Capecitabine monotherapy had activity in recurrent/metastatic nasopharyngeal carcinoma (NPC) as demonstrated previously in a small pilot study. We conducted a retrospective review of patients who received capecitabine for recurrent and metastatic NPC to further evaluate its clinical benefits.
Forty-nine patients with recurrent and metastatic NPC received capecitabine at a dose of 1–1.25 G/m2 twice daily for 14 days in 3-week cycles. Disease sites were locoregional in 29%, distant in 45% and locoregional plus distant in 26%. All except one had prior platinum-based chemotherapy for relapse or as adjunctive treatment. Median follow-up was 10 months (range: 3–41).
Treatment was generally well tolerated. Hand-foot syndrome was common and occurred in 86% (25% Grade 3). Grade 3 hematological toxicity occurred in 6%. Partial response rate was 31% (95% CI: 18%, 44%) and complete response rate was 6% (95% CI: 0%, 13%), for an overall response rate of 37% (95% CI: 23%, 50%). Median time-to-progression was 5 months and median survival was 14 months. One- and two-year survival rates were 54 and 26%, respectively. Significantly better survival was observed in patients treated for locoregional recurrence and those with severe hand-foot syndrome.
Capecitabine has single agent activity in NPC and severe hand-foot syndrome predicts favorable outcome. Based on our experience, capecitabine monotherapy should be considered in patients with recurrent/metastatic NPC.
Using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT), the clinical significance of 18F-FDG uptake was evaluated in patients with primary breast cancer.
Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC).
High SUV level was significantly correlated with tumor invasive size (≤2 cm) (P <0.0001), higher score of nuclear grade (P <0.0001), nuclear atypia (P <0.0001) and mitosis counts (P <0.0001), negative hormone receptor status (P = 0.001), high score of c-erbB-2 expression (P = 0.006), lymph node metastasis (P = 0.002), and IDC in comparison with invasive lobular carcinoma (P = 0.004). Multivariate analyses showed tumor invasive size, nuclear grade and estrogen receptor negativity were significantly correlated with SUV in primary breast cancer (P <0.0001,<0.0001, and <0.012, respectively), and nuclear grade was significantly correlated with SUV in tumors of invasive size 2 cm or less (P <0.0001). Tumors with high SUV (cutoff value 4.0) showed higher relapse and mortality rate compared to those with low SUV (P <0.0001).
High uptake of 18F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18F-FDG PET/CT could be a useful tool to pretherapeutically predict biological characteristics and baseline risk of breast cancer.
Gastric cancer is the leading cause of death from cancer in Japan. In 2004, there were 50 562 deaths from gastric cancer; they accounted for 15.8% of the total number of cancer deaths. Since 1983, under the Health Service Law for the Aged, gastric cancer screening has been conducted nationwide for all residents aged 40 years and over.
On the basis of the standardized method developed for the Japanese Guidelines for Cancer Screening, the efficacies of various methods for gastric cancer screening were evaluated and the guideline was developed.
Four methods for gastric cancer screening were evaluated: photofluorography, endoscopy, serum pepsinogen testing and Helicobacter pylori antibody testing. On the basis of the analytic framework involving key questions, 1715 articles, published from January 1985 to February 2005, were selected using MEDLINE, the Japanese Medical Research Database and other methods. After the systematic literature review, 10 articles were identified as direct evidence and 49 articles as indirect evidence. The studies that evaluated mortality reduction from gastric cancer included five case–control and two cohort studies for radiographic screening. On the basis of the balance of benefits and harms, the recommendations for population-based and opportunistic screening were formulated. Gastric cancer screening using photofluorography was recommended for both screening programs. The other methods were not recommended for population-based screening due to insufficient evidence.
The guideline for gastric cancer screening guideline was developed based on the previously established method. Gastric cancer screening using photofluorography is recommended for population-based and opportunistic screening in Japan.
We previously reported that arterial infusion chemotherapy improved the response rate and survival of the patients with pancreatic cancer at advanced stages in an open trial. We conducted a Phase I trial of arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for advanced pancreatic cancer after vascular supply distribution via superselective embolization.
