Radiotherapy of locally recurring colorectal tumors. Prognostic factors, follow-up diagnosis and results

From 1979 through April, 1985, 74 patients were treated by percutaneous irradiation for local recurrences of colorectal carcinomas. The treatment consisted of a contralateral irradiation up to a dose of 40 Gy and a small-volume boost up to 60 to 66 Gy. In case of progressive remote metastases, the treatment was finished at 50 Gy. 53 patients received a dose of 50 Gy or more and were followed for at least six months. The decisive prognostic parameter was the presence of remote metastases when the recurrence appeared (n = 32). The median survival was six months, in patients without remote metastases at this moment it was 15 months. A complete or considerable relief of pain was obtained in 78%; it continued for a median period of 8.5 months, although most of the patients showed a new local tumor progression after an interval of three to 26 months. Computed tomography showed only small regressions or, in most cases, unchanged volumes of the tumors.     

Sonographic diagnosis of head and neck tumors in association with therapy

Basing on the experience with 558 patients suffering from tumours or suspicious lesions in the head and neck region, sonographic pointers that have been inadequately noted so far, are pointed out to improve diagnosis, follow-up, and post-therapeutic care. Among the possibilities offered by sonography are: to confirm or exclude bony involvement of the mandible in tumours of the oral cavity and the oropharynx, to objectify the results of antineoplastic chemotherapy, to offer possibilities to optimize radiotherapy, as well as to show criteria for the early detection of a relapse under consideration of the primary therapy.     

Magnitude and clinical relevance of translational and rotational patient setup errors: a cone-beam CT study

PURPOSE: To establish volume imaging using an on-board cone-beam CT (CB-CT) scanner for evaluation of three-dimensional patient setup errors. METHODS AND MATERIALS: The data from 24 patients were included in this study, and the setup errors using 209 CB-CT studies and 148 electronic portal images were analyzed and compared. The effect of rotational errors alone, translational errors alone, and combined rotational and translational errors on target coverage and sparing of organs at risk was investigated. RESULTS: Translational setup errors using the CB-CT scanner and an electronic portal imaging device differed <1 mm in 70.7% and <2 mm in 93.2% of the measurements. Rotational errors >2 degrees were recorded in 3.7% of pelvic tumors, 26.4% of thoracic tumors, and 12.4% of head-and-neck tumors; the corresponding maximal rotational errors were 5 degrees , 8 degrees , and 6 degrees . No correlation between the magnitude of translational and rotational setup errors was observed. For patients with elongated target volumes and sharp dose gradients to adjacent organs at risk, both translational and rotational errors resulted in considerably decreased target coverage and highly increased doses to the organs at risk compared with the initial treatment plan. CONCLUSIONS: The CB-CT scanner has been successfully established for the evaluation of patient setup errors, and its feasibility in day-to-day clinical practice has been demonstrated. Our results have indicated that rotational errors are of clinical significance for selected patients receiving high-precision radiotherapy.     

Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer

PURPOSE: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. PATIENTS AND METHODS: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m(2)/day) and carboplatin (70 mg/m(2)/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38 days in concomitant boost technique. RESULTS: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p = 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. CONCLUSIONS: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.     

Cone-beam CT based image-guidance for extracranial stereotactic radiotherapy of intrapulmonary tumors

Cone-beam CT (CB-CT) based image-guidance was evaluated for extracranial stereotactic radiotherapy of intrapulmonary tumors. A total of 21 patients (25 lesions: prim. NSCLC n = 6; pulmonary metastases n = 19) were treated with stereotactic radiotherapy (1 to 8 fractions). Prior to every fraction a CB-CT was acquired in treatment position, errors between planned and actual tumor position were measured and corrected. Intra- and inter-observer variability of manual evaluation of tumor position error was investigated and this manual method was compared with automatic image registration. Based on CB-CTs from 66 fractions the discrepancy (3-D vector) between planned and actual tumor position was 7.7 mm +/-1.3 mm. Tumor position error relative to the bony anatomy was 5.3 mm +/-1.2 mm, the correlation between bony anatomy and tumor position was poor. Intra-observer and inter-observer variability of manual evaluation of tumor position error was 0.9 mm +/-0.8 mm and 2.3 mm +/-1.1 mm, respectively. Automatic image registration showed highly reproducible results (<1 mm). However, compared with manual registration a systematic error was found in direction of predominant tumor breathing motion (2.5 mm vs 1.4 mm). Image-guidance using CB-CT was validated for high precision radiotherapy of intrapulmonary tumors. It was shown that both the planning reference and the verification image study have to consider tumor breathing motion.     

