Kazuhisa Furutani

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.

RADIOTHERAPY FOR PATIENTS WITH METASTASES TO THE SPINAL COLUMN: A REVIEW OF 603 PATIENTS AT SHIZUOKA CANCER CENTER HOSPITAL

PURPOSE Long- and short-course radiotherapy have similar outcomes in the treatment of spinal metastases. Long-course radiotherapy is recommended for patients with good predicted survival to reduce the risk of in-field recurrence, whereas short-course radiotherapy is used for those with poor predicted survival. Therefore, prediction of prognosis and local control is required for selecting the optimal course of radiotherapy. METHODS AND MATERIALS The subjects were 603 patients with spinal metastases who received radiotherapy at the Shizuoka Cancer Center Hospital between September 2002 and February 2007. Factors associated with survival and local control were retrospectively investigated by multivariate analyses. Local recurrence was defined as regrowth within the irradiated field or exacerbation of symptoms such as pain and motor deficits. RESULTS Of the 603 patients, 555 (92%) were followed for 12 months or until death. The survival rates after 6, 12, and 24 months were 50%, 32%, and 19%, respectively, with a median survival of 6.2 months. The median survival periods after long- and short-course radiotherapy were 7.9 and 1.8 months, respectively. In multivariate analysis, primary tumor site, good performance status, absence of previous chemotherapy, absence of visceral metastasis, single bone metastasis, younger age, and nonhypercalcemia were associated with good survival. The local control rates after 6, 12, and 24 months were 91%, 79%, and 69%, respectively, and non-mass-type tumor, breast cancer, and absence of previous chemotherapy were predictors of good local control. CONCLUSIONS Identification of factors associated with good local control and survival may allow selection of an optimal radiotherapy schedule for patients with spinal metastases.

A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer

OBJECTIVE To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. METHODS A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. RESULTS The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). CONCLUSIONS We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.

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.

Prognostic Factors and a Scoring System for Survival After Radiotherapy for Metastases to the Spinal Column A Review of 544 Patients at Shizuoka Cancer Center Hospital

To optimize selection of a radiotherapy schedule for patients with spinal metastases, the authors analyzed prognostic factors and developed a scoring system to predict survival in such patients.

Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer

PURPOSE To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy. PATIENTS AND METHODS Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed. RESULTS Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade 2 RP (p < 0.01). The incidences of grade 2 RP were 13%, 33%, and 78% in patients with V20s of 24%, 25-36%, and 37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis. CONCLUSION DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.

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.

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.

Phase I study of combination chemotherapy with 5-fluorouracil (5-FU) and nedaplatin (NDP): Adverse effects and recommended dose of NDP administered after 5-FU

When nedaplatin (NDP) was used as a single agent in the phase I study, the dose-limiting toxicity (DLT) was thrombocytopenia and the recommended dose (RD) was 100 mg/m2. However, the DLT, maximum tolerated dose (MTD) and RD of NDP used in combination with 5-fluorouracil remained unknown. Therefore, we performed this study to assess the DLT and RD of NDP administered after 5-fluorouracil (5-FU). In this study, 5-FU was administered to 38 patients at a fixed dose (700 mg/m2/d on days 1–5) and NDP administered on day 6 at an initial dose of 80 mg/m2, which was subsequently increased to 100, 120, 130, 140, 150, and 160 mg/m2. The DLT of NDP was leukopenia and its MTD and RD were 160 and 150 mg/m2, respectively. Concerning impairment of renal function, only two patients had a grade I increase in serum creatinine. There were 19 responders (50%, 19/38) achieving partial response or complete response in the evaluation of antitumor effect. The result of this study is notable in that administration of 5-FU before NDP allows the dose of NDP to be substantially increased.