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Objective Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

Aim: We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in biopsies and transurethral resections prior to external beam radiotherapy with or without androgen deprivation. Methods: Cohort 1 consisted of 118 intermediate risk prostate cancer patients treated by radiotherapy, with biochemical relapse as primary end-point (median follow-up 6.5 years). Cohort 2 consisted of 132 high risk patients, enrolled in a phase III randomised trial (EORTC 22863) comparing radiotherapy alone to radiotherapy with long-term androgen deprivation (LTAD) with clinical progression free survival as primary end-point (median follow-up 9.1 years). Presence of IDC-P was identified after central review. Multivariable regression modelling and Kaplan-Meier analysis were performed with IDC-P as dichotomous variable. Results: IDC-P was a strong prognosticator for early (

Objectives To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast. Materials and Methods Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma » and « breast ». Additional papers were identified by reviewing references of relevant articles. Results ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients. Conclusions ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

Positron emission tomography is a functional imaging technique that allows the detection of the regional metabolic rate, and is often coupled with other morphological imaging technique such as computed tomography. The rationale for its use is based on the clearly demonstrated fact that functional changes in tumor processes happen before morphological changes. Its introduction to the clinical practice added a new dimension in conventional imaging techniques. This review presents the current and proposed indications of the use of positron emission/computed tomography for prostate, bladder and testes, and the potential role of this exam in radiotherapy planning.

Resume Introduction Le seminome secretant de l’hormone chorionique gonadotrope (HCG) est une entite rare faisant partie des seminomes pures. Methode La recherche bibliographique a ete realisee sur Medline® avec les mots : seminoma, human chorionic gonadotropin, HCG combines avec radiotherapy, chemotherapy, surveillance, management et prognostic. Nous avons etendu notre recherche de references similaires par la fonction related articles, en lisant la bibliographie des articles identifies et les publications disponibles sur Medline® de ces memes auteurs. Cette recherche a ete limitee aux publications de langues anglaise ou francaise. Les articles etaient eligibles s’il s’agissait d’etudes randomisees, prospectives, retrospectives ou de revues systematiques de la litterature. Resultats Peu d’articles ont ete retrouves sur le sujet. Nous avons retenu les series les plus pertinentes tout en resumant les differents parametres (epidemiologiques, cliniques, therapeutiques et pronostiques). Conclusions Les caracteristiques anatomocliniques et evolutives des seminomes secretants la HCG ne devraient pas etre differentes de celles des formes non secretantes. Les seminomes secretants la HCG ne semblent pas etre plus radio- ou chimio-resistants que les non secretants. La radiotherapie reste un traitement de choix pour les stades I et IIA de la maladie avec la chimiotherapie comme alternative. Le pronostic global est excellent. Le risque de rechute est plus important apres surveillance dans les stades I HCG-positifs que dans les stades I HCG negatifs.

Head and neck squamous cell carcinomas are frequently diagnosed at an advanced stage. Their treatment remains controversial, and has to be multidisciplinary. External beam radiotherapy is a recognized treatment option after radical curative surgery in order to improve local control. Different adjuvant treatment options have been studied in order to improve the outcome of these patients. We review in this paper the different prognostic factors indicating an adjuvant treatment and the interest of treatment intensification in bad prognostic patients.

Resume La prise en charge des tumeurs rares est souvent controversee. Le role des traitements adjuvants (radiotherapie et/ou chimiotherapie) est incertain. Generalement, le nombre limite de patients inclus dans les etudes ne permet pas une analyse statistique consistante. De ce fait, il n'est generalement pas possible de determiner ni les facteurs pronostiques de la maladie ni l'impact des traitements locoregionaux et systemiques adjuvants sur le controle local et la survie a long terme. Le reseau des tumeurs rares (Rare Cancer Network 1 ) regroupe plus de 70 institutions de 21 pays. Il a ete cree en 1993 avec comme objectif l'initiation de larges etudes retrospectives a partir d'un recueil de donnees multicentriques. L'analyse de larges series de tumeurs rares doit permettre ainsi une meilleure evaluation des facteurs pronostiques et de la prise en charge diagnostique et therapeutique. Jusqu'a present, 32 projets ont ete mis en place. Dans cet article consacre aux tumeurs rares etudiees dans notre groupe, nous rapportons les donnees les plus importantes ayant un impact potentiel sur les pratiques et dont plusieurs etaient meconnues avant d'etre etudies au sein de notre reseau.