Is chemosensitivity testing for peri-operative treatment planning in gastro-intestinal cancer by the human tumour colony assay worthwhile?

Based on the concept of a combined modality cancer treatment in surgical oncology, the use of the human tumour colony assay for routine chemosensitivity testing and prospective treatment planning was investigated in 204 surgical biopsies of primary human solid tumours. The majority of the tumours (135/204) were of gastro-intestinal (GI) origin. Sufficient growth for drug testing occurred in 29-67% of all tumours depending on the tumour type, with a mean of 36% in GI-carcinomas. Chemosensitivity testing in vitro against standard anti-cancer agents correlated well with clinical experience, 5-FU and FUDR being the most active drugs (27% respectively 24% sensitive tumours in vitro) in GI-carcinomas. Relatively good agreement of in vitro/in vivo correlations was seen with an overall of 25/32 correct predictions in GI and other tumours. Predictivity was particularly good for loco-regional chemotherapy. Nevertheless, the limited in vitro growth rate of gastro-intestinal tumour specimens and their chemoresistance restrict the use of this method-in particular with respect to individual treatment planning.     

Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells

PURPOSE: Published clinical studies provide conflicting data regarding the prognostic significance of carbonic anhydrase IX (CA IX) overexpression as an endogenous marker of tumor hypoxia and its comparability with other methods of hypoxia detection. We performed a systematic analysis of CA IX protein levels under various in vitro conditions of tumor hypoxia in HT 1080 human fibrosarcoma and FaDu human pharyngeal carcinoma cells. Because sorting of live CA IX positive cells from tumors provides a tool to study the radiosensitivity of chronically hypoxic cells, we modified and tested a CA IX flow cytometry protocol on mixed hypoxic/aerobic suspensions of HT 1080 and FaDu cells. METHODS AND MATERIALS: HT 1080 and FaDu cells were treated with up to 24 h of in vitro hypoxia and up to 96 h of reoxygenation. To test the effect of nonhypoxic stimuli, glucose and serum availability, pH and cell density were modified. CA IX protein was quantified in Western blots of whole-cell lysates. Mixed suspensions with known percentages of hypoxic cells were prepared for CA IX flow cytometry. The same mixtures were assayed for clonogenic survival after 10 Gy. RESULTS: Hypoxia-induced CA IX protein expression was seen after >6 h at < or =5% O(2), and protein was stable over 96 h of reoxygenation in both cell lines. Glucose deprivation abolished the hypoxic CA IX response, and high cell density caused CA IX induction under aerobic conditions. Measured percentages of CA IX-positive cells in mixtures closely reflected known percentages of hypoxic cells in HT 1080 and were associated with radioresistance of mixtures after 10 Gy. CONCLUSION: CA IX is a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. Except the time course of accumulation, all properties of this marker resembled our previous findings for hypoxia-inducible factor-1alpha. A modified flow cytometry protocol provided good separability of CA IX-negative and -positive cells in vitro and can be applied to sort chronically hypoxic cells from tumors.     

Late small bowel toxicity after adjuvant treatment for rectal cancer

Background For locally advanced rectal cancer surgery as sole treatment results in poor local control and survival. After adjuvant radiotherapy for locally advanced rectal cancer, small bowel toxicity has been the most frequent and serious side effect. The gain in survival and local control was accompanied by severe late chronic toxicity reducing the benefit of adjuvant treatment.Review Clinical factors, pathology and treatment of late small bowel toxicity after adjuvant radiotherapy for locally advanced rectal cancer will be discussed. This review will focus on different surgical and radiotherapeutic means reducing the risk of late small bowel damage.