Fraction External Beam Radiotherapy Research Articles

23 Stereotactic Body Versus Conventional Fractionation External Beam Radiotherapy (EBRT) Boost for High-Risk Prostate Cancer (HR-PC); Early Results of PBS: A Phase II Randomized Trial (NCT03380806)

23 Stereotactic Body Versus Conventional Fractionation External Beam Radiotherapy (EBRT) Boost for High-Risk Prostate Cancer (HR-PC); Early Results of PBS: A Phase II Randomized Trial (NCT03380806)

Hypofractionated versus conventional fractionation external beam radiotherapy in intermediate and high risk localized prostate cancer

BackgroundProstate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics.ObjectiveTo compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC).MethodologyWe retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23.Results114 patients were selected according to the inclusion criteria. Mean age was 68 years (61–75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant).ConclusionHypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

73: Erectile Function After 60 GY in 20 Fractions External Beam Radiotherapy to the Prostate

73: Erectile Function After 60 GY in 20 Fractions External Beam Radiotherapy to the Prostate

Early health economic analysis of 1.5 T MRI-guided radiotherapy for localized prostate cancer: Decision analytic modelling

Background and purpose1.5 Tesla magnetic resonance imaging radiotherapy linear accelerator (MR-Linac) is gaining interest for treatment of localized prostate cancer. Clinical evidence is lacking and it therefore remains uncertain whether MR-Linac is cost-effective. An early health economic analysis was performed to calculate the necessary relative reduction in complications and the maximum price of MR-Linac (5 fractions) to be cost-effective compared to 5, 20 and 39 fractionation schedules of external beam radiotherapy (EBRT) and low-dose-rate (LDR) brachytherapy. Materials and methodsA state transition model was developed for men with localized prostate cancer. Complication rates such as grade ≥2 urinary, grade ≥2 bowel and sexual complications, and utilities were based on systematic literature searches. Costs were estimated from a Dutch healthcare perspective. Threshold analyses were performed to identify the thresholds of complications and costs for MR-Linac to be cost-effective, while holding other outcomes such as biochemical progression and mortality constant. One-way sensitivity analyses were performed to outline uncertainty outcomes. ResultsAt €6460 per patient, no reductions in complications were needed to consider MR-Linac cost-effective compared to EBRT 20 and 39 fractions. Compared to EBRT 5 fractions and LDR brachytherapy, MR-Linac was found to be cost-effective when complications are relatively reduced by 54% and 66% respectively. Results are highly sensitive to the utilities of urinary, bowel and sexual complications and the probability of biochemical progression. ConclusionsMR-Linac is found to be cost-effective compared to 20 and 39 fractions EBRT at baseline. For MR-Linac to become cost-effective over 5 fractions EBRT and LDR brachytherapy, it has to reduce complications substantially or be offered at lower costs.

Advances in Radiobiology of Stereotactic Ablative Radiotherapy.

Radiotherapy (RT) has been developed with remarkable technological advances in recent years. The accuracy of RT is dramatically improved and accordingly high dose radiation of the tumors could be precisely projected. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), are rapidly becoming the accepted practice in treating solid small sized tumors. Compared with the conventional fractionation external beam radiotherapy (EBRT), SABR with very high dose per fraction and hypo-fractionated irradiation yields convincing and satisfied therapeutic effects with low toxicity, since tumor cells could be directly ablated like radiofrequency ablation (RFA). The impressive clinical efficacy of SABR is greater than expected by the linear quadratic model and the conventional radiobiological principles, i.e., 4 Rs of radiobiology (reoxygenation, repair, redistribution, and repopulation), which may no longer be suitable for the explanation of SABR's ablation effects. Based on 4 Rs of radiobiology, 5 Rs of radiobiology emphasizes the intrinsic radiosensitivity of tumor cells, which may correlate with the responsiveness of SABR. Meanwhile, SABR induced the radiobiological alteration including vascular endothelial injury and the immune activation, which has been indicated by literature reported to play a crucial role in tumor control. However, a comprehensive review involving these advances in SABR is lacking. In this review, advances in radiobiology of SABR including the role of the 4 Rs of radiobiology and potential radiobiological factors for SABR will be comprehensively reviewed and discussed.

