Radiation-induced oesophagitis in lung cancer patients. Is susceptibility for neutropenia a risk factor?

BACKGROUND: Radiation-induced oesophagitis is a major side effect of concurrent chemotherapy and radiotherapy. A strong association between neutropenia and oesophagitis was previously shown, but external validation and further elucidation of the possible mechanisms are lacking. METHODS AND PATIENTS: A total of 119 patients were included at two institutions. The concurrent group comprised 34 SCLC patients treated with concurrent carboplatin and etoposide, and concurrent chest irradiation, and 36 NSCLC patients with concurrent cisplatin and etoposide, and concurrent radiotherapy, while the sequential group comprised 49 NSCLC patients received sequential cisplatin and gemcitabine, and radiotherapy. RESULTS: Severe neutropenia was very frequent during concurrent chemoradiation (grade: 4 41.4%) and during induction chemotherapy in sequentially treated patients (grade 4: 30.6%), but not during radiotherapy (only 4% grade 1). In the concurrent group, the odds ratios of grade 3 oesophagitis vs. neutropenia were the following: grade 2 vs. grade 0/1: 5.60 (95% CI 1.55-20.26), p = 0.009; grade 3 vs. grade 0/1: 10.40 (95% CI 3.19-33.95); p = 0.0001; grade 4 vs. grade 0/1: 12.60 (95% CI 4.36-36.43); p < 0.00001. There was no correlation between the occurrence of neutropenia during induction chemotherapy and acute oesophagitis during or after radiotherapy alone. In the univariate analysis, total radiation dose (p < 0.001), overall treatment time of radiotherapy (p < 0.001), mean oesophageal dose (p = 0.038) and neutropenia (p < 0.001) were significantly associated with the development of oesophagitis. In a multivariate analysis, only neutropenia remained significant (p = 0.023). CONCLUSION: We confirm that neutropenia is independently correlated with oesophagitis in concurrent chemoradiation, but that the susceptibility for chemotherapy-induced neutropenia is not associated with radiation-induced oesophagitis. Further studies focusing on the underlying mechanisms are thus warranted.

High-dose hyperfractionated accelerated radiotherapy in non-small cell lung cancer.

The observation that improved local tumour control also results in increased survival rates, even in a disease such as non-small cell lung cancer (NSCLC), has fuelled the interest in strategies aimed at local tumour eradication. It has been demonstrated that a clear dose-response relationship exists for radiotherapy, i.e. higher doses of radiation lead to increased local tumour control. However, prolongation of the overall treatment time beyond 4-5 weeks renders radiotherapy less effective because of increased proliferation of tumour cells. It is therefore of interest to deliver as high doses as possible in short overall treatment times. An extreme example of this strategy is stereotactic body radiotherapy (SBRT), where a few large radiation doses, equalling very high biological doses, delivered in a short overall treatment time has resulted in at least 90 % tumour control in stage I NSCLC. However, when large volumes or critical normal structures such as the main bronchi are in the high-dose radiation volumes, more extensive fractionation schedules have been used, such as 70 Gy in 35 daily fractions of 2 Gy. As the overall treatment time than exceeds 4-5 weeks, hyperfractionated radiotherapy schedules have been introduced, which all delivered 2-3 relatively small fractions per day to total doses that are similar to the so-called standard regimen. Several randomized phase III trials and a meta-analysis based on individual patient data have demonstrated a superior 5-year survival with this strategy, without increased side effects. Our group has also shown that individualised hyperfractionated accelerated radiotherapy (INDAR) makes treatment with curative intent even in patients with large tumour volumes possible with few important side effects. Early results of INDAR with concurrent chemotherapy or with cetuximab are promising.

Radiotherapy issues in non-small cell lung cancer: radiotherapy versus surgery in the treatment of early stage.

