Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy.

BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. RESULTS: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. CONCLUSION: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions.

Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer.

BACKGROUND: Everolimus is an agent frequently associated with specific toxicities. Predictive markers of efficacy are needed to help define which patients could benefit from it. The goal of this exploratory study was to identify potential predictive biomarkers in the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activation pathway using primary tumor samples collected during the phase II tamoxifen plus everolimus (TAMRAD) trial. PATIENTS AND METHODS: Tumor tissues were collected retrospectively from the TAMRAD trial. Immunohistochemistry was carried out using specific antibodies directed toward proteins that result in mTORC1 activation [canonical phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mTOR or alternative pathways]. DNA was extracted from the tumor tissue; mutation screening in the PIK3CA gene (exons 9 and 20) and the KRAS gene (exons 2 and 3) was first carried out using Sanger direct sequencing, and then completed by next-generation sequencing for PIK3CA. An exploratory analysis of everolimus efficacy in terms of a time-to-progression (TTP) increase was carried out in each biomarker subgroup (high versus low expression referring to the median percentage of marked cells). RESULTS: A total of 55 primary tumor samples from the TAMRAD trial­25 from the tamoxifen-alone group and 30 from the tamoxifen/everolimus group­were evaluated for biomarkers. The subgroups most likely to have an improvement in TTP with tamoxifen/everolimus therapy, compared with tamoxifen alone, were patients with high p4EBP1, low 4EBP1, low liver kinase B1, low pAkt, and low PI3K. Among the 45 samples screened for mutation status, nine samples (20%; 95% CI 9.6-34.6) had a PIK3CA mutation. KRAS mutation was observed in one patient. CONCLUSIONS: A positive correlation between late effectors of mTORC1 activation, a positive correlation between Akt-independent mTORC1 activation, and an inverse correlation between canonical PI3K/Akt/mTOR pathway and everolimus efficacy were observed in this exploratory analysis. However, these correlations need to be validated in larger studies before applying the findings to routine clinical practice.

Nivolumab in patients with advanced renal cell carcinoma in France: interim results of the observational, real-world WITNESS study.

BACKGROUND: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452). PATIENTS AND METHODS: This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here. RESULTS: A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%. CONCLUSIONS: Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.

[Leg ulcerations and sunitinib]. / Ulcérations des membres inférieurs sous sunitinib.

BACKGROUND: Sunitinib is an antiangiogenic tyrosine kinase inhibitor indicated in the treatment of metastatic renal cancer and gastrointestinal stromal tumours (GIST). We report a case of leg ulcer apparently triggered by this drug and we discuss the potential implication of the antiangiogenic effect of sunitinib in ulcer genesis. CASE REPORT: A 73-year-old woman with a history of deep venous thrombosis of the lower limbs was treated with sunitinib for renal cancer with hepatic and pulmonary secondaries. While on this treatment, she developed painful ulcers of the right lower limb, despite having never previously presented leg ulceration. On discontinuation of sunitinib, the lesions improved, and resumption of this drug, even at a lower dosage, resulted in relapse of her ulcers. DISCUSSION: Although questions may legitimately be asked about the contribution of the patient's venous condition, withdrawal of sunitinib followed by a positive rechallenge tend to suggest the role of this drug in recurrence of ulcers. Their recurrence despite the decreased dosage of the drug points to a nondose-dependent pathogenic mechanism.

Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer.

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.

Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study.