Prognostic Index for Localized Liver Radiation – Metastatic (PILLiR-M): Development and Analysis of a Clinical Prognostic Tool to Improve Patient Selection for Liver Directed Radiotherapy for Liver Metastases

Liver metastases are common and associated with a high mortality rate. With improved treatment planning and delivery techniques, external beam radiotherapy (EBRT) is increasingly utilized for treating liver metastases. Many of these patients, however, are unlikely to live long enough to reap the benefits. The aim of this study was to develop a prognostication tool to aid in patient selection for liver directed EBRT in patients with liver metastases. A prospectively collected liver radiotherapy database was used to identify patients who had been treated with EBRT to the liver with local control intent. Exclusion criteria: single fraction EBRT, primary HCC or cholangiocarcinoma, benign pathology, lost to follow-up < 4 months. Pre-treatment patient and tumor characteristics associated with early death (<4 months) were identified using univariate analysis. Variables found to be significant were entered into a multiple logistic regression model using forward selection to identify factors independently predicting early death. Three fold cross validation and bootstrapping using 500 random samples was performed. The PILLiR-M was created based on this model. Two hundred twelve patients who had received liver EBRT were identified. One hundred nine patients were excluded (single fraction EBRT n=17, HCC n=63, cholangiocarcinoma n=22, benign pathology n=1, follow-up <4 months n=6). One hundred three patients remained for analysis with a 4 month mortality rate of 27.2%. Ascites, elevated bilirubin, low serum albumin, Child-Pugh score, ECOG performance status, non-colorectal primary, presence of extrahepatic disease and previous liver directed therapy were found to be significant predictors for early death on univariate analysis and were included in the multiple logistic regression model. Using forward selection to maximize the area under the curve, non-colorectal primary, ECOG, presence of extrahepatic disease and serum albumin were found to best predict patients unlikely to live longer than 4 months. A prognostic index (PILLiR-M) was created with 1 point for each of the following: non-colorectal primary, presence of extrahepatic disease, ECOG ≥2 and serum albumin<35g/L (AUC 0.852). Four month mortality was 0%, 3.1%, 43.6%, 66.7%, and 100% for patients with 0 (n=16), 1 (n=32), 2 (n=39), 3 (n=9), and 4 (n=3) points, respectively. Non-colorectal primary, presence of extrahepatic disease, poor performance status and decreased serum albumin were found to be risk factors for mortality less than 4months in patients being considered for liver directed EBRT for metastatic disease. We successfully created the PILLiR-M to aid clinicians in determining which patients are unlikely to live long enough to benefit from liver EBRT. Future work includes validating the PILLiR-M with an independent dataset.

A randomized trial of conventional fraction versus hypofraction radiotherapy for bone metastases from hepatocellular carcinoma.

External beam radiotherapy (EBRT) has been reported to be effective in palliating painful bone metastases, but the optimal fractions and doses for treating bone metastases from hepatocelluar carcinoma (HCC) are not established. This study aimed to compare toxicity and efficacy for conventional fraction versus hypofraction schedules. From January 2009 through December 2014, 183 patients with HCC bone metastases were randomly assigned to conventional fraction EBRT (Group A) or hypofraction radiotherapy (Group B). Study outcomes were pain relief, response rate and duration, overall survival, and toxicity incidence. Median follow-up time was 9.3 months. Response times were 6.7 ± 3.3 fractions in Group A and 4.1 ± 1.2 fractions in Group B (p <0.001). Pain relief rates were 96.7% and 91.2% in Group A and B, respectively (p=0.116). Time to treatment failure for Group A was significantly longer than Group B (p=0.025). Median overall survival was similar between two groups (p=0.628). Toxicity incidence in both groups was minimal, with no significant differences observed.In conclusion, hypofractionated radiotherapy is safe for patients with HCC bone metastases and may achieve earlier pain relief compared to conventional radiotherapy. This protocol should be considered for patients with shorter predicted survival times.