Patients were treated after arterial embolization for hemodynamic change to restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery). Arterial infusion chemotherapy consisted of gemcitabine in doses that were increased from 600 to 1000 mg/m2 in subsequent cohorts on Day 1 plus continuous infusion of 5-fluorouracil 300 mg/m2/day on Days 1–5 every 2 weeks.
Twelve patients were enrolled. The maximum tolerated dose of gemcitabine was determined to be Level 3 (1000 mg/m2). Only very mild hematological and non-hematological toxicities were noted. The overall response rate was 33.3%. The median survival time was 22.7 (95% CI; 9.5–24.5) months and the 1- and 2-year overall survival rates were 83.3 and 25.0%, respectively.
Arterial infusion chemotherapy using 1000 mg/m2 gemcitabine on Day 1 and 300 mg/m2/day 5-fluorouracil on Days 1–5 every 2 weeks warrants a Phase II study.
We investigated the interobserver variation in the prostate target volume and the trend toward the use of diagnostic computed tomography (CT) or magnetic resonance (MR) images for treatment planning.
Twenty-five radiation oncologists were asked to draw the external contour of the prostate on CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also answered a questionnaire regarding the use of diagnostic CT or MR images for the contouring.
Of the 25 physicians, 28% rarely or never referred to the diagnostic CT images. In contrast, the physicians tended to refer to the MR images more frequently. Approximately 50% of the physicians believed in the usefulness of contrast-enhanced images for the delineation of the prostate. As for the variation of the prostate contouring, the median craniocaudal prostate length was 36 mm (range, 21–54 mm), and the median prostate volume was 43.5 cm3 (range, 23.8–98.3 cm3). The interobserver variability was not significant in the duration as a radiation oncologist, the board certification status as radiation oncologists, and the number of treatment plans developed for prostate cancer during the last 1 year.
A wide variety of the definitions of the prostate was found among Japanese radiation oncologists.
As a risk classification system of metastatic germ cell tumors, the International Germ Cell Consensus (IGCC) classification was proposed in 1997 and has received broad approval. Since the IGCC classification was based on patients treated between 1975 and 1990, we aimed to investigate whether survival has improved for more recently treated Japanese patients.
We analyzed 296 patients with metastatic germ cell tumors treated at seven hospitals in Japan between 1990 and 2001. These cases are classified as good, intermediate or poor prognosis groups by the IGCC classification. The 5-year progression-free and the 5-year overall survivals were calculated for each prognosis group.
The median follow-up period of all patients was 53 months. In 227 non-seminomatous germ cell tumor cases, the 5-year progression-free survival (95% confidence interval) for good (n = 55), intermediate (n = 106) and poor (n = 66) prognosis was 96% (91–100), 71% (62–80) and 52% (39–65) (P < 0.001), respectively. The 5-year overall survival was 94% (88–100), 81% (73–89) and 61% (49–73) (P < 0.001), respectively. In 69 seminoma cases, the 5-year progression-free survival for good (n = 64) and intermediate (n = 5) prognosis was 78% (67–89) and 80% (45–100) (P = 0.98), respectively. The 5-year overall survival was 90% (82–99) and 80% (45–100) (P = 0.49), respectively.
There was a trend of increase in survival for any risk groups and, in particular, large increase in survival for patients with a poor prognosis. This increase is most likely attributed to more effective chemotherapy regimens and more extensive care in the experienced institutes.
To reduce cancer mortality, effective screening should be implemented properly. In Japan, the Research Group for Cancer Screening developed screening guidelines; however, the development process was not well established.
Based on the development processes of other guidelines, an original method, unique to Japan, was established to develop the Japanese cancer screening guidelines.
The guideline development process involved the following steps: topic selection, development of the analytic framework, systematic literature review, translation to recommendations, consultation and publication. Mortality reduction related to cancer screening was evaluated using both direct and indirect evidence. To select appropriate articles, an analytic framework for cancer screening program with key questions was developed. Direct evidence was defined as a single body of evidence that established the linkage between screening and health outcomes such as mortality and incidence. The use of indirect evidence to determine the level of evidence was limited to situations where test accuracy could be compared with that of a method whose evidence was supported by randomized, controlled trials. Eight levels of evidence were defined based on the study design and quality. The benefits of each screening modality were determined based on the level of evidence according to the results of the systematic review. Balancing the benefits and harms, five grades of recommendation were formulated for population-based and opportunistic screening. After organized consultations, three types of guidelines were published.
