Nobukazu Fuwa

New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion

We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.

A combination therapy of continuous superselective intraarterial carboplatin infusion and radiation therapy for locally advanced head and neck carcinoma

To improve the treatment result for locally advanced head and neck carcinoma, the authors used a combination of radiotherapy with superselective continuous intraarterial therapy using carboplatin. The dose limiting toxicity (DLT), maximum tolerated dose (MTD), and treatment effectiveness were tested in Phase I and II protocols.

Comparison of prognostic value of MRI and FIGO stage among patients with cervical carcinoma treated with radiotherapy.

PURPOSE To compare the efficacy of MRI and FIGO stage, we performed retrospective multicenter analysis of patients with Stage II-III disease treated with radiation alone. METHODS AND MATERIALS From three institutions, 164 patients diagnosed with cervical carcinoma were entered into the study. The majority of this cohort received intracavitary brachytherapy combined with external beam radiotherapy (n = 161). Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS The 5-year OAS, DFS, PC, and DMFS rates were 68.8%, 60.4%, 77.4%, and 71.7%, respectively. Using uni- and multivariate analyses, both large tumor size/volume and positive lymph node enlargement (LN) showed a significantly unfavorable influence on survival and local and/or distant failure (p < 0.05). Using these two prognostic factors, patients were divided into three subgroups; the 5-year DFS rates of patients with risk 0 (volume </=50 cc and negative LN), 1 (volume >50 cc or positive LN), and 2 (volume >50 cc and positive LN) were 72.9%, 53.3%, and 26.1%, respectively (p < 0.0001). Among patients with volume </=50 cc, disease stage proved to be a significantly prognostic factor of OAS, DFS, and PC (p < 0.05). However, these correlations were not observed in the large volume group (p > 0.05). CONCLUSION MRI will provide more useful and practical information than will FIGO stage classification for patients with bulky disease, although this will remain a prognostic factor for patients with nonbulky disease (volume </=50 cc). With the aid of MRI, accurate and practical evaluation of clinical outcome could be achieved.

Dose-Volume Comparison of Proton Radiotherapy and Stereotactic Body Radiotherapy for Non-Small-Cell Lung Cancer

PURPOSE This study designed photon and proton treatment plans for patients treated with hypofractionated proton radiotherapy (PT) at the Southern Tohoku Proton Therapy Center (STPTC). We then calculated dosimetric parameters and compared results with simulated treatment plans for stereotactic body radiotherapy (SBRT), using dose--volume histograms to clearly explain differences in dose distributions between PT and SBRT. METHODS AND MATERIALS Twenty-one patients with stage I non-small-cell lung cancer (stage IA, n = 15 patients; stage IB, n = 6 patients) were studied. All tumors were located in the peripheral lung, and total dose was 66 Gray equivalents (GyE) (6.6 GyE/fraction). For treatment planning, beam incidence for proton beam technique was restricted to two to three directions for PT, and seven or eight noncoplanar beams were manually selected for SBRT to achieve optimal planning target volume (PTV) coverage and minimal dose to organs at risk. RESULTS Regarding lung tissues, mean dose, V5, V10, V13, V15, and V20 values were 4.6 Gy, 13.2%, 11.4%, 10.6%, 10.1%, and 9.1%, respectively, for PT, whereas those values were 7.8 Gy, 32.0%, 21.8%, 17.4%, 15.3%, and 11.4%, respectively, for SBRT with a prescribed dose of 66 Gy. Pearson product moment correlation coefficients between PTV and dose--volume parameters of V5, V10, V15, and V20 were 0.45, 0.52, 0.58, and 0.63, respectively, for PT, compared to 0.52, 0.45, 0.71, and 0.74, respectively, for SBRT. CONCLUSIONS Correlations between dose--volume parameters of the lung and PTV were observed and may indicate that PT is more advantageous than SBRT when treating a tumor with a relatively large PTV or several tumors.

Continuous selective intraarterial chemotherapy in combination with irradiation for locally advanced cancer of the tongue and tongue base

We retrospectively evaluated the results of the concurrent combination therapy of selective continuous intraarterial chemotherapy and radiotherapy in 39 patients with locally advanced cancer of the tongue and tongue base between September 1992 and January 2000. Thirty patients were fresh cases (stage II, 10 patients; stage III, 15; stage IV, five) and nine were recurrent cases. The primary lesion was present in the mobile tongue in 33 patients and the tongue base in six. External irradiation (median dose, 48.6 Gy) was performed in all patients, and interstitial brachytherapy using an Au grain or Cs needle (median dose, 50 Gy) in 21. In intraarterial chemotherapy, a catheter was selectively inserted into the lingual artery via the superficial temporal artery, and carboplatin (CBDCA) was continuously infused (median dose, 460 mg/m(2)) concurrently with radiotherapy. In 13 patients with cervical lymph node metastasis, two courses of systemic chemotherapy with 5-FU (700 mg/m(2) x 5 days) and cisplatin (40-50 mg/m(2)x2 days) or its analog was also performed. In 37 (94.9%) of the 39 patients in whom this combination therapy was completed, the response rate was 94.6%. The 3-year local control rate, progression-free survival rate, and overall survival rate by Kaplan-Meiers method were 79.2, 53.2, and 58.9%, respectively. This combination therapy was effective for locally advanced cancer of the tongue and tongue base without causing severe adverse side effects, and a local control rate comparable to that by surgery can be expected.

