Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial.

BACKGROUND: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). PATIENTS AND METHODS: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. RESULTS: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash. CONCLUSION: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

A randomized trial of induction docetaxel-cisplatin-5FU followed by concomitant cisplatin-RT versus concomitant cisplatin-RT in nasopharyngeal carcinoma (GORTEC 2006-02).

Background: Concomitant chemotherapy (CT)-radiotherapy (RT) is a standard of care in locally advanced nasopharyngeal carcinoma (NPC) and a role for induction CT is not established. Methods: Patients with locally advanced NPC, WHO type 2 or 3, were randomized to induction TPF plus concomitant cisplatin-RT or concomitant cisplatin-RT alone. The TPF regimen consisted of three cycles of Docetaxel 75 mg/m2 day 1; cisplatin 75 mg/m2 day 1; 5FU 750 mg/m2/day days 1-5. RT consisted of 70 Gy in 7 weeks plus concomitant cisplatin 40 mg/m2 weekly. Results: A total of 83 patients were included in the study. Demographics and tumour characteristics were well balanced between both arms. Most of the patients (95%) in the TPF arm received three cycles of induction CT. The rate of grade 3-4 toxicity and the compliance (NCI-CTCAE v3) during cisplatin-RT were not different between both arms. With a median follow-up of 43.1 months, the 3-year PFS rate was 73.9% in the TPF arm versus 57.2% in the reference arm [hazard ratio (HR) = 0.44; 95% confidence interval (CI): 0.20-0.97, P = 0.042]. Similarly the 3 years overall survival rate was 86.3% in the TPF arm versus 68.9% in the reference arm (HR = 0.40; 95% CI: 0.15-1.04, P = 0.05). Conclusion: In conclusion, several important aspects can be emphasized: the compliance to induction TPF was good and TPF did not compromise the tolerance of the concomitant RT-cisplatin phase. The improved PFS and overall survival rates needs to be confirmed by further trials.

Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases.

BACKGROUND: Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases. PATIENTS AND METHODS: The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle. RESULTS: Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients. CONCLUSION: Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.

Thermal ablation techniques: a curative treatment of bone metastases in selected patients?

INTRODUCTION: Thermal ablation techniques (radiofrequency-ablation/cryotherapy) can be indicated with a curative intent. The success rate and prognostic factors for complete treatment were analysed. MATERIAL/METHODS: The medical records of all patients who had undergone curatively intended thermal ablation of bone metastases between September 2001 and February 2012 were retrospectively analysed. The goal was to achieve complete treatment of all bone metastases in patients with oligometastatic disease (group 1) or only of bone metastases that could potentially lead to skeletal-related events in patients with a long life expectancy (group 2). We report the rate of complete treatment according to patient characteristics, primary tumour site, bone metastasis characteristics, radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2). RESULTS: Eighty-nine consecutive patients had undergone curatively intended thermal ablation of 122 bone metastases. The median follow-up was 22.8 months [IQR = 12.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment rate was 67% (95%CI: 50%-76%). In the multivariate analysis the favourable prognostic factors for complete local treatment were oligometastatic status (p = 0.02), metachronous (p = 0.004) and small-sized (p = 0.001) bone metastases, without cortical bone erosion (p = 0.01) or neurological structures in the vicinity (p = 0.002). CONCLUSION: Thermal ablation should be included in the therapeutic arsenal for the cure of bone metastases. KEY POINTS: • Thermal ablation techniques are currently performed to palliate pain caused by bone metastases. • In selected patients, thermal ablation can also be indicated with a curative intent. • Oligometastatic and/or metachronous diseases are good prognostic factors for local success. • Small-size (<2 cm) bone metastases and no cortical erosion are good prognostic factors.

Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer.

BACKGROUND: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients. METHODS: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models. RESULTS: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs -, ≤2 cells per spot) and CD68 (+, >0 vs -, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. CONCLUSION: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.

Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data.

