A case of isolated paraaortic lymph node recurrence from colon cancer successfully treated with chemoradiotherapy.

Isolated paraaortic lymph node (PALN) recurrence from colorectal cancer is rare and has no established treatment. A 56-year-old woman was referred to our hospital for the treatment of PALN recurrence in June 2005. She had undergone right hemicolectomy for ascending colon cancer two years earlier. The pathological diagnosis in 2003 was a well-differentiated adenocarcinoma with positive PALN metastasis in 3 of 4 dissected nodes (T3, N1b, M1a, stage IVa). At our hospital, chemoradiotherapy was started, with the radiation field determined from positron emission tomography (PET) images. Oral tegafur/uracil (600 mg/day) plus leucovorin (75 mg/day) therapy was also started. Radiotherapy (1.5 Gy/ fraction, total of 45 Gy) was completed in August 2005, while oral chemotherapy was discontinued 3 weeks after it was started due to diarrhea and epigastric discomfort. The serum carcinoembryonic antigen level was 193 ng/ml (N < 5) before treatment and decreased to within normal limits 3 months after initiation of chemoradiotherapy. Complete remission was confirmed by computed tomography (CT) and PET in December 2005 and has continued for more than 6 years. This case shows that chemoradiotherapy is potentially curative for PALN recurrence from colorectal cancer. To our knowledge, this is the first report of more than 5 years disease-free survival in a patient with PALN recurrence from colon cancer treated with chemoradiotherapy.

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.

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.

Concurrent chemoradiotherapy with docetaxel for T2 laryngeal carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of concurrent chemoradiotherapy with docetaxel (DOC) for T2 laryngeal carcinoma. METHOD: Twelve patients with T2 laryngeal cancer received concurrent chemoradiotherapy (60-70Gy) with weekly DOC (10 mg/m2) (CCRT group). The clinical files of the patients were retrospectively reviewed and survival rates and laryngeal preservation rates were analyzed compared with the group treated with conventional radiation therapy alone (RT group). RESULTS: Complete response was observed in 11 of 12 patients (91.7%) in the CCRT group. Overall 5-year survival rates by Kaplan-Meier's method were 90% for the CCRT group and 78% for the RT group. The disease free survival with anterior commisure involvement was 90% in CCRT group and 53% in RT group, respectively. Toxicity over grade III was noticed in 3 patients. CONCLUSION: Concurrent chemoradiotherapy with DOC is a feasible and effective treatment modality for organ preservation in T2 laryngeal cancer in the outpatient setting. Efficacy and safety of this treatment modality in an outpatient setting were discussed.

Predictors of tumor downsizing and regression with preoperative radiotherapy alone and with concomitant tegafur/uracil (UFT) for resectable advanced rectal adenocarcinoma.

BACKGROUND/AIMS: Predictors of sensitivity to preoperative radiotherapy (RT) may differ from those of chemo-radiotherapy (CRT). This study attempts to evaluate retrospectively the significance of apoptosis-related and proliferative indexes in biopsy specimens obtained before treatment as predictors of sensitivity to RT or to CRT for locally advanced rectal adenocarcinoma. METHODOLOGY: The subjects were 96 patients with clinical T3-4/Nx/M0 adenocarcinoma of the middle third or lower third of the rectum. Sixty-one patients were treated with preoperative RT alone (20 Gy in 10 fractions) [RT group] during 1991-1998, and 35 patients received concurrent oral tegafur/uracil (UFT) [CRT group] since 1999. Radical surgery including TME and pelvic nerve preservation with 15 Gy of intraoperative RT was performed two weeks after completion of the preoperative radiation. We evaluated apoptotic index (AI) and p53, p21 and Ki-67 protein expression in the biopsy specimens, and histological differentiation, pathologic regression in the resected specimens and the degree of tumor shrinkage based on the double contrast barium enema images. RESULTS: AI-positivity, p53-negativity, p21-positivity and well differentiated adenocarcinoma were predictors of high sensitivity in RT group, whereas AI-positivity alone was the predictor in CRT group. The addition of UFT to RT increased sensitivity in patients with p53-positivity, p21-negativity and moderately differentiated adenocarcinoma. CONCLUSIONS: Predictors of sensitivity are different between RT and CRT.

Prediction of tumor control by tumor regression at 40 Gy/4 weeks of external beam irradiation for oropharyngeal carcinoma.

PURPOSE: To predict tumor control on the basis of tumor regression at 40 Gy/4 weeks of external beam radiotherapy (EBRT) for oropharyngeal carcinoma. METHODS: From 1990 to 1997, 55 patients (9 Stage I+II, 15 Stage III, and 31 Stage IV) with squamous cell carcinoma of the oropharynx were treated with curative EBRT (median dose, 66 Gy). Tumor response at 4 weeks was compared with loco-regional control. RESULTS: The five-year loco-regional control rate was 52%. Regression of primary tumors was more rapid and occurred at a rate higher than that of nodal lesions; however, nodal response served as a superior predictor of tumor control. Predictive factors for loco-regional control were tumor stage, loco-regional response at 4 weeks, and pathological differentiation. Stage III and non-well-differentiated stage IV tumors demonstrating >50% regression at 4 weeks were controlled initially at 74% (17/23) and ultimately at 83% (19/23) by salvage therapy. In contrast, stage III+IV tumors displaying <50% regression and well-differentiated stage IV tumors exhibiting >50% regression were controlled initially at 9% (2/23) and ultimately at 22% (5/23). CONCLUSION: Tumor regression at 40 Gy/4 weeks of EBRT is an important parameter in terms of prediction of loco-regional control for stage III and IV disease.