Sparing the surgical area with stereotactic body radiotherapy for combined treatment of spinal metastases: a treatment planning study

Introduction: Decreasing the radiation dose in the surgical area is important to lower the risk of wound complications when surgery and radiotherapy are combined for the treatment of spinal metastases. The purpose of this study was to compare the radiation dose in the surgical area for spinal metastases between single fraction external beam radiotherapy (EBRT), single fraction stereotactic body radiotherapy (SBRT) and single fraction SBRT with active sparing (SBRT-AS) of the posterior surgical area.Methods: Radiotherapy treatment plans for EBRT, SBRT and SBRT-AS of the posterior surgical area were created for 13 patients with spinal metastases. A single fraction of 8Gy was prescribed to the spinal metastasis in the EBRT plan. For the SBRT treatment plans, a single fraction of 18Gy was prescribed to the metastasis and 8Gy to the rest of the vertebral body. For the SBRT plan with active sparing the dose in the designated surgical area was minimized without compromising the dose to the organs at risk.Results: The median dose in the surgical area was 2.6Gy (1.6–5.3Gy) in the SBRT plan with active sparing of the surgical area compared to a median dose of 3.7Gy (1.6–6.3Gy) in the SBRT plan without sparing and 6.5Gy (3.5–9.1Gy) in the EBRT plans (p < .001). The radiation doses to the spinal metastases and organs at risk were not significantly different between the SBRT plan with and without sparing the surgical area.Conclusions: The radiation dose to the surgical area is significantly decreased with the use of SBRT compared to EBRT. Active sparing of the surgical area further decreased the mean radiation dose in the surgical area without compromising the dose to the spinal metastasis and the organs at risk.

Standard fractionation external beam radiotherapy with and without intraoperative radiotherapy for locally recurrent rectal cancer: the role of local therapy in patients with a high competing risk of death from distant disease.

We sought to evaluate the effectiveness and safety of utilizing radiotherapy (RT) with standard fractionation, with or without intraoperative RT (IORT), to treat locally recurrent rectal cancer (LRRC). Retrospective review of 25 patients with LRRC treated with standard fractionation RT from 2005 to 2011. 15 patients (60%) had prior pelvic RT and 10 (40%) had synchronous metastases. The median equivalent dose in 2-Gy fractions was 30 and 49.6 Gy in patients with and without prior RT, respectively. 23 patients (92%) received concurrent chemotherapy and 16 (64%) underwent surgical resection. Eight patients (33.3%, four with and four without prior RT) received IORT. A competing risks model was developed to estimate the cumulative incidence of local failure with death treated as a competing event. Median follow-up was 36.9 months after the date of local recurrence. 3-year rates of overall survival (OS), local control (LC) and death with LC were 51.6%, 73.3% and 69.2%, respectively. On multivariable analysis, surgical resection was significantly predictive of improved OS (p < 0.05). If surgical resection were removed from the multivariable model, given the collinearity between IORT delivery and surgical resection, then IORT also became a significant predictor of OS (p < 0.05). Systemic disease at the time of local recurrence was not associated with either LC or OS. No patient had grade ≥3 acute or late toxicity. RT with standard fractionation is safe and effective in the treatment of patients with LRRC, even in patients with significant risk of systemic disease and/or history of prior RT. Advances in knowledge: The utility of RT with standard fractionation, generally with chemotherapy, in the treatment of LRRC is demonstrated. In this high-risk cohort of patients with a 40% incidence of synchronous metastatic disease, surgical resection of the recurrence was the major predictor of OS, though a benefit to IORT was also suggested. No patients had grade ≥3 acute or late toxicity, though 40% had undergone prior RT, underscoring the tolerability of standard fractionation RT in this setting.

Single Fraction External Beam Radiotherapy for Localised Prostate Cancer: a Planning Study

Single Fraction External Beam Radiotherapy for Localised Prostate Cancer: a Planning Study

Clinical comparison of brachytherapy versus hypofractionated external beam radiation versus standard fractionation external beam radiation for non-melanomatous skin cancers.

