Preoperative Adjuvant Treatment Research Articles

Validity of Norwegian Rectal Cancer Registry data at a major university hospital 1997–2005

Background. The Norwegian Rectal Cancer Registry (NRCR) has been used extensively to monitor patient treatment and outcomes since its establishment in 1993. Control of data validity is crucial to ensure reliable information, but an audit of the NRCR data validity has not been performed so far. This study aims to validate NRCR data on patients diagnosed in the period 1997–2005, Department of Surgery, Haukeland University Hospital.Material and methods. The material comprises NRCR data on all 482 patients diagnosed with rectal cancer in the period 1997–2005 at a major Norwegian university hospital. We checked 50 variables for discrepancies by comparing NRCR data with the medical records. All erroneous registrations were recorded.Results. One hundred patients (21%) had one or more data discrepancies in the registry, and 131 errors (0.5%) were noted in total. Sixteen variables (32%) had no erroneous registrations. Pre-operative CT and type of surgical procedure had the highest proportion of erroneous registrations (2.1%). Recorded errors were grouped into five variable categories: Pre-operative evaluation and adjuvant treatment (40 errors), surgical treatment (44 errors), pathological evaluation (20 errors), complications (7 errors) and oncological outcomes (20 errors). The majority of erroneous registrations (45%) were considered minor in severity, 27% were moderate and 28% were major.Conclusion. Assessment of the NRCR data from a nine-year period showed a good data validity in this hospital cohort.

High Expression of SOX2 and OCT4 Indicates Radiation Resistance and an Independent Negative Prognosis in Cervical Squamous Cell Carcinoma

Radiotherapy (RT) as a preoperative or postoperative adjuvant or primary treatment is the most common management modality for locally advanced cervical cancer. Radioresistance of tumor cells remains a major therapeutic problem. Consequently, we aimed to explore if the stem cell biomarkers SOX2 and OCT4 protein could be used to predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). These 132 patients were divided into two groups (radiation-resistant and radiation-sensitive groups) according to progress-free survival (PFS). Using pretreatment paraffin-embedded tissues, we evaluated SOX2 and OCT4 expression using immunohistochemical staining. The percentage of overexpression of SOX2 and OCT4 in the radiation-resistant group was much higher than that in the radiation-sensitive group (p<0.001 and p <0.001, respectively). The patients with high expression of SOX2 and OCT4 showed a shorter PFS than those with low expression. Our study suggests that the expression of SOX2 and OCT4 in tumor cells indicates resistance to radiotherapy and that these two factors were important predictors of poor survival in patients with LACSCC (hazard ratio [95% CI], 2.294 [1.013, 5.195] and 2.300 [1.050, 5.037], respectively; p=0.046 and p=0.037, respectively).

Biochemical outcome of small volume or insignificant prostate cancer treated with radical prostatectomy.

279 Background: We examined biochemical outcome of small volume prostate cancers (&lt;0.5 cc, SVCa), and insignificant prostate cancers (&lt;0.5 cc and Gleason scores &lt;7, InsigCa) treated with radical prostatectomy. Methods: Between April 2000 and May 2011, 609 patients with prostate cancer were treated with radical prostatectomy in Hirosaki University Graduate School of Medicine. Of these, 237 were excluded from analysis because of pre-operative adjuvant treatment. The remaining 372 patients were eligible in the present study. Along with the routine pathological assessment, tumor volume (TV) was assessed in all patients. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) levels of greater than 0.2ng/ml. Results: The median age was 68 (48 to 78) and median pre-treatment PSA was 7.50 ng/ml.Average follow up period was 45.9 month. Mean tumor volume (TV) was 2.16 cc. We investigated 372 patients and found SVCa (&lt;0.5 cc) in 60 patients (16.3%), and InsigCa in 14 patients (3.7%). The five year BCR-free survival rate for TV greater than or equal to 0.5 group and SVCa was 67.3% and 87.1% respectively. A significant difference was seen in the log-rank test between the two groups ( p=0.008). We could not identify BCR in InsigCa patients. Conclusions: Despite the limited number of cases, in our study InsigCa were clinically insignificant but in SVCa group 12.9% patients developed PSA failure after radical prostatectomy. SVCa is not identical to InsigCa. Therefore new biomarker is needed to examine what the prognostic relevance is of SVCa.

