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Chemoradiation therapy (CRT) is a standard treatment for various cancers, including squamous cell carcinoma of the head and neck, non-small cell lung cancer, and rectal cancer. Regarding the sequence of radiation therapy and chemotherapy, concurrent CRT has yielded superior clinical results. However, CRT causes an increase in acute and late toxicities, despite improving local control and survival rates. The introduction of high-precision radiation therapy such as intensity modulated radiation therapy and newly developed chemotherapeutic drugs or molecularly targeted agents may further improve clinical outcomes while keeping treatment-related toxicities at an acceptable level.

Concurrent chemoradiotherapy is the gold standard of care for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). Proton beam therapy (PBT) can reduce the doses for normal lungs because of the penetration energy peak. PBT with concurrent chemotherapy for locally advanced NSCLC has been introduced in National Cancer Center Hospital East since December 2011. Thirty-three patients received PBT with concurrent chemotherapy for 2 years. Nine patients received PBT because they were not suited for radical photon radiotherapy due to excessive V20 Gy or doses to the spinal cord. Thirty-one patients received cisplatin plus vinorelbine; the remaining 2 patients received weekly carboplatin and paclitaxel, or daily carboplatin. All but 1 patient received the planned PBT dose (60 GyE[n=15]or 66 GyE[n=17]). PBT was terminated in 1 patient after the delivery of 36 GyE because of the development of liver metastases. PBT was suspended in 8 patients because of the development of febrile neutropenia (n=6) and esophagitis (n=3). Two patients (6%) experienced grade 3 esophagitis. The grade 2 toxicities included esophagitis (n=12), dermatitis (n=10), and pneumonitis (n=2). Grade 3 pneumonitis was not observed. Disease progression was observed in 17 patients. In-field recurrence was observed in 4 patients, distant metastases were observed in 14 patients, and both types of recurrence were observed in 1 patient. With a median follow-up time of 6.0 months for censored cases, the median progression-free survival time was 9.9 months (95% confidence interval: 5.2-14.6). Our retrospective study demonstrates that PBT with concurrent chemotherapy is feasible, although the possible complications, such as radiation esophagitis and dermatitis, might be rather severe compared with standard chemoradiotherapy using photons.

Molecular target-based drugs combined with radiation therapy have been expected as promising approach in cancer treatment, and clinical trials using combined modalities have been performed to evaluate the feasibility and efficacy of this approach. In order to obtain maximum radiotherapeutic gain, a detailed understanding of the mechanism underlying the interaction between radiation and molecular target-based drugs is indispensable. Among molecular target-based drugs, inhibitors targeting EGFR and its signal transduction pathways have been vigorously investigated, and mechanisms regarding the radiosensitizing effect have been getting clear. In addition, the results of randomized clinical trials demonstrated that radiation therapy combined with cetuximab resulted in improvement of overall and disease-specific survival rate compared with radiation therapy in locally advanced head and neck cancer. In this review, established and potential molecular targets for potentiation of radiation-induced cell killing are summarized, especially focusing on EGFR and its signal transduction pathways; also, clinical trials of combined radiation therapy plus molecular target-based drug therapy are summarized.

Hyperfractionated radiation therapy has been established as a radical treatment for head and neck cancer. The radiobiological hypothesis for hyperfractionation has been derived from that of fractionated radiation therapy, and it enables us to improve therapeutic gain by delivering a small fraction dose at optimal interfraction intervals, i. e., 1) reduction of normal tissue complication while maintaining tumor control probability, 2)improvement of tumor control probability while maintaining the incidence of normal tissue complications within an acceptable level. The understanding of radiobiological hypothesis or theory is important in clinical application of hyperfractionation.

HDAC inhibitor has been focused as a molecular target agent for cancer treatment because of unique pharmacological activity. HDAC inhibitors induce cancer cells to undergo growth arrest, differentiation or induce apoptosis in vitro, and also inhibit the growth of transplanted tumors in vivo, but the enhancement effect or interaction of HDAC inhibitors with other chemotherapeutic agents or radiation has not yet been fully investigated. Biade et al examined the effect of trichostatin A (TSA), and reported synergistic enhancement of radiosensitivity in human cancer cell lines. We also confirmed the similar results in vitro by using TSA in combination with radiation. The main purpose of this paper is to review the current status of HDAC inhibitor in clinical use, and evaluate the potential possibility for the potentiation of radiation-induced cell killing including the results of our research.

The incidence of prostate cancer has been increasing gradually in Japan, and the optimal use of radiation therapy is important to improve therapeutic outcome and quality of life. The clinical trials conducted by RTOG and EORTC have made it clear that dose escalation results in improvement of the local control rate in early stage localized prostate cancer and androgen ablation in combination with radiation therapy improves biochemical control and the progression-free survival rate in locoregionally advanced prostate cancer. To select optimal patients for dose escalation study and to determine the optimal use of androgen ablation, it has become clear that the Gleason score and pretreatment PSA value provide valuable information in addition to clinical stage. In terms of prophylactic irradiation to pelvic lymph nodes, there has been no definitive evidence that prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph nodes improves the overall survival rate. Brachytherapy including 125-I or 103-Pd permanent implants and high-dose-rate brachytherapy is now widely used in the treatment of prostate cancer, but clear indications have not yet been determined because of the lack of clinical trials. In this paper, we summarize evidence concerning the role of radiation therapy in the treatment of prostate cancer and also describe the biological basis of prostate cancer, which influences the optimal selection of treatment modalities.