Treatment outcomes of particle radiotherapy using protons or carbon ions as a single-modality therapy for adenoid cystic carcinoma of the head and neck

BACKGROUND AND PURPOSE The aim of this study was to retrospectively analyse the outcomes of cases of adenoid cystic carcinomas (ACCs) of the head and neck that were treated at a single institution with particle therapy consisting of either protons or carbon ions. METHODS AND MATERIALS Between February 2002 and March 2012, 80 patients were treated with proton therapy (PT) or carbon ion therapy (CIT) alone. PT and CIT were employed in 40 (50%) patients each, and more than half of the patients received 65.0 GyE in 26 fractions (n=47, 59%). RESULTS The median duration of follow-up was 38 months (range, 6-115 months). For all patients, the 5-year for overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate were 63%, 39%, and 75%, respectively. No significant differences between PT and CIT were observed. The 5-year LC rates for T4 and inoperable cases were 66% and 68%, respectively. Twenty-one patients (26%) experienced grade 3 or greater late toxicities, including three patients who developed grade 5 bleeding from nasopharyngeal ulcers. CONCLUSIONS Particle radiotherapy for ACC achieves favourable LC, and its efficacy in inoperable or T4 cases is promising. There were no significant differences between PT and CIT in terms of OS, PFS and LC.

Clinical Usefulness of [(18)F] Fluoro-2-Deoxy-d-Glucose Uptake in 178 Head-and-Neck Cancer Patients With Nodal Metastasis Treated With Definitive Chemoradiotherapy: Consideration of Its Prognostic Value and Ability to Provide Guidance for Optimal Selection of Patients for Planned Neck Dissection

PURPOSE To evaluate the clinical effectiveness of pretreatment [18F] fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. METHODS AND MATERIALS Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. RESULTS The patients with a nodal SUV≥6.00 had a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p=.004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p=.04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p=.05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p=.016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV (≥6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p=.04, hazard ratio, 2.36; 95% CI, 1.00-5.85). CONCLUSION Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection.

Aichi Cancer Center Initial Experience of Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer Using Helical Tomotherapy

PURPOSE To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. RESULTS The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. CONCLUSION HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer.

Clinical assessment by MRI for patients with Stage II cervical carcinoma treated by radiation alone in multicenter analysis: are all patients with Stage II disease suitable candidates for chemoradiotherapy?

PURPOSE From recent randomized trials, patients with Stage II cervical carcinoma are thought to be candidates for chemoradiotherapy. To refine the strategy for Stage II patients, we performed a retrospective multi-institutional analysis using MRI. METHODS AND MATERIALS From three institutions, 84 patients with Stage II cancer diagnosed by MRI were entered into the study. All patients received intracavitary brachytherapy with (n = 83) or without (n = 1) external beam radiotherapy. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS The 5-year DFS rate of patients with maximal tumor size (D(max)) > or =50 mm (46.2%) was significantly lower than that for patients with D(max) <50 mm (88.0%; p <0.0001). Large size or volume and lymph node swelling were also significant prognostic factors of OAS, DFS, PC, and DMFS. In the multivariate model, size or volume was a significant prognostic factor of OAS, DFS, PC, and DMFS, and lymph node swelling was a prognostic factor for DFS, PC, and DMFS. Using these two prognostic factors, patients were divided into 3 subgroups. The 5-year DFS rate of patients with risk 0 (D(max) <50 mm and negative lymph node swelling), 1 (D(max) > or =50 mm or positive lymph node swelling), and 2 (D(max) > or =50 mm and positive lymph nodes) was 93.2%, 53.3%, and 25.0%, respectively (p <0.0001). CONCLUSION In this stage-limiting analysis, we clarified the stratification according to clinical risk with the aid of MRI. For patients with low-risk factors, especially for elderly patients, radiation alone would probability be a feasible option. In the future, a randomized trial using criteria with MRI would help to identify the optimal strategy for patients with Stage II disease.

Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study

5613 Background: Nasopharyngeal cancer (NPC) is characterized by a high frequency of distant metastasis and mucositis was a marked problem even when radiotherapy (RT) alone was performed. Considering these characteristics of NPC, alternating chemoradiotherapy (ALT-CRT) may be a useful method of treating NPC because sufficient amount of anti-tumor agents can be administered together with a low frequency of mucositis compared to concurrent chemoradiotherapy (CRT). METHODS The subjects consisted of 16 patients with stage II, 25 patients with stage III and 26 patients with stage IV . Using 6 MV photon, RT was performed at an exposure of 1.8Gy 5 times a week. That is, a total absorbed dose of 36 Gy was irradiated between the basal of skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 30-34Gy was additionally given thereafter. One course of chemotherapy (CT) consisted of the administration of 5-FUdepends on document reviewat a dose of 800 mg/m2/24 h for 5 days (days 1-5) and CDDP at a dose of 50 mg/m2/24 h for 2 days (days 6-7), and a total of 3 courses of CT was performed. During the ALT-CRT, CT was performed initially; and 2-3 days after completing the CT, RT was performed for 4 weeks. Thereafter, CT and RT were performed alternately. RESULTS The scheduled courses of ALT-CRT were completed in 57 (87%) of 67 patients. No severe adverse effects were noted in any other patients. In these 67 patients, the overall 3-year survival rate was 93%, and the progression free survival rate was 80% (The median follow up times was 33 months). CONCLUSIONS This method of ALT-CRT yielded higher or at least similar survival rate and lower toxicities than concurrent CRT, and we believed that this method can be used in a controlled clinical trial in the future to compare therapeutic results with those of the Intergroup 0099 Trial No significant financial relationships to disclose.