HannaH (NCT00950300) and PrefHer (NCT01401166) studies validated the subcutaneous (H-s.c.) formulation of trastuzumab as effective and safe as intravenous (H-i.v.) and highly preferred by patients in early breast cancer. The present randomised MetaspHer trial (NCT01810393) is the first study assessing patient's preference in metastatic setting. METHODS: Patients with HER2-positive metastatic breast cancer who completed a first line chemotherapy with trastuzumab and achieved a long-term response lasting more than 3 years were randomised to receive 3 cycles of 600-mg fixed-dose adjuvant H-s.c., followed by 3 cycles of standard H-i.v., or the reverse sequence. Primary end-point was overall preference for H-s.c. or H-i.v. at cycle six, assessed by Patient Preference Questionnaire (PPQ). Secondary end-points included healthcare professional (HCP) satisfaction; safety and tolerability; quality of life. RESULTS: Hundred and thirteen patients were randomised and treated. H-s.c. was preferred by 79/92 evaluable intent-to-treat patients (85.9%, 95% confidence interval [CI; 78.8-93.0]; p < 0.001), 13/92 preferred H-i.v. (14.1%, 95% CI [7.0-21.3]). HCPs were most satisfied with H-s.c. (56/88 available data, 63.6%, [53.6-73.7]). On the safety population, adverse events occurred in 73 (67.6%) and 49 (44.1%) patients during the H-s.c. and H-i.v. periods, respectively; 7 (6.5%) and 4 (3.6%) were grade ≥ III, 3 (2.8%) and 2 (1.8%) were serious. CONCLUSION: The safety was consistent with the known H-i.v. and H-s.c. profiles without safety concern raised. Definitively, patients preferred H-s.c. as reported in early stage by PrefHer study.

Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.

PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.

Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group.

The activity of glufosfamide (beta-D-glucosylisophosphoramide mustard) was tested in a multicentre phase II clinical trial in patients with advanced non-small cell lung cancer (NSCLC) who had received one prior line of platinum-based chemotherapy. Patients were treated with 5000 mg/m(2) glufosfamide by a 1-h intravenous (i.v.) infusion every 3 weeks following registration at the European Organisation for Research and Treatment of Cancer (EORTC) Data Center. Patients were randomised between hydration and no hydration to evaluate the nephroprotective effects of forced diuresis. Patients experiencing >/= 35 micromol/l increase of serum creatinine compared with baseline values were taken off the treatment. The Response evaluation criteria in solid tumours (RECIST) criteria were applied for the response assessment. Blood sampling was performed for a pharmacokinetic analysis. 39 patients from seven institutions were registered and a median of three cycles was given (range 0-6) cycles; 20 patients were randomised to the hydration arm. Haematological toxicity was mild, but treatment-related metabolic and electrolytic abnormalities and increases of serum creatinine occurred in several patients. Hydration did not have any significant influence on the plasma pharmacokinetics of glufosfamide and did not show any nephroprotective effect. Only one confirmed partial remission was observed (response rate 3%; 95% (Confidence Interval (CI) 0-14) and 18 cases with stable disease (49%) were recorded as assessed by an independent panel. Median survival of all patients treated was 5.8 months (95% CI 4.2-7.9). In conclusion, glufosfamide administered by a 1-h infusion every 3 weeks has modest activity in advanced NSCLC patients after one prior platinum-based chemotherapy.

A phase II trial of radiochemotherapy with daily carboplatin, after induction chemotherapy (carboplatin and etoposide), in locally advanced nonsmall-cell lung cancer: final analysis.