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8/=16, 16-24, and24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35-76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20-331 months). In a median period of 12 months (range 5-139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy +/-postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41-73%) and 38% (95% CI, 21-55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41-73%) and 48% (95% CI, 32-64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22-50%) and 18% (95% CI, 2-34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy +/-salvage surgery, with 39% having organ preservation.

Resume Si l'on considere la radiotherapie de conformation dans le cancer bronchique non a petites cellules, les erreurs dues a des variations de positionnement de patients ou aux mouvements physiologiques peuvent etre la cause d'echec du traitement. Les systemes d'immobilisation n'ont ete evalues que recemment de facon scientifique dans les tumeurs intrathoraciques, peut-etre parce qu'en apparence ce probleme est moins important que celui des mouvements physiologiques internes. Une enquete internationale a montre qu'environ la moitie des centres de radiotherapie concernes utilisent des techniques d'irradiation conformationnelles, mais que, parmi ces centres, seuls deux sur trois emploient des systemes d'immobilisation. Une petite minorite utilise des systemes de reperes internes. Les donnees sur les erreurs de positionnement montrent des variations moyennes de l'ordre de 5 mm, qui peuvent chez certains patients atteindre plus de 15 mm. Une etude a demontre que les patients immobilises necessitaient moins de corrections de positionnement en cours de traitement, et un autre travail semblait indiquer qu'il n'y avait pas de difference entre un systeme de support avec barre en ≪ T ≫ et un systeme a base de mousses chimiques. D'autres travaux indiquent qu'il y a une assez grande variation dans les mouvements internes de tumeurs bronchiques en fonction de leur localisation. Plusieurs groupes recherchent le moyen de minimiser les consequences des mouvements internes, mais les techniques proposees actuellement sont lourdes et peu pratiques. De nouvelles etudes seront necessaires pour ameliorer les connaissances au sujet du positionnement quotidien et sur l'effet des mouvements internes, et dans l'intervalle il convient d'etre prudent avant d'employer systematiquement de faibles marges dans l'irradiation de conformation.

About one third of lung cancers initially present with a localised disease, without any curative surgery potential, because of local spread or comorbidity. Definitive radiation, alone or combined with chemotherapy, then represents the treatment of choice for these patients. The results, however, are disappointing, with a biopsy-proven local control of 10% at two years and a 5-10% five-year survival rate. These poor results may be partially explained by the difficulties in delineating the tumour volume as well as the dose limitations due to poor tolerance of surrounding normal organs. Lung parenchyma sequelae remain daily worrying events for the oncologist. The advent of 3D conformal radiation therapy (3DRT) allows progress and innovations, including the use of modern imaging techniques, sophisticated dosimetry and treatment planning, efficient immobilisation devices and on-line verification procedures. With more precise (and time-consuming) procedures, 3DRT will allow a better tumour volume delineation, an increased tumour dose and a dose limitation in normal tissues. These improvements may help increase local control and survival results. 3DRT, which has been used for several years for prostate cancer and benefits from recent imaging improvements, will now allow treatment of other locations, such as lung cancer, with conformal therapy. The few preliminary results are encouraging. This work reviews the current data and remaining questions regarding lung cancer treated with 3DRT, and presents and discusses the literature before discussing future trends in this area.

Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in cells by HPLC is an analytical challenge since the concentration of dNTP present in mammalian cells is several orders of magnitude lower than the corresponding NTP. Hence, the quantitation of dNTP in cells is generally performed after selective oxidation or removal of the major NTP. The procedures reported so far are lengthy and cumbersome and do not enable the simultaneous determination of NTP. We report the development of a simple, direct HPLC method for the simultaneous determination of dNTP and NTP in colon carcinoma WiDr cell extracts using a stepwise gradient elution ion-pairing HPLC with uv detection at 260 nm and with a minimal chemical manipulation of cells. Exponentially growing WiDr cells were harvested by centrifugation, rinsed with phosphate-buffered saline, and carefully counted. The pellets were suspended in a known volume of ice-cold water and deproteinized with an equal volume of 6% trichloroacetic acid. The acid cell extracts (corresponding to 2. 5 x 10(6) cells/100 microl) were centrifuged at 13,000g for 10 min at 4 degrees C. The resulting supernatants were stored at -80 degrees C prior to analysis. Aliquots (100 microl) were neutralized with 4.3 microl saturated Na2CO3 solution prior the injection of 40 microl onto the HPLC column (injection speed 250 microl/min). Chromatographic separations were performed using two Symmetry C18 3. 5-microm (2 x 3.9 x 150 mm) columns (Waters), connected in series equipped with a Sentry guard column (3.9 x 20 mm i.d.) filled with the same packing material. The HPLC columns were kept at 30 degrees C. The mobile phase was delivered at a flow rate of 0.5 ml/min, with the following stepwise gradient elution program: % solvent A/solvent B, 100/0 at 0 min --100/0 at 1 min --36/64 at 5 min --31/69 at 90 min --31/69 at 105 min --0/100 at 106 min --0/100 at 120 min; 50/50 MeOH/solvent B from 121 to 130 min; 100% solvent A from 131 to 160 min. Solvent A contained 0.01 M KH2PO4, 0.01 M tetrabutylammonium chloride, and 0.25% MeOH and was adjusted to pH 7. 0 (550 microl 10 N NaOH for 1 liter solvent A). Solvent B consisted of 0.1 M KH2PO4, 0.028 M tetrabutylammonium chloride, and 30% MeOH and was neutralized to pH 7.0 (1.4 ml 10 N NaOH for 1 liter solvent B). Even though dNTPs are minor components of cell extracts, satisfactory regression coefficients were obtained for their calibration curves (r20.99) established with the addition-calibration methods up to 120 pmol/40-microl injection. The applicability of the method was demonstrated by in vitro studies of the modulation of NTP and dNTP pools in WiDr colon carcinoma cell lines exposed to various pharmacological concentrations of cytostatic drugs (i.e., FMdC, IUdR, gemcitabine). In conclusion, this optimized, simplified, analytical method enables the simultaneous quantitation of NTP and dNTP and may represent a valuable tool for the detection of minute alterations of cellular dNTP/NTP pools induced by anticancer/antiviral drugs and diseases.

To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5- and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically significant factors influencing the outcome were Karnofsky index, pT-classification, pN-classification, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors influencing outcome were pT-classification, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis.

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

Squamous cell carcinoma of the head and neck (SCCHN) is a common disease that develops in the upper aerodigestive epithelium. The most important risk factors are tobacco and alcohol consumption. There is also increasing evidence that human papillomavirus plays an important role in the cause of SCCHN. The complex anatomy, the vital functions of the upper aerodigestive tract and the close proximity to vital structures, explain that the goal of treatment is not only to improve survival outcomes, but also to preserve organ function. Radiotherapy and surgery are the standard modalities of treatment, reflecting the locoregional predominance of SCCHN. Chemotherapy plays an important role in the treatment of patients with locoregionally advanced disease, in conjunction with radiotherapy and surgery. Indeed, standard therapy for resectable locoregionally advanced (stage III or IV) SCCHN cancers consists either of surgery and adjuvant chemoradiotherapy or definitive concomitant chemoradiotherapy, depending upon disease site, stage and resectability of the tumour, or institutional experience. Concomitant chemoradiotherapy has been shown in several randomised trials to improve disease-free and overall survival in the postoperative setting for resected disease with poor prognostic factors. Furthermore, multiple randomised studies and meta-analyses have shown that definitive chemoradiotherapy, as well anti-epidermal growth factor receptor treatment in one randomised study, improved disease-free and overall survival when compared with radiotherapy alone. This overview reviews the most relevant published studies on the multidisciplinary management of SCCHN and discusses future strategies to reduce locoregional failures.

The term “primary breast lymphoma” (PBL) is used to define malignant lymphoma primarily occurring in the breast in the absence of other previously detected lymphoma localizations. The first definition was proposed by Wiseman and Liao in 1972 [49]. The clinical pathological criteria for the definition of PBL include: “the clinical site of presentation is the breast, the absence of disseminated lymphoma or preceding extra-mammary lymphoma at the time of diagnosis, adequate pathological specimen evaluation, histological evidence of a close association between the mammary tissue and the lymphomatous infiltrate, and presence of homolateral axillary lymph nodes that may be involved if they develop simultaneously with the primary breast tumor”.

