Yukio Ohizumi

Prognostic factors of reirradiation for recurrent head and neck cancer.

We analyzed outcomes and prognostic factors to assess the value of reirradiation for recurrent head and neck cancer. Forty-four patients with recurrent squamous-cell carcinoma had undergone external beam reirradiation with cumulative dosing of more than 80 Gy. Six and 38 cases exhibited recurrent stage III and stage IV cancers, respectively. The complete response rate was 32%. Median relapse-free survival time was 4 months, and the 5-year survival was 6%. The major prognostic factor was anatomical location (p < 0.0001). Favorable sites were the nasopharynx, larynx, or oropharynx; unfavorable sites were the oral cavity, nasal cavity, or hypopharynx. Poorly differentiated cancer, no prior surgery, cumulative dose more than 125 Gy, and overlapping field less than 40 cm2 between the initial and reirradiation fields were also favorable factors. Multivariate analysis revealed that anatomical location and overlapping field were significant (0.001 and 0.019, respectively) in relapse-free survival. On exclusion of anatomical location from the analysis, history of prior surgery, and cumulative dose were significant (p = 0.002 and p = 0.023, respectively). Severe late complications occurred in only 1 of 14 (7%) patients followed up for longer than 1 year. Reirradiation would be indicative for nasopharyngeal, oropharyngeal, or laryngeal cancer with small overlapping field, or cancer receiving a cumulative dose more than 125 Gy without prior surgery.

Liposome‐Encapsulated Hemoglobin Ameliorates Tumor Hypoxia and Enhances Radiation Therapy to Suppress Tumor Growth in Mice

We hypothesize that liposome-encapsulated hemoglobin with high O₂ affinity (P₅₀0₂ = 12 mm Hg, h-LEH) may increase O₂ delivery to hypoxic tumors and enhance radiation therapy synergistically to suppress tumor growth. First, h-LEH (5, 10, and 20 mL/kg) was intravenously infused 30 min before radiation (20 Gy) of SCCVII tumor grown in C3H/HeN mice. Second, 10 mL/kg of h-LEH was administered 30, 60, 90, and 120 min prior to radiation to determine optimal timing. Tumor size was monitored thereafter to titrate tumor growth suppression. Third, additional mice with SCCVII tumor were infused with h-LEH or empty liposome (EL), and tumors were excised at various time points for immunohistochemical examination of h-LEH and hypoxia-inducible factor-1α (HIF-1α). h-LEH was most effective at 10 mL/kg in comparison to 5 or 20 mL/kg of h-LEH or EL. Tumor growth was most suppressed when the interval between h-LEH infusion and radiation was shortest, 30 min. As a result, 10 mL/kg of h-LEH infusion 30 min prior to radiation prolonged 5-fold tumor-growth time from 20.0 days (radiation and EL) to 26.5 days, P<0.01, synergy ratio 1.42. While human hemoglobin (h-LEH) was detected in tumors 0.5 to 24 h after administration, HIF-1α accumulation was sparse and became significantly reduced compared to controls 48 and 72 h after h-LEH infusion. h-LEH (10 mL/kg) was highly effective in enhancing radiation therapy synergistically under ambient respiration against tumor growth in mice. Decreased accumulation of HIF-1α in h-LEH-treated tumor may suggest targeted tumor oxygenation as a potential mechanism.

Intraoperative radiation therapy for curatively resected rectal cancer

PURPOSE: Intraoperative radiotherapy has been used for local control of locally advanced rectal cancer. The aim of this study was to investigate the efficacy of intraoperative radiotherapy for curatively resected rectal cancer. METHODS: Between 1982 and 1998, intraoperative radiotherapy was administered in combination with curative resection in 78 patients with adenocarcinoma of the middle or lower third of the rectum (intraoperative radiotherapy group). Sixty-two of the patients had received preoperative radiotherapy with 20 Gy. Intraoperative radiotherapy was performed by a new strategy in which an electron beam was administered as uniformly as possible to the entire dissected surface of the pelvis. Retrospective comparisons were made with 248 patients treated by surgery alone during the same period (non-intraoperative radiotherapy group). RESULTS: The differences in tumor stage or surgical procedures between the two groups were not statistically significant. Survival, disease-free survival, and local recurrence-free survival in the intraoperative radiotherapy group were significantly more favorable than in the non-intraoperative radiotherapy group (P=0.01,P=0.04, andP=0.02). Differences in survival were observed in Stage II patients but not in Stage I or Stage III patients. The local failure rate was 2.6 percent in the intraoperative radiotherapy group and 11.3 percent in the non-intraoperative radiotherapy group, and the difference was significant (P=0.02). The distant metastasis rate was 18.0 percent in the intraoperative radiotherapy group and 19.5 percent in the non-intraoperative radiotherapy group, and the difference was not significant. There was a significantly higher rate of wound infection in the intraoperative radiotherapy group, but no infections were serious. CONCLUSIONS: In patients with adenocarcinoma of the middle or lower third of the rectum, intraoperative radiotherapy to the entire dissected surface of the pelvis reduced local recurrence in Stage II and Stage III patients and improved survival in Stage II patients.