We developed a unique, standardized method for developing cancer screening guidelines in Japan. Based on this process, previously developed cancer screening guidelines have been revised.
We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.
Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.
In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed ~1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.
For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.
Salvage surgery after definitive radiotherapy with or without chemotherapy is still controversial, especially in cases of hypopharyngeal cancer because of the poor prognosis and surgical complications. Irradiation of the skin results in loss of flexibility of the skin and impairment of the normal healing processes, thereby increasing the risk of wound infections, which could be potentially life-threatening. In an attempt to diminish the risk of major complications, we performed planned cervical skin replacement with salvage total pharyngolaryngectomy (TPL).
From 2005 to 2006, six patients underwent salvage TPL and cervical reconstruction with a deltopectoral flap at our hospital. The cervical skin replacement was determined pre-operatively and not according to the intraoperative status.
There were no major post-operative complications. Both the prolongation of the operation time and of the duration of hospitalization were within acceptable limits.
Planned cervical skin reconstruction appears to be an appropriate and acceptable procedure with salvage pharyngolaryngectomy to avoid major complications.
S-1, an oral fluoropyrimidine carbamate, is an active and well-tolerated agent against solid cancer. However, the clinical efficacy of S-1 in patients with metastatic breast cancer has not been determined.
We retrospectively evaluated the efficacy of S-1 and identified its adverse effects in patients with metastatic breast cancer who had failed to respond to prior chemotherapy regimens. All the patients were treated at the National Cancer Center Hospital and received S-1 twice daily at a dose of 80 mg/m2 for 4 weeks, followed by a 2-week rest interval.
Between 2003 and 2007, 37 women with metastatic breast cancer received S-1 as a third line or greater chemotherapy regimen. All the patients had been previously treated with both anthracyclines and taxanes prior to S-1 chemotherapy. The median order of S-1 administration was as a fifth-line treatment, and 23 patients (62%) received S-1 as their final anticancer drug. One (3%) partial response and two (5%) stable diseases were observed. The median time to progression (TTP) was 84 days. Grade 2 adverse events, such as diarrhea, stomatitis and neutropenia occurred in 5 (16%), 1 (3%) and 1 (3%) patients, respectively.
S-1 was safety administered to heavily treated metastatic breast cancer patients with limited efficacy. Further evaluation of S-1 is necessary to elucidate its clinical role in breast cancer treatment.
A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.
Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m2, iv on days 1 and 8; and doxifluridine, 600 mg/m2, po on days 1–14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.
From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49–75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.
The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
We investigated the pharmacokinetics of gemcitabine and its metabolite in two male patients (52 and 56-year-old) with advanced urothelial cancer receiving hemodialysis three times a week.
Gemcitabine, 1000 mg/m2 in 100 ml of saline, was intravenously administered for 30 min. The concentration of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) was measured at several given time points using a high-pressure liquid chromatography assay. Pharmacokinetic parameters were determined using the two-compartment modeling program.
Gemcitabine was rapidly eliminated from plasma even in patients with renal dysfunction. No obvious differences in pharmacokinetic parameters such as the t1/2, AUC and Cmax of gemcitabine were observed between the patients on hemodialysis and those with normal renal function in previous reports. On the other hand, dFdU showed a sustained level until hemodialysis was initiated. Hemodialysis could reduce the plasma dFdU level by approximately 50%.
According to the previous information, no dose modification of gemcitabine may be required for patients with renal impairment or hemodialysis. However, gemcitabine should be given with caution because only limited information is available, and the clinical effect of sustained and/or accumulated dFdU is unknown.
Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer.
We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method.
The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12–3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36–3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39–5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21–0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14–0.98; p = 0.05) among smokers.
It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.
We evaluated the efficacy and feasibility of high-intensity-focused ultrasound (HIFU) for localized prostate cancer.