PURPOSE: To evaluate feasibility and efficacy of concomitant radiochemotherapy (CRCT) in Stage IIIB nonsmall-cell lung cancer (NSCLC), two induction chemotherapy cycles combining etoposide and carboplatin were first delivered, followed by CRCT with daily radiation fraction in association with carboplatin. METHODS AND MATERIALS: Forty patients with biopsy-proven, locally advanced unresectable nonmetastatic NSCLC were enrolled. Induction chemotherapy consisted of two cycles (day 1 and day 28) of etoposide (VP16:100 mg/m2, days 1 to 3) and carboplatin (CBDCA:350 mg/m2, day 1). Irradiation starting at day 56, delivered 66 Gy in 2 Gy daily fraction, 5 days a week, along with a daily dose of CBDCA (15 mg/m2) given intravenously 2 to 4 h before radiation. In nonprogressive patients under induction chemotherapy, two additional cycles of VP16-CBDCA were administered 4 weeks after the completion of CRCT. RESULTS: Out of the 40 patients enrolled (38 males, 2 females), 37 (93%) received induction chemotherapy as scheduled, with 38% Grade 3-4 hematological toxicity. Response rate to induction chemotherapy was 11% (4/37). No tumor became resectable. CRCT was delivered to 32 of these 37 patients, with full doses given to 91% of them. Clinical and hematological Grade 3-4 toxicity rates were 21 and 13%, respectively. Additional chemotherapy was delivered in 12 of 26 nonprogressive patients. At final evaluation, performed 3 months after the end of CRCT, 38% of 26 evaluable patients were responders (4 complete and 6 partial), leading to a 25% (10 of 40) overall objective response rate. Of these 10 responders, 8 became responders after CRCT only. Overall, the 1-year local control rate was 28% (11 of 40). The median survival time was 9 months and the 1-year and 2-year overall survival rates were 38 and 15%, respectively. Thirty-six patients died from local progression (25 patients), distant metastasis (9 patients), or pulmonary fibrosis (2 patients). CONCLUSION: Concomitant CRCT with CBDCA is feasible with acceptable induction chemotherapy-related toxicity and a 1-year local control rate of 28%. Response rate to induction chemotherapy was low and better chemotherapy combination should be used to reduce distant failure probability and to improve local response rate before CRCT.

Brain metastases from epithelial ovarian carcinoma.

BACKGROUND: Brain metastases from epithelial ovarian carcinoma are rare. We reviewed our experience to evaluate the results of different treatments and their prognosis. Discussion is based on a review of the literature. METHODS: From 1974 to 1998, eight of 704 patients treated for epithelial ovarian carcinoma at our large cancer center developed brain metastases. The median time before occurrence of brain metastases was 15 months after the diagnosis of the ovarian cancer. Six patients had a single lesion and two had multiple parenchymal lesions. Brain was the only site of disease in one patient, while seven had concomitant dissemination. Seven out of eight patients underwent a treatment for brain metastases. The treatment consisted of either radiotherapy (2 cases), chemotherapy (2 cases), surgery and radiotherapy (1 case), or combined treatment of the three modalities (2 cases). RESULTS: Median survival from diagnosis of brain lesions was 3 months (range 1-12). One patient without treatment died one month later. Survival after complete surgical resection and radiotherapy was 12 months. One patient treated by complete surgical resection followed by radiotherapy and chemotherapy is still alive (+ 5 months). The patient who underwent partial surgical resection followed by radiotherapy and chemotherapy died 7 months later. Two patients treated by radiotherapy alone died, respectively, 2 and 3 months later. After systemic chemotherapy alone, survival times were 1 and 3 months. Conclusions. The prognosis of patients with brain metastases from ovarian carcinoma is poor. A better outcome might be obtained by a multimodal treatment.

[Standards, Options, and Recommendations for using erythropoietin in cancerology]. / Standards, Options et Recommandations pour l'utilisation de l'érythropoïétine en cancérologie.

UNLABELLED: The "Standards, Options and Recommendations" (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop a clinical practice guideline with definitions of Standards, Options and Recommendations for the use of recombinant human erythropoietin (rHuEPO) in oncology. METHODS: Data have been identified by literature search using Medline (up to march 1996) and Current Contents (up to october 1996) and personal references lists. The main end points considered were hemoglobin level, haematocrit, quality of life, transfusion requirements, incidence and length of hospital stays, efficacy of cancer treatment, safety and costs. Once the guideline was defined, the document was submitted to 39 reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The key recommendations are: 1) the use of recombinant human erythropoietin in oncology is validated for chemotherapy-induced anemia when the chemotherapeutic regimen contains platinum. In other cases, we recommend to suggest patients participating in prospective clinical trials; 2) for chemotherapy (platinum based)-induced anemia, the benefits/risks ratio for anemia therapy (i.e. transfusion or erythropoietin therapy) must be analysed for each individual patient; 3) we recommend participation in studies to identify predictive factors for non-response to erythropoietin therapy to select non-responding patients; 4) to investigate the clinical benefit of erythropoietin therapy for anemia due to intensive cytotoxic chemotherapy and radiation therapy, we recommend to suggest patients participating in large multicentre phase III trials; 5) at the present time, there is insufficient evidence to recommend the use of erythropoietin therapy in children.