Re-irradiation for Metastatic Brain Tumors with Whole-brain Radiotherapy

OBJECTIVE To determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. METHODS A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. RESULTS The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re-irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade ≥2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re-irradiation were the location of the primary cancer (P = 0.003) and the Karnofsky performance status at the time of re-irradiation (P = 0.008). A Karnofsky performance status ≥70 was significant based on multivariate analysis (P = 0.050). CONCLUSIONS Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high.

In vivo Distributions of 111In and/or 3H Labeled Lymphocyte in C3H/He Mouse

Although 99mTc and 51Cr have been used for lymphocyte labeling, these radionuclides have several disadvantages for study on immunological behaviour of lymphocyte; very high rate elution and low labeling efficiency for both radionuclides, and short half life for 99mTc. Indium-111 has quite suitable physical properties for clinical nuclear medicine, i.e. desirable photon energy (247,173 keV) and 2.8 day half life. 111In-oxine is lipid soluble and is known to pass through the cell membrane and attaches firmly to cytoplasmic component of the cell. On the other hand, 3H-thymidine is well known substance which incorporated to nucleic acid in the cell. In this study, distribution patterns of 111In-oxine and/or 3H-thymidine labeled lymphocyte in C3H/He mice were examined and the suitability of 111In-oxine labeled lymphocyte for radionuclide imaging in vivo was discussed. Thirty minutes after intravenous injection of 3H and/or 111In labeled lymphocyte, about 12% of lymphocyte were found in the lungs and rest of them were distributed mainly in the blood, kidneys and liver. After 24 hours the activity in the lung decreased markedly and the activity in the liver and kidneys increased with time. Between lymphocyte labeled with 111In-oxine and 3H-thymidine, there is not so much differences in terms of distribution patterns. From this study, it is concluded that the 111In-oxine labeled lymphocyte distributes in the same way as 3H labeled one, in spite of different labeling sites. This 111In-oxine labeling method can be used as a useful tool of radionuclide imaging in kinetic studies of lymphocyte in vivo.

Primary radiotherapy for tongue cancers with a tumor thickness exceeding 1 cm

AbstractBackground. In tongue cancers with a tumor thickness exceeding 1 cm, the validity of radiotherapy as an initial treatment remains controversial. Methods. Between 1979 and 1991, 26 patients with tongue cancer that was 1 cm or more in tumor thickness, and who were without clinical adenopathy underwent interstitial radiotherapy (mean dose, 64 Gy) following external irradiation (mean dose, 35 Gy). Results. In 16 (62%) of the 26 patients control was achieved at the primary site (i.e., no local recurrence till the last follow-up of 41–120 months). In 5 of the 10 patients with recurrence rescue was achieved with a salvage operation. All 3 patients who developed nodal metastases were salvaged. One patient with osteonecrosis and 2 patients with tongue ulcers were operated upon. The whole tongue remained in 13 of the 26 patients and the cumulative 5-year survival was 80%. Conclusion. Radiotherapy is a suitable initial treatment for patients with tongue cancers exceeding 1 cm tumor thickness except for T4 tumors.

Biological Effectiveness of Fractionated Dose of Pions in Microscopic SCCVII Tumors: Comparison between Tumor Control Dose and Tumor Growth Time Assays

The relative biological effectiveness (RBE) of fractionated pions for tumor growth time (TGT) assay changes with the endpoints, so it is essential to determine the RBE for tumor control dose (TCD) assay. For this purpose, the TCD50 of fractionated pions was compared with that of photons, and the RBEs for TGT and TCD assays were concurrently compared as a function of the effect level. A “convenient” RBE (cRBE) was substituted for the RBE when the comparison was made between similar fractionation schedules with different dose per fraction. SCCVII tumors (2 ×104 or 2 × 105 cells) were implanted into the feet of C3H mice and irradiated starting from 2 days after implantation at a total dose range of either 9.6–38.4 Gy pions (2.4–6.4 Gy per fraction) or 14.4–50.4 Gy photons (3.6–7.2 Gy per fraction) in 2–10 fractions over 5–6 days. The cRBE and the RBE at the iso‐effective level of 30 days TGT were 1.53–1.60 for 2.4–4.8 Gy pions and 1.50 for 4‐fracrionated pions, respectively: there were only small differences within these schedules used. However, the cRBE values decreased from 1.60 to 1.15 with increasing TGT from 30 to 75 days. In contrast, the cRBE values for TCD50 increased from 1.08 to 1.40 (95% confidence limits [CL]; 1.18–1.63) with increasing evaluation time from 60 to 100 days: pions significantly inhibited late tumor appearance. The TCD50 at 100 days was 28.7 Gy (CL; 25.0–32.5 Gy) for pions and 40.3 Gy (CL; 36.3–44.2 Gy) for photons. In conclusion, the RBE for TCD50 was not predictable from the RBE for TGT assay. The cRBE value of 1.4 for microscopic tumor control was in close agreement with the reported values for skin reaction.