Seventy patients received HIFU using Sonablate® 500 (Focus Surgery, IN, USA). In patients whose cancer was confined to only one lobe by multi-regional biopsies, total peripheral zone and a half portion of transitional zone were ablated (focal therapy). Otherwise, patients received whole organ ablation (whole therapy). Scheduled biopsies were performed at 6 and 12 months after treatment. Pre- and post-HIFU serum testosterone levels were measured.
The 2-year biochemical disease-free survival (DFS) rates in patients at low, intermediate and high risk were 85.9, 50.9 and 0%, respectively, (P = 0.0028). After 12 months, 81.6% (40/49) of patients were biopsy negative; 84.4% in patients who received whole therapy, whereas 76.5% in those with focal therapy. The 2-year biochemical DFS rates for the patients at low and intermediate risk was 90.9 and 49.9%, respectively, in patients with whole therapy, whereas 83.3 and 53.6% in patients with focal therapy. In patients without neoadjuvant androgen deprivation, serum testosterone levels continuously decreased after whole therapy, whereas no changes were seen in those with focal therapy. The patients whose follow-up biopsies were positive tended to have significantly higher changes in prostate-specific antigen levels than biopsy-negative patients.
In patients with low-risk prostate cancer, HIFU monotherapy resulted in comparable immediate cancer control with other modalities. Particularly, focal therapy might offer a feasible minimally invasive therapeutic option, which maintained serum testosterone level. To our knowledge, this is the first report that whole, but not focal, therapy affects the serum testosterone level.
The outcomes of patients with localized or locally advanced prostate cancer treated with external-beam radiotherapy are not well known in Japan.
Thirty-four institutions combined data on 679 patients with localized or locally advanced prostate cancer treated with a total dose ≥60 Gy between 1995 and 2002.
With a median follow-up of 46 months, the 5-year overall, clinical progression-free, and biochemical relapse-free survival rate were 93.0, 95.3 and 71.9% for all patients, respectively. The 5-year progression-free, and biochemical relapse-free survival rates according to the risk group were 100%, 90.8% in the low-risk group, 98.3%, 75.7% in the intermediate-risk group and 93.6%, 67.6% in the high-risk group, respectively. The multivariate analysis for biochemical relapse-free survival revealed that prostate-specific antigen (relative risk, 1.002; 95% CI, 1.001–1.003; P = 0.0041), Gleason score (relative risk, 1.166; 95% CI, 1.046–1.302; P = 0.0055), T classification (relative risk, 2.897; 95% CI, 1.999–4.230; P = 0.0000), pelvic irradiation (relative risk, 2.042; 95% CI, 1.328–3.273; P = 0.0008), and androgen abletion (relative risk, 0.321; 95% CI, 0.240–0.427; P = 0.0000) were significant prognostic factors. Only 1.1% of patients experienced late morbidity of Grade 3.
Radiotherapy for prostate cancer seemed to be effective, with little risk of normal tissue complications.
Height and early-life environments have received attention as risk factors for prostate cancer. However, the evidence is sparse in Japan. To elucidate the associations of height and early-life factors with prostate cancer risk in Japanese men, we conducted a hospital-based case–control study. In addition, to investigate whether the associations vary between prostate cancer and other major cancers, we conducted a comparative study within the same case–control study.
Study subjects consisted of 282 prostate cancer cases, 584, 461, 231, and 156 male stomach, lung, colon and rectal cancer cases, respectively, and 1730 male hospital controls, aged 50 and over admitted to a single hospital in Miyagi Prefecture from 1997 to 2003. Information on height and early-life factors including birthplace and stature at 12 years was collected using a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for each exposure variable.
A significant positive association was found between height and prostate cancer risk (OR, 1.52; 95% CI, 1.00–2.31, between the highest and lowest quartiles; P for trend = 0.03). A significant association of urban-born with prostate cancer risk was also found (OR, 1.48; 95% CI, 1.03–2.13). Analyses by stage revealed that height might be more strongly associated with the risk of advanced prostate cancer. For other major cancers, no significant association with height and early-life factors was observed.
Height and early-life factors were significantly associated with prostate cancer risk. Compared with other major cancers, these associations were specific to prostate cancer.
This study was aimed at investigating the effectiveness and safety of once-weekly epoetin beta for anaemic cancer patients receiving chemotherapy.