THE APPLICATION OF NANOMATERIALS IN DIAGNOSIS AND TREATMENT FOR MALIGNANT PRIMARY BRAIN TUMORS

Malignant primary brain tumors have a very high morbidity and mortality. Even though enormous advances have been made in primary brain tumor management, in the case of malignant primary brain tumors, current diagnostic strategies cannot identify exact infiltrating margins, surgery alone cannot achieve total mass resection, and adjuvant therapies cannot improve survivals. Therefore, there is an urgent need to explore novel strategies to diagnose and treat such infiltrating brain tumors. Nanomaterials, particularly zero-dimensional and one-dimensional platforms, can carry various compounds such as contrast agents, anticancer drugs and genes into brain tumor cells specifically. Thus, contrast agent-based nanomaterials can selectively present infiltrating tumor outlines, while anticancer agent-based nanomaterials can specifically kill malignant tumor cells. In addition, dual-targeting nanomaterials, multifunctional nanocarriers, theranostic nanovehicles as well as convection-enhanced delivery technology hold promise to increase drug accumulation in tumor tissues, which could largely improve anticancer efficacy. In this review, we will mainly focus on the application of nanomaterials in preoperative diagnosis, intraoperative diagnosis and adjuvant treatment for malignant primary brain tumors.

Surgical Treatment for Early Esophageal Squamous Cell Carcinoma

More studies are needed to clarify treatments and prognosis of early esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to review the outcome of surgical treatment for early ESCC, evaluate the results of a left thoracotomy for selected patients with early ESCC, and identify factors affecting lymph node metastases and survival. The clinicopathological data of 228 patients with early ESCC who underwent transthoracic esophagectomy with lymphadenectomy without preoperative adjuvant treatment were reviewed. The χ(2) test or Fisher's exact test were used to detect factors related to lymph node metastasis. Univariate and multivariate analyses were performed to identify prognostic factors. There were 152 males and 76 females with a median age of 55 years. Two hundred and eight patients underwent a left thoracotomy, and the remaining 20 patients with lymph nodes in the upper mediastinum more than 5 mm in short-axis diameter by computed tomography scan underwent a right thoracotomy. No lymph node metastasis was found in the 18 patients with carcinoma in situ, while lymph node metastases were detected in 1.6% (1/62) of patients with mucosal tumours and 18.2% (27/148) of patients with submucosal tumours. Only 7 patients showed upper mediastinal lymph node metastases in the follow-up. The 5- and 10-year overall survival rates were 81.4% and 70.1%, respectively. Only histologic grade (P<0.001) and pT category (P=0.001) significantly correlated with the presence of lymph node metastases. In multivariate analysis, only histologic grade (P=0.026) and pT category (P=0.008) were independent prognostic factors. A left thoracotomy is acceptable for selected patients with early ESCC. Histologic grade and pT category affected the presence of lymph node metastases and were independent prognostic factors for early ESCC.

The Relation Between Serum CEA Response and the CTscan Finding After Neoadjuvant Therapy in Rectal Cancer Patients