[Updating 1999 of Standards, Options and Recommendations (SOR) for the clinical use of erythropoietin in oncology. FEDERATION OF THE FRENCH CANCER CENTRES (FNCLCC)]. / Eléments de la mise à jour 1999 des Standards, Options, Recommandations pour l'utilisation de l'érythropoïétine en cancérologie.

CONTEXT: The <> (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. The initial guidelines are being updated in case of new evidence. OBJECTIVES: To update the clinical practice guideline [39] with definitions of new Standards, Options and Recommendations for the use of recombinant human erythropoietin (rHuEPO) in oncology. METHODS: Data have been identified by literature search using Medline, Current Contents, Embase, Cancerlit (march 1996-march 1999). The main end points considered were hemoglobin level, haematocrit, quality of life, transfusion requirements, incidence and length of hospital stays, efficacy of cancer treatment, safety and costs. Once the guideline was updated and defined, the document was submitted to 42 reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement. RESULTS: The new key recommendations are: 1) The use of recombinant human erythropoietin in oncology is an alternative to treat chemotherapy-induced anemia when the chemotherapeutic regimen contains platinum; 2) Cancer-induced anemia reduces patients' quality of life. Treatment of anemia by transfusions of erythropoietin may improve quality of life; 3) We recommend assessment of haemoglobin levels during radiation therapy and the possible use of erythropoietin to optimise the efficacy of radiation therapy; 4) Erythropoietin is effective in others pathologies (multiple myeloma, non-Hodgkin lymphoma, non-platinum based chemotherapy.) and also in pediatric patients but the risk/benefit ratio for anemia therapy (i.e. transfusion or erythropoietin therapy) must be analysed for each individual; 5) We recommend an economic analysis of the need of erythropoietin within the context of the french health care system.

[Long term continuous combination of cisplatin and 5 fluorouracil in advanced breast neoplasms. A retrospective study of 77 patients]. / Association cisplatine et 5-fluorouracile continu à long terme dans les cancers du sein avancés. Etude rétrospective de 77 patientes.

Seventy-seven pre-treated patients with advanced breast cancer were administered a combination chemotherapy with cisplatin 50 mg/sqm d1, 5-fluorouracil 300 mg/sqm/d protracted continuous infusion d1-d28, allopurinol 600 mg/d po d1-d28, q29d. Overall response rate was 26%, median survival time 46 weeks, survival rate 43.3% at 1 year, 20.2% at 2 years, 10.6% at 3 years. Response rate was rather high in CNS and meningeal involvement (6/10).

[Standards, options and recommendations for the management of locally advanced non small cell lung carcinoma]. / Standards, otions et recommandationspour la prise en charge thérapeutique des patients atteints d'un cancer bronchopulmonaire primitif non à petites cellules localement avancé.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of locally advanced non small cell lung carcinoma. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations are: 1) The management of the locally advanced non small cell lung carcinoma has two main goals: firstly to obtain local control of the disease (or to at least delay local progression in order to improve the survival or relapse free survival), and secondly to prevent the development of metastases. 2) There is a consensus that locally advanced non small cell lung carcinoma should be irradiated. External beam radiotherapy should be of optimal quality and delivered at a minimal dose of 60 Gy by standard fractionation. For patients with a poor life expectancy, this can be delivered as a split-course or hypofractionated scheme. 3) Treatment for patients with a performance status of 0-1 should consist of short duration induction chemotherapy (with a least two drugs one of which must be cisplatin), combined sequentially with conventional radiotherapy. 4) Surgery is contraindicated in extensive N3 disease. Combined radio-chemotherapy (adjuvant or neoadjuvant) is not indicated outside clinical trials. Surgery is justified in stage N2 disease as good local control can be achieved. T4-N0 disease should be treated surgically with curative intent.

[High dose endobronchial brachytherapy: a curative treatment]. / La curiethérapie endobronchique de haut débit de dose: un traitement curatif.