BACKGROUND: Many randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy. METHODS: We included randomised trials, not confounded by additional therapeutic differences between the two groups and that started randomisation on or after Jan 1, 1965, which compared surgery plus adjuvant chemotherapy versus surgery alone, or surgery plus adjuvant radiotherapy and chemotherapy versus surgery plus adjuvant radiotherapy. Updated individual patient data were collected, checked, and included in meta-analyses stratified by trial. The primary endpoint was overall survival, defined as time from randomisation until death by any cause. All analyses were by intention to treat. FINDINGS: The first meta-analysis of surgery plus chemotherapy versus surgery alone was based on 34 trial comparisons and 8447 patients (3323 deaths). We recorded a benefit of adding chemotherapy after surgery (hazard ratio [HR] 0.86, 95% CI 0.81-0.92, p<0.0001), with an absolute increase in survival of 4% (95% CI 3-6) at 5 years (from 60% to 64%). The second meta-analysis of surgery plus radiotherapy and chemotherapy versus surgery plus radiotherapy was based on 13 trial comparisons and 2660 patients (1909 deaths). We recorded a benefit of adding chemotherapy to surgery plus radiotherapy (HR 0.88, 95% CI 0.81-0.97, p=0.009), representing an absolute improvement in survival of 4% (95% CI 1-8) at 5 years (from 29% to 33%). In both meta-analyses we noted little variation in effect according to the type of chemotherapy, other trial characteristics, or patient subgroup. INTERPRETATION: The addition of adjuvant chemotherapy after surgery for patients with operable non-small-cell lung cancer improves survival, irrespective of whether chemotherapy was adjuvant to surgery alone or adjuvant to surgery plus radiotherapy. FUNDING: UK Medical Research Council, Institut Gustave-Roussy, Programme Hospitalier de Recherche Clinique (AOM 05 209), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Radiofrequency ablation versus surgical resection for the treatment of oligometastatic lung disease.

PURPOSE: The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease. MATERIALS AND METHODS: This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates. RESULTS: Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P<0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P>0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size>2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P<0.01). CONCLUSION: RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. MATERIAL & METHODS: Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. RESULTS: In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor. CONCLUSION: Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

Prediction and diagnosis of bone metastases in well-differentiated gastro-entero-pancreatic endocrine cancer: a prospective comparison of whole body magnetic resonance imaging and somatostatin receptor scintigraphy.

PURPOSE: Our purpose was to compare the sensitivity of whole body (WB) magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS) for the diagnosis of bone metastases (BMs) in patients with well-differentiated gastro-entero-pancreatic endocrine cancer (WD-GEP-EC) and to determine predictive factors of BM. PATIENTS AND METHODS: WB-MRI and SRS were prospectively performed in 79 patients with bronchial (11), thymic (five), gastric (two), duodeno-pancreatic (24), ileal (26), colic (one), or unknown primary (10) WD-GEP-EC. RESULTS: A total of 36 patients (46%) had 333 BMs involving 119 skeletal segments. WB-MRI and SRS were equally sensitive for detecting patients with BM (86 vs. 81%; P = 0.56), with 33% of the patients diagnosed with only one procedure. WB-MRI detected more BMs than SRS (80 vs. 57%; P = 0.017). Compared with SRS, WB-MRI detected more spine BMs (96 vs. 45%; P < 0.001) and tended to detect more pelvic and lower limb BMs (P = 0.054 and P = 0.06, respectively). Compared with WB-MRI, SRS detected more skull BMs (100 vs. 0%; P < 0.001) and tended to detect more rib BMs (P = 0.08). Sternal and upper-limb BMs were equally detected with WB-MRI and SRS (P = 0.32 and P = 0.46, respectively). Bone staging with SRS and spine MRI rather than WB-MRI would have detected 92% of the patients with BMs and 83% of all BMs. The extent of liver involvement and bronchial-thymic primary tumors were independent predictive factors for BM. CONCLUSIONS: We recommend bone staging with SRS and spine MRI in all patients with bronchial-thymic or unknown primary WD-GEP-EC. In case of duodeno-pancreatic or ileal primary, bone imaging may be restricted to patients with liver metastases.

Quantitative methylation analyses of resection margins predict local recurrences and disease-specific deaths in patients with head and neck squamous cell carcinomas.

This study sought to determine whether the presence of hypermethylated genes in the surgical margins can predict local recurrences in head and neck squamous cell carcinomas (HNSCCs). We prospectively collected tumour and surgical margin specimens from patients with HNSCCs who had undergone surgical resections. Quantitative methylation-specific PCR (QMSP) of CDKN2A, CCNA1 and DCC were performed in these specimens and correlated with clinical data. Of the 42 patients eligible for the study, 27 were hypermethylation informative for the above three genes. This latter group was associated with longer disease-free survivals (P=0.007) and longer time to disease-specific deaths (P=0.004). Multivariate analyses confirmed hypermethylation non-informative tumours as an independent prognosticating factor for disease-specific deaths (risk ratio 3.8, P=0.026). Quantitative MSP of the margins of 24 hypermethylation informative tumours revealed that 11 patients had molecularly positive margins, of which, five developed disease-specific events (DSEs, three local recurrences and two metastases), compared to none in patients with molecularly negative margins, after a median follow-up of 48 months. Log-rank analyses showed that molecularly positive margins were associated with shorter time to local recurrences and disease-specific deaths (P=0.03 and 0.01, respectively). This study demonstrated that QMSP of hypermethylated promoters in surgical margins predicted all the local recurrences in our series of HNSCC patients. We have also identified hypermethylation non-informative tumours as an independent predictor for the development of DSEs.

