A prospective study of health-related quality of life outcomes among men treated for intermediate- and high-risk prostate cancer: the impact of primary and secondary therapies.

INTRODUCTION: To assess the impact of primary and secondary therapies for high- and intermediate-risk prostate cancer on health-related quality of life (HRQoL). MATERIALS AND METHODS: A prospective study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL from baseline (pre-treatment) to 5 years post-diagnosis were examined for patients with high- and intermediate-risk prostate cancer, treated by radical prostatectomy (RP) or external beam radiation therapy (EBRT). Change in HRQoL was modeled using linear regression models fit with generalized estimating equations. The probability of maintaining HRQoL was compared between patients receiving RP only versus RP with secondary treatment. RESULTS: Of 445 men with high- and intermediate-risk prostate cancer, 228 underwent RP and 143 had EBRT± androgen deprivation therapy (ADT). Fifty received secondary therapy (EBRT and/or ADT or chemotherapy) after RP. RP patients showed a greater decline over time in sexual function and bother and urinary function compared to EBRT±ADT patients. Patients who had secondary therapy after RP were less likely to maintain their HRQoL compared to those who had RP alone. These differences were most pronounced for sexual and hormonal function. CONCLUSIONS: Prostate cancer patients experience significant declines in HRQoL after primary therapy. Additional secondary therapy after RP, in the form of EBRT and/or ADT, appears to be responsible for further deterioration in HRQoL outcomes.

Limb-sparing management with surgical resection, external-beam and intraoperative electron-beam radiation therapy boost for patients with primary soft tissue sarcoma of the extremity: a multicentric pooled analysis of long-term outcomes.

BACKGROUND OR PURPOSE: A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS). METHODS AND MATERIALS: Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study. RESULTS: From 1986-2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316 years), 5-year local control (LC) was 82 %. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p < 0.001). With regard to IOERT in-field control, incomplete resection (HR 4.88, p = 0.001) and higher IOERT dose (≥ 12.5 Gy; HR 0.32, p = 0.02) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that an IOERT dose ≥ 12.5 Gy increases the rate of IOERT in-field control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo- and adjuvant systemic therapy.

Radiation therapy of esophageal cancer.

Radiation therapy has been used extensively in the management of patients with cancer of the esophagus. It has demonstrated an ability to cure a small minority of patients. Cure is likely to be limited to patients who have lesions less than 5 cm in length and have minimal, if any, involvement of lymph nodes. Esophagectomy is likely to cure a similar, small percentage of patients with the same presentation of minimal disease but has a substantial acute postoperative mortality rate and greater morbidity than irradiation. Combining surgery and either preoperative or postoperative irradiation may cure a small percentage of patients beyond the number cured with either modality alone. Radiation has demonstrated benefit as an adjuvant to surgery following the resection of minimal disease. However, radiation alone has never been compared directly with surgery for the highly select, minimal lesions managed by surgery. Radiation provides good palliation of dysphagia in the majority of patients, and roughly one third may have adequate swallowing for the duration of their illness when "radical" doses have been employed. Surgical bypass procedures have greater acute morbidity but appear to provide more reliable, prolonged palliation of dysphagia. They constitute the best approach for patients with persistent or recurrent dysphagia following esophageal irradiation. Several approaches to improving the efficacy of irradiation are currently under investigation. Fewer large fractions appear to be equivalent to conventionally fractionated radiotherapy in terms of local control and survival but produce more prompt palliation and shorten courses of palliative therapy. Multiple-daily-fractionation schedules and hyperfractionation have theoretical appeal and clear basis for investigation from the early suggestions of improved response rates in advanced squamous-cell cancer of the head and neck. Hypoxic-cell radiosensitizers, neutron-beam, and helium-ion therapy results have not been overly encouraging in esophageal cancer, thus far. However, the new generation of particle beams and the new radiation-sensitizer drugs require further evaluation. Better means of dealing with the high incidence of disseminated disease are clearly needed. It is clear that combined-modality approaches using both local and systemic therapy will ultimately be desirable in esophageal-cancer treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Tumor basal area and metastatic death after proton beam irradiation for choroidal melanoma.

