[Hyperfractionated radiation therapy for head and neck cancers].

Among various altered fractionation regimens, hyperfractionated radiotherapy (HFRT) has been considered effective to raise survival rate(SR)as well as local control rate(LCR)in head and neck cancers. We reviewed our results of HFRT (117 cases) treated between 1995 and 2004 and compared with those of conventionally fractionated radiotherapy (CFRT; 80 cases) treated during the same period. By disease site, naso-/oro-/hypopharynx/larynx were 5/23/44/45 vs. 10/6/10/54. There were more advanced-stage cases in HFRT group (stage I/II/III/IV = 19/36/23/35 vs. 42/16/8/ 14). Median RT dose were 72 Gy vs. 66 Gy. In 71 cases, chemotherapy was added (HF/CF = 54/17). In stage III and IV cases, there was a borderline significant difference in LCR (at 5 years; 44.3% for HFRT group vs. 24.5% for CFRT group; p = 0.0502), and a tendency in SR(at 5 years; 50.7% for HFRT group vs. 16.7% for CFRT group; p = 0.1210). By disease site, LCR of HFRT group was higher in hypopharynx(p = 0.0005)and oropharynx(p = 0.0003), and SR of HFRT group was higher in hypopharynx(p = 0.0023). Acute toxicity was heavy but in most cases it was tolerable and there were no severe late toxicities. From our data, it was suggested that HFRT might be effective in certain kinds of head and neck cancers.

Therapeutic results for 100 patients with cancer of the mobile tongue treated with low dose rate interstitial irradiation.

AIM: To evaluate the conservativeness of low dose rate interstitial irradiation (LII) for cancer of the mobile tongue. PATIENTS AND METHODS: Between 1975 and 2002, 100 consecutive patients (71 men, 29 women) underwent LII as curative treatment. Stages were I/IIIII/IV = 16/63/16/4. Seventy-one cases were treated with LII alone and 29 cases treated combined with external irradiation. Median total dose of LH was 70 Gy/7 days. RESULTS: Overall, 5- and 10-year local control and LII-treated patients' survival rates were 93% and 91%, 64% and 57%, respectively. Delayed neck metastases were observed in 21% of initially N0 cases, 56% of which could be salvaged by operation. Early stage and well-differentiated tumors carried better prognoses. CONCLUSION: LII of cancers of the mobile tongue results in good local control and survival. With careful monitoring of patients to ensure early detection of delayed metastases, LII should allow organ conservation and yield favourable therapeutic results compared with those of surgery.

[How to select the treatment options in prostate cancer].

Radiation therapy (RT) for prostate cancer has been developing dramatically during the past 10 years in Japan as well as in USA. There are several ways to treat prostate cancer by RT. As for external-beam RT (EBRT), a more sophisticated technique beyond 3-dimensional conformal RT called intensity modulated RT was developed and has been in use in many Japanese RT centers. It can raise the total radiation dose and is expected to increase the biochemical control rate. As for brachytherapy, a low-dose-rate seed implant using iodine-125 was initiated in 2003 and has become widespread throughout Japan in only a few years. High-dose-rate brachytherapy using iridium-19 2 has also been used in more advanced cases combined with EBRT. Brachytherapy offers an ideal RT dose concentration and can avoid rectal complications. As for particle therapy, we have carbon and proton in several institutions in Japan. Particles have the merit of good dose distributions and for carbons, relative biological effectiveness. Furthermore, some centers are considering the stereotactic hypofractionated RT due to the relatively low alfa-beta ratio of prostate cancer. Recent reports showed that after a certain period of followup, the biochemical control rate was similar either with external beam high-quality RT, brachytherapy, heavy ion RT and surgery. Therefore, the choice of treatment should depend on the adverse effects, quality of life, medical costs, and the lifestyle of the patient. The merits and demerits of each treatment modality were discussed. Longer follow-up is still necessary and informed consent is mandatory when choosing a treatment modality.

Induction chemotherapy followed by hyperfractionated radiotherapy with concurrent chemotherapy for locally advanced head and neck cancer.

