain microvessels. We also revisited the controversy concerning the efficacy of single-dose-fraction vs. multifraction schedules.Results: This paper outlines parameters within which radiation therapy's role might be defined, and proposes a clinical radiation-biology scoring program to evaluate radiation effects, based on the SOMA concept.Conclusion: A prospective, controlled clinical trial is feasible and is indicated to determine radiation therapy's role in managing the proliferative component of age-related macular degeneration. (C) 1998 Elsevier Science Inc.

PURPOSE:A study was developed to evaluate the use of combined photons and protons for the treatment of locally advanced carcinoma of the prostate. This report is a preliminary assessment of treatment-related morbidity and tumor response. METHODS AND MATERIALS:One hundred and six patients in stages T2b (B2), T2c (B2), and T3 (C) were treated with 45 Gy photon-beam irradiation to the pelvis and an additional 30 Cobalt Gray Equivalent (CGE) to the prostate with 250-MeV protons, yielding a total prostate dose of 75 CGE in 40 fractions. Median follow-up time was 20.2 months (range: 10-30 months). Toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) grading system; local control was evaluated by serial digital rectal examination (DRE) and prostate specific antigen (PSA) measurements. RESULTS:Morbidity evaluation was available on 104 patients. The actuarial 2-year rate of Grade 1 or 2 late morbidity was 12% (8% rectal, 4% urinary). No patients demonstrated Grade 3 or 4 late morbidity. Treatment response was evaluated on 100 patients with elevated pretreatment serum PSA levels. The actuarial 2-year rate of PSA normalization was 96%, 97%, and 63% for pretreatment PSAs of > 4-10, > 10-20, and > 20, respectively. The 13 patients with rising PSA demonstrated local recurrence (3 patients), distant metastasis (8 patients), or no evidence of disease except increasing PSA (2 patients). CONCLUSIONS:The low incidence of side effects, despite the tumor dose of 75 CGE, demonstrates that conformal protons can deliver higher doses of radiation to target tissues without increasing complications to surrounding normal tissues. The initial tumor response, as assessed by the high actuarial rate of normalization with pretreatment PSA < or = 20, and the low rate of recurrences within the treatment field (2.8%), are encouraging.