[Hypofractionad radiotherapy for elderly with head and neck cancer]. / Radiothérapie hypofractionnée des cancers ORL chez le sujet âgé.

Thirty percent of patients with head and neck cancer are over 70 years. Radiotherapy approach in elderly is a challenge. On one hand, radiotherapy side effects, as well as the number of sessions required, could be a burden. On the other hand, omission of local treatment is not an option due to the symptoms of the tumor. Patients in good general condition may receive standard fractionnated radiotherapy. For frail patients unsuitable for standard fractionated radiotherapy, more convenient shorter course of radiotherapy are commonly used. Physicians have to choose the best radiotherapy schedule according to the objective of the treatment. In case of palliative intend: hypofractionated radiotherapy delivered with a single short course could be recommanded. This course could be followed by other subsequent courses if the patient's condition improves during the treatment. For patients treated in curative intend, the choice of hypofractionation schedule depends on the general condition: split course hypofractionated radiotherapy for unfit patients, or accelerated radiotherapy with concomitant boost for fit patients. In all cases, a high-quality radiotherapy technique and appropriate supportive care are mandatory to minimize the side effects. The ELAN RT trial, soon to be completed, will rule on the non-inferiority of hypofractionated radiotherapy compared to standard radiotherapy for unfit patients.

Sentinel node biopsy in early oral squamous cell carcinomas: Long-term follow-up and nodal failure analysis.

OBJECTIVES: Evaluate the reliability of sentinel node biopsy (SNB) in T1/T2 cN0 oral squamous cell carcinoma (OSCC), and compare recurrence-free time (RFT) and overall survival (OS) between patients undergoing SNB and neck dissection (ND). PATIENTS AND METHODS: Patients with T1/T2 cN0 OSCC underwent SNB followed by systematic ND in the first cohort and SNB followed by selective ND in case of positive sentinel nodes (SN) in the second cohort. RESULTS: A total of 229 patients were followed (first cohort 50, second cohort 179). SNs were successfully detected in 93.9% (215/229) of cases. Median follow-up was 5.6 years. Recurrence occurred in 38/215 patients, with isolated nodal recurrence in 18/215 patients. At 5 years, the rate of recurrence-free patients was 80.0% and the rate of patients without isolated nodal recurrence was 90.4%. Negative predictive value of SNB was 92.7%. No statistically significant difference was observed between the two groups regarding RFT and OS. In 83% (10/12) of ipsilateral isolated nodal recurrences, primary tumor was located in anterior part of oral cavity. Only 43% (3/7) of SN+ patients with nodal recurrence were eligible for salvage surgery, compared to 91% (10/11) of SN- patients. SNB resulted in fewer complications than ND (8% vs 28%, p < 0.0001). CONCLUSION: SNB is a reliable staging tool for T1/T2 cN0 OSCC, without adverse effect on patient survival and fewer complications. No late recurrences occurred in long-term follow-up. Close follow-up is mandatory for SN+ patients, who are at higher risk of nodal recurrence and have worse prognosis.

Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography.

OBJECTIVE: Patients with adrenocortical cancer are submitted to multiple imaging procedures for diagnosis of recurrence and staging. The aim of this prospective study was to evaluate the diagnostic and prognostic values of fluorodeoxyglucose (FDG) using a combined positron emission tomography and computed tomography (PET/CT) modality, compared with thoracoabdominopelvic computed tomography (TAP-CT). METHODS: Twenty-eight consecutive patients with adrenocortical cancer referred from November 2003 to December 2004 to the Institut Gustave Roussy were included. Mean time between PET/CT and TAP-CT was 16 d. Independent readers analyzed images of each modality. The gold standard was progression on follow-up TAP-CT or pathology. RESULTS: A total of 269 lesions in 57 organs were depicted in 22 patients. The sensitivities for the detection of distinct lesions and the diagnosis of metastatic organs were 90 and 93% for PET/CT and 88 and 82% for TAP-CT, respectively. Twelve percent of the lesions were seen on PET/CT only and 10% on TAP-CT only. Eighteen percent of the metastatic organs were diagnosed with PET/CT only and 7% with TAP-CT only. Thirty-eight percent of the local relapses were seen only with PET/CT. PET/CT depicted three false-positive lesions. Treatment modalities were modified by PET/CT findings in five cases among which one was falsely positive. Tumor size and mitotic rate were significantly associated with FDG uptake. The intensity of FDG uptake (maximum standardized uptake value > 10) and the volume of FDG uptake (>150 ml) were significant prognostic factors for survival. CONCLUSIONS: We show that FDG-PET/CT is complementary to TAP-CT and of special interest in the diagnosis of local relapses.

Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients.

OBJECTIVE: To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA). MATERIALS AND METHODS: Seventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates. RESULTS: The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13-4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22-4.82]; p = 0.011, respectively). CONCLUSION: PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

Cost effectiveness of day 5 G-CSF (Lenograstim) administration after PBSC transplantation: results of a SFGM-TC randomised trial.