PURPOSE: New endobronchial techniques of treatment allow a good unblocking. Nevertheless, only high dose rate brachytherapy delivers a curative treatment for invasive carcinomas. This study analyses the results of the first 33 consecutive patients treated with curative intent by this technique from 1994 to 1997, and followed-up more than one year. PATIENTS AND METHODS: Thirty-seven lesions were treated, with usual schedule delivering 30 Gy at 1 cm depth in six fractions and three to five weeks. All the patients were meticulously selected on the local involvement of the tumour and absolute contraindications to a surgical treatment. All of them have a pulmonary disease history or a general contraindication. RESULTS: With a 14-month follow-up, the local control at two months after the treatment was 95% (endoscopic and histologic), and 90% of the patients presented a prolonged local control. Four patients died of the treated cancer, another of a controlateral cancer. Ten patients died of another disease, five of them from a respiratory insufficiency. The overall survival rate at two years was 53% and the specific survival rate 80%. The acute tolerance was good, without incident. Asymptomatic bronchial stenoses, described by endoscopic follow-up, were described for seven patients. CONCLUSION: We conclude that, on the basis of a good selection of the patients and a respect of the indications, high dose rate endobronchial brachytherapy is an effective curative treatment. It offers a new curative option and must be proposed for the small invasive carcinomas in non-operable patients.

[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy]. / Standards, Options et Recommandations pour la prise en charge des patients atteints d'un cancer bronchique primitif de stade I ou II traités par irradiation exclusive.

CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

Spirituality in history taking.

Andrew Taylor Still, MD, DO, included in his founding postulates of osteopathy the concept that a patient's health includes the health of a patient's spirit. In the recent past, medicine as a whole, and osteopathic medicine specifically, has neglected this postulate. Recent research has confirmed the validity of Still's postulate, and many medical training institutions have received grants and established programs to incorporate spirituality into their curriculum. As with any patient evaluation, the history and physical examination is the starting platform. This article describes several tools that can be easily incorporated into the history and physical examination, along with some of the obstacles in evaluating the health of the patient's spirit.

Observatory clues to aid in the diagnosing of diastasis symphysis pubis: an underreported complication of parturition.

Diagnosis of diastasis symphysis pubis in the postpartum period need not depend on radiographic findings. This diagnosis can be made with simple observation techniques. Entertaining a high index of suspicion and observation of the patient are the most important contributions the physician can make. Parameters triggering a tentative diagnosis would include, but not be limited to, a large infant, a small pelvis, a rapid second stage of delivery, or application of forces to abduct the thighs. The diagnosis of diastasis symphysis pubis should be ruled out if the following conditions are present postpartum: the flattened abdomen (the postpartum "pooch" is absent); the patient is incontinent of urine when changing position from supine/prone to upright; the patient has pain in the hips or sacral region when walking; or the patient waddles when walking. The change in gait, or the pain on walking may not be noticed until 24 hours or more after delivery. However, the change in abdominal contour and incontinence is noticed immediately. Using these observational clues, the physician can institute treatment sooner, thereby expediting recovery.

[Pancoast-Tobias syndrome disclosing a primary pulmonary non-Hodgkin lymphoma]. / Syndrome de Pancoast-Tobias révélant un lymphome non hodgkinien pulmonaire primitif.

INTRODUCTION: Pancoast's syndrome is generally due to superior sulcus tumors, generally bronchial cancer. In rare cases, other causes are found, but these are potentially curable. CASE-REPORT: A 78-year old woman with a long history of tobacco intake presented with Pancoast's syndrome in the form of a locally invasive left apical lung mass. Despite her advanced age and the diagnosis of the high probability of lung cancer, a transparietal biopsy procedure was nevertheless performed, with the subsequent diagnosis of primary malignant pulmonary lymphoma. The patient was satisfactorily treated by combined chemotherapy. CONCLUSION: The present study has shown that malignant non-Hodgkin lymphomas should be considered in the etiology of the disease, and as a rare but potentially treatable cause of Pancoast's syndrome.