PurposeNon-melanomatous skin cancer (NMSC) is the single most common cancer in the US. Radiation therapy is an excellent treatment alternative to surgery. High-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) are commonly used radiation treatment modalities but little data is published comparing these modalities. We present our institution's experience and outcomes with these therapeutic options.Material and methodsFrom June 2005 to March 2013, 61 patients were treated with HDR brachytherapy (n = 9), hypofractionated EBRT (n = 30), or standard fractionation EBRT (n = 22) for NMSC. The primary outcome measure was local control at most remote follow-up and secondary outcome measures were overall survival, cosmetic outcome, and toxicity. Univariate analysis was performed to compare outcomes between treatment modalities. Kaplan-Meier analysis and log-rank test were used to compare overall survival.ResultsMedian follow-up was 30 months. The most common histologies were BCC (47%) and SCC (44%); mean patient age was 83.3 years. Local control was 81% and 2-year actuarial overall survival was 89%. There was no statistical difference in local control or overall survival between treatment modalities. There was no statistical difference in cosmetic outcome or toxicity between treatment modalities, although five of six “poor” cosmetic outcomes and the only grade 3 toxic events were found in the standard fractionation EBRT group.ConclusionsAll modalities investigated represent effective treatments for NMSC and have good cosmetic outcomes and acceptable toxicity profiles. The finding of higher grade toxicity and a greater portion of patients experiencing toxicity among standard fractionation therapy is counter to expectations. There was no statistical significance to the finding and it is not likely to be meaningful.

WITHDRAWN: A randomized trial of conventional fraction versus hypofraction radiotherapy for bone metastases from hepatocellular carcinoma

External beam radiotherapy (EBRT) has been reported to be effective in palliating painful bone metastases, but the optimal fractions and doses for treating bone metastases from hepatocelluar carcinoma (HCC) are not established. This study aimed to compare toxicity and efficacy for conventional fraction versus hypofraction schedules. From January 2009 through December 2014, 183 patients with HCC bone metastases were randomly assigned to conventional fraction EBRT (Group A) or hypofraction radiotherapy (Group B). Study outcomes were pain relief, response rate and duration, overall survival, and toxicity incidence. Median follow-up time was 9.3 months. Response times were 6.7 ± 3.3 fractions in Group A and 4.1 ± 1.2 fractions in Group B (p <0.001). Pain relief rates were 96.7% and 91.2% in Group A and B, respectively (p=0.116). Time to treatment failure for Group A was significantly longer than Group B (p=0.025). Median overall survival was similar between two groups (p=0.628). Toxicity incidence in both groups was minimal, with no significant differences observed. In conclusion, hypofractionated radiotherapy is safe for patients with HCC bone metastases and may achieve earlier pain relief compared to conventional radiotherapy. This protocol should be considered for patients with shorter predicted survival times.

Cost-effectiveness analysis of single fraction of stereotactic body radiotherapy compared to single fraction of external beam radiotherapy for palliation of vertebral bone metastases.

26 Background: Stereotactic body radiotherapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may confer better pain control. A Phase III clinical trial comparing SBRT with single fraction external beam radiotherapy (EBRT) is now ongoing. We performed a cost-effectiveness analysis to compare these strategies. Methods: A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost effectiveness of SBRT (16 or 18 Gy in 1 fraction) to 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, one-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000/QALY gained. Results: Base case pain relief after the treatment was assumed as 20% higher in SBRT. Treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552/QALY gained. In one-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain (range: $89,330 to $592,720/QALY gained); the utility of relieved pain post-treatment and median survival were also sensitive to variation. If median survival is ≥11 months (base case estimate: 9 months), SBRT cost &lt;$100,000/QALY gained. Probabilistic sensitivity analysis demonstrated that SBRT was favored in 30% of model iterations at a WTP threshold of $100,000/QALY gained. Conclusions: SBRT for palliation of vertebral bone metastases is not cost-effective compared to EBRT based upon the ICER analysis with the WTP of $100,000/QALY gained. However, if median survival is ≥11 months, SBRT is economically reasonable, suggesting that selective SBRT usage in patients with longer expected survival may be the most cost-effective approach.

