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.

Unresectable esophageal cancer treated with multiple chemotherapies in combination with chemoradiotherapy: A case report.

BACKGROUND: Definitive chemoradiotherapy (dCRT) using cisplatin plus 5fluorouracil (CF) with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma (ESCC). Recently, induction chemotherapy has received attention as an effective treatment strategy. CASE SUMMARY: We report a successful case of a 59-year-old female with unresectable locally advanced T4 ESCC treated by two additional courses of chemotherapy with CF after induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by dCRT. Initial esophagogastroduodenoscopy (EGD) detected a type 2 advanced lesion located on the middle part of the esophagus, with stenosis. Computed tomography detected the primary tumor with suspected invasion of the left bronchus and 90° of direct contact with the aorta, and upper mediastinal lymph node metastasis. Pathological findings from biopsy revealed squamous cell carcinoma. We initially performed induction chemotherapy using three courses of DCF, but the lesion was still evaluated unresectable after DCF chemotherapy. Therefore, we subsequently performed dCRT treatment (CF and radiation). After dCRT, prominent reduction of the primary tumor was recognized but a residual tumor with ulceration was detected by EGD. Since the patient had some surgical risk, we performed two additional courses of CF and achieved a clinically complete response. After 14 mo from last administration of CF chemotherapy, recurrence has not been detected by computed tomography and EGD, and biopsy from the scar formation has revealed no cancer cells. CONCLUSION: We report successful case with tumor remnants even after DCF and subsequent dCRT, for whom a complete response was finally achieved with two additional courses of CF chemotherapy. Additional CF chemotherapy could be one radical treatment option for residual ESCC after treatment with induction DCF followed by dCRT to avoid salvage surgery, especially for high-risk patients.

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.

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.

Adjuvant radiotherapy after prostatectomy for prostate cancer in Japan: a multi-institutional survey study of the JROSG.

In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54-77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9-284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0-2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1-6 months). A total dose of ≥ 60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤ 0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤ 3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).

Clinical characteristics of brain metastases from lung cancer according to histological type: Pretreatment evaluation and survival following whole-brain radiotherapy.

The histological type of lung cancer in patients with brain metastases may affect response to treatment and survival. We evaluated the clinical characteristics of brain metastases from lung cancer according to histological type in 70 consecutive patients with brain metastases from histologically confirmed lung cancer, who had been previously treated with whole-brain radiotherapy (WBRT). Histological type was divided into three categories: adenocarcinoma, small-cell lung carcinoma (SCLC) and other non-small cell lung cancer (NSCLC). The number, size and maximum diameter of brain metastases, the size and maximum diameter of peritumoral edema, the ratio of tumor and peritumoral edema, the asymptomatic ratio, the tumor size reduction rate, the complete response (CR) rate, the intracranial progression-free survival (PFS) and the overall survival (OS) were also evaluated. The median survival time for all patients was 26.2 weeks. Patients with SCLC exhibited a significantly smaller edema size and maximum diameter of edema compared to patients with other NSCLC (P=0.016 and 0.010, respectively). The ratio of tumor and peritumoral edema was also significantly lower in patients with SCLC compared to that in patients with adenocarcinoma and other NSCLC (P= 0.001). Significant differences in intracranial PFS and OS between adenocarcinoma and other NSCLC were also observed (P=0.018 and 0.004, respectively). Patients with adenocarcinoma who were treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) following WBRT, demonstrated a significant improvement in intracranial PFS and OS (P=0.008 and 0.004, respectively). The findings presented in this study may provide useful information for the management of brain metastases. Patients with SCLC exhibit a tendency to develop peritumoral edema to a lesser extent, compared to patients with other histological tumor types. Findings in the present study suggest that patients with adenocarcinoma, particularly those treated with EGFR-TKIs, exhibit improved survival rates.

Definitive chemoradiotherapy of limited-disease small cell lung cancer: Retrospective analysis of new predictive factors affecting treatment results.

The aim of this study was to evaluate potential predictive factors in the treatment of limited-disease small cell lung cancer (LD-SCLC). A total of 33 patients with LD-SCLC who underwent definitive chemoradiotherapy at our institute between April 1996 and May 2007 were enrolled in our retrospective study. The relationship between a range of potential predictive factors and the initial response, time to progression and pattern of failure was analyzed. The factors evaluated included the tumor markers Pro-gastrin-releasing peptide (Pro-GRP) and neuron-specific enolase; net tumor size (sum of each lesion mass on computed tomography at 1-cm intervals); total radiation dose; biological effective dose (BED); overall treatment time (OTT); time between the start of any type of treatment and the end of radiation therapy (SER). In addition, the novel factors of radiation dose-intensity (RDI = BED/OTT) and RDI/NTS (= RDI/net tumor size) were defined. Of the 33 patients evaluated in our study, 22 (67%) achieved a complete response (CR) and 27 (82%) experienced treatment failure or recurrence. High RDI/NTS values showed a significant correlation with CR (P=0.043). Prolonged OTT and lower values of RDI and RDI/NTS showed a significant correlation with recurrence within 12 months (P=0.022, 0.033 and 0.015, respectively). The lower values of RDI and RDI/NTS showed a significant correlation with distant metastasis as a first failure site (P=0.038 and 0.044, respectively). Patients with RDI/NTS ≥0.08 had a more favorable prognosis (P=0.045). Thus, RDI and RDI/NTS may become beneficial predictive factors in the treatment of LD-SCLC. However, further studies are required to confirm our preliminary results.

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.

Efficient preparation of cationized gelatin for gene transduction.

We previously reported gene therapy using cationized gelatin microspheres of φ20-32 µm, prepared from pig skin, as a transducing agent, but although the gelatin offered various advantages, its yield was extremely low (only 0.1%). In this study, we markedly improved the yield of φ20-32 µm cationized gelatin microspheres and prepared a newly less than φ20 µm cationized gelatin. Conventionally, cationized gelatin is prepared by cationization, particulation by agitation, and cross-linking. The yield is determined by the particulation step, for which we had used a three-necked distillation flask of 500 mL and an agitation speed of 420 rpm. The yield was significantly increased from 0.13 ± 0.02% to 8.80 ± 1.90% by using a smaller flask of 300 mL and an agitation speed of 25000 rpm (p ＜ 0.01). We could also prepare cationized gelatin of less than φ20 µm, which had not been possible previously. We confirmed that efficient gene introduction into peritoneal macrophages could be achieved with the new cationized gelatin.

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.