BACKGROUND: Tumor dimension is an established prognostic factor for metastasis-related death after radiotherapy for uveal melanoma. OBJECTIVE: To compare various methods of modeling the relationship between tumor dimension and metastatic death. PATIENTS AND METHODS: The analyses were based on a consecutive series of 1204 patients with primary choroidal melanoma treated with proton beam irradiation (70 cobalt-gray equivalent in 5 fractions) at the Harvard Cyclotron Laboratory, Boston, Mass, between January 1985 and December 1998. Largest basal diameter and largest perpendicular basal diameter were recorded at the time of surgical placement of tantalum rings used for tumor localization during proton treatment. The height of the tumor and the axial diameter of the eye were measured by ultrasonography prior to treatment. Using proportional hazards regression, we compared the prognostic influence of different indices of tumor size with estimated risk ratios and death rates according to tumor basal area and largest basal diameter. All estimates were adjusted for other established prognostic factors. RESULTS: Patients were followed up annually through June 30, 2000. Of the 1204 patients analyzed, 193 died of melanoma metastasis. The median follow-up among survivors was 7.9 years. The 5- and 10-year metastatic death rates were 12.8% and 20.7%, respectively. Among various approaches for modeling tumor dimension, the logarithm of tumor basal area had the highest log-likelihood and performed better than other approaches in 85% of the simulations. Based on this model, the covariate-adjusted rate ratio for any doubling in tumor basal area was 1.92 (95% confidence interval, 1.62-2.28). CONCLUSION: Tumor basal area is a better prognostic indicator than largest tumor diameter and tumor volume in the prediction of metastatic death after proton beam irradiation for uveal melanoma.

Survival after proton-beam irradiation of uveal melanomas.

PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood.

BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood. METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy. The risks of hearing loss were calculated on cochlear dose for each treatment. Three types of health-related quality of life (HRQOL) of EQ-5D, HUI3 and SF-6D were used for estimation of quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for proton beam therapy compared with X-ray radiotherapy was calculated for each HRQOL. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The ICER for EQ-5D, HUI3 and SF-6D were $21 716/QALY, $11 773/QALY, and $20 150/QALY, respectively. One-way sensitivity analyses found that the results were sensitive to discount rate, the risk of hearing loss after proton therapy, and costs of proton irradiation. Cost-effectiveness acceptability curve analysis revealed a 99% probability of proton therapy being cost effective at a societal willingness-to-pay value. CONCLUSIONS: Proton beam therapy with cochlear dose reduction improves health outcomes at a cost that is within the acceptable cost-effectiveness range from the payer's standpoint.

The role of elective neck dissection in patients undergoing salvage laryngectomy.

BACKGROUND: We investigated the risk of neck metastases in patients undergoing salvage total laryngectomy in association with previous radiotherapy. METHODS: The medical records of 42 patients (51 neck specimens) with clinical N0 classification who underwent salvage total laryngectomy in 2 cancer centers were reviewed. Fourteen patients had previous radiotherapy to the central neck and 28 to the central and lateral neck. RESULTS: Staging before salvage total laryngectomy was similar in both groups. The risk of neck metastases in the central and central/lateral radiation groups was 12% and 18%, respectively (p = .69). Subgroup analysis revealed that 4 of 8 patients initially presenting with clinically N+ had neck metastases before surgery, versus 2 of 26 for those with clinically N0 (p = .015; relative risk [RR] = 4.67). The risk or metastases in the contralateral neck was 0 of 9. CONCLUSION: The risk of neck metastases in patients who undergo either central or central/lateral neck radiotherapy is similar. Elective neck dissection seems appropriate in patients undergoing SLR.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer.

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Bone sarcoma: treatment by irradiation, amputation, or a combination of the two.

A retrospective survey of all cases of osteosarcoma of the femur and tibia treated at the major centres in the United Kingdom during 1952-9 was carried out in an attempt to assess the respective value of treatment by surgery and radiotherapy and the feasibility of a larger prospective study. Of the 192 patients available for the comparison, those treated by radiotherapy alone did least well. A combination of the two treatments-radiotherapy followed by amputation-produced better results, in terms of survival, than amputation alone; however, the comparatively small numbers involved and the inadequacy of information about the factors dictating the choice of treatment make firm conclusions impossible. A controlled clinical trial on a larger scale might provide answers to the outstanding questions.

[Radiation therapy of intracranial germ cell tumors].

The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1% for germinomas and 38.1% for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis irradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.