Current status of intensity-modulated radiation therapy for prostate cancer: History, clinical results and future directions.

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity-modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity-modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity-modulated radiation therapy is image-guided radiation therapy. The clinical benefit for prostate image-guided radiation therapy has been assessed by comparing the outcomes of patients with either the image-guided radiation therapy or non-image-guided radiation therapy technique. These studies have shown that image-guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta-analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity-modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity-modulated radiation therapy, new techniques for intensity-modulated radiation therapy, hypofractionation and future directions for prostate cancer.

Phase II study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.

PURPOSE: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m(2)/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. RESULTS: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. CONCLUSIONS: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

[Contribution to survival rate improvement].

For patients with locally advanced HNSCC, where the outcome with conventional radiotherapy is poor, meta-analysis and collective data showed a high level of evidence of loco-regional control improvement by altered fractionated radiotherapy, chemo-radiotherapy with a concomitant approach. For these patients, much evidence indicates overall survival may be improved by concomitant chemo-radiotherapy or hyper-fractionated radiotherapy delivered with increased total dose. There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years. The benefit was significantly higher with hyper-fractionated radiotherapy (8% at 5 years)than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years). The effect was greater for the primary tumor than for nodal disease. The effect was also more pronounced in younger patients and in those with good performance status. Hyper-fractionation seemed to yield a more consistent advantage for survival than accelerated fractionated radiotherapy. However, accelerated radiotherapy might be associated with higher non-cancer-related death. Despite hundreds of clinical trials in patients with advanced disease, there is no absolute consensus about patient selection for altered fractionation regimens, type of chemo-radiotherapy association, and radiation of chemotherapy dose schedule. We have to evaluate whether the benefit of hyper-fractionated radiotherapy versus standard radiotherapy persists when combined with concomitant chemotherapy and the benefit of IMRT compared with altered fractionation.

Current status of intensity-modulated radiation therapy (IMRT).

External-beam radiation therapy has been one of the treatment options for prostate cancer. The dose response has been observed for a dose range of 64.8-81 Gy. The problem of external-beam RT for prostate cancer is that as the dose increases, adverse effects also increase. Three-dimensional conformal radiation therapy (3D-CRT) has enabled us to treat patients with up to 72-76 Gy to the prostate, with a relatively acceptable risk of late rectal bleeding. Recently, intensity-modulated radiation therapy (IMRT) has been shown to deliver a higher dose to the target with acceptable low rates of rectal and bladder complications. The most important things to keep in mind when using an IMRT technique are that there is a significant trade-off between coverage of the target, avoidance of adjacent critical structures, and the inhomogeneity of the dose within the target. Lastly, even with IMRT, it should be kept in mind that a "perfect" plan that creates completely homogeneous coverage of the target volume and zero or small dose to the adjacent organs at risk is not always obtained. Participating in many treatment planning sessions and arranging the beams and beam weights create the best approach to the best IMRT plan.

Treatment and prognosis of squamous cell carcinoma of the external auditory canal and middle ear: a multi-institutional retrospective review of 87 patients.

PURPOSE: To examine the relative roles of surgery, radiotherapy, and chemotherapy in the management of patients with squamous cell carcinomas of the external auditory canal and middle ear. METHODS AND MATERIALS: The records of 87 patients with histologically confirmed squamous cell carcinoma who were treated between 1984 and 2005 were reviewed. Fifty-three patients (61%) were treated with surgery and radiotherapy (S + RT group) and the remaining 34 patients with radiotherapy alone (RT group). Chemotherapy was administered in 34 patients (39%). RESULTS: The 5-year actuarial overall and disease-free survival (DFS) rates for all patients were 55% and 54%, respectively. On univariate analysis, T stage (Stell's classification), treatment modality, and Karnofsky performance status had significant impact on DFS. On multivariate analysis, T stage and treatment modality were significant prognostic factors. Chemotherapy did not influence DFS. The 5-year DFS rate in T1, T2, and T3 patients was 83%, 45%, and 0 in the RT group (p < 0.0001) and 75%, 75%, and 46% in the S + RT group (p = 0.13), respectively. The 5-year DFS rate in patients with negative surgical margins, those with positive margins, and those with macroscopic residual disease was 83%, 55%, and 38%, respectively (p = 0.007). CONCLUSIONS: Radical radiotherapy is the treatment of choice for early-stage (T1) diseases, whereas surgery (negative surgical margins if possible) with radiotherapy is recommended as the standard care for advanced (T2-3) disease. Further clarification on the role of chemotherapy is necessary.

[3D-CRT and intensity modulated radiation therapy (IMRT)].

Three-dimensional conformal radiation therapy (3D-CRT) conforms a high dose region closer to the target volume than does 2D radiation therapy. IMRT is the advanced form of 3D-CRT. With IMRT technique, using multiple intensity modulated beams, one can deliver a high dose of radiation to the target and a low dose to the surrounding normal structures. IMRT planning provides improved tumor target coverage when compared to 3D-CRT treatment planning. There is significant sparing of critical structures and other normal tissues. IMRT also produces dose distributions capable of delivering different dose prescriptions to multiple targets, providing a new opportunity for differential dose painting to increase the dose selectively to specific image-defined regions. Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. The initial results of clinical studies demonstrate reduced xerostomia in head and neck cancer and also effectively reduced acute and late occurring toxicities, improving the QOL of patients treated for prostate cancer. According to these studies, IMRT will allow dose escalation, leading to better tumor control without normal tissue damage. On the other hand, there are some problems for IMRT in Japan: There are few medical physicists, which results in radiation technologists playing most clinical technological roles, including some dosimetrical and physical activities. Social recognition and economical and legal support for medical physicists should be established in providing better patient care services.