This is one of the few studies that have explored the value of baseline symptoms and health-related quality of life (HRQOL) in predicting survival in brain cancer patients. Baseline HRQOL scores (from the EORTC QLQ-C30 and the Brain Cancer Module (BN 20)) were examined in 490 newly diagnosed glioblastoma cancer patients for the relationship with overall survival by using Cox proportional hazards regression models. Refined techniques as the bootstrap re-sampling procedure and the computation of C-indexes and R(2)-coefficients were used to try and validate the model. Classical analysis controlled for major clinical prognostic factors selected cognitive functioning (P=0.0001), global health status (P=0.0055) and social functioning (P, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Progress in assurance and quality control in radiotherapy, up to 25 MeV energy, come from daily verification of the quality of irradiations in terms of reproduction of positioning of the patient, of irradiation beams and of focused blocs interposed between the source of the beam and the patient. These improvements are now possible thanks to a new imager such as IRIS (Interactive Radiotherapy Imaging System), with improved image quality. IRIS is used in daily verification at the Centre Hospitalier Universitaire Vaudois, Lausanne, to control on-line the patient position and organs motion during the post-operative radiotherapy of a pancreatic cancer. IRIS is capable of producing up to 10 images/sec, and is based on a large area pixel matrix manufactured in thin film amorphous silicon technology, with wide dynamic range. The results are: the beam positioning adjustments and comparison to reference image in daily use for the different field of irradiation. The visualization and identification of several inner structures and organs (measuring amplitudes of movements of organs). The review of the treatment on a session to session basis. IRIS, on-line dynamic imager has the potential to quality treatment, especially in conformal radiotherapy and in irradiations where the amplitude of organ motion is are important.

Fifty-three patients had 54 third-body areas irradiated for breast and prostate bone metastases using the third-body irradiation technique during a period of 6 years. These patients were previously treated with chemotherapy, hormonal therapy and limited field irradiation. Seventy percent responded completely and 24% partially. This modality is safe and effective for pain relief.

Aim: One standard option in the treatment of stage IIIA/N2 NSCLC is neoadjuvant chemotherapy followed by surgery. We investigated in a randomized trial whether the addition of neoadjuvant radiotherapy would improve the outcome. Here we present the final results of this study. Methods: Patients (pts.) with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, and adequate organ function were randomized 1:1 to chemoradiation (CRT) with 3 cycles of neoadjuvant chemotherapy (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost radiotherapy (RT) with 44 Gy in 22 fractions in 3 weeks, or neoadjuvant chemotherapy alone (CT), with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 232 pts. were randomized in 23 centers, the median follow-up was 53 months. Two thirds were men, median age was 60 years (range 37-76). Histology was squamous cell in 33%, adenocarcinoma in 43%. Response rate to CRT was 61% vs. 44% with CT. 85% of all pts. underwent surgery, 30-day postoperative mortality was 1%. The rate of complete resection was 91% (CRT) vs. 81% (CT) and the pathological complete remission (pCR) rate was 16% vs. 12%. The median EFS was 13.1 months (95% CI 9.9 - 23.5) for the CRT group vs. 11.8 months (95% CI 8.4 – 15.2) in the CT arm (p 0.665). The median overall survival (OS) with CRT was 37.1 months (95% CI 22.6 -50), with CT 26.1 months ( 95% CI 26.1 – 52.1, p 0.938). The local failure rate was 23% in both arms. In the CT arm 12 pts. were given postoperative radiotherapy (PORT) for R1 resection, 6 pts. received PORT in violation of the protocol. Pts. with a pCR, mediastinal downstaging to ypN0/1 and complete resection had a better outcome. Toxicity of chemotherapy was substantial, especially febrile neutropenia was common, whereas RT was well tolerated. Conclusions: This is the first completed phase III trial to evaluate the role of induction chemoradiotherapy and surgery, in comparison to neoadjuvant CT alone followed by surgery. RT was active, it increased response, complete resection and pCR rates. However, this failed to translate into an improvement of local control, EFS or OS. Notably, surgery after induction treatment was safe, including pneumonectomy. The overall survival rates of our neoadjuvant regimen are very encouraging, especially for a multicenter setting. Disclosure: M. Pless: Advisory Board for Sanofi; R. Cathomas: Advisory Board Sanofi D.C. Betticher: Advisory Board Sanofi. All other authors have declared no conflicts of interest.