We discussed in this article about the role of surgery, in a broad sense, and radiotherapy for the treatment of early stage of non-small cell lung cancer (NSCLC), and we also examined if patients' outcomes after radiation therapy are comparable to the ones after surgery. Radiotherapy is at present a less attractive alternative to surgery in operable patients with early stage of NSCLC. Indeed, radiotherapy is frequently reserved for patients who are deemed unfit for surgery due to poor pulmonary function or other comorbidities. This introduces a large patient selection bias compared to surgery, rendering overall survival less suitable for comparison. When we compare patients who are deemed operable but refuse surgery, the 5-year overall survival rate observed, after a high effective dose, is equivalent to the outcome after surgery. On the other hand, it is difficult to enroll patients in randomized clinical trials for this purpose, propensity matched analysis allows to compares the effectiveness of radiotherapy and surgery using comparable series of patients, using this methodology two studies obtained similar results. This data support the need of continuous investigation for non-surgical alternatives in this disease, radiotherapy can be a good option. Until then, surgery remains the treatment of choice for early stage of NSCLC.

Analysis of the relative deformation of lung lobes before and after surgery in patients with NSCLC.

An accurate assessment of the extent of the tumor is critical for successful local treatment of lung cancer by surgery and/or radiotherapy. Guidelines to establish the extent of treatment margins may be derived from correlation studies between pre-treatment imaging and histopathology. Deformations occur, however, between in-vivo CT imaging and ex-vivo pathology due to the softness of lung tissue and pathology processing. The first aim of this study was to quantify these deformations in tissue around non-small cell lung cancer. The second aim was to explore factors associated with the magnitude of the deformations. The study was performed in 25 patients who underwent lobectomy after preoperative CT. Non-rigid registration was employed to evaluate tissue deformations around the gross tumor volume (GTV), taking into account potential differences in elasticity between tumor and healthy lung tissue. Tissue was found to be compacted by approximately 60% depending on circularity of the tumor and orientation of the specimen on the pathology table during processing. The deformations give rise to potential underestimation of the treatment margins in pathology studies that do not take this aspect into account.

[Pathophysiology and clinical significance of the abdominal compartment syndrome]. / Pathophysiologie und Bedeutung des abdominellen Kompartmentsyndroms.

Different causes, for example posttraumatic and postoperative complications, can lead to an elevated intra-abdominal pressure. Increased intraabdominal pressure effects cardiovascular, pulmonary and renal systems. The abdominal compartment syndrome can be defined as organ failure caused by an increased intra-abdominal pressure. Clinically the syndrome is characterised by a tensely distended abdomen, oliguria or anuria and/or inadequate ventilation. Early decompression by simple laparotomy and delayed closure is the treatment of choice. If untreated the abdominal compartment syndrome is lethal. Even treated it has a high morbidity and mortality as shown in our series where 2 out of 7 patients with this syndrome died despite surgical decompression.

[Mohs' method of micrographic surgery as treatment for recurrent basal cell carcinoma]. / Micrografische chirurgie volgens Mohs als behandeling voor recidief van basalecelcarcinoom.

OBJECTIVE: Evaluation of Mohs' micrographic surgery as treatment for recurrent basal cell carcinoma of the skin. DESIGN: Retrospective. SETTING: University Hospital Maastricht, the Netherlands. METHOD: In the period April 1992 to December 1995, 91 recurrent basal cell carcinomas (88 patients) were treated by Mohs' micrographic surgery. Medical records were analysed retrospectively with respect to different aspects. RESULTS: The mean age of the patients was 69 years. The recurrent basal cell carcinomas, with an mean diameter of 19.7 mm, were mainly localized on the nose and forehead. There were equal numbers of solid and morphea-like types of basal cell carcinomas. Most of these tumours had been treated by means of surgical excision in the past. The last treatment had taken place 3 years previously on average. Reconstruction was performed by means of primary closure, a graft or a flap. The mean follow-up period after Mohs' micrographic surgery was 12 months, in which one tumour recurred. CONCLUSION: Mohs' micrographic surgery is a surgical technique which provides the best prospect of total tumour removal together with maximal functional and cosmetic preservation. Mohs' micrographic surgery is of particular value for the treatment of recurrent basal cell carcinomas.