A total of 104 patients with a haemoglobin level of ≤11.0 g/dL were enrolled. Patients received a once-weekly subcutaneous dose of 36 000 IU epoetin beta for 12 weeks. If the increase in the haemoglobin level was <1.0 g/dL after 6 weeks, or a red blood cell transfusion was required between days 15 and 42, the dose of epoetin beta was increased to 54 000 IU from the subsequent week. The primary endpoint was the percentage of patients who achieved a haemoglobin increase of ≥2.0 g/dL; the haemoglobin response rate. Quality of life (QOL) was assessed using the Functional Assessment of Cancer Therapy-Anaemia (FACT-An) questionnaire.
The haemoglobin response rate was 66.3% among the 98 patients (breast cancer: n = 25; malignant lymphoma: n = 21; ovarian cancer: n = 20; lung cancer: n = 15; other cancers: n = 17) assessable for a haemoglobin response. Thirty-nine patients (39.8%) required a dose escalation to 54 000 IU. At the end of the study, QOL assessable patients (n = 96) showed a mean improvement in the FACT-An total fatigue subscale score (FSS) of 0.3 points from baseline. Patients with a haemoglobin response had a mean change in the total FSS of +3.2, compared with –3.4 for patients without a haemoglobin response. No serious adverse event of epoetin beta was observed.
Epoetin beta administered at an initial dose of 36 000 IU once-weekly was well tolerated, with increased haemoglobin levels and improved QOL in anaemic cancer patients receiving myelosuppressive chemotherapy.
The main purpose of this investigation was to measure the delay from the first symptom to treatment in esophageal cancer and to analyse the relation between the delay and stage at the time of treatment.
A total of 80 patients who were consecutively found to have esophageal cancer between 1 January 2007 and 30 July 2007 at Qilu Hospital of Shandong University in Jinan (China) were included in the retrospective study. Two groups of patients were compared, one group with good prognosis (patients in Stages I and II) and the other group with poor prognosis (patients in Stages III and IV). The symptom-to-treatment delay between the two patient groups was compared using the Mann–Whitney U-test.
The median symptom-to-treatment delay was 2.1 months (range from 0.5 to 24). The total symptom-to-treatment delay was made up with the following components: (i) delay from the first symptoms to first contacting the health-care system (69%); (ii) delay from first contacting the health-care system to histological diagnosis of esophageal cancer (20%); and (iii) delay from histological diagnosis to end point (11%). A significantly shorter median symptom-to-treatment delay was found for patients with Stages I and II compared with III and IV (P = 0.0177).
Long delays still occur in patients with esophageal cancer. A few months delay before final treatment of esophageal cancer may have an impact on the stage of the cancer, and thereby on the patients' prognosis. Shorting the delay may result in early detection of esophageal cancer.
High-dose thoracic radiation therapy (HDTRT) alone has been an alternative to surgery in stage I/II non-small cell lung cancer patients with medical co-morbidities and/or poor performance status. Here, we report on the outcome and safety of HDTRT at 3.0 Gy per fraction for reduced treatment duration.
HDTRT alone at 3.0 Gy per fraction was given to 35 patients (22 at stage I and 13 at stage II). The median age was 73 years old and 14 patients had ECOG performance above 2. The median radiation dose to the primary lesion was 60 (54–66) Gy over 27 (23–38) days, and the dose to the mediastinum was individualized.
After the median follow-up of 24 (3–72) months, local in-field progression developed in 11 patients (31.4%) and distant metastases in 14 (40.0%). The median survival period and the 3- and 5-year overall survival (OS) rates for all patients were 24.0 (95% CI: 13.57–34.43) months, 31.4 and 11.2%. Intercurrent deaths were observed in 11 patients. Treatment-related acute and subacute morbidities were observed in 20 patients (57.1%); however, there was neither treatment interruption nor long-term morbidity.
On the basis of the above observations, we achieved treatment outcomes comparable with those of conventional protracted fractionation schedules at considerably shorter duration and lower cost by HDTRT at 3.0 Gy per fraction.
To evaluate pathological complete response rate and to identify the predictor of response after primary systemic chemotherapy (PST) with weekly docetaxel and epirubicin for locally advanced breast cancer.