Aims Patients with non-resectable soft tissue sarcomas of the extremities do not live longer if they are treated by amputation or disarticulation. In order to avoid major amputations, we tested isolated limb perfusion (ILP) with tumour necrosis factor α (TNF)+melphalan+/−interferon-γ (IFN) as a pre-operative, neoadjuvant limb salvage treatment. Methods Twenty-two patients were included (six men and 16 women; three upper limb and 19 lower limb tumours). The AJCC stage was IIA in four patients, III in seven and IV in 11. Thirteen cases were recurrent or progressive after previous therapy; five tumours had a diameter ≥20 cm, and four were multiple or regionally metastatic. There were six malignant fibrous histiocytomas, five liposarcomas, four malignant peripheral nerve sheath tumours, three rhabdomyosarcomas, two leiomyosarcomas, one recurrent extraskeletal osteosarcoma and one angiosarcoma. Results Twenty-four ILPs were performed in the 22 patients, and 18 (82%) experienced an objective response: this was complete in four (18%) and partial in 14 (64%). Three patients had a minimal or no response and the tumour progressed in one case. All patients had fever for 24 hours but only one developed a reversible grade 3 distributive shock syndrome with no sequelae. There was no grade 4 toxicity. Seventeen patients (77%) underwent limb-sparing resection of the tumour remnants after a median time of 3.4 months: 10 resections were intracompartmental and seven extracompartmental. Surgery included flaps or skin grafts in five patients, arterial replacement in two and knee arthrodesis in one. Adjuvant chemotherapy was given to eight patients and radiotherapy to six. In one patient amputation was necessary after a second ILP. Secondary amputations were performed for recurrence in two patients, resulting in an overall limb salvage rate of 19/22 (86%). After a median follow-up of 18.7 months, 10 recurrences were recorded: seven were both local and systemic and three were only local. The median disease free and overall survival times have been >12.5 and 18.7 months respectively: this is similar to the outcome after primary amputations for similar cases. Conclusion ILP with TNF and chemotherapy is an efficient limb sparing neoadjuvant therapy for a priori non-resectable limb soft tissue sarcomas.

Inactivation of p53 by binding to simian virus 40-T antigen (SV40-T) and human papilloma virus type 16 protein E6 (HPV 16 E6) in transfected human diploid fibroblasts causes enhanced radioresistance. The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: upregulation in C4-1, downregulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. In C4-1 and SW 756 cells, treatment with dexamethasone induces radioresistance, and changes in expression levels of HPV 18 genes E6 and E7 do not correlate with the changes in radiosensitivity. Dexamethasone-induced radioresistance has previously been observed in HeLa cells, another human cervical carcinoma cell line. This leads us to speculate that dexamethasone-induced radioresistance may be important in certain clinical situations, and that therefore, the phenomenon deserves further study.

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.