Radiation therapy for primary and metastatic tumors of the liver

Hepatic tumors can be either primary disease (i.e., hepatocellular carcinoma) or a site of metastases from other solid malignancies. The primary therapy for all liver tumors is resection, but only a minority of patients present with resectable disease. Various nonsurgical ablative techniques have been investigated to cure or palliate unresectable hepatic tumors by improving locoregional control. The objective of this article is to review the radiotherapy options in managing primary or metastatic liver cancer. Two emerging radical radiotherapy options include stereotactic body radiation therapy (SBRT) and selective internal radiotherapy (SIRT). SBRT delivers ablative doses of radiation in a hypofractionated course and has been used in metastatic disease to the brain, spine, lung, and liver. The local tumor control for SBRT appears to exceed that of conventional fractionation external beam radiotherapy (EBRT). SIRT, also known as radioembolization, is the intraarterial delivery of microspheres impregnated with yttrium-90 (Y90) via the hepatic artery. The evidence is limited to cohort and comparative studies with historical controls; nonetheless, results appear to be promising. Both SBRT and SIRT to liver tumors may serve as a bridge to liver transplantation (LT) and as a treatment strategy for metastasis from colorectal cancer to achieve the effect of metastasectomy. Meanwhile, combining molecular-targeted agents with radiotherapy is an emerging strategy to enhance the therapeutic ratio. SBRT and/or SIRT are promising local ablative modalities for management of unresectable liver tumors. Further well-designed trials are warranted to establish the proper combination of different therapeutic modalities.

Treatment outcome in patients with vulvar cancer: comparison of concurrent radiotherapy to postoperative radiotherapy

PurposeTo evaluate outcome and morbidity in patients with vulvar cancer treated with radiotherapy, concurrent chemoradiotherapy or postoperative radiotherapy.Materials and MethodsThe records of 24 patients treated with radiotherapy for vulvar cancer between July 1993 and September 2009 were retrospectively reviewed. All patients received once daily 1.8-4 Gy fractions external beam radiotherapy to median 51.2 Gy (range, 19.8 to 81.6 Gy) on pelvis and inguinal nodes. Seven patients were treated with primary concurrent chemoradiotherapy, one patient was treated with primary radiotherapy alone, four patients received palliative radiotherapy, and twelve patients were treated with postoperative radiotherapy.ResultsTwenty patients were eligible for response evaluation. Response rate was 55% (11/20). The 5-year disease free survival was 42.2% and 5-year overall survival was 46.2%, respectively. Fifty percent (12/24) experienced with acute skin complications of grade III or more during radiotherapy. Late complications were found in 8 patients. 50% (6/12) of patients treated with lymph node dissection experienced severe late complications. One patient died of sepsis from lymphedema. However, only 16.6% (2/12) of patients treated with primary radiotherapy developed late complications.ConclusionOutcome of patients with vulvar cancer treated with radiotherapy showed relatively good local control and low recurrence. Severe late toxicities remained higher in patients treated with both node dissection and radiotherapy.

Methodology for biologically-based treatment planning for combined low-dose-rate (permanent implant) and high-dose-rate (fractionated) treatment of prostate cancer

The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning. Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (alpha, beta, potential doubling time for prostate cancer cells [T(pot)], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens. The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning. We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.

Improvement in relapse-free survival throughout the PSA era in patients with localized prostate cancer treated with definitive radiotherapy: Year of treatment an independent predictor of outcome