Sixty-three patients with locally advanced breast cancer received three cycles PST on day 1 and 8 of each 3-week cycle with epirubicin and docetaxel (epirubicin 45 mg/m2 intravenous bolus, docetaxel 35 mg/m2 in 100 ml normal saline infused 1 h), followed by surgery and adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil. The pathological complete response was defined as no invasive carcinoma in breast and axillary nodes after PST.
The median tumor sizes (by ultrasound) before and after PST were 6.2 and 2.5 cm, respectively. The negative estrogen receptor (ER) by immunochemical stain was found in 33 (52.4%) patients and HER-2/neu-overexpression in 12 (19.0%) patients. Clinical overall response rate (ORR) was 89% (95% confidence intervals (95% CI: 81–97), including 38% complete response (95% CI: 26–50), sonographical ORR was 97% (95% CI: 93–100). The pathological complete response were found in 11 patients (18%, 95% CI: 9–27), and 15(24%, 95% CI: 13–35) patients achieved breast only pathological complete response. Nine (27.3%) of thirty-three ER (–) patients and 5 (41.7%) of 12 HER2-positive patients achieved pathological complete response.
PST with weekly docetaxel and epirubicin were well-tolerated and very high pathological complete response rate was achieved in HER-2/neu-overexpression tumors.
Low levels of serum adiponectin are associated with increased risk and aggressiveness of obesity-related cancer. The purpose of the study reported here was to investigate the association between serum adiponectin levels and clinicopathological parameters of renal cell carcinoma.
Preoperative serum total and high-molecular-weight (HMW) adiponectin levels were measured in 118 patients with renal cell carcinoma, and their association with clinicopathological parameters was analysed.
There were no statistically significant associations between total adiponectin and HMW adiponectin and pathological stage, regional lymph node involvement, histological grade, histological type (clear cell carcinoma versus other types) or presence of venous invasion. Total and HMW adiponectin levels in patients with metastasis, however, were significantly lower than in patients without metastasis (P = 0.044 for total adiponectin and P = 0.041 for HMW adiponectin). Low total and HMW adiponectin levels were significantly associated with metastasis in patients with a normal BMI (<25 kg/m2) (P = 0.034 for total adiponectin and P = 0.028 for HMW adiponectin) but not in overweight and obese patients (P = 0.652 for total adiponectin and P = 0.489 for HMW adiponectin). Multivariate logistic regression analysis showed that total adiponectin level was an independent predictor of metastasis of renal cell carcinoma in all patients (P = 0.024, 95% CI = 1.031–1.560) and in patients with a normal BMI (P = 0.040, 95% CI = 1.043–6.534).
Serum total and HMW adiponectin levels were decreased in patients with metastatic renal cell carcinoma. Adiponectin might be a molecular link between obesity and the progression of renal cell carcinoma.
To determine complete resection and sphincter preservation rates, down-staging, local control and survival associated with concurrent chemoradiotherapy (CCRT) using a moderately high pelvic radiation dose before surgery in rectal cancer.
Fifty-seven patients with histologically proven adenocarcinoma of the mid to lower rectum were treated using preoperative CCRT and surgery. Median radiation dose to the pelvis was 5400 cGy (5040–5580 cGy). CCRT was administered during the first and fifth weeks of radiotherapy with bolus intravenous 5-fluorouracil (5-FU) 400 mg/m2/day and leucovorin (LV) 20 mg/m2/day for 5 days. Surgery was attempted 4–8 weeks after completing preoperative CCRT. Post-operative chemotherapy was then added for up to four cycles of intravenous 5-FU and LV.