Serum Carcinoembryonic Antigen (CEA) levels are the most widely used tumor marker for colorectal cancer. Elevated serum CEA has been reported to be associated with an increased risk of relapse and poor patient outcome. Whether this marker would be altered with preoperative adjuvant treatment of rectal cancer prior to resection and can this alteration reflect any changes in the tumor have not been yet investigated. If so, this might guide us to predict curative from palliative resection and to correlate between the marker level and future tumor response to the adjuvant therapy. Aim: This review was undertaken to assess the effect of preoperative neoadjuvant therapy on serum CEA level and the re- lationship between these effect on CEA and changes of the tumor in CT scan in advanced rectal cancer patient before de- finitive surgery. Methods: Between January 2002 and October 2007, a retrospective review using the colorectal database for all rectal can- cer patients treated in King Faisal Specialist Hospital and Research Center was performed. All patients received preopera- tive long course radiotherapy alone, or combined with 5- fluorouracil. Serum CEA and CT scan was done for the patients before starting the neoadjuvant therapy, and repeated again prior to surgery. Surgical resection was planned 6 - 8 weeks following the completion of treatment. We determined the criteria of the tumor response in the CT scan findings and compared the results with the CEA level after the neoadjuvant therapy. Results: Out-off the 77 patients, 38 received radiotherapy alone, while 39 patients received chemoradiotherapy, CT scan was done for all patients in both groups (pre and post neoajuvent therapy). Patients divided into 2 groups based on the CT scan findings to: CT responder and CT non-responder patients. In the radiation only group, 21 (55 %) patients had raised CEA levels before the treatment, 18 (86%) of them showed a decrease in CEA with CT response, while 3(14%) patients' demonstrated further increase and CT non-response. 17(45%) patients with normal CEA. 15 (89%) of them showed normal CEA post treatment 12 (80%) of them showed CT response and 3 of them shows CT non-response. 2/17 (11%) patients showed further increase in CEA level and CT non-response as well. In the chemoradiotherapy group, 17 (43%) patients had high CEA level before the treatment. 16 (95%) of them showed a decrease in CEA and CT response while 1(5%) patient showed increase in CEA level and CT non-response post treat- ment. 22/39(57%) showed normal CEA where all of them remained in normal level post treatment and only 1 patient (5%) showed CT non-response. All patients with CEA and CT scan response are operable patients and we can consider them for curative resection, while all patients with CEA and CT scan non response are non operable or can get a palliative treatment due to ( metastasis or carcinomatosis). 4 patients of normal CEA post treatment CT scan shows ( increase in thickening and single new lesion in the liver with suspicious of metastasis ) but still operable patients with intension to cure. Conclusions: There is an obvious relation between serum CEA level and CT scan findings during neoadjuvant therapy. CEA level post neoadjuvent therapy can differentiate between operable and non operable patients. CT scan can be used for patients with increase CEA level as further investigation before surgery and can be eliminated for those with CEA normal or dropped level. Further studies are needed to correlate this finding with post operative histopathological finding and patient outcome

Outcomes of Japanese breast cancer patients treated with pre‐operative and post‐operative anastrozole or tamoxifen

The present study examined long-term efficacy outcomes in a subgroup of postmenopausal, estrogen receptor-positive Japanese breast cancer patients from the Pre-Operative "Arimidex" Compared with Tamoxifen trial, following pre-operative (3 months) and post-operative (5 years) adjuvant treatment with either anastrozole or tamoxifen. Patients with large, potentially operable, locally-advanced breast cancer were randomized to receive anastrozole (1 mg/day) plus tamoxifen placebo or tamoxifen (20 mg/day) plus anastrozole placebo pre-operatively. After surgery at 3 months, patients continued on the same study medication as adjuvant therapy for up to 5 years or until recurrence, intolerable toxicity or withdrawal of patient consent. Recurrence-free survival and overall survival were measured from the date of randomization to the date of recurrence or death, whichever occurred first. Patients were monitored for adverse events throughout the study period and up to 30 days following administration of the last study medication. During post-operative adjuvant therapy, 4/48 (8%) anastrozole and 25/49 (51%) tamoxifen patients experienced recurrence. There was a significant difference in recurrence-free survival between the two groups (hazard ratio 0.14; 95% confidence interval 0.05-0.41; P = 0.0003). There was a significant increase in overall survival with anastrozole (0.21; 0.05-0.96; P = 0.0436) and there were 2/48 (4%) and 10/49 (20%) deaths with anastrozole and tamoxifen, respectively. Most patients responding to pre-operative therapy remained recurrence-free. Sequential pre-operative/post-operative treatment with anastrozole resulted in lower recurrence and death rates, compared with tamoxifen.

El abordaje multidisciplinar es útil para la optimización de la hemoglobina preoperatoria en cirugía neoplásica colorrectal

Introduction Optimising haemoglobin (Hb) levels less than 13 g/dl in the preoperative period can reduce the transfusion rate. With this aim, we developed a multidisciplinary protocol in our hospital for the treatment of patients proposed for colorectal cancer surgery. Patients and method A study was conducted on 437 patients who had surgery performed for colorectal cancer in the period 2005-2009. The data recorded were: demographic data, Hb and iron metabolism (Fe) at the time of diagnosis, Hb on the day of the surgery and on discharge, tumour location, preoperative adjuvant treatment (chemotherapy and/or radiotherapy), tumour stage (TNM), iron treatment, transfusion rate, and complications at 30 days. Patients were classified into Group A; Hb < 13 g/dl and/or abnormal Fe metabolism, and Group B; Hb > 13 g/dl and/or normal Fe metabolism. Results Of the total, 53.3% were in Group B and were treated with Fe; 73.6% intravenous (IV), and the rest oral. The mean dose of IV Fe was 867 mg. The mean intraindividual difference between the Hb on the day of surgery and at the initial value, increased by 0.6 g/dl in Group A, while it decreased by 0.8 g/dl in Group B. The mean intraindividual difference between the Hb at discharge and the diagnosis decreased by 0.4 g/dl in Group A compared to 2.5 g/dl in Group B. The overall transfusion rate was 8.6%. No statistically significant differences were observed in complications. Conclusions A multidisciplinary and early treatment of colorectal cancer enables patients with a low haemoglobin (Group A) to be optimised, as well as achieving a lower transfusion rate.

Hemipelvectomy- only a salvage therapy?

After the first hemipelvectomy in 1891 significant advances have been made in the fields of preoperative diagnosis, surgical technique and adjuvant treatment in patients with pelvic tumors. The challenging surgical removal of these rare malignant bone or soft tissue tumors accompanied by interdisciplinary therapy is mostly the only chance of cure, but bares the risk of intensive bleeding and infection. The reconstruction after hemipelvectomy is of importance for the later outcome and quality of life for the patient. Here, plastic surgery with microvascular free flaps or local rotational flaps improved the reconstruction and reduced infection rates. Average local recurrence rates of 14% demonstrate good surgical results, but 5 year survival rates of only 50% are described for some tumor entities, showing the importance of a multimodal collaboration. On a basis of a selective literature review the history, indications, treatment options and outcome of hemipelvectomies are presented.

The Multidisciplinary Approach is Useful for Optimising reoperative Haemoglobin in Colorectal Cancer Surgery

IntroductionOptimising haemoglobin (Hb) levels less than 13g/dl in the preoperative period can reduce the transfusion rate. With this aim, we developed a multidisciplinary protocol in our hospital for the treatment of patients proposed for colorectal cancer surgery. Patients and methodA study was conducted on 437 patients who had surgery performed for colorectal cancer in the period 2005–2009. The data recorded were: demographic data, Hb and iron metabolism (Fe) at the time of diagnosis, Hb on the day of the surgery and on discharge, tumour location, preoperative adjuvant treatment (chemotherapy and/or radiotherapy), tumour stage (TNM), iron treatment, transfusion rate, and complications at 30 days. Patients were classified into Group A; Hb<13g/dl and/or abnormal Fe metabolism, and Group B; Hb>13g/dl and/or normal Fe metabolism. ResultsOf the total, 53.3% were in Group B and were treated with Fe; 73.6% intravenous (IV), and the rest oral. The mean dose of IV Fe was 867mg. The mean intraindividual difference between the Hb on the day of surgery and at the initial value, increased by 0.6g/dl in Group A, while it decreased by 0.8g/dl in Group B. The mean intraindividual difference between the Hb at discharge and the diagnosis decreased by 0.4g/dl in Group A compared to 2.5g/dl in Group B. The overall transfusion rate was 8.6%. No statistically significant differences were observed in complications. ConclusionsA multidisciplinary and early treatment of colorectal cancer enables patients with a low haemoglobin (Group A) to be optimised, as well as achieving a lower transfusion rate.

High-quality clinical practice: laparoscopic rectal cancer resection

Modern current and emerging technology and scientific expertise drive the outcomes of patients with potentially curable, nonmetastatic solid cancer. Despite advances in multimodal therapeutics, current failure rates in both locoregional and distant systemic treatment remain alarmingly high resulting in the death of most patients with advanced colorectal cancer. Current day-to-day good clinical practice in the treatment of rectal cancer has to overcome several challenges. These difficulties include (1) accurate pretreatment TNM staging that aids decisions on preoperative or postoperative adjuvant treatment; (2) optimal surgical complete resection (R0) of the primary tumor and regional lymph nodes without surgical overtreatment that limits quality of life (QOL) and increases complications; and (3) selection of the best available adjuvant treatment, including radiotherapy and a safe and effective combination of chemotherapeutic and targeted agents for individual patients.

Is laparoscopic colorectal cancer surgery equal to open surgery? An evidence based perspective

Laparoscopic colorectal surgery (LCS) is an evolving subject. Recent studies show that LCS can not only offer safe surgery but evidence is growing that this new technique can be superior to classical open procedures. Fewer perioperative complications and faster postoperative recovery are regularly mentioned when studies of LCS are presented. Even though the learning curve of LCS is frequently debated when limitations of laparoscopic surgeries are reviewed, studies show that in experienced hands LCS can be a safe procedure for colorectal cancer treatment. The learning curve however, is associated with high conversion rates and economical aspects such as higher costs and prolonged hospital stay. Nevertheless, laparoscopic colorectal cancer surgery (LCCR) offers several advantages such as less co-morbidity and less postoperative pain in comparison with open procedures. Furthermore, the good exposure of the pelvic cavity by laparoscopy and the magnification of anatomical structures seem to facilitate pelvic dissection laparoscopically. Moreover, recent studies describe no difference in safety and oncological radicalness in LCCR compared to the open total mesorectal excision (TME). The oncological adequacy of LCCR still remains unproven today, because long-term results do not yet exist. To date, only a few studies have described the results of laparoscopic TME combined with preoperative adjuvant treatment for colorectal cancer. The aim of this review is to examine the various areas of development andcontroversy of LCCR in comparison to the conventional open approach.

Elevation of Serum NT-Pro BNP Correlates with Asymptomatic Cardiac Dysfunction Induced by Doxorubicin.

Abstract Background: Cardiac dysfunction is one of the major limitations of anthracycline treatment in cancer patients. Current reliable investigation to detect early cardiac damage from anthracycline is not available. There are several serum cardiac markers useful in other types of cardiomyopathy including NT-pro BNP, Troponin-T, and CK-MB. We chose to investigate potential application of these serum biomarkers in the cancer patients receiving anthracycline.Patients and methods: We prospectively collected data from a cohort of 52 female breast cancer patients who receiving doxorubicin and cyclophosphamide (AC) regimen every 3 weeks for 4 cycles for preoperative or postoperative adjuvant treatment. Cardiac function evaluations by echocardiography were done at baseline and post 4th cycle chemotherapy. Patients' blood samplings were serially measured for cardiac biomarkers at baseline, after 1st cycle, and after 4th cycle chemotherapy.Results: All patients were in good performance status with ECOG scale 0-1.The mean cumulative dose of doxorubicin in this study was 236.69 mg/m2. There was no symptomatic heart failure detected during study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from 70.73 ± 5.97% at baseline to 66.96 ± 5.48% (p&amp;lt;0.001). The severities of LVEF declination were 17.4% in grade1 and 3.8% in grade 2 by clinical toxicity criteria of NCI version 2. We found significant elevation of serum NT-proBNP (p = 0.044) following the first dose of chemotherapy when compared the measurements in patients who had reduction of LVEF to those with normal LVEF. Measurement of serum Troponin-T and CK-MB showed no significant correlation with changes in LVEF. Generalized-estimating-equations correlation analysis demonstrated that the reduction of fractional shortening (FS) was significantly associated with the elevation NT-pro BNP (r = -0.016, p = 0.014). At cutoff level 45 pg/mL, serum NT-proBNP had 100% sensitivity and 66.67% specificity for the detection of cardiotoxicity in patients under 50 year-old.Conclusion: Asymptomatic reductions in cardiac function are common in patients treated with doxorubicin. NT-pro BNP may serve as a potential convenient serum biomarker for early detection of cardiotoxicity induced by anthracycline. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4003.

Neoadjuvant therapy for advanced rectal carcinoma in China: Whether radiochemotherapy is superior to radiotherapy?

To verify whether the 30 Gy preoperative radiotherapy regimen is effective to advanced rectal cancer, and whether the preoperative chemoradiation offers an advantage in sphincter preservation and tumor control compared with irradiation alone. A total of 141 patients administered neoadjuvant treatment with resectable lower rectal carcinoma from 2002 to 2006 were collected retrospectively. The patients were divided into two groups: preoperative radiotherapy alone (30Gy by 10 fractions) (PRT group) and preoperative chemoradiotherapy (PCRT group). All patients underwent radical surgery after neoadjuvant treatment. The overall sphincter-preservation rate was 68.8% (97/141), with no significant difference between the two groups. The overall downstaging rate was 48.2% (68/141), including 4 patients completely response (2.8%). The T and N downstaging rate were 30.5% (43/141) and 53.8% (57/106) respectively, showing no statistically difference between the two groups. The 2-year overall survival rate was 93.6%; no survival benefit were observed in PCRT group. The 2-year cumulative local recurrence rates were similar as well (4.2% vs 6.7%, P=0.63). Two patients with severe marrow suppression higher than grade 3 and 1 patient with severe perineum ulcer was observed in PCRT group, which did not occur in PRT group. The preoperative adjuvant treatment of 30Gy radiotherapy alone may be an optional treatment for Chinese lower rectal carcinoma. Preoperative chemoradiotherapy does not show actual superiority compared with radiotherapy alone.

Neoadjuvant treatment for locally advanced esophageal cancer

Neoadjuvant therapy refers to preoperative adjuvant treatment based on the experiences of successful postoperative adjuvant treatment. The neoadjuvant therapy, which aims at increasing the possibility of cancer resection and improving patients survival, includes neoadjuvant chemotherapy, neoadjuvanl radiother-apy and neoadjuvant chemoradiation. Neoadjuvant chemoradiation may be the preferred neoadjuvant modality to increase resection rate and improve survival rate in patients with locally advanced esophageal cancer. Key words: Esophageal neoplasms; Chemotherapy, adjuvant; Badiotherapy, adjuvant; Survival

Current status of chemoradiotherapy for gastric cancer in Japan

Chemoradiotherapy (CRT) is the latest modality to be explored as a treatment for gastric cancer. Advances have been made in the United States with CRT as preoperative or postoperative adjuvant treatment. The rationale for preoperative or postoperative adjuvant CRT is to increase the curability of surgery or to prevent local recurrence, because standard surgery (D0 or D1) is not sufficient to control local relapse and improve survival where disease has become advanced. D2 is standard in Japan and D2 gastrectomy plus postoperative adjuvant chemotherapy with S-1 is currently standard for stage II and III cancer. Predominant recurrence patterns associated with these advanced disease stages are peritoneal dissemination and hematogenous metastasis. Local relapse or regional nodal recurrence is infrequent. CRT has been provided at only a limited number of institutions in Japan. The response to and safety of CRT for gastric cancer, in combination with various chemotherapeutic agents, are currently being studied in patients with unresectable or recurrent disease. Considering the high response rate, CRT seems to be an attractive option. In the near future, an examination will be made to ascertain whether neoadjuvant CRT in combination with extensive surgery has survival benefits in the treatment of locally advanced disease. Prior to this, a phase I/II study should be conducted in patients with unresectable or recurrent disease.

Surgical treatment of superficial esophageal cancer, its result and perspective

Our objective was to review the results of surgical treatment for superficial esophageal cancer to obtain the proper indications for the recently proposed esophagus-preserving strategies. The clinicopathological data of 290 consecutive patients with superficial thoracic or abdominal esophageal cancer who underwent esophagectomy with radical lymph node dissection without preoperative adjuvant treatment from 1984 to 2005 were examined in terms of tumor depth (ep, lpm, mm, sm1, sm2, sm3) and TNM pStage. The category sm1 was subclassified into sm1(0–200): lesions with 200 μm or less vertical tumor invasion depth in the submucosal layer, and sm1(200-): deeper sm1, to make our results referable to endoscopically resected lesions. About 8% of the patients with mm or deeper tumors were classified as TNM pStage IV. Around 20% of mm and sm1(0–200) tumors were associated with lymph node involvement. The 5-year survival rate of the 211sm cancers was 74.8% ± 3.3%; the mean survival time was 11.47 ± 0.68 years. The survival of TNM pStage IV patients was no worse than that of pStage IIB patients. Endoscopic mucosal resection/endoscopic submucosal dissection (EMR/ESD) is definitely indicated for ep or lpm lesions. Any tumors with deeper invasion including mm and sm1(0–200) should be regarded as potentially lymph node positive, and the most reliable treatment is still radical esophagectomy. Recent attempts to treat superficial esophageal cancer while preserving the esophagus should be performed with caution and with informed consent. A randomized controlled trial is necessary to compare the results of the recent esophagus-preserving strategies to the results of radical esophagectomy.

137 INVITED Treatment of localized gastric cancer: pre-operative versus post-operative adjuvant treatment

A sensitive and precise LC-ESI-MS/MS method for the determination of vandetanib (ZD6474) in human plasma and cerebrospinal fluid (CSF) using [13C,d3]-ZD6474 as an internal standard (ISTD) was developed and validated. Sample preparation consisted of a simple liquid–liquid extraction with tert-butyl methyl ether containing 0.1% or 0.5% ammonium hydroxide. ZD6474 and ISTD were separated on a Kinetex C18 column (2.6 μm, 50 mm × 2.1 mm) at ambient temperature with an isocratic mobile phase (acetonitrile/10 mM ammonium formate = 50/50, v/v, at pH 5.0) delivered at 0.11 mL/min. The retention time of both compounds was at 1.60 min in a runtime of three min. Detection was achieved by an API-3200 LC–MS/MS system, monitoring m/z 475.1/112.1 and m/z 479.1/116.2 for vandetanib and ISTD, respectively. The method was linear in the range of 0.25–50 ng/mL (R2 ≥ 0.990) for the CSF curve and from 1.0 to 3000 ng/mL (R2 ≥ 0.992) for the plasma curve. The mean recovery for vandetanib was 80%. Within-day and between-day precisions were ≤8.8% and ≤5.9% for CSF and plasma, respectively. Within-day and between-day accuracies ranged from 95.0 to 98.5% for CSF, and from 104.0 to 108.5% for plasma. Analysis of plasma from six different sources showed no matrix effect for vandetanib (MF = 0.98, %CV ≤ 4.97, n = 6). This method was successfully applied to the analysis of pharmacokinetic samples from children with brain tumors treated with oral vandetanib.

Reconstruction with pasteurized autograft‐total hip prosthesis composite for periacetabular tumors

With the development of preoperative adjuvant treatment, imaging techniques, and improvement of surgical technique, limb salvage is now possible even in patients with pelvic tumors. However, reconstruction after periacetabular resection is complicated and challenging. We retrospectively evaluated the usefulness of pasteurized autograft-total hip composite in pelvic reconstruction with regard to graft survival, union, graft-related complications, and functional outcome in 14 patients with periacetabular tumor. The 5-year and 10-year survival rates of the pasteurized bones were 64.3% and 32.1%, respectively. Major complications that necessitated graft removal included infection in three, fracture in two, and loosening in three patients. The average functional score of seven long-term successful patients was 25.6 (85.2%). In spite of the high complication rate, pasteurized autograft can be considered as an option for periacetabular reconstruction in the selected patients who meet the following criteria. First, iliopectineal and ilioischial lines are radiologically intact; second, the tumor volume is small (preferably less than 100 ml).

Rectal Cancer: Changing Patterns Of Referral For Radiation Therapy 1982-1997

The purpose of the present study was to evaluate the changing role of radiation therapy in rectal cancer and to determine the patterns of referral of patients during a 15-year period. From 1982 to 1997, 464 patients with carcinoma of the rectum were referred to the Department of Radiation Oncology, Royal Prince Alfred Hospital: 79% of patients had locoregional disease alone and 21% had distant metastasis. Radiation therapy consisted of irradiation (definitive or palliative) alone to the primary tumour in 9.7% of cases; preoperative radiation in 7.3% of cases: preoperative chemoradiation in 7.5% of patients: postoperative radiation in 15.3% of patients: postoperative chemoradiation in 12.31% of patients: treatment of pelvic recurrence in 23.5% of patients and treatment of metastases in 9.1% of patients. The remainder were treated elsewhere (1.9%) or not treated (13.4%). There was an average annual 14% increase in referrals over the accrual period. Recurrent rectal cancer decreased from approximately 30% of referrals during 1982-91 to approximately 10% in 1995-7. The use of postoperative adjuvant radiation reached a peak of 50% in 1993. The use of preoperative radiation increased suddenly in 1994 from < 10% to a sustained rate of approximately 30% of referrals. The use of chemoradiation commenced in 1990 for postoperative adjuvant treatment and in 1994 for preoperative treatment. The median survival time from initial diagnosis was 35 months, with 2- and 5-year survival rates of 62 and 28%, respectively. Survivals at 5 years for patients treated with preoperative and postoperative radiation (with or without chemotherapy) and with recurrent disease were 56, 44 and 21%, respectively. The present study illustrates the changing role of radiation therapy in the management of rectal cancer. The increase in referrals over the observation period was due to increased multidisciplinary input into the initial management of these patients, based on reported clinical trials. The steady increase in the use of adjuvant therapy has paralleled a decrease in referrals for treatment of recurrence and reflects current clinical results. The sequencing of adjuvant therapy is changing currently, with greater emphasis on preoperative adjuvant treatment. Currently most adjuvant therapy includes chemotherapy.