This randomised trial was designed to compare two groups treated with different G-CSF administration schedules with a third group receiving no G-CSF, after autologous peripheral blood stem cell transplantation (APBSCT). Children and adults with haematological malignancies or solid tumours were randomly assigned to receive either 150 microg/m2/day of Lenograstim starting on day 1 (G1) or on day 5 (G5) post APBSCT, or no Lenograstim (G0). Randomisation was stratified according to the conditioning regimen (Busulfan vs TBI vs no Busulfan and no TBI) and the graft CD 34+ cell count. A total of 240 patients were randomised; 239 were evaluable. All three patient groups were comparable. Median duration of neutropenia was 9 days (4-40), and 10 days (5-15) in the G1 and G5 groups, respectively, significantly shorter than in the G0 group, 13 days (7-36) (P < 0.0001). No difference was observed in the duration of thrombocytopenia, transfusion support and extra-haematological complications. The duration of post transplant hospitalisation was significantly shorter in adults who received G-CSF. Clinical and cost arguments favour the initiation of G-CSF on day 5 in adults. The same policy could be applied in children given that clinical management is easier and costs are similar.

[Implication of nurses in transfusion safety: knowledge assessment and practice evaluation at the Gustave-Roussy institute]. / Implication du personnel infirmier dans la sécurité transfusionnelle: évaluation des connaissances et de la pratique à l'institut Gustave-Roussy.

BACKGROUND: A first survey on nurses transfusion practices at our Hospital revealed poor knowledge. Good Transfusion Practices were written, a training program was implemented and a second survey was carried out two years later. STUDY DESIGN AN METHODS: We conducted the second survey in which 4 of the questions were identical to those in the first survey in order to assess the impact of this training strategy. The 4 questions were on blood sample identification, checking patient identification, checking "use by date" on blood product bag and the pre-transfusion bedside compatibility test. Behaviours were evaluated by checking the pre-transfusion procedures, including interpretation of bedside compatibility tests. We investigated the impact of attendance at the training course, the period of employment, day versus night shift and attempted to correlate these factors with the results of the second survey. RESULTS: A significant improvement was observed in knowledge of Good Practices between the first and the second survey (P = 10(-4)). However, the multivariate analysis showed that the impact of training was heterogeneous. Pre-transfusion protocol checks have improved significantly (P = 0.05) as well as pre-transfusion bedside compatibility test interpretation of ABO compatibility (P = 0.007). CONCLUSION: In our study, the implementation of Good practices has significantly improved nurses' knowledge about transfusion safety requirements but it is essential to continue and adapt the training and cheek regularly the impact of these implementations.

[Epidemiology of head and neck carcinomas]. / Epidémiologie des carcinomes des voies aérodigestives supérieures.

Head and neck carcinomas, i.e. oral cavity, pharynx and larynx cancers, are frequent among men in France. They are mostly squamous-cell carcinomas. The main risk factors are alcohol and tobacco, and their effects are multiplicative. In France, alcohol and tobacco consumptions are decreasing in the male population leading to decrease in head and neck carcinoma incidence and mortality. The best way to prevent head and neck carcinoma is the reduction of alcohol and tobacco consumption.

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients.

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.

Review article: critical review of meta-analyses of randomized clinical trials in hepatogastroenterology.

BACKGROUND: This review attempts to identify meta-analyses performed in hepatogastroenterology, and to assess their quality and to identify simple criteria of good quality. METHODS: Meta-analyses of randomized clinical trials in hepatogastroenterology published as full papers before 1993 were included. A quality score was defined as the sum of 27 items evaluated in each publication and coded 2 if adequate, 1 if partial and 0 if missing. Quality criteria were identified by discriminant analysis through three groups of meta-analyses defined by their quality score (poor, middle, high). RESULTS: From 1981 to 1992, 62 publications were identified, including 42% in the last 2 years. Nineteen per cent concerned peptic ulcers, 18% oesophageal varices and 6% digestive cancers. They reported 180 meta-analyses. The quality score ranged from 14 to 40, the median was 29. Twenty-five per cent of the studies obtained a score lower than 23 and 25% a score higher than 34. Several stages of meta-analysis were poorly performed: identification and selection of trials, study of trial quality, data extraction and achievement of sensitivity analyses, subgroup and indirect analyses. Some of them led to biases and questions about the validity of results. Five criteria were significantly associated with high quality: presence of a protocol, assessment of trial quality, only randomized trials pooled, achievement of sensitivity analyses, and peer-reviewed publication. CONCLUSIONS: In hepatogastroenterology, there is an exponential increase in publication of meta-analyses but their quality is heterogeneous. In particular, the control of the biases has to be better performed.