Toxicities during CCRT were generally mild and manageable: Grade 1/2 anemia, 3.5%; Grade 1/2 leukopenia, 45.6%; Grade 3 leukopenia, 3.5%; Grade 1/2 diarrhea, 22.8%; Grade 1/2 abdominal discomfort, 7%; and perianal skin reaction, 5.3%. No late complication requiring surgical intervention occurred. Complete surgical resection with a negative resection margin was achieved in 98.2% of patients, and the down-staging rate was 52.6% (30/57; 95% CI 39.6–65.6%). Complete pathologic response was obtained in 5.3% patients (3/57; 95% CI 0-11.1%) and in other 2 patients only sporadic tumor cells nests were noted in surgical specimens. The sphincter preservation rate was 77.2% (44/57; 95% CI 66.3–88.1%). Of 30 patients with tumors located within 5 cm from the anal verge, sphincter preservation was possible in 18 patients (60.0%; 95% CI 47.3–72.7%). With a median follow-up duration of 40 months, overall and disease-free survival (DFS) rates over 3 years were 91.8% (95% CI 85.5–98.2%) and 79.7% (95% CI 71.2–88.2%), respectively. At univariate analysis, significant factors for DFS was LN involvement status (P = 0.024). Local and distant failure rates over the same period were 5.3 and 21.1%, respectively.
Preoperative CCRT produced encouraging down-staging rates and was found to facilitate complete resection and sphincter saving in distal rectal cancer with acceptable toxicity. Further studies are warranted using this moderately high radiation dose to the pelvis to improve the local control.
Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program.
Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50–80, (iii) serum prostate-specific antigen (PSA) ≤20 ng/ml, (iv) one or two positive cores per 6–12 systematic biopsy cores, (v) Gleason score ≤6, and (vi) cancer involvement in positive core ≤50% were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003. PSA was measured bimonthly for 6 months and every 3 months thereafter. Trigger of treatment recommendation was PSA-doubling time (PSADT) of ≤2 years or pathological progression at re-biopsy. Primary endpoint was ‘%PSADT > 2y’, which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of ‘%PSADT > 2y’ was expected to be >80%.
One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of ‘%PSADT > 2y’ was 71.2% (84/118, 95% CI: 62.1–79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired.
The primary endpoint, ‘%PSADT > 2y’, did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.
A high body mass index (BMI) and a low testosterone level were recently reported to be prognostic factors for prostate-specific antigen (PSA) recurrence following radical prostatectomy (RP). The goal of this study was to clarify their relationship and influences on biochemical recurrence after RP.
We analysed 126 patients whose data, including the pre-operative BMI and pre-operative serum total testosterone level, were available. All patients underwent RP at our institution between March 1998 and April 2006 without any adjuvant therapy or pelvic lymph node metastasis. The Cox proportional hazards model was used for the multivariate analysis regarding PSA recurrence for the variables of age, operation period, BMI, clinical stage, PSA, Gleason's sum, pre-operative serum total testosterone level and margin status.
There were no internal correlations among the parameters we used, even between BMI and the total testosterone level. The total testosterone level was not different between two BMI groups (BMI <26.4 and
The current study suggests that high BMI independently contributes to PSA recurrence but that the total testosterone level does not. Although the mechanism by which obesity promotes PSA recurrence in RP patients has not been established, careful observation is needed for patients with high BMI.
The prevalence of AIDS-related lymphoma (ARL) is increasing in South Korea. The aim of this study is to identify the clinical features of ARL in South Korea.
From 1998 through 2006, we retrospectively analysed a total of 23 cases of ARL from seven institutions.
The patients consisted of 20 males and 3 females at a median age of 40 (range, 20–72) on diagnosis of AIDS. ARL developed at their median age of 41 (range, 24–72). The histological diagnosis was aggressive B cell lymphoma in the majority, but rare T cell and NK/T cell lymphoma were also included. Ten of 23 (43.5%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. Fifteen of twenty-three patients were given combination chemotherapy with/without radiation, four were given radiation alone, and four did not receive any treatment against medical advice. Of 20 patients followed-up, nine were alive in remission, two alive in disease, one died of treatment related complication, four died of progressive lymphoma, four died of AIDS related causes. The response to treatment included CR in eight (44.4%), PR in four (22.2%) and PD in three (16.7%). The response to HARRT was evaluable in 13 patients based on CD4+ cell count and HIV viral load, among which nine (69.2%) responded. Estimated median survival time was 43.9 months.
Although the population of patients is small, this is the first clinical data analyses of Korean ARL patients. As a substantial portion of the patients remains alive disease free, the impact of HAART on the clinical course of ARL needs further follow-up and evaluation.