BACKGROUND: The aim of this study was to improve tumor control, the survival rate and organ preservation for locally advanced head and neck cancer by using induction chemotherapy followed by hyperfractionated radiotherapy and concurrent chemotherapy. MATERIALS AND METHODS: Thirty-five patients with stage III-IVB head and neck cancer were treated with this protocol. Induction chemotherapy consisted of cisplatin and fluorouracil and concurrent chemotherapy consisted of carboplatin and doxifluridin. Radiotherapy was administered twice a day until a dose of 72 Gy was reached. RESULTS: Twenty-two (63%) and 13 patients (37%) achieved complete responses and partial responses, respectively. In terms of non-hematological toxicities, grade 3 mucositis was observed in 49% of the patients. The overall 5-year survival was 53.5% and the progression-free survival was 40.6%. CONCLUSION: Response to induction chemotherapy was useful as a predictive factor for ultimate outcome and organ conservation. More intensive regimen or other combination chemotherapy is needed to improve treatment outcome with hyperfractionated radiotherapy.

Radiotherapy with concurrent docetaxel for advanced and recurrent breast cancer.

BACKGROUND: Docetaxel has shown remarkable radiosensitizing properties in vitro. In this study we investigated whether the addition of docetaxel to radiotherapy enhanced tumor response in patients with advanced or recurrent breast cancer. METHODS: A total of 35 patients were enrolled in this study. Docetaxel was administered concurrently during radiotherapy. Radiation doses were 54 to 69 Gy (median 60 Gy). In those enrolled through January 2000, docetaxel 40 mg/m2 was administered biweekly (once every two weeks), with subsequent dose adjustments based on tolerance and bone marrow and liver function. Beginning in February 2000, a weekly docetaxel schedule was used instead. This new regimen was based on data suggesting reduced myelosuppression with this regimen. The weekly dose rate was 20 mg/m2, with dose reductions for impaired organ function. RESULTS: All patients were evaluated for toxicity and response and a total of 40 irradiated sites were evaluated for local response. The overall response rate of irradiated sites was 95% and the CR rate was 68%. CR and PR were achieved in 40%, 37% of patients, respectively. Acute toxicities were tolerated by most patients: 17% had Grade 3-4 neutropenia, 6% had Grade 3-4 radiation dermatitis, and 3% had Grade 3-4 pneumonitis. CONCLUSION: The combination of docetaxel with radiotherapy is an active and safe regimen in patients with inoperable advanced or recurrent breast cancer. We determined the recommended dose of docetaxel with concomitant radiotherapy to be 20 mg/m2 weekly for a Phase II study. Further study is necessary to assess the impact of this treatment on long-term outcome.

Acute adverse effects of radiation therapy on HIV-positive patients in Japan: study of 31 cases at Tokyo Metropolitan Komagome Hospital.

Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV-positive patients.

Hyperthermia combined with intra-thoracic chemotherapy and radiotherapy for malignant pleural mesothelioma.

BACKGROUND: Prognosis for patients with malignant pleural mesothelioma (MPM) remains poor and such patients require intensive treatment. Few studies have examined hyperthermia for MPM. The present study investigated the feasibility of hyperthermia combined with weekly chemo-radiotherapy for patients with MPM and estimated the efficacy of this regimen. METHODS: A total of 11 patients (median patient age was 67 and all had pleural effusion) with MPM were enrolled in this study. The treatment regimen comprised of weekly thermo-radiotherapy with intra-thoracic chemotherapy 2-5 times at initiation of treatment. Hyperthermia was performed once per week for approximately 60 min. Hemithorax external radiotherapy was administered once weekly on the same day as hyperthermia and just before thermochemotherapy. Median total radiation dose was 6 Gy (range, 2-10 Gy). Chemotherapy was administered into the thoracic cavity through a tube. Chemotherapeutic agents administered were CDDP for seven patients, carboplatinum (CBDCA) for three patients and both CDDP and CBDCA for one patient. Dose of CDDP was 50 mg/body and dose of CBDCA was 200-300 mg m-2. Response rate and median survival time (MST) and palliative effect were investigated. RESULTS: Complete response was not achieved in any of the 11 patients. Partial response was achieved in three of 11 patients (27.3%), SD in six patients (54.5%) and PD in two patients (18.2%). There was no correlational relationship between thermal parameters and response. MST was 27.1 months. Pleural fluid decreased in all patients after therapy, while all patients displayed improved performance status and could be discharged from hospital. Patients with partial response had a relatively longer survival time than SD or PD. All patients underwent the complete course of treatment and only one of 11 patients developed grade 4 thrombocytopenia. CONCLUSION: It was therefore concluded that hyperthermia combined with intra-thoracic chemotherapy using cisplatinum or carboplatinum may be tolerable. This approach appears effective and more acceptable for patients with MPM with pleural effusion than other multi-modality therapy.