Purpose/Objective: To assess the feasibility and efficacy of accelerated weekly 6 fractionated 66-Gy postoperative radiation therapy (RT) using a single fraction regimen from Monday to Thursday and a concomitant boost in the Friday afternoon sessions in patients with advanced head and neck cancer (AHNC). Materials/Methods: Between December 1997 and June 2002, 89 (male to female ratio: 68/21; median age: 60 years [range: 36-81]) consecutive patients (refusing to participate or ineligible for the EORTC 22931 study comparing postoperative RT vs. RT plus chemotherapy) with pT1-pT4 and/or pN0-pN3 AHNC (28 oropharynx, 26 oral cavity, 18 hypopharynx, 6 larynx, 5 unknown primary, 4 salivary gland, and 2 paranasal sinus) were included in this prospective study. Postoperative RT was indicated because surgical margins were not free of tumor (n = 22) or for T4 tumors (n = 4) in 26 (29%) patients; or because of extranodal infiltration with (n = 33) or without (n = 30) positive surgical margins in 63 (71%) patients. Median interval between surgery and RT was 6 weeks (3-15). RT consisted of 66 Gy (2 Gy/fr) in 5 weeks and 3 days. Median RT duration was 39 days (range: 35-67). Prophylactic percutaneous endoscopic gastrostomy was applied in 26 (29%) patients. Median follow-up was 21 months (range: 2-59). Results: All but one patient (not finishing the treatment because of non treatment-related reasons at 56 Gy) received the planned total dose without unplanned interruption. Acute morbidity was acceptable: grade 3 mucositis in 20 (22%) patients, grade 3 dysphagia in 22 (25%) patients, grade 3 skin erythema in 18 (20%) patients. Median weight loss of was 2 kg (range: 0-14.5). No grade 4 toxicity was observed. Considering the late effects, grade 0, 1, 2, or 3 xerostomia was observed in 15 (17%), 57 (64%), 11 (12%), and 6 (7%) patients, respectively; grade 0, 1, 2, and 3 edema in 29 (33%), 46 (52%), 12 (13%), and 2 (2%) patients, respectively. Median time to locoregional relapse was 10 months (range: 2-21); only 4 (4%) local and 9 (10%) regional relapses were observed, and 18 (20%) patients developed distant metastases (all locally controlled but with regional relapses in 4 cases). The 2-year overall, cause-specific, and disease-free survival rates were 70%, 75%, and 63%, respectively; and 2-year actuarial-local and locoregional control rates were 94% and 80%, respectively. Distant metastasis probabilities at 2 and 4 years were 20% and 38%, respectively. Univariate analyses revealed that pT-stage, 3 or more lymph node metastases, and extranodal extension in 2 or more lymph nodes were Related Articles in ScienceDirect significant. Multivariate analysis (Cox model) revealed that pT-stage (pT1, 2 vs. pT3, 4) and extranodal extension (0, 1 vs. 2 or more) were the two factors independently influencing the outcome. Conclusions: We conclude that reducing the overall treatment time using postoperative accelerated RT by weekly concomitant boost (6 fractions per week) is easily feasible with excellent local control. Acute and late RT-related morbidity is highly acceptable. Given the disease progression pattern (distant metastases), adjuvant chemotherapy should be considered.

Forty-four eyes in 38 children were treated between 1963 and 1991 by external radiotherapy for retinoblastoma. Treatment modalities varied widely during this period; in addition to radiotherapy there was chemotherapy (16/44), photocoagulation (14/44), and laser therapy or cryotherapy (14/44). Treatment technique and dose fractionation also varied widely; lateral beam technique (39/44) versus anterior or anterior/lateral beam; doses per fraction ranged from 1 to 4.5 Gy, total doses from 30 to 61.5 Gy, and overall times from 22 to 49 days. Patients were followed at 3-month intervals, and actuarial survival at 10 years was 88%, with 62% local control. Ten eyes showed clinical evidence of retinopathy. A multivariate analysis of factors associated with increased risk of retinopathy was carried out using the Cox proportional hazards model and the mixture model of Farewell. The estimated latent time was 17 months (95% confidence interval, 14-20 months). The only factors found to be significantly associated with retinopathy were total dose multiplied by dose per fraction, or total dose normalized to the equivalent total dose in 2-Gy fractions as estimated from the LQ model, and these gave equivalent descriptions. There were trends (not significant) for increased risk of retinopathy when treatments included chemotherapy or photocoagulation, and for decreased risk (also not significant) when cryotherapy was used in conjunction with radiotherapy. No significance could be attached to any of the following: number of sites per eye, Reese-Ellsworth stage, and family history. We conclude that hypofractionation carries a significant risk for retinopathy in the treatment of retinoblastoma.

Little progress has been made in the systemic treatment of melanoma, that is for disseminated stage IV disease. However, the tumour resistance to therapy, especially chemotherapy can be overcome in melanoma by high doses of anticancer agents administered regionally. The purpose of this paper is to illustrate this concept by two modes of regional treatment namely: (1) isolation perfusion of the limbs with high doses of cytokines and chemotherapy under hyperthermia and (2) local treatment of metastatic melanoma. The third part will be devoted to the role of another regional treatment, radiotherapy, where the association with hyperthermy also looks promising.