Gerhard G. Grabenbauer

The disappointing results of surgical therapy alone of ductal pancreatic cancer can only be improved using multimodal approaches. In contrast to adjuvant therapy, neoadjuvant chemoradiation is able to facilitate resectability with free margins and to lower lymphatic spread. Another advantage is better tolerability which consecutively allows applying multimodal treatment in a higher number of patients. Furthermore, the synopsis of the overall survival results of neoadjuvant trials suggests a higher rate compared to adjuvant trials. As there are no prospectively randomised studies for neoadjuvant therapy, the Interdisciplinary Study Group of Gastrointestinal Tumours of the German Cancer Aid has started such a trial. The study investigates the effect of neoadjuvant chemoradiation in locally resectable or probably resectable cancer of the pancreatic head without distant metastasis on median overall survival time compared to primary surgery. Adjuvant chemotherapy is integrated into both arms. The protocol of the study is presented in condensed form after an introducing survey on adjuvant and neoadjuvant therapy in pancreatic cancer.

Purpose: Tumor-infiltrating lymphocytes (TIL) are a possible prognostic factor in solid tumors. Cytotoxic TILs are generally considered as prognostically favorable, whereas regulatory T cells (Treg) may have adverse effects by virtue of their ability to inhibit effector cells. We have evaluated the effect of T-cell subsets on survival in patients with anal squamous cell carcinoma following radiochemotherapy.

Purpose: Treatment of recurrent and progressive meningiomas remains a challenge in clinical neurooncology. This study was designed to evaluate the efficacy of the simultaneous application of 3d-conformal radiotherapy and chemotherapy with hydroxyurea (HU). Patients and methods: Twenty-one patients with recurrent or progressive meningiomas (13 benign, 4 atypical and malignant, 4 with unproven histology) received treatment by fractionated 3d-conformal radiation (55.8–59.4 Gy) and concurrent HU, administered for a median time of three months with a daily dosage of 20 mg/kg. Response was evaluated using clinical and neuro-imaging data. Results: Disease stabilization was achieved in 14/21 patients (pts). Three pts had significant improvement of tumor associated neurological symptoms with imaging criteria of minor response. Progression free survival rates 1 year and 2 years after the initiation of radio-chemotherapy were 84% and 77%, respectively. At the time of analysis a total of 6/21 pts presented with progressive disease with a median time to progression of 59 weeks. Documented radio- and chemotherapy associated toxicity was minimal; only one patient discontinued HU treatment due to gastrointestinal symptoms such as anorexia and weight loss. Conclusion: Results obtained in this study indicate that treatment with HU and simultaneous radiotherapy is safe and effective with disease stabilization in the majority of patients. Randomized trials comparing radiosurgery versus radiochemotherapy versus fractionated radiotherapy are warranted.

This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival. Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the anal margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26-84) years. T categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m (2)/day as 120 hours of continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10 mg/m (2)/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1-16) years. Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (< or =75 percent vs. >75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival. With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.

According to recent data medial location of early breast cancer was associated with a higher risk of systemic relapse and breast cancer death compared with lateral location. This paper will focus on literature data and will also present own data on the prognostic impact of radiation therapy (RT) to internal mammary nodes (IMNs) in early breast cancer patients with medial hemisphere tumor location. Four large recent series of the literature reporting on > 50,000 patients with special focus on the impact of tumor location were evaluated. No systematic RT to IMNs was applied. At the Department of Radiation Oncology, University of Erlangen, Germany, a total of 822 patients (492 with lateral and 330 with medial lesions) with early breast cancer were treated by surgery and postoperative RT with or without chemotherapy (1985-1996). All patients with medial lesions received RT to IMNs by a mixed-beam approach (50% photons, 50% electrons) with a total dose of 50 Gy. In patients with lateral lesions RT was directed to the breast alone (50.4 Gy total dose, boost 12-16 Gy). The magnitude of the negative impact of medial tumor location was relatively similar in all four studies available. According to Zucali et al., the hazard ratio (HR) for distant metastases was 1.29. The HR for breast cancer-specific survival (BCSS) varied between 1.46 (Lohrisch et al.) and 1.31 (Gaffney et al.). 5-year systemic disease-free survival (SDFS) rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (p < 0.005). Corresponding BCSS were 75.7% and 80.8%, respectively (p < 0.03, Lohrisch et al.). For all 822 patients following treatment on IMNs, 5-year overall survival (OS) for lateral lesions and medial lesions was 76.2% and 79.1% (n.s.), and SDFS for lateral and medial tumors 72.6% and 72.9% (n.s.), respectively. No subgroup could be identified in which prognosis of patients with medial tumors was inferior to survival data for patients with lateral lesions. In postmenopausal women, OS was significantly better for patients with medial versus lateral tumors (77.6% vs. 72.7%; p = 0.05); in patients receiving adjuvant chemotherapy SDFS (5 years) was better for those with medial versus lateral tumors (80.5% vs. 67.6%; p = 0.02). Consistent literature data exist indicating a diminished survival in patients with inner versus outer quadrant breast cancer. According to our data, RT with a total dose of 50 Gy to IMNs in breast cancer patients with medial lesions was associated with OS and SDFS rates comparable to patients with lateral tumors.