Predictive factors of tumor shrinkage and histological regression in patients who received preoperative radiotherapy for rectal cancer.

OBJECTIVE: In order to determine the reliable predictors of response to radiotherapy for rectal cancer, we assessed apoptosis, p53 and p21 in biopsy specimens collected before treatment, and investigated the relationships to the histological effect of irradiation and the degree of tumor shrinkage. METHODS: Ninety-three patients with advanced rectal adenocarcinoma were treated with preoperative irradiation of 20 Gy in 10 fractions in combination with intraoperative electron beam irradiation of 15 Gy. We evaluated tumor grade, pathological tumor regression, biological markers associated with apoptosis and proliferation [apoptotic index (AI), p53, p21 and Ki67], and the degree of tumor shrinkage. RESULTS: Considering positivity of p21 and of apoptosis and negativity of p53 as favorable factors in tumor shrinkage, we compared the degree of shrinkage among the patients using the number of favorable factors as the score. The degree of shrinkage was 41.5 +/- 8.5% in patients with three favorable factors, 31.4 +/- 9.7% in patients with two favorable factors and 26.5 +/- 11.2% in patients with one favorable factor. However, there was no significant difference in the proportion of marked regression according to the number of favorable factors. CONCLUSIONS: Histological examination of apoptosis, p21 and p53 in biopsy specimens and scoring were considered to be useful predictive methods for assessing the efficacy of radiotherapy for rectal cancer.

Clinical investigation: Reliability and validity of the Japanese version of quality of life radiation therapy instrument (QOL-RTI) for Japanese patients with head and neck malignancies.

PURPOSE: To evaluate the reliability and validity of the Japanese translation of Quality of Life Radiation Therapy Instrument (QOL-RTI) and the head and neck module (H&N) for Japanese patients being treated with radiotherapy for head and neck malignancies. MATERIALS & METHODS: The QOL-RTI/H&N was translated into Japanese by a preliminary QOL research working group of JASTRO and was used in this clinical trial. From 1998 to 2001, 70 patients with head and neck malignancies for whom radical radiotherapy was planned were entered into this study. Patients were requested to answer the questions before radiotherapy at baseline, twice during week 4 of therapy (for test-retest reliability), at the end of treatment, and 3 months, 6 months, 1 year and 2 years from the beginning of radiotherapy. Internal consistency was assessed by Cronbach's alpha coefficient. Validity was assessed by comparing the results with EORTC-QLQ-C30 and with QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ADC). Patient compliance and test sensitivity were also analyzed. RESULTS: Cronbach's alpha coefficient was 0.79 to 0.93 depending on the time point for the evaluation. Test-retest reliability was acceptable, with a Pearson coefficient of 0.83 for QOL-RTI and 0.92 for H&N module. Compliance with this scheme was 98.2%. The QOL-RTI was sensitive enough to detect significant changes in the QOL score during and after the course of radiotherapy. Agreement with the EORTC-C30 was good with a high Pearson correlation coefficient of 0.648 and that with QOL-ADC was also good with a coefficient of 0.566. The factors analyzed consisted of 11 functional/health-oriented questions, 5 emotional/ psychological, 5 socio-economic/ family and 2 general. CONCLUSION: The Japanese version of QOL-RTI with H&N module was found to be reliable and sensitive enough to evaluate variation of QOL in patients with head and neck malignancies during and after radiotherapy.

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.

Complications following re-irradiation for head and neck cancer.

PURPOSE: Re-irradiation may induce serious complications because of overdosage to previously irradiated areas. A few reports do exist that describe the incidence and factors related to late complications. In the present study we analyze complications following re-irradiation for head and neck cancers. MATERIALS AND METHODS: Between 1984 and 1998, 91 patients presenting with squamous cell carcinoma of the head and neck were re-irradiated with a total dose of 80-144 Gy and overlap fields of 4-128 cm(2). Re-irradiation was administered exclusively with external beam irradiation with conventional (n = 47), hyper- (n = 10), or hypofractionation (n = 34). Chemotherapy was combined with the initial course of irradiation (n = 34) or re-irradiation (n = 18). Follow-up time ranged from 3 to 84 months. RESULTS: Severe acute reactions occurred in 6.6% of patients. Moreover, incidence was significantly higher (40%) in elderly patients older than 80 years. Severe late complications developed 3-10 months after re-irradiation. The incidence was 13% in 78 patients followed for more than 3 months and 21% in 42 patients with tumor-free status. The complications were observed in 19% of patients previously receiving locoregional irradiation, compared with those receiving local irradiation alone (0%), and in 20% of patients undergoing re-irradiation to the neck, compared with those receiving re-irradiation to the head (3%). These factors were all significant by multivariate analysis. Radiation dose, fractionation method, and overlap area were not significant. CONCLUSION: Care should be exercised with respect to the potential for acute complications in elderly patients and late complications in those patients having previously received locoregional irradiation and re-irradiation to the neck.