Purpose In patients treated with radical prostatectomy in the prostate-specific antigen (PSA) era, it has been demonstrated that the year of treatment in the PSA era is associated with better pathologic parameters and outcomes, independently of other well-recognized parameters such as clinical stage, pretreatment PSA level, or Gleason score. The purpose of the present study was to study a similar phenomenon with definitive radiotherapy (RT). Methods and materials The inclusion criteria were as follows: clinical Stage T1–T2, available pretreatment PSA level and biopsy Gleason score, treatment delivered before January 2000 with standard fractionation external beam radiotherapy to at least 70 Gy, no adjuvant androgen deprivation (AD), all neoadjuvant AD limited to ≤6 months, and a minimum of 3 years of PSA follow-up. A total of 467 cases treated between January 1986 and December 1999 were included. Short-course AD in the adjuvant or neoadjuvant setting for ≤6 months was given in 124 cases (27%). The median radiation dose was 74 Gy (range 70.0–78.0). A conformal technique was used in 293 cases (63%). The median follow-up was 62 months (range 37–189). A total of 4931 follow-up PSA levels were available for analysis (average 11 per patient). A multivariate analysis for factors affecting biochemical relapse-free survival rates using the proportional hazards model was performed for all cases using the following variables: age (continuous variable), race (black vs. white), clinical T stage (T1–T2a vs. T2b–T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), use of AD (yes vs. no), radiation dose (continuous variable), and year of treatment (continuous variable: 1986–1999). Results The projected 8-year biochemical relapse-free survival rate was 74%. The projected 5-year biochemical relapse-free survival rate for the 143 patients treated in the 1986–1995 period was 58% vs. 82% for the 324 patients treated in the 1996–1999 period ( p <0.001). The difference was attributable to a multitude of factors (earlier stage cancer, higher radiation doses, shorter follow-up). To study the confounding effects of these factors on the year of therapy, a multivariate analysis was performed. The multivariate analysis revealed the initial PSA level ( p <0.001), Gleason score ( p <0.001), RT dose ( p = 0.045), and year of treatment ( p <0.001) to be independent predictors of outcome. Age ( p = 0.41), race ( p = 0.14), T stage ( p = 0.10), and use of AD ( p = 0.58) were not. Conclusion When controlling for tumor, treatment, and follow-up parameters, the year in which RT was performed was still an independent predictor of outcome, consistent with observations made for radical prostatectomy patients. This indicates a more favorable presentation of localized prostate in current years probably related to a combination of factors such as screening and increased patient awareness leading to earlier diagnosis. Outcome predictions should be based on contemporaneous series.

The SORTIE trial: palliation with stent (S) or radiation therapy (RT) 20 Gy in 5 fractions intervention for esophageal cancer dysphagia: a multicenter trial for T-4, M+/- squamous or adenocarcinoma of the esophagus. a randomized trial relief from dysphagia and quality of life (QOL) analysis

Purpose/Objective: SORTIE, multicenter, randomized trial tests Ultraflex® ∗stent versus high fraction external beam radiotherapy for palliation of dysphagia for patients with locally advanced, non-resectable esophageal cancer. A secondary goal compared Quality of Life.

Safety and Efficacy of Concurrent Cisplatin and Radiotherapy in Inoperable or Metastatic Squamous Cell Esophageal Cancer

Between August 1996 and May 1999, 50 consecutive, previously untreated patients with carcinoma of the esophagus and who were inoperable for various reasons were treated with weekly doses of cisplatin (35 mg/m 2 , maximum 7 cycles) concurrent with either 66 Gy/33 fractions external beam radiotherapy (EBRT) (n=42) or 50 Gy/25 fractions EBRT and two insertions of high-dose-rate intraluminal radiotherapy of 6 Gy each, spaced a week apart (n=8). Eighty-two percent (41/50) of the patients received the stipulated radiotherapy (RT) dose. Seventy-six percent (38/50) received at least 6 cycles of chemotherapy. Neutropenia in the form of WHO grade II-12% (6/50) and grade III-2% (1/50) was observed. Grade III emesis was seen in 8% (4/50). Improvement in the swallowing status was seen in 84% (42/50). Median duration of dysphagia relief was 6 months. The median overall survival was 9 months with 17% estimated to be alive after 4 years. Combined treatment with single agent cisplatin and definitive radiotherapy for inoperable cancer of the esophagus is safe, well tolerated and reasonably efficacious.

Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts

Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60Co teletherapy unit. Control groups received saline, unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Subcutaneous CEA-expressing LS174T human colon carcinoma tumors were measured over time. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 μCi, 175 μ.Ci, and 225 μCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 μCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 μCi and 175 μCi resulted in growth delays of 9 and 19 days, respectively. The 120 μCi dose delivered an estimated absorbed tumor dose of I080 cGy to WiDr tumors. In summary, for the radiosensitive LS 174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity.