Adjuvant Radio Research Articles

Repeated transoral laser microsurgery for early and advanced recurrence of early glottic cancer after primary laser resection

To analyze the oncological results of repeated transoral laser microresection (TLM) in case of failure after primary laser resection of early glottic cancer (pTis-pT2). Fifty-six patients with local or loco-regional recurrence of early glottic cancer were treated between 1988 and 2005 by repeated TLM followed, if necessary, by neck dissection and/or adjuvant radio- or radiochemotherapy. Data on overall survival, disease-specific survival, and loco-regional control rates were analyzed retrospectively and calculated by the Kaplan-Meier method. Forty-four patients (78.6%) presented with early local recurrence (rTis-rT2N0; Stage I/II) and 12 patients (21.4%) had advanced local or loco-regional recurrence (pT3 and pT4N0/N+; Stage III/IV). Three- and five-year overall survival rates for patients with early and advanced recurrence were 75.1% vs. 51.6% and 61.6% vs. 25.8%, respectively. The corresponding three- and five-year disease-specific survival rates were 87.2% vs. 85.7% and 81.0% vs. 85.7%, respectively. Three- and five-year loco-regional control was significantly higher for patients treated for early recurrence (67.6% vs. 27.5% and 63.6% vs. 27.5%, respectively; p=0.02). Salvage laryngectomy rates for patients with early and advanced recurrence were 9.1 and 25.0%, respectively. In patients with early local recurrence, anterior commissure involvement (n=11) did not affect the oncological results. In case of early local recurrence after primary TLM of early glottic cancer, further TLM seems to be justified as an organ-preserving treatment option. In contrast, salvage laryngectomy should be considered early for patients with advanced local or loco-regional recurrence.

Intraoperative radiotherapy during radical prostatectomy for intermediate-risk to locally advanced prostate cancer: treatment technique and evaluation of perioperative and functional outcome vs standard radical prostatectomy, in a matched-pair analysis

To evaluate a novel approach with intraoperative radiotherapy (IORT) administered in the surgical field, after pelvic lymphadenectomy (PL) and before radical retropubic prostatectomy (RRP), evaluating acute and late toxicity, complications and biochemical progression-free survival (bPFS), as the adequate treatment of locally advanced prostate cancer is still a controversial issue. Between June 2005 and October 2007, 33 consecutive patients with intermediate-risk or locally advanced prostate cancer were selected for PL + IORT + RRP. IORT was delivered by a mobile linear accelerator in the operating room (electron beam, 12 Gy at 90% isodose). According to the pathological findings further adjuvant radio- or hormone therapy could be administered. The median follow-up was 16 months. This group was compared retrospectively with a historical group of 100 patients who had undergone RRP and further adjuvant therapy, selected with equivalent criteria. The comparison was conducted as a matched-pair analysis. The perioperative outcomes (surgical time, estimated blood loss, blood transfusions, days of catheterization, days of drainage, days of hospitalization), continence as the functional outcome, acute and late toxicity, rate of complications and bPFS were evaluated and compared. The baseline characteristics of the two groups were equivalent but the node count and the number of positive lymph nodes was higher in the IORT group. The IORT group had longer surgery, and a shorter hospital stay and catheterization. There were no differences in continence rate, and no major complications in either group. The acute and late toxicity and bPFS were equivalent. A retrospective comparison and the short follow-up were the major limitations. IORT administered before RRP seems a feasible approach, with little effect on the variables evaluated.

Adenoviral‐mediated interleukin‐18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats

Glioma is the most common primary intracranial malignant tumor. Despite advances in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for patients with glioma remains poor. We have explored the effects of using genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in rats. Mesenchymal stem cells isolated from Sprague-Dawley rats can directly suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can also significantly inhibit the growth of glioma and prolong survival in C6 glioma-bearing models. MSCs producing Interleukin-18 infected by adenoviral vector inhibited glioma growth and prolonged the survival of glioma-bearing rats. Transplantation of IL-18 secreting MSCs was associated with enhanced T cell infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma.

Hypersensitivity pneumonitis associated with the use of temozolomide

The aim of the present study was to investigate a case of hypersensitivity pneumonitis associated with the use of temozolomide in the treatment of gliosarcoma. A 54-yr-old female developed dyspnoea, cough and hypoxia after surgical resection for gliosarcoma and adjuvant radio- and chemotherapy with temozolomide. A high-resolution computed tomography scan of the thorax showed a bilateral ground-glass pattern. Bronchoscopy with bronchoalveolar lavage and lung biopsies was performed. Bronchoalveolar lavage demonstrated significant lymphocytic alveolitis and transbronchial lung biopsies revealed lymphocytic infiltration with foamy macrophages, consistent with hypersensitivity pneumonitis. There was no evidence of other causes, including infections. After withdrawing temozolomide and initiating prednisolone therapy, the patient had no further pulmonary symptoms. To the present authors' knowledge, this is the first definitively described case of temozolomide-associated hypersensitivity pneumonitis.

Outcome of patients after treatment for a squamous cell carcinoma of the oropharynx

This study evaluates the oncologic outcome with regard to survival and locoregional tumor control in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) treated according to a uniform algorithm. Retrospective chart review. A total of 427 consecutive patients with OPSCC were treated from 1990 to 2006. Treatment modalities were surgery alone (n = 102), surgery with adjuvant radio(chemo)therapy (n = 159), and primary radio(chemo)therapy (n = 166). Study endpoints were the five-year overall survival (OS) and disease-specific survival (DSS) stratified for primary tumor subsite, stage, T and N category, and age. The five-year OS and DSS for the entire cohort were 57.9% and 68.6%, respectively. OS and DSS for surgery alone were 70.3% and 76.5%, for surgery with radiation 66.6% and 78.9%, and for primary radiation 40.8% and 52.6%, respectively. Survival was significantly better for low stages (stage I/II vs. III/IV), small tumors (T1/2 vs. T3/4), limited nodal involvement (N0/1 vs. N2/3), and younger age at diagnosis. Together with our previous study on quality of life, we were able to show that our selection process gives excellent oncologic outcome in combination with high levels of function and quality of life. Surgery alone for early OPSCC and surgery followed by radiation for advanced OPSCC remain valuable treatment options. Primary radiochemotherapy is a strong alternative for patients who are not candidates for function-preserving surgery.

Der Stellenwert der dorsalen Dekompression und Instrumentation im Behandlungskonzept von Wirbelsäulenmalignomen

From 1986 to 1990 50 patients with increasing spinal instability due to pathologic fractures of one or more vertebrae were operated in the Orthopedic Department of Mainz University Hospital. In the course of 57 operations anterior decompression and stabilization were performed 3 times, whereas dorsal spondylodesis was done with Cotrel-Dubousset's instrumentation (CDI) 32 times, with Luque's 7 times and with Harrington's 1 time; a combination of CDI and Luque was chosen in 2 cases, a combination of Harrington and Luque in 1 case. 3 times a single-stage combination and 4 times a two-stage combination of ventral and dorsal stabilization was used. The application of the CDI required no postoperative external support. 35 patients suffered from major neurologic deficits preoperatively--among them 11 from a complete and 6 from an incomplete paraparesis--which made spinal cord decompression necessary in advance of the dorsal stabilization. Of these, 16 improved significantly; however, deterioration of the neurologic status occurred in 4 cases with a paraparesis in 3 of them. Survival time postoperatively was approximately 13 months in 27 patients. 9 of these died within half a year after the operative intervention. Failure of fixation as a result of tumor lesion was found in 2 cases of CDI procedure and in 1 case of the Harrington instrumentation. All required a revisional operation. 3 patients developed a radiologic lysis of methylmethacrylate implants fixed by an anterior procedure. Posterior decompression and stabilization render possible resolution of spine pain as well as restoration of mobility until a few days before exitus letalis without restricting adjuvant radio- or chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary neural stem/progenitor cells expressing endostatin or cytochrome P450 for gene therapy of glioblastoma.

Despite recent technical improvements in surgical excision techniques and adjuvant radio- and chemotherapy, the clinical outcome of patients with grade IV astrocytoma (glioblastoma) remains very poor, with a median survival of less than 12 months. A promising approach to therapy employs gene-engineered neural stem/progenitor cells (NSCs) as a cellular therapeutic delivery system, to track glioblastoma cells and deliver anticancer molecules. However, most results on their tumor tropism have been derived by immortalized NSCs. We now report that primary murine gene-engineered NSCs displayed in vivo tropism for glioblastoma cells. Ten days after injection into the brain, many NSCs continued to express the transgene and the NSC marker, nestin. NSCs transduced with a retroviral vector co-expressing a secretable form of human endostatin and eGFP (NSC/endo-eGFP) released potentially antiangiogenetic concentrations of endostatin into the culture medium. Conditioned medium of NSC/endo-eGFP cells inhibited the growth of mouse pulmonary microvascular endothelial cells (PMVECs). A good correlation between endostatin levels and PMVEC growth inhibition was observed. In NSCs co-expressing cytochrome P450 2B6 (CYP2B6) and eGFP (NSC/CYP2B6-eGFP), the forced expression of CYP2B6 resulted in intracellular activation of CPA and subsequent cell death. In the presence of NSC/CYP2B6-eGFP, we observed CPA cytotoxicity to DsRed-expressing U87Mg glioma cells. In vivo treatment of intracranial GL-261 glioblastoma with NSC/endo-eGFP caused a 65% reduction in tumor size, compared to untreated control mice or mice treated with NSC/eGFP cells. Our data suggest that primary NSCs transduced with retroviral vectors expressing endostatin and/or CYP2B6 have a potential role in glioblastoma therapy.

Surgical impact on brain tumor invasion: A physical perspective

It is conventional strategy to treat highly malignant brain tumors initially with cytoreductive surgery followed by adjuvant radio- and chemotherapy. However, in spite of all such efforts, the patients' prognosis remains dismal since residual glioma cells continue to infiltrate adjacent parenchyma and the tumors almost always recur. On the basis of a simple biomechanical conjecture that we have introduced previously, we argue here that by affecting the 'volume-pressure' relationship and minimizing surface tension of the remaining tumor cells, gross total resection may have an inductive effect on the invasiveness of the tumor cells left behind. Potential implications for treatment strategies are discussed.

Malignant fibrous histiocytoma of the face: report of a case

BackgroundSoft tissue sarcomas in the head and neck region are rare and often present a difficult differential diagnosis. The aim of our presentation is to point out the complexity of the diagnosis, treatment and follow up.Case presentationAn eighty-seven year old female patient was referred to our unit with a fast growing brownish lump on the face. Four months beforehand, a benign fibrous histiocytoma (BFH) had been removed from the same location by excision biopsy with wide tumour-free resection margins. Excision biopsy of the recurrent lesion revealed a malignant fibrous histiocytoma (MFH). Radical tumour resection was completed by extended parotidectomy and neck dissection; the skin defect was covered by a regional bi-lobed flap. No adjuvant radio- or chemotherapy was administered. Full functional and cosmetic recovery was achieved; follow-up has been uneventful more than two years postoperatively.DiscussionMalignant transformation of BFH is extremely rare and if so, extended radical surgery may give a fair chance for a favourable outcome even in patients with advanced age.

Bystander Killing of Malignant Glioma by Bone Marrow–derived Tumor-Infiltrating Progenitor Cells Expressing a Suicide Gene

Adult stem cells are promising cellular vehicles for therapy of malignant gliomas as they have the ability to migrate into these tumors and even track infiltrating tumor cells. However, their clinical use is limited by a low passaging capacity that impedes large-scale production. In the present study, a bone marrow-derived, highly proliferative subpopulation of mesenchymal stem cells (MSCs)-here termed bone marrow-derived tumor-infiltrating cells (BM-TICs)-was genetically modified for the treatment of malignant glioma. Upon injection into the tumor or the vicinity of the tumor, BM-TICs infiltrated solid parts as well as the border of rat 9L glioma. After intra-tumoral injection, BM-TICs expressing the thymidine kinase of herpes simplex virus (HSV-tk) and enhanced green fluorescent protein (BM-TIC-tk-GFP) were detected by non-invasive positron emission tomography (PET) using the tracer 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG). A therapeutic effect was demonstrated in vitro and in vivo by BM-TICs expressing HSV-tk through bystander-mediated glioma cell killing. Therapeutic efficacy was monitored by PET as well as by magnetic resonance imaging (MRI) and strongly correlated with histological analysis. In conclusion, BM-TICs expressing a suicide gene were highly effective in the treatment of malignant glioma in a rat model and therefore hold great potential for the therapy of malignant brain tumors in humans.

Toxicity of adjuvant sequential chemo- and radiotherapy of high-risk endometrial carcinoma (HREC)—Results of a phase II multicenter feasibility NOGGO study

16074 Background: Isolated adjuvant radio- or chemotherapy (CHT) only reduces local or distant relapses in HREC without impact on overall-survival. Therefore a multicenter feasibility study on adjuvant sequential chemo- and radiotherapy of HREC was initiated in order to evaluate safety and toxicity. Planned number of patients was 40, if after 17 pts. no termination of therapy because of toxicity was necessary, study can be closed and a phase III-study can be initiated. The data on toxicity are presented. Methods: Eligibility criteria: adenocarcinomas G1/G2 stage IC or G3 stage IA-IC or all stages II and IIIA (histological), all tumours with more than 2 cm diameter in size or non endometrioid cancers stage IA-C, II and IIIA and all cases with vessel invasion. Surgery: abdominal hysterectomy with bilateral adnexectomy without lymphadenectomy or with pelvic and para-aortic lymphadenectomy and positive lymph nodes. Further: Karnofsky-Index > 70, normal bone marrow, kidney, and liver function with laboratory tests not higher than 1.5 times of the normal local reference values. CHT: 175 mg/m2 paclitaxel plus carboplatin AUC 5, q 3 weeks for 4 cycles beginning latest 6 weeks after surgery. Within 6 further weeks after CHT an external beam irradiation (total dose 50.4 Gy, 28 fractions with 1.8 GY/d) plus 3 intracavitary HDR-iridium-192- brachytherapy courses with 3 x 5 GY were performed. Results: To date 17 pts (mean 64.1 years) completed 68 cycles CHT and following radiotherapy. There was no termination of therapy. Grade III leucopenia was observed in 9 % with 2 pts. requiring prolongation of treatment interval. There were 3 and 1 % grade II anemia and thrombocytopenia respectively. Further grade II toxicity: alopecia 38, fatigue 12, nausea/emesis 3, sensory neuropathy 12 %. Administration of G-CSF (pegfilgrastim) and epoitin (darbepoetin) was necessary in 2 and 6 % of cycles. Conclusions: Adjuvant sequential chemo- and radiotherapy of HREC is feasible by safety and toxicity and a phase III study can be initiated. No significant financial relationships to disclose.

Das Merkel-Zell-Karzinom des Oberlides

Merkel cell carcinoma (MCC) of the skin is a rare form of cutaneous malignancy of neuroendocrine origin with a propensity to form cutaneous and lymphogenous metastases. The tumor, affecting predominately elderly patients, has a significantly higher incidence in female patients (80%) compared to male patients (20%). The mainstay of therapy is surgical resection with possible adjuvant radio- or chemotherapy. A case of a 78-year-old patient with a MCC of the upper lid without lymph node involvement or distant metastasis is described. The tumor was resected and the defect closed by a temporal skin flap performing a temporary cantholysis. The clinical follow-up revealed an undisturbed eye lid function without any clinical or radiological signs of a locoregional or distant recurrence.

Compliance to clinical guidelines for early-stage epithelial ovarian cancer in relation to patient outcome

Objectives To assess compliance to current surgical staging and adjuvant treatment guidelines for patients with early-stage epithelial ovarian carcinoma and its impact on overall survival. Methods Patients diagnosed between 1991 and 1997 with early-stage ovarian cancer were recruited from the Regional Cancer Registry of the central region in the Netherlands. Demographic data, tumour characteristics, surgical findings and therapeutic data were abstracted from medical records. Patients were classified into optimal and non-optimal surgical staging. Overall survival was estimated using Kaplan–Meier method. To adjust for age hazard ratios for overall survival were estimated with a Cox Proportional Hazards model. Results One hundred and twenty-five patients were included in the study, 41 of them (32.8%) were optimally staged. Guidelines for adjuvant radio- or chemotherapy were adequately followed in all 62 grade I patients and in 44 out of 59 grade II and III patients (74.6%). During 734.6 person-years of follow up 31 patients died. Five-year overall survival figures were 97.6% in the optimally staged group and 68.5% in the non-optimally staged group. Patients who were non-optimally staged, had a significant higher risk to die than those who were optimally staged (HR: 7.4; 95% CI: 1.7–32.2). In patients with a grade II and III tumours, complete surgical staging still had a significant influence on survival (HR: 3.8; 95% CI 1.7–8.3). In women with grade II or III tumours, adjuvant radio- or chemotherapy administered in accordance to the guidelines did not improve overall survival regardless whether they were optimally staged or not. Conclusion Incomplete staging in early-stage ovarian cancer leads to gross mis-classification in grade II and III tumours and to a lesser extent in grade I tumours. This leads to undertreatment in both surgical and adjuvant therapy. Subsequently unnecessary deaths may occur. More effort must be put in identifying obstacles interfering with compliance of guidelines

59. Targeted Gene Therapy of Malignant Glioma with Adult Stem Cells

Malignant gliomas still have a dismal prognosis despite advances in neurosurgical resection and adjuvant radio- and chemotherapy. One major reason is their infiltrative growth pattern with single tumor cells migrating distantly from the solid tumor mass and infiltrating normal brain tissue. These cells are responsible for recurrent tumors near the resection cavity or even far away from it and should therefore be the main target cell population for new therapeutic interventions.

Adjuvante und palliative Chemotherapie des kolorektalen Karzinoms in Deutschland außerhalb kontrollierter Studien

Colorectal cancer is the second most common malignant tumour in Germany with an unfavorable prognosis especially in a locally advanced or metastasizing stage. Although adjuvant and palliative chemotherapy significantly improve 5-year survival, consensus recommendations have in the past been inadequately transformed into clinical practice. It was the aim of this study to analyse the implementation of existing guidelines in a cohort from a defined area of Germany. In a multicentre study done between January 2000 and January 2002, tumour stage, primary care, adjuvant or palliative chemotherapy and follow-up of 444 patients (216 males, 228 females) with newly diagnosed colorectal cancer were recorded. 301 patients had colonic and 143 patients rectal cancer. The median age at diagnosis was 65 11.3 years. 36 of 96 (38%) patients with stage II colon cancer and 66 of 87 (76%) with stage III disease received adjuvant chemotherapy. 8 of 51 (16%) patients with rectal cancer stage II and 22 of 38 (58%) patients with stage III underwent adjuvant radio- and chemotherapy. The 68 of 84 (81%) patients with stage IV CRC who received palliative chemotherapy were given almost exclusively 5-FU monotherapy. Initial or sequential combination chemotherapy with oxaliplatin or irinotecan were performed in only 24 of 84 (29%) patients. Stage III colon cancer was predominantly treated according to the existing standard guidelines. In contrast combined radio- and chemotherapy for rectal cancer stage II and III was only performed in one third of the patients, another third receiving neither adjuvant radiation nor chemotherapy. Initial combined or sequential combined chemotherapy for metastasizing colorectal cancer was rarely performed.

Population-Based Registration of Unselected Colorectal Cancer Patients: Five-Year Survival in the Region of Bonn/Rhine-Sieg, Germany

Epidemiological data of colorectal cancer are sparse and often incomplete. Therefore, we initiated a population-based examination of five-year survival of colorectal cancer patients. For complete registration, diagnosis and tumour stage of all patients in the region of Bonn/Rhine-Sieg were assessed independently according to reports of medical practitioners and pathologists. Each patient was followed by a standardised questionnaire during a period of five years. Between June and November, 1994 348 patients were registered. Median age at diagnosis was 69 years for males (n = 160) and 72 years for females (n = 188). According to the UICC classification 18, 26, 23 and 26 % had stage I-IV tumours, respectively; the tumour stage remained unclear in 7 %. Adjuvant (radio)-chemotherapy was indicated in 89 patients, but only 49 % of these were treated. Five-year overall survival (OS) and relative overall survival were 41 and 54 %, respectively. Although disease-free survival (DFS) was significantly better for early stage colorectal cancer, OS did not differ significantly between stage I and stage III tumours. Young patients diagnosed before the age of 50 had a significantly lower DFS. These data were comparable with other European countries but were lower than data reported in the USA. The high rate of patients with stage IV colorectal cancer and the low proportion of patients receiving adjuvant (radio)-chemotherapy according to international or national consensus recommendations were disappointing. Although data were comparable with other European countries more efforts are necessary to establish effective screening programs for asymptomatic patients and to increase the willingness for standardised adjuvant treatment.

Das Epithelioidsarkom der Hand, selten primär richtig diagnostiziert

The epithelioid sarcoma of the hand is often misdiagnosed. This tumor occurs most frequently in children and young adults, has an uncharacteristic course, and carries a high risk for local recurrence and metastases. The characteristic histopathology is helpful in establishing the correct diagnosis. Differential diagnosis includes synovialoma, fibromatosis and Dupuytren's contracture. Multinodular appearance is not uncommon. Three young patients (one male and two female) were operated on the hand for treatment of Dupuytren's contracture, synovialoma and fibromas, respectively. The necessity for surgical revision in these patients led to a reevaluation of the primary histological data. The original diagnosis having been found to be incorrect, the correct diagnosis was established namely, epithelioid sarcoma. Surgical revision was performed, which involved partial amputation of the extremity. None of the patients underwent adjuvant radio- or chemotherapy. The patients were followed-up for ten, four and two and a half years, respectively. They are currently free of recurrences. Prognosis depends on the size and the location of the tumor. Adequate treatment requires early radical excision; amputation may be required if the primary tumor is located in the fingers or treatment of recurrent growth. The tumor tends to metastasize via the lymphatic system. Patients must be monitored with yearly lung X-rays since recurrence or metastasis may occur many years after the initial diagnosis and treatment.

Optimized radiation of pelvic volumes in the clinical setting by using a novel bellyboard with integrated gonadal shielding

The purpose of this study was to determine the feasibility of a custom-made, modified bellyboard to reduce radiotherapy side effects on small bowel, bladder, skin, and male gonads. Two groups of 10 consecutive patients each were treated from January 2003 through April 2003 with neoadjuvant (45 Gy) or adjuvant (54 Gy) radio(chemo)therapy in single fractions of 5 days a week 1.8 Gy for rectal carcinoma, using a photon energy of 15 MV. One group was positioned in a prone position without an immobilization device, the other group was positioned on our bellyboard. Treatment planning was calculated by using a 4- and a 3-field box technique. Differences in the dose of organs of risk were calculated. For 1 male patient, a gonadal shielding was developed and integrated. All patients examined with the bellyboard demonstrated an anterior and cranial dislocation of the small bowel. Using a 4-field box, the mean dose to the small bowel of patients treated on our bellyboard was 56.5% as compared to 63.1% when treated without the bellyboard. When a 3-field box was used, the mean dose to the small bowel was 52.4% when the bellyboard was used, as compared to a mean dose of 63.1% without the bellyboard. Regarding the dose volume effects to the bladder, the mean dose for patients treated with a 4-field box was about 14.5% higher as compared to patients treated with a 3-field box. The mean dose to the hip joints and skin also depended on the radiation technique. The patient who received gonadal shielding received a maximal total gonadal dose of about 75.0 cGy in single fractions of maximal 3.0 cGy (TL-dosimeters). Daily setup variations evaluated by a beam’s-eye view were similar in both groups and ranged from 0.5 cm 1.0 cm. For daily use, our bellyboard appears to be an ideal compromise due to effectiveness, its easy handling, and reproductive positioning; moreover, it can also be used in combination with gonadal shielding.

Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.

Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.